UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM10-Q

   QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the quarterly period ended April 3, 20202, 2021
or
   TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Commission File Number: 000-30235
exel-20210402_g1.jpg
EXELIXIS, INC.
(Exact name of registrant as specified in its charter)

Delaware04-3257395
(State or other jurisdiction of incorporation or organization)(I.R.S. Employer Identification Number)

1851 Harbor Bay Parkway
Alameda,CA94502
(650) (650) 837-7000
(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)
Securities registered pursuant to Section 12(b) of the Act:
Title of each classTrading Symbol(s)Name of each exchange on which registered
Common Stock $.001 Par Value per ShareEXELThe Nasdaq Stock Market LLC
Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days).    Yes  ý No 
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).    Yes  ý No 
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filerAccelerated filer
Non-accelerated filerSmaller reporting company
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Securities Act. ¨
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).    Yes   No ý
As of April 27, 2020,26, 2021, there were 306,658,794313,387,205 shares of the registrant’s common stock outstanding.



EXELIXIS, INC.
QUARTERLY REPORT ON FORM 10-Q
INDEX
Page
Item 1.
Item 2.
Item 3.
Item 4.
Item 1.
Item 1A.
Item 2.
Item 3.
Item 4.
Item 5.
Item 6.

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PART I - FINANCIAL INFORMATION
Item 1. Financial Statements
EXELIXIS, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except per share amounts)
(unaudited)
 March 31, 2020 December 31, 2019
ASSETS   
Current assets:   
Cash and cash equivalents$357,340
 $266,501
Short-term investments597,028
 585,742
Trade receivables, net137,338
 119,073
Inventory15,417
 12,886
Prepaid expenses and other current assets29,773
 26,988
Total current assets1,136,896
 1,011,190
Long-term investments486,036
 536,385
Property and equipment, net48,489
 48,892
Deferred tax assets, net163,187
 172,374
Goodwill63,684
 63,684
Other long-term assets57,312
 53,145
Total assets$1,955,604
 $1,885,670
LIABILITIES AND STOCKHOLDERS’ EQUITY   
Current liabilities:   
Accounts payable$15,321
 $11,581
Accrued compensation and benefits26,687
 37,364
Accrued clinical trial liabilities34,969
 38,777
Rebates and fees due to customers23,006
 18,719
Accrued collaboration liabilities8,663
 11,856
Other current liabilities31,831
 24,449
Total current liabilities140,477
 142,746
Long-term portion of deferred revenue14,133
 6,596
Long-term portion of operating lease liabilities47,883
 48,011
Other long-term liabilities5,459
 2,347
Total liabilities207,952
 199,700
Commitments

 

Stockholders’ equity:   
Preferred stock, $0.001 par value, 10,000 shares authorized and no shares issued
 
Common stock, $0.001 par value; 400,000 shares authorized; issued and outstanding: 305,780 and 304,831 at March 31, 2020 and December 31, 2019, respectively306
 305
Additional paid-in capital2,258,307
 2,241,947
Accumulated other comprehensive income (loss)(222) 3,069
Accumulated deficit(510,739) (559,351)
Total stockholders’ equity1,747,652
 1,685,970
Total liabilities and stockholders’ equity$1,955,604
 $1,885,670

 March 31, 2021December 31, 2020
ASSETS
Current assets:
Cash and cash equivalents$370,209 $319,217 
Short-term investments815,285 887,319 
Trade receivables, net177,673 160,875 
Inventory24,757 20,973 
Prepaid expenses and other current assets46,341 57,011 
Total current assets1,434,265 1,445,395 
Long-term investments328,860 330,751 
Property and equipment, net78,453 67,384 
Deferred tax assets, net160,598 156,711 
Goodwill63,684 63,684 
Other long-term assets124,682 73,408 
Total assets$2,190,542 $2,137,333 
LIABILITIES AND STOCKHOLDERS’ EQUITY
Current liabilities:
Accounts payable$13,821 $23,632 
Accrued compensation and benefits37,945 51,189 
Accrued clinical trial liabilities59,762 52,251 
Rebates and fees due to customers31,468 20,683 
Accrued collaboration liabilities13,461 12,456 
Other current liabilities56,880 44,447 
Total current liabilities213,337 204,658 
Long-term portion of deferred revenues9,760 3,755 
Long-term portion of operating lease liabilities52,837 49,086 
Other long-term liabilities3,421 721 
Total liabilities279,355 258,220 
Commitments and contingencies00
Stockholders’ equity:
Preferred stock, $0.001 par value, 10,000 shares authorized and 0 shares issued
Common stock, $0.001 par value; 400,000 shares authorized; issued and outstanding: 313,262 and 311,627 at March 31, 2021 and December 31, 2020, respectively313 312 
Additional paid-in capital2,354,103 2,321,895 
Accumulated other comprehensive income2,740 4,476 
Accumulated deficit(445,969)(447,570)
Total stockholders’ equity1,911,187 1,879,113 
Total liabilities and stockholders’ equity$2,190,542 $2,137,333 
The accompanying notes are an integral part of these Condensed Consolidated Financial Statements.

3

EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF INCOME
(in thousands, except per share amounts)
(unaudited)
 Three Months Ended March 31,
 20212020
Revenues:
Net product revenues$227,212 $193,880 
License revenues27,528 20,879 
Collaboration services revenues15,490 12,156 
Total revenues270,230 226,915 
Operating expenses:
Cost of goods sold13,198 9,289 
Research and development159,288 101,877 
Selling, general and administrative102,351 62,940 
Total operating expenses274,837 174,106 
Income (loss) from operations(4,607)52,809 
Interest income2,682 7,220 
Other income (expense), net(90)
Income (loss) before income taxes(2,015)60,035 
Provision for (benefit from) income taxes(3,616)11,423 
Net income$1,601 $48,612 
Net income per share:
Basic$0.01 $0.16 
Diluted$0.00 $0.15 
Weighted-average common shares outstanding:
Basic312,473 305,388 
Diluted321,287 315,839 
 Three Months Ended March 31,
 2020 2019
Revenues:   
Net product revenues$193,880
 $179,581
License revenues20,879
 25,564
Collaboration services revenues12,156
 10,342
Total revenues226,915
 215,487
Operating expenses:   
Cost of goods sold9,289
 7,501
Research and development101,877
 63,289
Selling, general and administrative62,940
 60,138
Total operating expenses174,106
 130,928
Income from operations52,809
 84,559
Interest income7,220
 6,087
Other income, net6
 25
Income before income taxes60,035
 90,671
Provision for income taxes11,423
 14,896
Net income$48,612
 $75,775
Net income per share:   
Basic$0.16
 $0.25
Diluted$0.15
 $0.24
Weighted-average common shares outstanding:   
Basic305,388
 300,542
Diluted315,839
 314,644
The accompanying notes are an integral part of these Condensed Consolidated Financial Statements.

EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)
(in thousands)
(unaudited)
Three Months Ended March 31,
20212020
Net income$1,601 $48,612 
Other comprehensive income (loss):
Net unrealized losses on available-for-sale debt securities, net of tax impact of $499 and $941, respectively(1,736)(3,291)
Comprehensive income (loss)$(135)$45,321 
 Three Months Ended March 31,
 2020 2019
Net income$48,612
 $75,775
Other comprehensive (loss) income:   
Net unrealized (losses) gains on available-for-sale debt securities, net of tax impact of $941 and ($394), respectively(3,291) 1,429
Comprehensive income$45,321
 $77,204
The accompanying notes are an integral part of these Condensed Consolidated Financial Statements.
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EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(in thousands)
(unaudited)
Three Months Ended March 31, 2021
Common StockAdditional
Paid-in
Capital
Accumulated Other Comprehensive IncomeAccumulated
Deficit
Total
Stockholders’
Equity
SharesAmount
Balance at December 31, 2020311,627 $312 $2,321,895 $4,476 $(447,570)$1,879,113 
Net income— — — — 1,601 1,601 
Other comprehensive loss— — — (1,736)— (1,736)
Issuance of common stock under equity incentive plans1,635 4,201 — — 4,202 
Stock transactions associated with taxes withheld on equity awards— — (6,646)— — (6,646)
Stock-based compensation— — 34,653 — — 34,653 
Balance at March 31, 2021313,262 $313 $2,354,103 $2,740 $(445,969)$1,911,187 
Three Months Ended March 31, 2020
Common StockAdditional
Paid-in
Capital
Accumulated Other Comprehensive Income (loss)Accumulated
Deficit
Total
Stockholders’
Equity
SharesAmount
Balance at December 31, 2019304,831 $305 $2,241,947 $3,069 $(559,351)$1,685,970 
Net income— — — — 48,612 48,612 
Other comprehensive loss— — — (3,291)— (3,291)
Issuance of common stock under equity incentive plans949 4,171 — — 4,172 
Stock transactions associated with taxes withheld on equity awards— — (1,793)— — (1,793)
Stock-based compensation— — 13,982 — — 13,982 
Balance at March 31, 2020305,780 $306 $2,258,307 $(222)$(510,739)$1,747,652 
The accompanying notes are an integral part of these Condensed Consolidated Financial Statements.

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EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
(unaudited)
 Three Months Ended March 31,
 20212020
Net income$1,601 $48,612 
Adjustments to reconcile net income to net cash provided by operating activities:
Depreciation3,227 2,175 
Stock-based compensation34,653 13,982 
Non-cash lease expense1,221 1,174 
Deferred taxes(3,388)10,128 
Other, net6,578 (888)
Changes in operating assets and liabilities:
Trade receivables, net(17,690)(18,270)
Inventory(2,090)(4,695)
Prepaid expenses and other assets1,872 (2,863)
Deferred revenue13,422 8,850 
Accounts payable and other liabilities138 (2,131)
Net cash provided by operating activities39,544 56,074 
Cash flows from investing activities:
Purchases of property, equipment and other(13,557)(2,961)
Purchases of investments(331,612)(251,505)
Proceeds from maturities and sales of investments407,424 287,086 
Net cash provided by investing activities62,255 32,620 
Cash flows from financing activities:
Proceeds from issuance of common stock under equity incentive plans2,791 3,938 
Taxes paid related to net share settlement of equity awards(5,441)(1,793)
Net cash (used in) provided by financing activities(2,650)2,145 
Net increase in cash, cash equivalents and restricted cash equivalents99,149 90,839 
Cash, cash equivalents and restricted cash equivalents at beginning of period320,772 268,137 
Cash, cash equivalents and restricted cash equivalents at end of period$419,921 $358,976 
Supplemental cash flow disclosures:
Non-cash operating activities:
Right-of-use assets obtained in exchange for lease obligations$4,893 $576 

The accompanying notes are an integral part of these Condensed Consolidated Financial Statements.

EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(in thousands)
(unaudited)

6
 Three Months Ended March 31, 2020
 Common Stock Additional Paid-in Capital Accumulated Other Comprehensive Income (Loss) Accumulated Deficit Total Stockholders’ Equity
 Shares Amount    
Balance at December 31, 2019304,831
 $305
 $2,241,947
 $3,069
 $(559,351) $1,685,970
Net income
 
 
 
 48,612
 48,612
Other comprehensive loss
 
 
 (3,291) 
 (3,291)
Issuance of common stock under equity incentive plans, net of tax949
 1
 2,378
 
 
 2,379
Stock-based compensation
 
 13,982
 
 
 13,982
Balance at March 31, 2020305,780
 $306
 $2,258,307
 $(222) $(510,739) $1,747,652


 Three Months Ended March 31, 2019
 Common Stock Additional Paid-in Capital Accumulated Other Comprehensive Income (Loss) Accumulated Deficit Total Stockholders’ Equity
 Shares Amount    
Balance at December 31, 2018299,876
 $300
 $2,168,217
 $(701) $(880,363) $1,287,453
Net income
 
 
 
 75,775
 75,775
Other comprehensive income
 
 
 1,429
 
 1,429
Issuance of common stock under equity incentive plans, net of tax1,644
 2
 7,832
 
 
 7,834
Stock-based compensation
 
 12,529
 
 
 12,529
Balance at March 31, 2019301,520
 $302
 $2,188,578
 $728
 $(804,588) $1,385,020

EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
(unaudited)
 Three Months Ended March 31,
 2020 2019
Net income$48,612
 $75,775
Adjustments to reconcile net income to net cash provided by operating activities:   
Depreciation2,175
 1,962
Stock-based compensation13,982
 12,529
Non-cash lease expense1,174
 440
Deferred taxes10,128
 
Other, net(888) 1,054
Changes in operating assets and liabilities:   
Trade receivables, net(18,270) 55,101
Inventory(4,695) (305)
Prepaid expenses and other assets(2,863) (11,165)
Deferred revenue8,850
 (1,313)
Accounts payable and other liabilities(2,131) 27,515
Net cash provided by operating activities56,074
 161,593
Cash flows from investing activities:   
Purchases of property, equipment and other(2,961) (2,307)
Purchases of investments(251,505) (239,869)
Proceeds from maturities and sales of investments287,086
 134,519
Net cash provided by (used in) investing activities32,620
 (107,657)
Cash flows from financing activities:   
Proceeds from issuance of common stock under equity incentive plans3,938
 6,817
Taxes paid related to net share settlement of equity awards(1,793) (1,580)
Other, net
 (11)
Net cash provided by financing activities2,145
 5,226
Net increase in cash, cash equivalents and restricted cash90,839
 59,162
Cash, cash equivalents and restricted cash at beginning of period268,137
 315,875
Cash, cash equivalents and restricted cash at end of period$358,976
 $375,037
Supplemental cash flow disclosures:   
Right-of-use assets obtained in exchange for lease obligations$576
 $8,170
Unpaid liabilities incurred for purchases of property and equipment$481
 $141

The accompanying notes are an integral partTable of these Condensed Consolidated Financial Statements.Contents

EXELIXIS, INC.
NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS
(unaudited)
NOTE 1. ORGANIZATION AND SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES
Organization
Exelixis, Inc. (Exelixis, we, our or us) is an oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Our drug discovery and development capabilities and commercialization platform are the foundations upon which we intend to bring to market novel, effective and tolerable therapies to provide cancer patients with additional treatment options.
Since we were founded in 1994, 4 products resulting from our discovery efforts have progressed through clinical development, received regulatory approval and established a commercial presence in various geographies around the world. NaN are derived from cabozantinib, our flagship molecule, an inhibitor of multiple tyrosine kinases including MET, AXL, VEGF receptors and RET. Our cabozantinib products are: CABOMETYX® (cabozantinib) tablets approved for advanced renal cell carcinoma (RCC), both alone and in combination with Bristol Myers Squibb Company’s OPDIVO® (nivolumab), and for previously treated hepatocellular carcinoma;carcinoma (HCC); and COMETRIQ® (cabozantinib) capsules approved for progressive, metastatic medullary thyroid cancer. For these types of cancer, cabozantinib has become or is becoming a standard of care. Beyond these approved indications, cabozantinib is currently the focus of a broad clinical development program and is being investigated both alone and in combination with other therapies in a wide variety of cancers.
The other 2 products resulting from our discovery efforts are: COTELLIC® (cobimetinib), an inhibitor of MEK, approved as part of a combination regimenmultiple regimens to treat advanced melanoma and marketed under a collaboration with Genentech, Inc. (a member of the Roche Group) (Genentech); and MINNEBRO® (esaxerenone), an oral, non-steroidal, selective blocker of the mineralocorticoid receptor, approved for the treatment of hypertension in Japan and licensed to Daiichi Sankyo Company, Limited (Daiichi Sankyo).
We remain committed to expanding our oncology product pipeline through our drug discovery efforts, which encompass both small molecule and biologics programs with multiple modalities and mechanisms of action.
Basis of Presentation
The accompanying Condensed Consolidated Financial Statements include the accounts of Exelixis and those of our wholly-owned subsidiaries. These entities’ functional currency is the U.S. dollar. All intercompany balances and transactions have been eliminated.
The accompanying unaudited Condensed Consolidated Financial Statements have been prepared in accordance with accounting principles generally accepted in the U.S. for interim financial information and pursuant to Form 10-Q and Article 10 of Regulation S-X of the Securities and Exchange Commission (SEC). Accordingly, they do not include all of the information and footnotes required by U.S. generally accepted accounting principles for complete financial statements. In our opinion, all adjustments (consisting only of normal recurring adjustments) considered necessary for a fair presentation of our financial statements for the periods presented have been included. Operating results for the three months ended March 31, 20202021 are not necessarily indicative of the results that may be expected for the year ending December 31, 20202021 or for any future period. The accompanying Condensed Consolidated Financial Statements and Notes thereto should be read in conjunction with our Consolidated Financial Statements and Notes thereto for the year ended December 31, 2019,2020, included in our Annual Report on Form 10-K filed withsubmitted to the SEC on February 25, 2020.10, 2021.
We have adopted a 52- or 53-week fiscal year policy that generally ends on the Friday closest to December 31st. Fiscal year 2020,2021, which is a 52-week fiscal year, will end on January 1,December 31, 2021 and fiscal year 2019,2020, which was a 53-week52-week fiscal year, ended on January 3, 2020.1, 2021. For convenience, references in this report as of and for the three months ended April 2, 2021 and April 3, 2020, and March 29, 2019, and as of and for the fiscal years endingyear ended January 1, 2021, and ended January 3, 2020, are indicated as being as of and for the three monthsfiscal periods ended March 31, 2021 and March 31, 2020 and March 31, 2019 and the years endingyear ended December 31, 2020, and ended December 31, 2019, respectively. Similarly, references in this report to the first day of the fiscal year ending January 1, 2021 are indicated as being as of January 1, 2020.
Reclassifications
Certain prior period amounts in the accompanying Condensed Consolidated Financial Statements have been reclassified to conform to the current period presentation. Such reclassifications did not impact previously reported total revenue, income from operations, net income, total assets, total liabilities or total stockholders’ equity.

Segment Information
We operate in 1 business segment that focuses on the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Our Chief Executive Officer, as the chief operating decision-maker, manages and allocates resources to our operations on a total consolidated basis. Consistent with this decision-making process, our Chief
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Executive Officer uses consolidated, single-segment financial information for purposes of evaluating performance, forecasting future period financial results, allocating resources and setting incentive targets.
All of our long-lived assets are located in the U.S. See “Note 2. Revenues” for enterprise-wide disclosures about product sales, revenues from major customers and revenues by geographic region.
Use of Estimates
The preparation of the accompanying Condensed Consolidated Financial Statements conforms to accounting principles generally accepted in the U.S., which requires management to make judgments, estimates and assumptions that affect the reported amounts of assets, liabilities, equity, revenues and expenses, and related disclosures. On an ongoing basis, we evaluate our significant estimates. We base our estimates on historical experience and on various other market-specific and other relevant assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results could differ materially from those estimates.
In March 2020, we receivedReclassifications
Certain prior period amounts in the 2020 preliminary fee noticeaccompanying Condensed Consolidated Financial Statements have been reclassified to conform to the current period presentation. Such reclassifications did not impact previously reported total revenues, income from the Internal Revenue Serviceoperations, net income, total assets, total liabilities or total stockholders’ equity.
Significant Accounting Policies
Except for the Branded Prescription Drug Feeforeign currency forward contracts for the 2018 sales year, which resulted in an increase innon-designated hedges, there have been no material changes to our estimate of such fees for the 2018 and 2019 sales years. Accordingly, we recorded an adjustmentsignificant accounting policies during the three months ended March 31, 20202021, as compared to increase selling, general and administrative expenses andthe significant accounting policies disclosed in Note 1 – Significant Accounting Policies included in the our accrual for these fees by $5.4 million. This adjustment resulted in a decrease of basic and diluted earnings per share of $0.02Annual Report on Form 10-K for the three monthsyear ended March 31, 2020. Our total accrual for the Branded Prescription Drug Fee was $13.4 million and $6.0 million as of March 31, 2020 and December 31, 2019, respectively,2020.
Foreign Currency Forward Contracts for Non-Designated Hedges
We may use forward foreign currency exchange contracts (forward contracts) to hedge certain operational exposures resulting from potential changes in foreign currency exchange rates. Our strategy is to enter into foreign currency forward contracts so that increases or decreases in our foreign currency exposures are offset by gains or losses on the foreign currency forward contracts thereby mitigating the risks and volatility associated with our foreign currency transactions. We do not apply hedge accounting treatment to these non-designated hedging instruments. We do not hold or issue derivative instruments for trading or speculative purposes.
Our foreign currency forward contracts are generally short-term in duration. Given the short duration of which $8.6 millionthe forward contracts, amounts recorded generally are not significant. We account for our derivative instruments as either assets or liabilities on our Condensed Consolidated Balance Sheets and $4.4 million was recordedmeasure them at fair value. Derivatives not designated as hedging instruments are adjusted to fair value through earnings in other current liabilities, and $4.8 million and $1.6 million was recordedincome (expense), net in other long-term liabilities.the Condensed Consolidated Statements of Income.
Recently Adopted Accounting Pronouncements
On January 1, 2020,2021, we adopted the Accounting Standards Board’s (FASB) Accounting Standards Update (ASU) No. 2018-18, Collaborative Arrangements (Topic 808): Clarifying the Interaction between Topic 808 and Topic 606 (ASU 2018-18). ASU 2018-18 clarifies that certain transactions between collaborative arrangement participants should be accounted for as revenue under Accounting Standards Codification (ASC) Topic 606, Revenue from Contracts with Customers (Topic 606) when the counterparty is a customer for a distinct good or service (i.e. a unit of account). For units of account that are in the scope of Topic 606, all of the guidance in Topic 606 should be applied, including the guidance on recognition, measurement, presentation and disclosure. ASU 2018-18 precludes entities from presenting amounts related to transactions with a counterparty in a collaborative arrangement that is not a customer as revenue from contracts with customers. If a portion of a distinct bundle of goods or services within an arrangement is not with a customer, then the unit of account is not within the scope of Topic 606, and the recognition and measurement of that unit of account shall be based on analogy to authoritative accounting literature or, if there is no appropriate analogy, a reasonable, rational, and consistently applied accounting policy election. Upon adoption of ASU 2018-18, we have presented revenue from performance obligations associated with our collaboration arrangements that are within the scope of Topic 606 (license revenues) separately from revenue from performance obligations that are not subject to Topic 606 (collaboration services revenues). The adoption of ASU 2018-18 was applied retrospectively, and prior periods have been restated to conform to the presentation proscribed by ASU 2018-18. The adoption of ASU 2018-18 did not impact total revenues for the prior period presented in our Condensed Consolidated Statements of Income.
On January 1, 2020, we adopted ASU No. 2017-04, Intangibles—Goodwill and Other (Topic 350): Simplifying the Test for Goodwill Impairment (ASU 2017-04). ASU 2017-04 simplifies goodwill impairment testing by eliminating the second step of the impairment test. The amended guidance requires an impairment charge to be recognized for the amount by which the carrying amount of a reporting unit exceeds its fair value under a one-step impairment test. The adoption of ASU 2017-04 did not impact our Condensed Consolidated Financial Statements.
On January 1, 2020, we adopted ASU No. 2016-13, Financial Instruments—Credit Losses (Topic 326) (ASU 2016-13). ASU 2016-13 implements an impairment model, known as the current expected credit loss model, that is based on expected losses rather than incurred losses. Under the new guidance, we will recognize our estimate of current expected credit losses

as an allowance on financial assets measured at amortized cost, including accounts receivable, unbilled collaboration revenue, and investments classified as available for sale. Current expected credit losses were immaterial as of the date of adoption, and the adoption of ASU 2016-13 did not have a significant impact on our Condensed Consolidated Financial Statements.
Investment Impairment
Quarterly, we assess each of our investments in available-for-sale debt securities whose fair value is below its cost basis to determine if the investment’s impairment is due to credit-related factors or noncredit-related factors. Factors considered in determining whether an impairment is credit-related include the extent to which the investment’s fair value is less than its cost basis, declines in published credit ratings, issuer default on interest or principal payments, and declines in the financial condition and near-term prospects of the issuer. If we determine a credit-related impairment exists, we will measure the credit loss based on a discounted cash flows model. Credit-related impairments on available-for-sale debt securities are recognized as an allowance for credit losses with a corresponding adjustment to other income, net in the accompanying Condensed Consolidated Statements of Income. The portion of the impairment that is not credit-related is recorded, net of applicable taxes, as a reduction of other comprehensive income.
We have elected to exclude accrued interest from both the fair value and the amortized cost basis of the available-for-sale debt security for the purposes of identifying and measuring an impairment. We write-off accrued interest as a reduction of interest income when an issuer has defaulted on interest payments due on the security.
Accounts Receivable
Trade receivables, net contain amounts billed to our customers for product sales, and amounts billed to our collaboration partners for development, regulatory and sales-based milestone payments, royalties on the sale of licensed products, profit-sharing arrangements, development cost reimbursements, and payments for product supply services. Our customers are primarily pharmaceutical and biotechnology companies that are located in the U.S., and collaboration partners that are located in Europe and Japan. We record trade receivables net of allowances for credit losses and chargebacks, and cash discounts for prompt payment. We apply an aging method to estimate credit losses and consider our historical loss information, adjusted to account for current conditions, and reasonable and supportable forecasts of future economic conditions affecting our customers.
Goodwill
We recorded goodwill amounts as the excess purchase price over tangible assets, liabilities and intangible assets acquired based on their estimated fair value. We review the carrying amount of goodwill for impairment annually and whenever events or changes in circumstance indicate that the carrying value may not be recoverable. We perform our annual assessment of the recoverability of our goodwill as of the first day of our fourth quarter. The assessment of recoverability may first consider qualitative factors to determine whether the existence of events or circumstances leads to a determination that it is more likely than not that the fair value of a reporting unit is less than its carrying amount. We perform a quantitative assessment if the qualitative assessment results in a more-likely-than-not determination or if a qualitative assessment is not performed. The quantitative assessment determines whether the carrying amount of a reporting unit exceeds its fair value, in which case an impairment charge is recognized for the amount by which the carrying amount of a reporting unit exceeds its fair value, limited to the goodwill balance. We operate in 1 business segment, which is also considered to be our sole reporting unit and therefore, goodwill is tested for impairment at the enterprise level. We did 0t recognize any impairment charges in any of the periods presented.
Collaboration Agreements
We assess whether our collaboration agreements are subject to ASC Topic 808, Collaborative Arrangements (Topic 808) based on whether they involve joint operating activities and whether both parties have active participation in the arrangement and are exposed to significant risks and rewards. To the extent that the arrangement falls within the scope of Topic 808, we apply the unit of account guidance under Topic 606 to identify distinct performance obligations, and then determine whether a customer relationship exists for each distinct performance obligation. If we determine a performance obligation within the arrangement is with a customer, we apply the guidance in Topic 606. If a portion of a distinct bundle of goods or services within an arrangement is not with a customer, then the unit of account is not within the scope of Topic 606, and the recognition and measurement of that unit of account shall be based on analogy to authoritative accounting literature or, if there is no appropriate analogy, a reasonable, rational, and consistently applied accounting policy election.

We enter into collaboration arrangements, under which we license certain rights to our intellectual property to third parties. The terms of these arrangements typically include payments to us for one or more of the following: non-refundable, up-front license fees; development, regulatory and sales-based milestone payments; product supply services; development cost reimbursements; profit-sharing arrangements; and royalties on net sales of licensed products. As part of the accounting for these arrangements, we develop assumptions that require judgment to determine the standalone selling price for each performance obligation identified in the contract. These key assumptions may include forecasted revenues, clinical development timelines and costs, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success.
Up-front License Fees: If the license to our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize revenues from nonrefundable, up-front fees allocated to the license when the license is transferred to the licensee and the licensee is able to use and benefit from the license. For licenses that are bundled with other promises, we utilize judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from non-refundable, up-front fees. We evaluate the measure of progress at the end of each reporting period and, if necessary, adjust the measure of performance and related revenue recognition.
Regulatory and Development Milestone Payments: At the inception of each arrangement that includes development milestone payments, we evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within our or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until uncertainty associated with the approvals has been resolved. The transaction price is then allocated to each performance obligation, on a relative standalone selling price basis, for which we recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, we re-evaluate the probability of achieving such development and regulatory milestones and any related constraint, and if necessary, adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis.
Product Supply Services: Arrangements that include a promise for the future supply of drug product for either clinical development or commercial supply at the licensee’s discretion are generally considered as options. We assess if these options provide a material right to the licensee and if so, they are accounted for as separate performance obligations.
Development Cost Reimbursements: Our collaboration arrangements may include promises of future clinical development and drug safety services, as well as participation on certain joint committees. When such services are provided to a customer, and they are distinct from the licenses provided to our collaboration partners, these promises are accounted for as a separate performance obligation which we estimate using internal development costs incurred and projections through the term of the arrangements. We record revenue for these services as the performance obligations are satisfied over time. However, if we conclude that our collaboration partner is not a customer for those collaborative research and development activities, we present such payments as a reduction of research and development expenses.
Profit-sharing Arrangements: Under the terms of our collaboration agreement with Genentech for cobimetinib, we are entitled to a share of U.S. profits and losses received in connection with the commercialization of cobimetinib. We account for this arrangement in accordance with Topic 606. We have determined that we are an agent under the agreement and therefore revenues are recorded net of costs incurred. We record revenue for the variable consideration associated with the profits and losses under the collaboration agreement when it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur.
Royalty and Sales-based Milestone Payments: For arrangements that include royalties and sales-based milestone payments, including milestone payments earned for the first commercial sale of a product, the license is deemed to be the predominant item to which such payments relate and we recognize revenue at the later of when the related sales occur or when the performance obligation to which the royalty has been allocated has been satisfied.
Recent Accounting Pronouncements Not Yet Adopted
In December 2019, the Financial Accounting Standards Board issued ASU 2019-12, Income Taxes (Topic 740)-Simplifying the Accounting for Income Taxes (ASU 2019-12). ASU 2019-12 simplifies the accounting for income taxes by removing certain exceptions to the general principles in ASCAccounting Standards Codification (ASC) Topic 740, Income Taxes and clarifying and amending existing

guidance. ASU 2019-12 will be effective for us in the first quarter of 2021 with earlyOur adoption permitted. We are currently assessing the impact of ASU 2019-12 did not have a significant impact on the accompanying Condensed Consolidated Financial Statements.
Recent Accounting Pronouncements Not Yet Adopted
There were no new accounting pronouncements issued since our filing of the Annual Report on Form 10-K for the year ended December 31, 2020, which could have a significant effect on our condensed consolidated financial statements.
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NOTE 2. REVENUES
Revenues consisted of the following (in thousands):
 Three Months Ended March 31,
 2020 2019
Product revenues:   
Gross product revenues$252,566
 $223,750
Discounts and allowances(58,686) (44,169)
Net product revenues193,880
 179,581
Collaboration revenues:   
License revenues20,879
 25,564
Collaboration services revenues12,156
 10,342
Total collaboration revenues33,035
 35,906
Total revenues$226,915
 $215,487

Three Months Ended March 31,
20212020
Product revenues:
Gross product revenues$314,205 $252,566 
Discounts and allowances(86,993)(58,686)
Net product revenues227,212 193,880 
Collaboration revenues:
License revenues27,528 20,879 
Collaboration services revenues15,490 12,156 
Total collaboration revenues43,018 33,035 
Total revenues$270,230 $226,915 
The percentage of total revenues by customer who individually accounted for 10% or more of our total revenues were as follows:
Three Months Ended March 31,
20212020
Affiliates of CVS Health Corporation15 %18 %
Affiliates of AmerisourceBergen Corporation14 %11 %
Affiliates of McKesson Corporation13 %15 %
Ipsen Pharma SAS13 %13 %
Affiliates of Optum Specialty Pharmacy%12 %
The percentage of trade receivables by customer who individually accounted for 10% or more of our trade receivables were as follows:
March 31, 2021December 31, 2020
Ipsen Pharma SAS22 %23 %
Affiliates of McKesson Corporation18 %12 %
Affiliates of AmerisourceBergen Corporation16 %11 %
Affiliates of CVS Health Corporation12 %11 %
Takeda Pharmaceutical Company Limited%10 %
Revenues by geographic region were as follows (in thousands):
Three Months Ended March 31,
20212020
U.S.$229,957 $196,596 
Europe33,806 29,036 
Japan6,467 1,283 
Total revenues$270,230 $226,915 
Total revenues include net product revenues attributed to geographic regions based on the ship-to location and license and collaboration services revenues attributed to geographic regions based on the location of our collaboration partners’ headquarters.
Net product revenues and license revenues wereare recorded in accordance with ASC Topic 606. The related goods and intellectual property license revenues have been recognized at a point in time.606, Revenue from Contracts with Customers (Topic 606). License revenues include the recognition of the portion of upfront and milestones payments allocated to the transfer of intellectual property licenses for which it had become probable in the current period that the
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milestone would be achieved and a significant reversal of revenues would not occur, as well as royalty revenues and our share of profits on the U.S. commercialization of COTELLIC.under our collaboration agreement with Genentech. Collaboration services revenues were recorded in accordance with ASU 2018-18, Collaborative Arrangements (Topic 808): Clarifying the Interaction between Topic 808 and Topic 606 and by analogy to Topic 606. Collaboration services revenues include the recognition of deferred revenuerevenues for the portion of upfront and milestone payments allocated to our research and development services performance obligations, development cost reimbursements earned under our collaboration agreements, product supply revenues, net of product supply costs, and the royalties we paid to GlaxoSmithKline (GSK) on sales by Ipsen Pharma SAS (Ipsen) of products containing cabozantinib.cabozantinib by our collaboration partners. We received notification that, effective January 1, 2021, Royalty Pharma plc (Royalty Pharma) acquired from GSK all rights, title and interest in royalties on net product sales containing cabozantinib for non-U.S. markets for the full term of the royalty and for the U.S. market through September 2026, after which time U.S. royalties will revert back to GSK.
Net product revenues by product were as follows (in thousands):
 Three Months Ended March 31,
 2020 2019
CABOMETYX$189,216
 $175,890
COMETRIQ4,664
 3,691
Net product revenues$193,880
 $179,581

The percentage of total revenues by customer who individually accounted for 10% or more of our total revenues were as follows:
 Three Months Ended March 31,
 2020 2019
Affiliates of CVS Health Corporation18% 15%
Affiliates of McKesson Corporation15% 12%
Ipsen13% 10%
Affiliates of AmerisourceBergen Corporation11% 10%
Affiliates of Optum Specialty Pharmacy12% 8%
Accredo Health, Incorporated8% 10%


Revenues by geographic region were as follows (in thousands):
 Three Months Ended March 31,
 2020 2019
U.S.$196,596
 $182,126
Europe29,036
 21,868
Japan1,283
 11,493
Total revenues$226,915
 $215,487

Net product revenues are attributed to geographic region based on the ship-to location. Collaboration revenues are attributed to geographic region based on the location of our collaboration partners’ headquarters.
Three Months Ended March 31,
20212020
CABOMETYX$223,595 $189,216 
COMETRIQ3,617 4,664 
Net product revenues$227,212 $193,880 
Product Sales Discounts and Allowances
The activities and ending reserve balances for each significant category of discounts and allowances, which constitute variable consideration, were as follows (in thousands):
 Chargebacks and Discounts for Prompt Payment Other Customer Credits/Fees and Co-pay Assistance Rebates Total
Balance at December 31, 2019$7,514
 $3,497
 $15,222
 $26,233
Provision related to sales made in:       
Current period37,686
 4,586
 15,821
 58,093
Prior periods41
 (167) 719
 593
Payments and customer credits issued(32,584) (4,842) (11,830) (49,256)
Balance at March 31, 2020$12,657
 $3,074
 $19,932
 $35,663

Chargebacks, Discounts for Prompt Payment and OtherOther Customer Credits/Fees and Co-pay AssistanceRebatesTotal
Balance at December 31, 2020$9,853 $3,279 $17,404 $30,536 
Provision related to sales made in:
Current period52,470 8,054 25,232 85,756 
Prior periods(27)(2)1,266 1,237 
Payments and customer credits issued(49,636)(5,622)(15,935)(71,193)
Balance at March 31, 2021$12,660 $5,709 $27,967 $46,336 
The allowance for chargebacks, and discounts for prompt payment isand other are recorded as a reduction of trade receivables, net and the remaining reserves are recorded as rebates and fees due to customers or as other current liabilities in the accompanying Condensed Consolidated Balance Sheets.
Contract Assets and Liabilities
We receive payments from our collaboration partners based on billing schedules established in each contract. Amounts are recorded as accounts receivable when our right to consideration is unconditional. We may also recognize revenue in advance of the contractual billing schedule and such amounts are recorded net of any allowance for credit losses, as a contract asset when recognized. Contract assets, which are presented in prepaid expenses and other current assets in the accompanying Condensed Consolidated Balance Sheets, were $0 and $1.1 million as of March 31, 2020 and December 31, 2019, respectively. We may be required to defer recognition of revenue for upfront and milestone payments until we perform our obligations under these arrangements, and such amounts are recorded as deferred revenue upon receipt or when due. Contract liabilities were $15.4 million and $6.6 million as of March 31, 2020 and December 31, 2019, respectively. The current portion of the contract liabilities, which are presented in other current liabilities in the accompanying Condensed Consolidated Balance Sheets, were $1.3 million and $0 as of March 31, 2020 and December 31, 2019, respectively. The remainder of the contract liabilities are presented in long-term portion of deferred revenue in the accompanying Condensed Consolidated Balance Sheets. For those contracts that have multiple performance obligations, contract assets and liabilities are reported on a net basis at the contract level. Contract assets and liabilities were as follows (in thousands):
Significant changes
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March 31, 2021December 31, 2020
Contract assets$$
Contract liabilities:
Current portion(1)
$9,207 $1,790 
Long-term portion(2)
9,760 3,755 
Total contract liabilities$18,967 $5,545 
____________________
(1) Presented in contract assets duringother current liabilities in the three months ended March 31, 2020, as compared to December 31, 2019, includeaccompanying Condensed Consolidated Balance Sheets.
(2) Presented in the impactlong-term portion of a $10.0 million milestone from Takeda Pharmaceutical Company Limited (Takeda) which was achieved, invoiced and collected duringdeferred revenues in the period.accompanying Condensed Consolidated Balance Sheets.
During the three months ended March 31, 20202021 and 2019,2020, we recognized $1.6$2.5 million and $1.3$1.6 million, respectively, in revenues that were included in the beginning deferred revenuerevenues balance for those years.periods.
During the three months ended March 31, 20202021, and 2019,2020, we recognized $18.8$27.8 million and $25.3$18.8 million, respectively, in revenues for performance obligations satisfied in previous periods. Such revenues were primarily related to

milestone and royalty payments allocated to ourthe license performance obligations offor our collaborations with Ipsen Pharma SAS (Ipsen), Takeda Pharmaceutical Company Limited (Takeda), Daiichi Sankyo Company, Limited (Daiichi Sankyo) and Daiichi Sankyo.Genentech Inc. (a member of the Roche Group) (Genentech).
As of March 31, 2020, $65.12021, $87.3 million of thethe combined transaction price wasprices for our Ipsen and Takeda collaborations were allocated to performance obligations that had not yet been satisfied, which was considered in the determination of contract assets and liabilities.satisfied. See “Note 3. Collaboration Agreements - Cabozantinib Commercial Collaborations - Performance Obligations and Transaction Prices for our Ipsen and Takeda Collaborations” to our Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 20192020 for information about the expected timing to satisfy these performance obligations.
NOTE 3. COLLABORATION AGREEMENTS AND IN-LICENSING ARRANGEMENTS
We have established multiple collaborations with leading pharmaceutical companies for the commercialization and further development of our cabozantinib franchise. Additionally, in linewe have entered into several research collaborations and in-licensing arrangements to further enhance our early-stage pipeline and expand our ability to discover, develop and commercialize novel therapies with our business strategy prior to the commercializationgoal of our first product, COMETRIQ, weproviding new treatment options for cancer patients and their physicians. We also entered into other collaborations with leading pharmaceutical companies for other compounds and programs in our portfolio. Under these collaborations, we are generally entitled to receive milestone and royalty payments, and for certain collaborations, payments for product supply services, development cost reimbursements, and/or profit-sharing payments. See “Note 2. Revenues” for additional information on revenues recognized under our collaboration agreements during the three months ended March 31, 2020 and 2019.
We have also established multiple collaborations with smaller, discovery-focused biotechnology companies to expand our product pipeline. Under these collaborations, we may be required to make milestone and royalty payments, and for certain collaborations, payments for option exercise fees and/or development cost reimbursements.
See “Note 3. Collaboration Agreements” to our Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 20192020, or as further described below, for a description ofadditional information on each of our collaboration agreements.agreements and in-licensing arrangements.
Cabozantinib Collaborations
Ipsen Collaboration
In February 2016, we entered into a collaboration and license agreement with Ipsen for the commercialization and further development of cabozantinib. Under the terms of the collaboration agreement, as amended, Ipsen received exclusive commercialization rights for current and potential future cabozantinib indications outside of the U.S., Canada and Japan. The collaboration agreement was subsequently amended on three occasions, including in December 2016 to include commercialization rights in Canada. We have also agreed to collaborate with Ipsen on the development of cabozantinib for current and potential future indications. The parties’ efforts are governed through a joint steering committee and appropriate subcommittees established to guide and oversee the collaboration’s operation and strategic direction; provided, however, that we retain final decision-making authority with respect to cabozantinib’s ongoing development.
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Revenues under the collaboration agreement with Ipsen were as follows (in thousands):
 Three Months Ended March 31,
 2020 2019
License revenues$17,949
 $13,963
Collaboration services revenues11,087
 7,905
Total$29,036
 $21,868

Three Months Ended March 31,
20212020
License revenues$22,451 $17,949 
Collaboration services revenues11,355 11,087 
Total$33,806 $29,036 
As of March 31, 2020, $46.62021, $44.8 million of the transactiontransaction price was allocated to our research and development services was related to performance obligations that hadhas not yet been satisfied.
Takeda Collaboration
In January 2017, we entered into a collaboration and license agreement with Takeda, which was subsequently amended effective March 2018, and May 2019 and September 2020 to, among other things, modify the amount of reimbursements we are eligible to receive for costs associated with our required pharmacovigilance activities, andmodify the amount of milestones we are eligible to receive. Underreceive, and modify certain cost sharing obligations related to the Japan-specific development costs associated with CONTACT-01 and CONTACT-02 clinical trials. Pursuant to this collaboration and license agreement, as amended, Takeda has exclusive commercialization rights for current and potential future cabozantinib indications in Japan, and the parties have agreed to collaborate on the clinical development of cabozantinib in Japan. The operation and strategic direction of the parties’ collaboration is governed through a joint executive committee and appropriate subcommittees.

Revenues under the collaboration agreement with Takeda were as follows (in thousands):
 Three Months Ended March 31,
 2020 2019
License revenues$
 $9,056
Collaboration services revenues1,069
 2,437
Total$1,069
 $11,493

Three Months Ended March 31,
20212020
License revenues$1,301 $
Collaboration services revenues4,135 1,069 
Total$5,436 $1,069 
As of March 31, 2020, $18.52021, $42.5 million of the transaction price was allocated to our research and development services was related to performance obligations that hadhas not yet been satisfied.
GSK & Royalty Pharma
In October 2002, we established a product development and commercialization collaboration agreement with GSK. We areGSK, that required us to pay a 3% royalty to GSK on the worldwide net sales of any product incorporating cabozantinib by us and our collaboration partners. As disclosed in Note 2, we received notification that, effective January 1, 2021, Royalty Pharma acquired from GSK all rights, title and interest in royalties on net product sales containing cabozantinib for non-U.S. markets for the full term of the royalty and for the U.S. market through September 2026, after which time U.S. royalties will revert back to GSK. Royalties earned by GSK and Royalty Pharma in connection with theour sales of cabozantinib are included in cost of goods sold for sales by us and as a reduction of collaboration services revenues for sales by our collaboration partners. Such royalties were $8.1$10.1 million and $7.3$8.1 million during the three months ended March 31, 20202021 and 2019,2020, respectively.
Genentech Collaboration
In December 2006, we out-licensed the development and commercialization of cobimetinib to Genentech under a worldwide collaboration agreement. In November 2015, the U.S. Food and Drug Administration (FDA) approved cobimetinib, under the brand name COTELLIC, in combination with Genentech’s ZelborafZELBORAF® (vemurafenib) as afor the treatment forof patients with BRAF V600E or V600K mutation-positive advanced melanoma. COTELLIC in combination with ZelborafZELBORAF has also been approved in the European Union and multiple additional countries for use in the same indication. In July 2020, the FDA also approved COTELLIC for use in combination with ZELBORAF and TECENTRIQ® (atezolizumab) for the treatment of patients with BRAF V600 mutation-positive advanced melanoma in previously untreated patients. License revenues under the collaboration agreement with Genentech were as follows (in thousands):
 Three Months Ended March 31,
 2020 2019
Profits on U.S. commercialization$1,407
 $1,055
Royalty revenues on ex-U.S. sales$1,309
 $1,490
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 Three Months Ended March 31,
 20212020
Profits on U.S. commercialization$1,794 $1,407 
Royalty revenues on ex-U.S. sales$951 $1,309 
Research Collaborations and In-Licensing Arrangements
In the first quarter of 2021, we entered into additional licensing and collaboration agreements in support of our preclinical pipeline with Adagene, Inc. (Adagene) and WuXi Biologics Ireland Ltd (WuXi Bio). As part of these agreements we made aggregate upfront payments of $14.0 million in exchange for licenses to develop and commercialize products. We committed to make payments to Adagene for potential future development milestones of $55.0 million, regulatory milestones of $200.0 million, and commercial milestones of $525.0 million, each in the aggregate, as well as royalties on future net product sales. We also committed to make payments to WuXi Bio for potential future development milestones of $18.5 million, regulatory milestones of $30.0 million, and commercial milestones of $80.0 million, each per product, as well as royalties on future net product sales.
NOTE 4. CASH AND INVESTMENTS
Cash, Cash Equivalents and Restricted Cash Equivalents
A reconciliation of cash, cash equivalents, and restricted cash equivalents reported within ourin the accompanying Condensed Consolidated Balance Sheets to the amount reported within the accompanying Condensed Consolidated Statements of Cash Flows was as follows (in thousands):
 March 31, 2020 December 31, 2019
Cash and cash equivalents$357,340
 $266,501
Restricted cash equivalents included in long-term investments1,636
 1,636
Cash, cash equivalents, and restricted cash equivalents as reported within the accompanying Condensed Consolidated Statements of Cash Flows$358,976
 $268,137

 March 31, 2021December 31, 2020
Cash and cash equivalents$370,209 $319,217 
Restricted cash equivalents included in other long-term assets49,712 1,555 
Cash, cash equivalents, and restricted cash equivalents as reported in the accompanying Condensed Consolidated Statements of Cash Flows$419,921 $320,772 
Restricted cash equivalents consistedare used to collateralize letters of credit and consist of money-market funds and certificates of deposit with original maturities of 90 days or less used to collateralize letters of credit.less. The classification of restricted cash equivalents are classified as other long-term isassets based upon the remaining term of the underlying restriction.

As of March 31, 2021, restricted cash equivalents included $48.2 million of short-term investments as collateral under our standby letter of credit entered into in January 2021 as guarantee of our obligation to fund our portion of the total tenant improvements related to our build-to-suit lease at our corporate campus.
Cash, Cash Equivalents, Restricted Cash Equivalents and Investments
Cash, cash equivalents, restricted cash equivalents and investments consisted of the following (in thousands):
March 31, 2020March 31, 2021
Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair ValueAmortized CostGross Unrealized GainsGross Unrealized LossesFair Value
Debt securities available-for-sale:       Debt securities available-for-sale:
Commercial paper$202,452
 $
 $
 $202,452
Commercial paper$667,071 $219 $(1)$667,289 
Corporate bonds741,315
 2,404
 (3,448) 740,271
Corporate bonds495,490 3,609 (275)498,824 
U.S. Treasury and government-sponsored enterprises152,922
 788
 
 153,710
U.S. Treasury and government-sponsored enterprises148,208 83 (7)148,284 
Municipal bonds15,148
 140
 
 15,288
Municipal bonds27,776 64 (8)27,832 
Total debt securities available-for-sale1,111,837
 3,332
 (3,448) 1,111,721
Total debt securities available-for-sale1,338,545 3,975 (291)1,342,229 
Cash8,905
 
 
 8,905
Cash52,757 52,757 
Money market funds273,497
 
 
 273,497
Money market funds105,775 105,775 
Certificates of deposit46,279
 2
 
 46,281
Certificates of deposit63,305 63,305 
Total cash and investments$1,440,518
 $3,334
 $(3,448) $1,440,404
Total cash, cash equivalents, restricted cash equivalents and investmentsTotal cash, cash equivalents, restricted cash equivalents and investments$1,560,382 $3,975 $(291)$1,564,066 
 December 31, 2019
 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value
Debt securities available-for-sale:       
Commercial paper$389,573
 $
 $
 $389,573
Corporate bonds752,295
 3,934
 (3) 756,226
U.S. Treasury and government-sponsored enterprises166,483
 187
 (5) 166,665
Total debt securities available-for-sale1,308,351
 4,121
 (8) 1,312,464
Cash40,964
 
 
 40,964
Money market funds2,467
 
 
 2,467
Certificates of deposit32,728
 5
 
 32,733
Total cash and investments$1,384,510
 $4,126
 $(8) $1,388,628
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December 31, 2020
Amortized CostGross Unrealized GainsGross Unrealized LossesFair Value
Debt securities available-for-sale:
Commercial paper$569,456 $372 $$569,828 
Corporate bonds543,520 5,244 (7)548,757 
U.S. Treasury and government-sponsored enterprises208,326 232 (4)208,554 
Municipal bonds28,680 83 (1)28,762 
Total debt securities available-for-sale1,349,982 5,931 (12)1,355,901 
Cash82,176 82,176 
Money market funds40,761 40,761 
Certificates of deposit60,004 60,004 
Total cash, cash equivalents, restricted cash equivalents and investments$1,532,923 $5,931 $(12)$1,538,842 
Interest receivable was $5.4$3.6 million and $6.2$4.5 million as of March 31, 20202021 and December 31, 2019,2020, respectively, and is included in prepaid expenses and other current assets in the accompanying Condensed Consolidated Balance Sheets.
Realized gains and losses on the sales of investments available-for-sale were insignificant during the three months ended March 31, 20202021 and 2019.2020.
We manage credit risk associated with our investment portfolio through our investment policy, which limits purchases to high-quality issuers and limits the amount of our portfolio that can be invested in a single issuer. The fair value and gross unrealized losses on investmentdebt securities available-for-sale in an unrealized loss position were as follows (in thousands):
March 31, 2021
Fair ValueGross Unrealized Losses
Commercial paper$4,722 $(1)
Corporate bonds131,468 (275)
U.S. Treasury and government-sponsored enterprises31,981 (7)
Municipal bonds12,120 (8)
Total$180,291 $(291)
March 31, 2020December 31, 2020
Fair Value Gross Unrealized LossesFair ValueGross Unrealized Losses
Corporate bonds$351,135
 $(3,448)Corporate bonds$28,445 $(7)
U.S. Treasury and government-sponsored enterprisesU.S. Treasury and government-sponsored enterprises21,989 (4)
Municipal bondsMunicipal bonds5,865 (1)
Total$351,135
 $(3,448)Total$56,299 $(12)

 December 31, 2019
 Fair Value Gross Unrealized Losses
Corporate bonds$14,529
 $(3)
U.S. Treasury and government-sponsored enterprises2,848
 (5)
Total$17,377
 $(8)

All securities presented have been in an unrealized loss position for less than 12 months as of March 31, 2020 and December 31, 2019.months. There were 14453 and 914 investments in an unrealized loss position as of March 31, 20202021 and December 31, 2019,2020, respectively. During the three months ended March 31, 20202021 and 2019,2020, we did 0t record an allowance for credit losses or other impairment charges on our investment securities. Based upon our quarterly impairment review, we determined that the unrealized losses were not attributed to credit risk but were primarily associated with changes in interest rates and market liquidity. Based on the scheduled maturities of our investments, we determined that it was more likely than not that we will hold these investments for a period of time sufficient for a recovery of our cost basis.
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The fair value of debt securities available-for-sale by contractual maturity was as follows (in thousands):
 March 31, 2020 December 31, 2019
Maturing in one year or less$641,070
 $789,913
Maturing after one year through five years470,651
 522,551
Total debt securities available-for-sale$1,111,721
 $1,312,464

 March 31, 2021December 31, 2020
Maturing in one year or less$1,021,369 $1,034,150 
Maturing after one year through five years320,860 321,751 
Total debt securities available-for-sale$1,342,229 $1,355,901 
NOTE 5. FORWARD CURRENCY CONTRACTS
In January 2021, we initiated an operational hedging program and entered into forward contracts to hedge certain operational exposures for the changes in foreign currency exchanges rates associated with assets or liabilities denominated in foreign currencies, primarily the Euro.
As of March 31, 2021, we had 1 forward contract outstanding to sell €9.3 million. The forward contract has a maturity of three months, is recorded at fair value and is included in prepaid expenses and other current assets in the Condensed Consolidated Balance Sheets. The fair value of the forward contract at March 31, 2021 was not material. The forward contract is considered a Level 2 in the fair value hierarchy of our fair value measurements. For the three months ended March 31, 2021, we recognized $0.4 million of gains on the maturity of our forward contracts, which is included in other income (expense), net on our Condensed Consolidated Statements of Income.
NOTE 5.6. FAIR VALUE MEASUREMENTS
Fair value reflects the amounts that would be received upon sale of an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. The fair value hierarchy has the following three levels:
Level 1 - quoted prices (unadjusted) in active markets for identical assets and liabilities;
Level 2 - inputs other than level 1 that are observable either directly or indirectly, such as quoted prices in active markets for similar instruments or on industry models using data inputs, such as interest rates and prices that can be directly observed or corroborated in active markets;
Level 3 - unobservable inputs that are supported by little or no market activity that are significant to the fair value measurement
The classifications within the fair value hierarchy of our financial assets that were measured and recorded at fair value on a recurring basis were as follows (in thousands):
March 31, 2021
Level 1Level 2Total
Commercial paper$$667,289 $667,289 
Corporate bonds498,824 498,824 
U.S. Treasury and government-sponsored enterprises148,284 148,284 
Municipal bonds27,832 27,832 
Total debt securities available-for-sale1,342,229 1,342,229 
Money market funds105,775 105,775 
Certificates of deposit63,305 63,305 
Total financial assets carried at fair value$105,775 $1,405,534 $1,511,309 
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 March 31, 2020
 Level 1 Level 2 Total
Commercial paper$
 $202,452
 $202,452
Corporate bonds
 740,271
 740,271
U.S. Treasury and government-sponsored enterprises
 153,710
 153,710
Municipal bonds
 15,288
 15,288
Total debt securities available-for-sale
 1,111,721
 1,111,721
Money market funds273,497
 
 273,497
Certificates of deposit
 46,281
 46,281
Total financial assets carried at fair value$273,497
 $1,158,002
 $1,431,499

 December 31, 2019
 Level 1 Level 2 Total
Commercial paper$
 $389,573
 $389,573
Corporate bonds
 756,226
 756,226
U.S. Treasury and government-sponsored enterprises
 166,665
 166,665
Total debt securities available-for-sale
 1,312,464
 1,312,464
Money market funds2,467
 
 2,467
Certificates of deposit
 32,733
 32,733
Total financial assets carried at fair value$2,467
 $1,345,197
 $1,347,664

December 31, 2020
Level 1Level 2Total
Commercial paper$$569,828 $569,828 
Corporate bonds548,757 548,757 
U.S. Treasury and government-sponsored enterprises208,554 208,554 
Municipal bonds28,762 28,762 
Total debt securities available-for-sale1,355,901 1,355,901 
Money market funds40,761 40,761 
Certificates of deposit60,004 60,004 
Total financial assets carried at fair value$40,761 $1,415,905 $1,456,666 
When available, we value investments based on quoted prices for those financial instruments, which is a Level 1 input. Our remaining investments are valued using third-party pricing sources, which use observable market prices, interest rates and yield curves observable at commonly quoted intervals for similar assets as observable inputs for pricing, which is a Level 2 input.
The carrying amount of our remaining financial assets and liabilities, which include cash, receivables and payables, approximate their fair values due to their short-term nature.
NOTE 6.7. INVENTORY
Inventory consisted of the following (in thousands):
 March 31, 2020 December 31, 2019
Raw materials$2,215
 $2,709
Work in process14,278
 9,447
Finished goods4,865
 4,367
Total$21,358
 $16,523
Balance Sheet classification:   
Current portion included in inventory$15,417
 $12,886
Long-term portion included in other long-term assets5,941
 3,637
Total$21,358
 $16,523

 March 31, 2021December 31, 2020
Raw materials$7,988 $7,773 
Work in process21,873 20,610 
Finished goods5,786 7,291 
Total$35,647 $35,674 

Balance Sheet classification:
Current portion included in inventory$24,757 $20,973 
Long-term portion included in other long-term assets10,890 14,701 
Total$35,647 $35,674 
Write-downs related to excess and expiring inventory were $2.1 million and $0.2 million for the three months ended March 31, 2021 and 2020, respectively.
NOTE 7.8. STOCK-BASED COMPENSATION
We allocated the stock-based compensation expense for our equity incentive plans and our 2000 Employee Stock Purchase Plan (ESPP) as follows (in thousands):
Three Months Ended March 31,
20212020
Research and development$12,396 $5,086 
Selling, general and administrative22,257 8,896 
Total stock-based compensation expense$34,653 $13,982 
 Three Months Ended March 31,
 2020 2019
Research and development$5,086
 $4,306
Selling, general and administrative8,896
 8,223
Total stock-based compensation$13,982
 $12,529
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Stock-based compensation for each type of award under our equity incentive plans and ESPP were as follows (in thousands):
Three Months Ended March 31,
20212020
Stock options$4,694 $4,994 
Restricted stock units11,669 7,797 
Performance stock units17,947 496 
ESPP343 695 
Total stock-based compensation expense$34,653 $13,982 
As of March 31, 2021, 9,272,614 shares were available for grant under the Exelixis, Inc. 2017 Equity Incentive Plan (as amended and restated, the 2017 Plan). The share reserve is reduced by 1 share for each share issued pursuant to a stock option and 1.5 shares for full value awards granted in the form of restricted stock units (RSUs). 
During the three months endedMarch 31, 2020,2021, we granted 271,370881,440 stock options with a weighted average exercise price of $18.84$21.75 per share and a weighted average grant date fair value of $8.27$9.88 per share.share. As of March 31, 2020,2021, there were 19,750,43815,688,044 stock options outstanding and there was $30.3$30.7 million of related unrecognized compensation expense related to our unvested stock options.expense.
During the three months endedMarch 31, 2020,2021, we granted 595,6853,059,698 service-based restricted stock units (RSUs) with a weighted average grant date fair value of $20.87$21.43 per share. As of March 31, 2020,2021, there were 9,104,1328,282,867 RSUs outstanding and there was $160.0$155.9 million of related unrecognized compensation expense related to our unvested RSUs.expense.
Stock options and RSUs granted to employees during the three months endedMarch 31, 20202021 have vesting conditions and contractual lives of a similar nature to those described in “Note 8. Employee Benefit Plans” of the Notes to Consolidated Financial Statements included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2019.2020.
In March 2021, we awarded 1,027,650 (the target amount) performance-based restricted stock units (PSUs), subject to a performance and a market condition (the 2021 PSUs). Pursuant to the terms of 2021 PSUs, the holders of the awards may earn up to 200% of the target amount of shares, depending on the level of achievement of the performance condition related to certain net product revenues and a total shareholder return (TSR) market condition. The TSR market condition is based on our relative TSR percentile rank compared to companies in the NASDAQ Biotechnology Index during the performance period, which is January 2, 2021 through December 29, 2023. NaN percent of the shares earned subject to the performance and market conditions will vest at the end of the performance period and the remainder will vest approximately one year later subject to employee’s continuous service. The 2021 PSUs will be forfeited if the performance condition at or above a threshold level is not achieved by December 29, 2023.
NOTE 8. INCOME TAXESA Monte Carlo simulation model was used to determine the grant date fair value of $24.54 for the 2021 PSUs based on the following assumptions:
Our effective income tax
Fair value of the Company’s common stock on grant date$21.31 
Expected volatility49 %
Risk-free interest rate0.29 %
Dividend yield%
The Monte Carlo simulation model also assumed correlations of returns of the stock prices of the Company’s common stock and the common stock of a peer group of companies and historical stock price volatility of the peer group of companies. The valuation model also used terms based on the length of the performance period and compound annual growth rate was 19.0%goals for total stockholder return based on the provisions of the award.
As of March 31, 2021, there were 8,767,305 PSUs outstanding and 16.4% during$161.2 million of related unrecognized compensation expense. Expense recognition for PSUs commences when it is determined that achievement of the performance target is probable. During the three months ended March 31, 2020 and 2019, respectively.2021, we achieved additional performance targets for 461,532 additional PSUs granted during 2019. For more information about our PSUs, see “Note 8. Employee Benefit Plans” of the Notes to Consolidated Financial Statements included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2020.
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NOTE 9. PROVISION FOR (BENEFIT FROM) INCOME TAXES
The effective tax rate for the three months ended March 31, 2021 differed from the U.S. federal statutory tax rate of 21% primarily due to excess tax benefits related to the exercise of certain stock options, in relation to the generation of a small pre-tax loss during the period. The effective tax rate for the three months ended March 31, 2020 differed from the U.S. federal statutory tax rate of 21% primarily due to excess tax benefits related to the exercise of certain stock options during the period and the generation of researchfederal tax credits. The effective tax rate for the three months ended March 31, 2019 differed from the U.S. federal statutory rate of 21% primarily due to excess tax benefits related to the exercise of certain stock options during the period.
NOTE 9.10. NET INCOME PER SHARE
Net income per share - basic and diluted, were computed as follows (in thousands, except per share amounts):
 Three Months Ended March 31,
 2020 2019
Numerator:   
Net income$48,612
 $75,775
Denominator:   
Weighted-average common shares outstanding - basic305,388
 300,542
Dilutive effect of employee stock plans10,451
 14,102
Weighted-average common shares outstanding - diluted315,839
 314,644
Net income per share - basic$0.16
 $0.25
Net income per share - diluted$0.15
 $0.24

Three Months Ended March 31,
20212020
Numerator:
Net income$1,601 $48,612 
Denominator:
Weighted-average common shares outstanding — basic312,473 305,388 
Dilutive securities8,814 10,451 
Weighted-average common shares outstanding — diluted321,287 315,839 
Net income per share — basic$0.01 $0.16 
Net income per share — diluted$0.00 $0.15 
Dilutive securities included outstanding stock options and PSOs, unvested RSUs and PSUs and ESPP contributions.
Certain potential common shares were excluded from our calculation of weighted-average common shares outstanding - diluted because either they would have had an anti-dilutive effect on net income per share or they arewere related to shares from stock options that have a market vesting condition and performance stock unitsPSUs that were contingently issuable for whichand the contingency had not been satisfied. Thesesatisfied at the end of the reporting period. The weighted-average potential common shares excluded from our calculation were as follows (in thousands):
Three Months Ended March 31,
20212020
Anti-dilutive securities and contingently issuable shares excluded10,007 12,014 
NOTE 11. COMMITMENTS AND CONTINGENCIES
In September 2019, we received a notice letter regarding an Abbreviated New Drug Application (ANDA) submitted to the FDA by MSN Pharmaceuticals, Inc. (MSN), requesting approval to market a generic version of CABOMETYX tablets. MSN’s initial notice letter included a Paragraph IV certification with respect to our U.S. Patent Nos. 8,877,776, 9,724,342, 10,034,873 and 10,039,757, which are listed in the Approved Drug Products with Therapeutic Equivalence Evaluations, also referred to as the Orange Book. MSN’s initial notice letter did not provide a Paragraph IV certification against U.S. Patent No. 7,579,473, the composition of matter patent, or U.S. Patent No. 8,497,284, a method of use patent. On October 29, 2019, we filed a complaint in the United States District Court for the District of Delaware for patent infringement against MSN asserting U.S. Patent No. 8,877,776 arising from MSN’s ANDA filing with the FDA. On November 20, 2019, MSN filed its response to the complaint, alleging that U.S. Patent No. 8,877,776 is invalid and not infringed. On May 5, 2020, we received notice from MSN that it had amended its ANDA to assert additional Paragraph IV certifications. The ANDA now requests approval to market a generic version of CABOMETYX tablets prior to expiration of the two previously unasserted CABOMETYX patents: U.S. Patent No. 7,579,473 and U.S. Patent No. 8,497,284. On May 11, 2020, we filed a complaint in the United States District Court for the District of Delaware for patent infringement against MSN asserting U.S. Patent No. 7,579,473 and U.S. Patent No. 8,497,284 arising from MSN’s amended ANDA filing with the FDA. Neither of our complaints alleges infringement of U.S. Patent Nos. 9,724,342, 10,034,873 and 10,039,757. On May 22, 2020, MSN filed its response to the complaint, alleging that each of U.S. Patent No. 7,579,473 and U.S. Patent No. 8,497,284 is invalid and not infringed. On March 23, 2021, MSN filed its First Amended Answer and Counterclaims (amending its prior filing from May 22, 2020), seeking, among other things, a declaratory judgment that U.S. Patent No. 9,809,549 is invalid and would not be infringed by
 Three Months Ended March 31,
 2020 2019
Anti-dilutive securities and contingently issuable shares excluded12,014
 5,089
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MSN if its generic version of CABOMETYX tablets were approved by the FDA. On April 7, 2021, we filed our response to MSN’s First Amended Answer and Counterclaims, denying, among other things, that U.S. Patent No. 9,809,549 is invalid or would not be infringed. In our complaints, we are seeking, among other relief, an order that the effective date of any FDA approval of the ANDA would be a date no earlier than the expiration of all of U.S. Patent No. 7,579,473, U.S. Patent No. 8,497,284 and U.S. Patent No. 8,877,776, the latest of which expires on October 8, 2030, and equitable relief enjoining MSN from infringing these patents. These lawsuits against MSN have been consolidated, and a bench trial has been scheduled for May 2022.
In May 2021, we received a notice letter from Teva Pharmaceuticals USA, Inc. (Teva) regarding an ANDA Teva submitted to the FDA, requesting approval to market a generic version of CABOMETYX tablets. Teva’s notice letter included a Paragraph IV certification with respect to our U.S. Patent Nos. 9,724,342 (formulations), 10,034,873 (methods of treatment) and 10,039,757 (methods of treatment), which are listed in the Orange Book and expire in 2033, 2031 and 2031, respectively. Teva’s notice letter did not provide a Paragraph IV certification against any additional CABOMETYX patents. We are reviewing the details of the Paragraph IV certification notice.
The sale of any generic version of CABOMETYX earlier than its patent expiration could significantly decrease our revenues derived from the U.S. sales of CABOMETYX and thereby materially harm our business, financial condition and results of operations. It is not possible at this time to determine the likelihood of an unfavorable outcome or estimate of the amount or range of any potential loss.
We may also from time to time become a party or subject to various other legal proceedings and claims, either asserted or unasserted, which arise in the ordinary course of business. Some of these proceedings have involved, and may involve in the future, claims that are subject to substantial uncertainties and unascertainable damages.
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.
This Quarterly Report on Form 10-Q contains forward-looking statements. These statements are based on Exelixis, Inc.’s (Exelixis, we, our or us) current expectations, assumptions, estimates and projections about our business and our industry and involve known and unknown risks, uncertainties and other factors that may cause our company’s or our industry’s results, levels of activity, performance or achievements to be materially different from any future results, levels of activity, performance or achievements expressed or implied in, or contemplated by, the forward-looking statements. Our actual results and the timing of events may differ significantly from the results discussed in the forward-looking statements. Factors that might cause such a difference include those discussed in “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q, as well as those discussed elsewhere in this report. These and many other factors could affect our future financial and operating results. We undertake no obligation to update any forward-looking statement to reflect events after the date of this report.
This discussion and analysis should be read in conjunction with our condensed consolidated financial statements and accompanying notes included in this report and the consolidated financial statements and accompanying notes thereto included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2019 filed with2020 submitted to the Securities and Exchange Commission (SEC) on February 25, 2020.10, 2021.
Overview
We are an oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Since we were founded in 1994, four products resulting from our discovery efforts have progressed through clinical development, received regulatory approval and established a commercial presence in various geographies around the world. Two are derived from cabozantinib, our flagship molecule, an inhibitor of multiple tyrosine kinases including MET, AXL, VEGF receptors and RET. Our cabozantinib products are: CABOMETYX® (cabozantinib) tablets approved for advanced renal cell carcinoma (RCC), both alone and in combination with Bristol-Myers Squibb Company’s (BMS) OPDIVO® (nivolumab), and for previously treated hepatocellular carcinoma (HCC); and COMETRIQ® (cabozantinib) capsules approved for progressive, metastatic medullary thyroid cancer (MTC). For these types of cancer, cabozantinib has become or is becoming a standard of care.
The other two products resulting from our discovery efforts are: COTELLIC® (cobimetinib), an inhibitor of MEK, approved as part of amultiple combination regimenregimens to treat a specific formforms of advanced melanoma and marketed under a collaboration with Genentech, Inc. (a member of the Roche Group) (Genentech); and MINNEBRO® (esaxerenone), an oral,
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non-steroidal, selective blocker of the mineralocorticoid receptor, approved for the treatment of hypertension in Japan and licensed to Daiichi Sankyo Company, Limited (Daiichi Sankyo).
The U.S. Food and Drug Administration (FDA) first approved CABOMETYX for previously treated patients with advanced RCC in April 2016, and in December 2017 the FDA expanded CABOMETYX’s approval to include previously untreated patients with advanced RCC. Additionally, in January 2019, the FDA approved CABOMETYX as afor the treatment forof patients with HCC who have been previously treated with sorafenib. Most recently on January 22, 2021, the FDA approved CABOMETYX in combination with OPDIVO as a first-line treatment of patients with advanced RCC.
To develop and commercialize CABOMETYX and COMETRIQ outside the U.S., we have entered into license agreements with Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited (Takeda). We granted to Ipsen the rights to develop and commercialize cabozantinib outside of the U.S. and Japan, and to Takeda the rights to develop and commercialize cabozantinib in Japan. Both Ipsen and Takeda also contribute financially and operationally to the further global development and commercialization of the cabozantinib franchise in other potential indications, and we continue to work closely with them on these activities. Utilizing its regulatory expertise and established international oncology marketing network, Ipsen has continued to execute on its commercialization plans for CABOMETYX, having received regulatory approvals and launched in multiple territories outside of the U.S., including in the European Union (EU) and Canada, as a treatment for advanced RCC and for HCC in adults who have previously been treated with sorafenib. In addition, in March 2021, Ipsen and BMS received regulatory approval from the European Commission (EC) for CABOMETYX in combination with OPDIVO as a first-line treatment for patients with advanced RCC , and both Ipsen and BMS plan to submit applications to approve the combination in other territories beyond the EU. With respect to the Japanese market, Takeda has achieved important regulatory milestones in 2020, including receipt of approvalreceived Manufacturing and Marketing Approvals from the Japanese Ministry of Health, Labour and Welfare (MHLW) to manufacture and marketof CABOMETYX as a treatment forof patients with curatively unresectable or metastatic RCC and the submissionas a treatment of itspatients with unresectable HCC who progressed after cancer chemotherapy. In October 2020, Takeda and Ono Pharmaceutical Co., Ltd. (Ono), BMS’ development and commercialization partner in Japan, submitted a supplemental application to the Japanese MHLW for Manufacturing and Marketing Approval of CABOMETYX as ain combination with OPDIVO for the treatment forof patients with unresectable, HCC who progressed after prior systemic therapy.advanced or metastatic RCC.
In addition to our regulatory and commercialization efforts in the U.S. and the support provided to our collaboration partners for rest-of-world regulatory and commercialization activities, we are also pursuing other indications for cabozantinib that have the potential to increase the number of cancer patients who could benefit from this medicine. We are evaluating cabozantinib, both as a single agent and in combination with other therapies, in a broad

development program comprising over 90100 ongoing or planned clinical trials across multiple indications. We, along with our collaboration partners, sponsor some of the trials, and independent investigators conduct the remaining trials through our Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP) or our investigator-sponsored trial program. Informed by the available data from these clinical trials, we continue to advance cabozantinib’sthe development program for the cabozantinib franchise with potentially label-enabling trials. One pivotal trial that has resulted from this effort is COSMIC-311, our ongoing phase 3 pivotal trial evaluating cabozantinib versus placebo in patients with radioiodineradioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) who have progressed after up to two VEGF receptor-targeted therapies. We plan to conduct an analysis in these first 100 patients enrolled inIn December 2020, we announced that COSMIC-311 for thehad met its co-primary endpoint of objective response rate (ORR), and an interim analysis ofdemonstrating significant improvement in progression-free survival (PFS), and in February 2021, we announced the second half of 2020.FDA had granted Breakthrough Therapy Designation to cabozantinib as a potential treatment for patients with RAI-refractory DTC who have progressed following prior therapy. We intend to discuss the study results, proposed changes to the study conduct, as well as plans for filing an sNDA with the FDA in 2021.
We are particularly interested in examiningcontinuing to evaluate cabozantinib’s potential in combination with immune checkpoint inhibitors (ICIs) to determine if suchthese combinations further improve outcomes for patients. Building on preclinical and clinical observations that cabozantinib may promote a more immune-permissive tumor environment potentially resulting in cooperative activity of cabozantinib in combination with these products, we are evaluating cabozantinib in combination with a variety of ICIs. The most advanced of these combination studies is CheckMate -9ER, a phase 3 pivotal trial evaluating the combination of cabozantinib and nivolumab compared to sunitinib in previously untreated advanced or metastatic RCC, for which we and our collaboration partner Bristol-Myers Squibb Company (BMS)BMS announced positive top-line results in April 2020. CheckMate -9ER2020, is reflective of this strategy. The trial met its primary endpoint of PFS at final analysis, as well as the secondary endpoints of overall survival (OS) at a pre-specified interim analysis and ORR. The resultsobjective response rate (ORR), and showed that the combination of cabozantinib with nivolumab significantly reducedimproved the three key efficacy outcomes as compared with sunitinib, doubling PFS and ORR and reducing the risk of disease progression or death by 40 percent compared with sunitinib (hazard ratio [HR]=0.51, p<0.0001)sunitinib. Data from CheckMate -9ER served as the basis for the FDA’s and EC’s approval of CABOMETYX in combination with OPDIVO as a first-line treatment of patients with advanced RCC in January 2021 and March 2021, respectively. We are also significantly improved OS compared to sunitinib (HR=0.60, p<0.001). We have also collaboratedcollaborating with BMS on CheckMate 040, a multi-cohort phase 1/2 trial evaluating cabozantinib in combination with nivolumab and in combination with both nivolumab and ipilimumab in patients with previously treated or previously untreated advanced HCC, for which initial clinically meaningful results were presented at American Society of Clinical Oncology’s (ASCO’s) Gastrointestinal Cancers Symposium in January 2020, and COSMIC-313, a phase 3
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pivotal trial evaluating the triplet combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC. We expect to complete enrollmentEnrollment for COSMIC-313 was completed in earlyMarch 2021, and we expect to report top-line results of the event-driven analyses from the trial in the 2022 timeframe.2022.
In an effort to diversifyexpand our exploration of combinations with ICIs, we have also initiated multiple trials evaluating cabozantinib in combination with F. Hoffmann-La Roche Ltd.’s (Roche) ICI, atezolizumab. COSMIC-312 is a phase 3 pivotal trial evaluating cabozantinib in combination with F. Hoffmann-La Roche Ltd.’s (Roche’s) ICI, atezolizumab versus sorafenib in previously untreated advanced HCC, for which we announced in August 2020 that enrollment was completed. Based on current event rates, we anticipate announcing top-line results in the second quarter of 2021, and if the data are supportive, we anticipate filing a supplemental New Drug Application (sNDA) with the FDA in the second half of 2021. COSMIC-021 is a broad phase 1b study evaluating the safety and tolerability of cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic solid tumors. COSMIC-021 is divided into two parts: a dose-escalation phase, which was completed in 2018; and an expansion phase, which is ongoing. Findings from the dose-escalation stage of COSMIC-021 demonstrated that the combination was well-tolerated and showed encouraging anti-tumor activity in patients with advanced RCC. The expansion phase of COSMIC-021 comprises 24 total cohorts, with 20 cohorts evaluating the combination of cabozantinib and atezolizumab and four cohorts evaluating cabozantinib or atezolizumab as single-agent therapies. Based on continuing encouraging efficacy and safety data certain cohorts have been or may be further expanded, including the cohorts of patients with non-small cell lung cancer (NSCLC) who have been previously treated with an ICI and metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with enzalutamide and/or abiraterone acetate and experienced radiographic disease progression in soft tissue. We anticipate enrollingcompleting enrollment of up to 1,732 patients in the trial in late 2020, whichthe first half of 2021, although both the timing isand final number of patients are subject to the initiation of additional cohorts or expansion of selected existing cohorts, as well as potentialany further delays resulting from the COVID-19 pandemic. Since itsthe initiation of the trial, data from COSMIC-021 have been instrumental in guiding our clinical development strategy for cabozantinib in combination with ICIs, including supporting plannedthe initiation of COSMIC-312, and three phase 3 pivotal trials in collaboration with Roche, CONTACT-01, CONTACT-02 and CONTACT-03, evaluating the combination of cabozantinib with atezolizumab in patients with metastatic NSCLC, mCRPC and RCC. Encouraging results from an interim analysis of the mCRPC cohort of COSMIC-021 were presented at ASCO’s Genitourinary Cancer Symposium in February 2020.advanced RCC, respectively. Based on regulatory feedback from the FDA, and if supported by the clinical data, we intend to file with the FDA for accelerated approval in an mCRPC indication as early asin 2021.
We also remain committed to buildingexpanding our oncology product pipeline through drug discovery efforts, which encompass both small molecule and biologics programs with multiple modalities and mechanisms of action. Our small molecule discovery programs are supported by discoveringa robust and developing newexpanding infrastructure, including a library of 4.6 million compounds. We have extensive experience in the identification and optimization of drug candidates against multiple target classes for oncology, inflammation and metabolic diseases. The first compound to advance from our recent drug discovery efforts is XL092, a next-generation oral tyrosine kinase inhibitor that targets VEGF receptors, MET, AXL, MER and other kinases implicated in cancer’s growth and spread. In designing XL092, we sought to build upon our experience with cabozantinib, retaining the target profile of cabozantinib while improving key characteristics, including the pharmacokinetic half-life. We are currently evaluating XL092 in STELLAR-001, a phase 1b clinical trial in patients with advanced solid tumors, for which dose-escalation cohorts evaluating the compound, both as a single agent and in combination with atezolizumab, are currently enrolling, and we expect the trial will begin to enroll patients in additional dose-escalation cohorts evaluating XL092 in combination with avelumab, an ICI developed by Merck KGaA, Darmstadt, Germany (Merck KGaA) and Pfizer Inc. (Pfizer), during the second quarter of 2021. We expect that once recommended doses of both single-agent XL092 and XL092 in combination with atezolizumab or avelumab are established, the trial will begin to enroll expansion cohorts for patients with clear cell and non-clear cell RCC, hormone-receptor positive breast cancer, therapies for patients. Notably,mCRPC and urothelial carcinoma (UC).
We also augment our internal small molecule discovery activities through research collaborations and in-licensing arrangements with other companies engaged in small molecule discovery. The most advanced compound to emerge from these efforts are led by somearrangements is XL102 (formerly AUR102), the lead program targeting cyclin-dependent kinase 7 under our collaboration with Aurigene Discovery Technologies Limited (Aurigene). In December 2020, based on encouraging preclinical data, we exercised our exclusive option to license XL102 from Aurigene. Following the FDA’s acceptance of our Investigational New Drug (IND) application in December 2020, we initiated a phase 1 clinical trial of the same experienced scientists that led thecompound in January 2021.
Beyond small molecules, we have additionally launched rigorous efforts to discover cabozantinib, cobimetinib and esaxerenone,advance biologic drug candidates, such as bispecific antibodies, antibody drug conjugates (ADCs) and other innovative biologics that have the potential to become anti-cancer therapies. To facilitate the growth of these biologics programs, we have established multiple research collaborations and in-licensing arrangements, expanding our access to antibodies or other binders, which are the starting point for use with additional technology platforms that we employ to generate next-generation ADCs or bispecific antibodies. Most recently, we entered into a collaboration and license agreement with Adagene Inc. (Adagene), focused on using Adagene’s SAFEbodyTM technology to develop novel masked ADCs or other innovative biologics with potential for improved therapeutic index, as well as an exclusive license agreement with WuXi Biologics Ireland Limited, a
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wholly owned subsidiary of WuXi Biologics (Cayman) Inc. (individually and collectively referred to as WuXi Bio), focused on leveraging WuXi Bio’s panel of monoclonal antibodies (mAbs) for the development of ADC, bispecific and certain other novel tumor-targeting biologics applications. We have been approvedalready made significant progress under our biologics-focused research collaborations and in-licensing arrangements and believe we will continue to do so during the remainder of 2021. For example, based on promising preclinical data for commercialization. UsingXB002 (formerly known as ICON-2), the lead Tissue Factor ADC program under our expertiseresearch collaboration with Iconic Therapeutics, Inc. (Iconic), we exercised our exclusive option to license XB002 in medicinal chemistry, tumor biologyDecember 2020. Following the FDA’s acceptance of our IND in April 2021, we expect to initiate a phase 1 clinical trial of XB002 during the second quarter of 2021. Also, in May 2021, we executed an asset purchase agreement with GamaMabs Pharma SA (GamaMabs), under which we will, upon the closing of the asset purchase and pharmacologysubject to certain conditions, acquire all rights, title and supported byinterest in GamaMabs’ antibody program directed at anti-Müllerian hormone receptor 2 (AMHR2), a novel oncology target with relevance in multiple forms of cancer.
We will continue to engage in business development initiatives aimed at acquiring and in-licensing promising oncology platforms and assets and then further characterize and develop them utilizing our in-licensing partners,established preclinical and clinical development infrastructure. In total, we are advancing drug candidates across approximately 20 ongoing discovery programs toward and through preclinical development, with plans for upand subject to three new compoundspreclinical data, we have the potential to reach Investigational New Drug (IND) filing status before the end of 2020.

The first compound to advance from our internal drug discovery efforts is XL092, a next-generation oral tyrosine kinase inhibitor that is currentlysubmit multiple INDs later in a phase 1 clinical trial in patients with advanced solid malignancies. We anticipate that dose expansion cohorts and potential combination cohorts with ICIs of this phase 1 trial will begin to enroll in 2020. We augment our internal drug discovery activities with business development initiatives aimed at identifying and in-licensing promising, early-stage oncology assets and then further develop them utilizing our established clinical development infrastructure. In furtherance of this strategy, in 2019, we entered into collaboration and license agreements with Aurigene Discovery Technologies Limited (Aurigene), which is focused on the discovery and development of novel small molecules as therapies for cancer, and Iconic Therapeutics, Inc. (Iconic), which is focused on the advancement of a next-generation antibody-drug conjugate (ADC) program targeting the tissue factor in solid tumors. Both the lead Aurigene program targeting CDK7 and tissue factor ADC program with Iconic are in preclinical development and could result in IND filings in 2020. We have also made progress under our 2018 collaborations with Invenra, Inc., which is focused on the discovery and development of multispecific antibodies for the treatment of cancer, and StemSynergy Therapeutics, Inc., which is focused on the discovery and development of novel oncology compounds aimed to inhibit tumor growth by targeting Casein Kinase 1 alpha. To further enhance our early-stage pipeline, we expect to enter into additional, external collaborative relationships around assets and technologies that complement our internal drug discovery and development efforts.2021.
COVID-19 Update
As of the date of this Quarterly Report, the COVID-19 pandemic has hadcontinues to have a relatively modest impact on our business operations, in particular on our clinical trial, and drug discovery and commercial activities. We are undertakinghave and continue to undertake considerable efforts to mitigate the various problems presented by this crisis, including as described below:
Clinical Trials.Clinical Trials. To varying degrees and at different rates across our clinical trials, being conducted in regions impacted by COVID-19, we have seen a declineexperienced declines in screening and enrollment activity during the early days of the COVID-19 pandemic, as well as delays in new site activations and restrictions on the access to treatment sites that is necessary to monitor clinical study progress and administration. However,Beginning during the second quarter of 2020 and throughout the rest of 2020 and the first quarter of 2021, however, that trend reversed, and screening and enrollment activity began to increase. As a result, we and our collaboration partners, including principal investigators and personnel at clinical trial sites, have thus far been successful atoverall in preventing material delays to our ongoing and planned clinical trials.trials due to the COVID-19 pandemic. We have done this through ongoing assessment of the COVID-19 pandemic’s impact and, wherever possible, taking proactive steps in compliance with guidance issued by the FDA, European Medicines Agency (EMA)EMA and other regulatory agencies to support the safety of our patients and their access to treatment, as well as to maintain the high quality of our clinical trials. We recognize, however, that we may have to make further operational adjustments to our ongoing and planned clinical trials and that patient enrollment, and new clinical trial site initiations may be further slowed ifdue to the COVID-19 pandemic, continues andespecially if it is further prolonged or grows in severity.
Drug Discovery and Preclinical Development. We have suspendedpartially resumed internal drug discovery in our laboratories temporarilyfollowing a temporary suspension of these activities while we observeobserved the shelter in place orders issued by the State of California and Alameda County. While always givingthis temporary suspension did not result in any significant changes to the health and safetytimelines for our late-stage discovery work, we did experience modest delays in the advancement of certain of our employees paramount importance, we are exploring various strategies for returning employees to work on-site to the extent it is critical for those employees to be on-site to be productive.early-stage programs. We also experienced some modest delays with respect to the portion of drug discovery work outsourced to third-party contractors in regions first impacted by COVID-19. However, those service providers have resumed discovery work and are now meeting their contractual obligations in accordance with planned timelines. PriorWith respect to the COVID-19 pandemic, we largely outsourced preclinical development work outsourced to third-party contractors, andto date that work has continued without substantial delay or interference due toresulting from the COVID-19 pandemic. While we continue to effectively utilize our resources to move new product candidates toward the clinic, we may ultimately be unable to achieve our drug discovery and preclinical development objectives within the previously disclosed timelines if the COVID-19 pandemic continues and grows in severity.
Supply Chain. We have not yet experienced production delays or seen significant impairment to our supply chain. In addition, we have substantial safety stock inventories for both our commercial drug substance and drug products, which should be sufficient to maintain regular supply over a long period of time. Nevertheless, we are working closely with our third-party contract manufacturers, suppliers, comparator drug sourcing vendors and collaboration partners to assess and be able to modify manufacturing and supply chain operations if the COVID-19 pandemic continues and grows in severity.
Commercial Activities. Although they are not traveling or otherwise engaged in personal in-officeOur field employees have partially resumed their in-person promotional activities our commercial field employeeswhile supplementing these activities with telephonic and medical science liaisonsvirtual interactions. These efforts enabled them to remain engaged with healthcare professionals and areto be available to them as an informational resource. With respect to CABOMETYX sales, we have not yet observed any meaningful changes in ordering patterns as a result ofOverall, despite the challenges posed by the COVID-19 pandemic.pandemic, we believe our commercial business has been only modestly impacted. We believe this is the case largely because of the gravity of the cancer conditions that our products are indicated to treat and the fact thatbecause CABOMETYX has been available as an orally administrable cancer treatment in the U.S. since 2016,

with a which means its safety and efficacy profile that is well known to most healthcare providers. It remains possible, however,professionals that overtreat the conditions for which it is indicated.
Supply Chain. We have not experienced production delays or seen any significant impairment to our supply chain as a longer period, obstaclesresult of the COVID-19 pandemic. In addition, we continue to maintain substantial safety stock inventories for
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our commercial drug substance and changesdrug products, which should be sufficient to standard salesmaintain robust long-term supply. We continue to work closely with our third-party contract manufacturers, distributors, suppliers, comparator drug sourcing vendors and marketing practices resulting fromcollaboration partners to safeguard both the timely production and delivery of our products.
General Business Operations. We have taken numerous temporary precautions to help mitigate the risk of transmission of the virus, including reducing the number of our employees working on-site at our Alameda headquarters under enhanced safety and social distancing protocols and initiating an on-site testing program. Although having most of our employees continue to work remotely has required that we devise new ways of working and collaborating, to date, the COVID-19 pandemic including the shift from in-person to telephonichas only had a modest impact on our productivity and virtual interactions with healthcare professionals, could diminish sales of our marketed products.
General Business Operations. Most of our Alameda-based employees have been working remotely since March 16, 2020, while a small number of employees have continued to work on-site in order to maintain critical operational activities. Although the limitations imposed by this new way of working present challenges, we havehas not experienced any material reduction in productivity orcaused significant interruptions in our general business operations. However, ifFor a discussion of workplace safety measures we have taken as a result of the COVID-19 pandemic, continuessee “Business—Environmental, Health and becomes more severe, it will likely impactSafety—Workplace Safety Measures in Response to COVID-19” in Part I, Item 1 of our abilityAnnual Report on Form 10-K for the fiscal year ended December 31, 2020, submitted to maintain that level of productivity, to grow the company as we have anticipated, and to executeSEC on our long-term business plans.February 10, 2021.
The circumstances surrounding the COVID-19 pandemic are volatile and subject to rapid change. Despite our mitigation efforts, we may experience delays or an inability to execute on our clinical and preclinical development plans, reduced revenues or other adverse impacts to our business, which are described in more detail in “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q. We recognize that this pandemic will continue to present unique challenges for us throughout 2020,2021, and potentially in future years should the aggressive spread and impact of the virus continue indefinitely.into 2022.
First Quarter 20202021 Business Updates and Financial Highlights
During the first quarter of 2020,2021, we continued to execute on our business objectives, generating significant revenuerevenues from operations and enabling us to continue to seek to maximize the clinical and commercial potential of our products and expand our product pipeline. Significant business updates and financial highlights for the quarter and subsequent to quarter-end include:
Business Updates
In January 2020,2021, the FDA approved the combination of CABOMETYX and OPDIVO as a first-line treatment of patients with advanced RCC, and we commenced the commercial launch of the combination upon such approval. The approval was based on positive results from the phase 3 pivotal trial, CheckMate -9ER, in which the combination met its primary endpoint of significantly improving PFS at final analysis, as well as the secondary endpoints of OS at a pre-specified interim analysis and ORR, versus sunitinib.
In January 2021, we announced the initiation of a phase 1 clinical trial evaluating XL102, both as a single agent and in combination with other anti-cancer therapies for the treatment of inoperable, locally advanced or metastatic solid tumors.
In February 2021, we announced a collaboration and license agreement with Adagene to utilize Adagene’s SAFEbody technology platform to generate masked versions of mAbs from our growing preclinical pipeline for the development of ADCs or other innovative biologics.
In February 2021, cabozantinib was the subject of multiple data presentations at the virtual American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2021), including updated trial results with extended follow-up and patient-reported outcomes from the CheckMate -9ER trial demonstrating continued superior PFS, OS and ORR vs. sunitinib across both the subgroup of 75 patients with sarcomatoid histology and the full study population, as well as significantly improved health-related quality of life. Additional cabozantinib presentations at ASCO GU 2021 included: positive results from PAPMET (also known as SWOG S1500), a randomized phase 2 trial conducted by the Southwest Oncology Group evaluating cabozantinib versus sunitinib in patients with metastatic papillary RCC; positive findings from an amendment to the protocol for COSMIC-021 to further expand patient enrollmentinternational retrospective study of cabozantinib in an existing mCRPC cohort to up to 130 patients.
In January 2020, clinically meaningful dataRCC patients with brain metastases; and positive final results from CheckMate 040, the phase 1/21 clinical trial sponsored and conducted by NCI-CTEP, including seven expansion cohorts, evaluating cabozantinib in combination with nivolumab and in combination with both nivolumab and ipilimumab in patients with previously treated or previously untreated advanced HCC, were presented at ASCO’s Gastrointestinal Cancers Symposium.refractory metastatic genitourinary tumors.
In January 2020, Takeda applied to the Japanese MHLW for approval to manufacture and market CABOMETYX as a treatment for patients with unresectable HCC who progressed after prior systemic therapy in Japan.
In February 2020, we presented clinically meaningful results from the mCRPC cohort of COSMIC-021 at ASCO’s Genitourinary Cancers Symposium.
In February 2020,2021, we announced the enrollment of the first 100 patients in COSMIC-311, the phase 3 pivotal trial ofFDA had granted Breakthrough Therapy Designation to cabozantinib versus placebo inas a potential treatment for patients with RAI-refractory DTC who have progressed after up to twofollowing prior VEGF receptor-targeted therapies.therapy.
In March 2020, Takeda received regulatory approval from2021, we announced an exclusive license agreement with WuXi Bio for a panel of mAbs, discovered based on WuXi Bio’s integrated technology platforms for the Japanese MHLWdevelopment of ADC, bispecific and certain other novel tumor-targeting biologics applications.
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In March 2021, we announced a clinical trial collaboration and supply agreement with Merck KGaA and Pfizer to manufactureevaluate the safety and market CABOMETYX as a treatment fortolerability of XL092 in combination with avelumab in patients with curatively unresectablelocally advanced or metastatic RCC in Japan.UC as part of the ongoing STELLAR-001 phase 1b dose escalation study.
In April 2020,March 2021, we announced that CheckMate -9ER, BMS’the completion of patient enrollment in COSMIC-313, a phase 3 pivotal trial evaluating the triplet combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or metastatic RCC, met itspoor-risk RCC. COSMIC-313 is a multicenter, randomized, double-blind, controlled phase 3 pivotal trial that enrolled approximately 840 patients globally. The primary endpoint of significantly improvingthe trial is PFS, and additional endpoints include OS and ORR.
In March 2021 and April 2021, Ipsen and BMS, respectively, received regulatory approval from the EC for CABOMETYX in combination with OPDIVO as wella first-line treatment for patients with advanced RCC.
In April 2021, we announced the FDA’s acceptance of the IND for XB002 and our plans to initiate a phase 1 trial during the second quarter of 2021.
In May 2021, we announced an asset purchase agreement with GamaMabs to acquire GamaMabs’ antibody program directed at AMHR2.
In May 2021, we received a notice letter from Teva Pharmaceuticals USA, Inc. (Teva) regarding an Abbreviated New Drug Application (ANDA) Teva submitted to the FDA, requesting approval to market a generic version of CABOMETYX tablets. Teva’s notice letter included a Paragraph IV certification with respect to our U.S. Patent Nos. 9,724,342 (formulations), 10,034,873 (methods of treatment) and 10,039,757 (methods of treatment), which are listed in the Approved Drug Products with Therapeutic Equivalence Evaluations, also referred to as the secondary endpointsOrange Book, and expire in 2033, 2031 and 2031, respectively. Teva’s notice letter did not provide a Paragraph IV certification against any additional CABOMETYX patents. We are reviewing the details of OS and ORR, versus sunitinib. More detailed results of CheckMate -9ER will be submitted for presentation at an upcoming medical conference.
In May 2020, we announced that cabozantinib will be the subject of 12 presentations at the 2020 ASCO Annual Meeting. Data presentations will include results from NSCLC, mCRPC and urothelial carcinoma cohorts of COSMIC-021, as well as updates from other externally sponsored studies.
In May 2020, we received notice from MSN Pharmaceuticals, Inc. (MSN) that it had amended its Abbreviated New Drug Application (ANDA), originally filed with the FDA in September 2019,Paragraph IV certification notice. We intend to continue to assert additional Paragraph IV certifications. The ANDA now requests approval to market a generic version of CABOMETYX tablets prior to expiration of two previously-unasserted CABOMETYX patents listed in the Approved Drug Products with Therapeutic Equivalence Evaluations, also referred to as the Orange Book: U.S. Patent No. 7,579,473, the composition of matter patent, and U.S. Patent No. 8,497,284, a method of use patent.  We are well prepared to respond and will vigorously defend our cabozantinib intellectual property estate.

Financial Highlights
Net product revenues for the first quarter of 2020 was $193.9 million, compared to $179.6 million for the first quarter of 2019.
Net product revenues for the first quarter of 2021 were $227.2 million, compared to $193.9 million for the first quarter of 2020.
Total revenues for the first quarter of 2021 were $270.2 million, compared to $226.9 million for the first quarter of 2020.
Research and development expenses for the first quarter of 2021 were $159.3 million, compared to $101.9 million for the first quarter of 2020.
Selling, general and administrative expenses for the first quarter of 2021 were $102.4 million, compared to $62.9 million for the first quarter of 2020.
Provision for (benefit from) income taxes for the first quarter of 2021 was $(3.6) million, compared to $11.4 million for the first quarter of 2020.
Net income for the first quarter of 2021 was $1.6 million, or $0.01 per share, basic and $0.00 per share, diluted, compared to net income of $48.6 million, or $0.16 per share, basic and $0.15 per share diluted, for the first quarter of 2020.
Cash, cash equivalents, restricted cash equivalents and investments were $1.6 billion as of March 31, 2021, compared to $1.5 billion as of December 31, 2020.
Total revenues for the first quarter of 2020 was $226.9 million, compared to $215.5 million for the first quarter of 2019.
Research and development expenses for the first quarter of 2020 was $101.9 million, compared to $63.3 million for the first quarter of 2019.
Selling, general and administrative expenses for the first quarter of 2020 was $62.9 million, compared to $60.1 million for the first quarter of 2019.
Provision for income taxes for the first quarter of 2020 was $11.4 million, compared to $14.9 million for the first quarter of 2019.
Net income for the first quarter of 2020 was $48.6 million, or $0.16 per share, basic and $0.15 per share, diluted, compared to $75.8 million, or $0.25 per share, basic and $0.24 per share diluted, for the first quarter of 2019.
Cash and investments were $1.4 billion at both March 31, 2020 and December 31, 2019.
See “Results of Operations” below for a discussion of the detailed components and analysis of the amounts above.
Challenges and Risks
In addition to the challenges and risks imposed by the COVID-19 pandemic and described under “—COVID-19 Update” above, we will also continue to face challenges and risks that may impact our ability to execute on our 20202021 business objectives, and some of these risks to our business have been or may be exacerbated by the COVID-19 pandemic. In particular, for the foreseeable future, we expect our ability to generate sufficient cash flow to fund our business operations and growth will depend upon the continued commercial success of CABOMETYX, both alone or in combination with other therapies, as a treatment for advanced RCC and previously treated HCC,the highly competitive indications for which it is approved, and possibly for other indications for which cabozantinib has been or is currently being evaluated in potentially label-enabling clinical trials, if warranted by the data generated from suchthese trials. However, we cannot be certain that the clinical trials we and our collaboration partners are currently conducting, or may conduct in the future, will demonstrate adequate safety and efficacy in these additional indications to receive regulatory approval in the major commercial markets where CABOMETYX
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is approved. Even if we and our collaboration partners receive the required regulatory approvals to market cabozantinib for additional indications, we and our collaboration partners may not be able to commercialize CABOMETYX effectively and successfully in these additional indications. In addition, CABOMETYX will only continue to be commercially successful if private third-party and government payers continue to provide coverage and reimbursement. However, as is the case for all innovative pharmaceutical therapies, obtaining and maintaining coverage and reimbursement for CABOMETYX is becoming increasingly difficult, both within the U.S. and in foreign markets, because of growing concerns over healthcare cost containment and corresponding policy initiatives and activities aimed at limiting access to, and restricting the prices of, pharmaceuticals.
Achievement of our 20202021 business objectives and the continued success of CABOMETYX will also depend on our ability to maintain a competitive position with respect to the shifting landscape of therapeutic strategy for the treatment of cancer, which we may not be able to do. While we have had success ofin adapting our development strategy for the cabozantinib franchise and commercialization strategiesother product candidates to navigate increased competition, including that from, but not limited to,address the useexpanding role of therapies that combine an ICItargeted agents with another targeted agentICIs and/or with other mechanisms of action, it is uncertain whether current and future clinical trials will lead to treat cancer.regulatory approvals, or whether physicians will prescribe regimens containing our products instead of competing product combinations. Moreover, the complexities of such a development strategy have required and are likely to continue to require collaboration with some of our competitors. In the longer term, we may eventually face competition from potential manufacturers of generic versions of our marketed products, including the proposed generic versionversions of CABOMETYX tablets that isare the subject of an ANDAANDAs submitted to the FDA by MSN which if approved,Pharmaceuticals, Inc. (MSN) and Teva, and the approval of either MSN’s or Teva’s ANDA could result in significant decreases in the revenuesignificantly decrease our revenues derived from the U.S. sales of CABOMETYX and thereby materially harm our business, financial condition and financial condition.results of operations. Separately, our research and development objectives may be impeded by the challenges of scaling our organization to meet the demands of expanded drug development, unanticipated delays in clinical testing and the inherent risks and uncertainties associated with internal drug discovery operations, all of which may be increased as a result of the COVID-19 pandemic. In connection with efforts to expand our product pipeline, we may be unsuccessful in discovering new drug candidates or identifying appropriate candidates for in-licensing or acquisition.
Some of these challenges and risks are specific to our business, and others are common to companies in the biotechnology, biopharmaceutical and pharmaceutical industries with development and commercial operations. Moreover, asAs described under “—COVID-19 Update” above, these risks have been or may be exacerbated by the COVID-19 pandemic. For a more detailed discussion of challenges and risks we face, including those relating to the COVID-19 pandemic, see “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q.

Fiscal Year Convention
We have adopted a 52- or 53-week fiscal year policy that generally ends on the Friday closest to December 31st.31st. Fiscal year 2020,2021, which is a 52-week fiscal year, will end on January 1,December 31, 2021 and fiscal year 2019,2020, which was a 53-week52-week fiscal year, ended on January 3, 2020.1, 2021. For convenience, references in this report as of and for the three months ended April 2, 2021 and April 3, 2020, and March 29, 2019, and as of and for the fiscal years endingyear ended January 1, 2021 and ended January 3, 2020, are indicated as being as of and for the three months ended March 31, 20202021 and March 31, 20192020, and the years endingyear ended December 31, 2020, and ended December 31, 2019, respectively.
Results of Operations
Revenues
Revenues by category were as follows (dollars in thousands):
 Three Months Ended March 31,Percent Change
 20212020
Net product revenues$227,212 $193,880 17 %
License revenues27,528 20,879 32 %
Collaboration services revenues15,490 12,156 27 %
Total revenues$270,230 $226,915 19 %
 Three Months Ended March 31,  Percentage Change
 2020 2019 
Net product revenues$193,880
 $179,581
 8 %
License revenues20,879
 25,564
 (18)%
Collaboration services revenues12,156
 10,342
 18 %
Total revenues$226,915
 $215,487
 5 %
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Net Product Revenues
Gross product revenues, discounts and allowances, and net product revenues were as follows (dollars in thousands):
Three Months Ended March 31,  Percentage Change Three Months Ended March 31,Percent Change
2020 2019  20212020
Gross product revenues$252,566
 $223,750
 13%Gross product revenues$314,205 $252,566 24 %
Discounts and allowances(58,686) (44,169) 33%Discounts and allowances(86,993)(58,686)48 %
Net product revenues$193,880
 $179,581
 8%Net product revenues$227,212 $193,880 17 %
Net product revenues by product were as follows (dollars in thousands):
 Three Months Ended March 31,Percent Change
 20212020
CABOMETYX$223,595 $189,216 18 %
COMETRIQ3,617 4,664 -22 %
Net product revenues$227,212 $193,880 17 %
 Three Months Ended March 31,  Percentage Change
 2020 2019 
CABOMETYX$189,216
 $175,890
 8%
COMETRIQ4,664
 3,691
 26%
Net product revenues$193,880
 $179,581
 8%
The increase in net product revenues for CABOMETYX for the three months ended March 31, 2020, as compared2021, relative to the comparablecorresponding prior year period, in 2019, was due primarily related to an increase in the average net selling price of the product and an increase in the number of units sold that was partially driven by the strong uptake for the combination therapy of CABOMETYX sold. and OPDIVO following approval by the FDA in January 2021. The stabilization of the CABOMETYX sales volume reflects the continued evolution of the metastatic RCC and HCC treatment landscapes. The increasedecrease in net product revenues for COMETRIQ for the three months ended March 31, 2020, as compared2021, relative to the comparablecorresponding prior year period, in 2019, was due to an increasea decrease in the number of units of COMETRIQ sold and an increase in the average net selling price of the product. COMETRIQ sales volumes have stabilized following the declines initially observed after the launch of CABOMETYX in April 2016.sold.
We expectproject our net product revenues for the remainder of 20202021 may increase relative to remain in-linethe corresponding prior year period, primarily as a result of the growth in the number of units sold following the FDA’s approval of CABOMETYX in combination with 2019.OPDIVO as a first line treatment of patients with advanced RCC, as well as an increase in selling price.
We recognize product revenues net of discounts and allowances that are described in “Note 1. Organization and Summary of Significant Accounting Policies” to our “Notes to Consolidated Financial Statements” included in our Annual Report on Form 10-K for the year ended December 31, 2019.2020. The increase in discounts and allowances for the three months ended March 31, 2020, as compared2021, relative to the comparablecorresponding prior year period, in 2019, was primarily the result of increasesan increase in Public Health Service hospital utilization and the dollar amount of the related chargebacks, and, to a lesser extent, increases in utilization

and the dollar amount of chargebacks associated with Veterans Affairs hospitals, as well as increases to other government and commercial rebates. We expect a moderatean increase in returns and allowances and an increase in Medicare utilization.
We project our discounts and allowances as a percentage of gross product revenues may increase during the remainder of 20202021 relative to the corresponding prior year period as the proportionnumber of our patients participating in government programs continues to increase and as the discounts given and rebates paid to government payers also increase.
License Revenues
License revenues include the recognition of the portion of milestone payments allocated to the transfer of intellectual property licenses for which it had become probable in the related period that the milestone would be achieved and a significant reversal of revenues would not occur, as well as royalty revenues and the profit on the U.S. commercialization of COTELLIC from Genentech.
Milestone revenues, which are allocated between license revenues and collaboration services revenues, were $0.1 million for the three months ended March 31, 2020, as compared to $10.0 million for the comparable period in 2019. Due to the nature and timing of milestone events, their achievement can vary significantly from period to period. Milestone revenues for the three months ended March 31, 2020 related to the recognition of deferred revenue for the portion of payments that have been allocated to research and development services performance obligations. Milestone revenues for the three months ended March 31, 2019 primarily related to $9.4 million in revenues recognized in connection with a $10.0 million milestone from Takeda for the then expected submission in April 2019 of a regulatory application for cabozantinib as a treatment for patients with advanced RCC to the Japanese MHLW.
Royalties increased primarily as a result of an increaseincreases in royalties earned on Ipsen’s net sales of cabozantinib outside of the U.S. and Japan. Ipsen royalties were $17.9$22.5 million for the three months ended March 31, 2020,2021, compared to $14.0$17.9 million for the comparable period in 2019.2020. Ipsen’s net sales of cabozantinib have continued to grow since their first commercial sale of the product in the fourth quarter of 2016, primarily due to increased demand of CABOMETYX, which, as of March 31, 2020,2021, is approved in 54 counties60 countries outside of the U.S. Royalties also increased due to the commercial launch of CABOMETYX for the treatment of patients with curatively unresectable or metastatic RCC in Japan by Takeda during the second quarter of 2020.
Our share of profits on the U.S. commercialization of COTELLIC under our collaboration agreement with Genentech was $1.4$1.8 million for the three months ended March 31, 2020, as2021, compared to $1.1$1.4 million for the comparable period in 2019.corresponding prior year
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period. We also earned royalties on ex-U.S. net sales of COTELLIC by Genentech of $1.3$1.0 million for the three months ended March 31, 2020,2021, compared to $1.5$1.3 million for the comparablecorresponding prior year period.
Due to uncertainties surrounding the timing and achievement of regulatory and development milestones, it is difficult to predict future milestone revenues and milestones can vary significantly from period in 2019.
to period. We expectproject our license revenues to decrease duringfor the remainder of 2020, as compared2021 to the same period in 2019,decrease, relative to fiscal 2020, as a result of a decreasethe anticipated achievement of fewer milestones in milestones expected to be achieved during the year. We expect license revenues for 2020 to include2021, partially offset by an increase in royalty revenues related to milestone payments we will receive from Takeda on the first sale of CABOMETYX as a treatment for patients with curatively unresectable or metastatic RCCan increase in Japan.product sales by Ipsen and Takeda.
Collaboration Services Revenues
Collaboration services revenues include the recognition of deferred revenuerevenues for the portion of upfront and milestone payments that have been allocated to research and development services performance obligations, development cost reimbursements earned under our collaboration agreements, product supply revenues, net of product supply costs and the royalties we paid to GlaxoSmithKline (GSK)pay on sales by Ipsen and Takeda of products containing cabozantinib. We received notification that, effective January 1, 2021, Royalty Pharma plc acquired from GlaxoSmithKline (GSK) all rights, title and interest in royalties on net product sales containing cabozantinib for non-U.S. markets for the full term of the royalty and for the U.S. market through September 2026, after which time U.S. royalties will revert back to GSK.
Development cost reimbursements were $14.4$18.3 million for the three months ended March 31, 2020, as2021, compared to $10.3$14.4 million for the comparable period in 2019.corresponding prior year period. The increase in development cost reimbursements was primarily a result of the reimbursements from Ipsen forand Takeda associated with their decision to opt in and co-fund CONTACT-02 and additional cohorts of COSMIC-021 studies in 2020 and their respective share of the increase in spending on the COSMIC-312CONTACT-02 study, partially offset by a decrease in spending on COSMIC-021 and COSMIC-021COSMIC-312 studies.
For the three months ended March 31, 2020, collaborationCollaboration services revenues were reduced by $2.4$3.3 million for the 3% royalty we are required to pay GSK on the net sales by Ipsen and Takeda of any product incorporating cabozantinib for the three months ended March 31, 2021, compared to $1.9$2.4 million in 2019.for the corresponding prior year period. As royalty generating sales of cabozantinib by Ipsen and Takeda have increased as described above, our royalty payments to GSK have also increased.
We expectproject our collaboration services revenues to increase duringmay decrease for the remainder of 2021, relative to fiscal 2020, as compared to the same period in 2019,primarily as a result of higherlower development cost reimbursements projected to be earned under our collaboration agreements.

Cost of Goods Sold
The cost of goods sold and our gross margin were as follows (dollars in thousands):
Three Months Ended March 31,  Percentage Change Three Months Ended March 31,Percent Change
2020 2019  20212020
Cost of goods sold$9,289
 $7,501
 24%Cost of goods sold$13,198 $9,289 42 %
Gross margin95% 96%  Gross margin94 %95 %
Cost of goods sold is related to our product revenues and consists primarily of a 3% royalty payable to GSK on U.S. net sales of any product incorporating cabozantinib, as well as the cost of inventory sold, indirect labor costs, write-downs related to expiring and excess inventory, and other third-party logistics costs. The increase in cost of goods sold for the three months ended March 31, 2020, as compared2021, relative to the comparablecorresponding prior year period, in 2019, was primarily the result of increasesan increase in write-downs for excess and expiring inventory, certain other period costs.costs, as well as an increase in royalties as a result of increased U.S. cabozantinib sales, partially offset by favorable purchase price variances. We do not expectproject our gross margin to change significantly during the remainder of 2020.2021.
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Research and Development Expenses
Research and development expenses were as follows (dollars in thousands):
 Three Months Ended March 31,  Percentage Change
 2020 2019 
Research and development expenses$101,877
 $63,289
 61%
Research and development expenses consist primarily of clinical trial costs, personnel expenses, the allocation of general corporate costs, stock-based compensation, license and other collaboration costs, and consulting and outside services.
The increase in research and development expenses for the three months ended March 31, 2020, as compared to the comparable period in 2019, was primarily related to increases in clinical trial costs, personnel expenses, license and other collaboration costs, and the allocation of general corporate costs, which were partially offset by the impact of development cost reimbursements. Clinical trial costs, which include services performed by third-party contract research organizations and other vendors who support our clinical trials, and comparator drug purchases, increased $25.2 million for the three months ended March 31, 2020, as compared to the comparable period in 2019. The increase in clinical trial costs was primarily due to costs associated with the expanding clinical trial program for cabozantinib, which includes COSMIC-312, COSMIC-313 and COSMIC-021. Personnel expenses increased $8.4 million for the three months ended March 31, 2020, as compared to the comparable period in 2019, primarily due to an increase in headcount to support our expanding discovery and development efforts. License and other collaboration costs increased $2.5 million for the three months ended March 31, 2020, as compared to the comparable period in 2019, primarily due to our research funding commitments to our collaboration partners and a development milestone achieved by one of those collaboration partners. General corporate costs, which include our costs for facilities, information technology, human resources, financial planning and analysis and purchasing, are allocated to cost of goods sold, research and development and selling general and administrative expenses based on headcount. The allocation of general corporate costs to research and development expenses increased $2.2 million for the three months ended March 31, 2020, as compared to the comparable period in 2019, primarily due to an increase in headcount to support our expanding discovery and development efforts. Research and development expenses for the three months ended March 31, 2020 were reduced by $2.1 million as a result of development cost reimbursements received in connection with our December 2019 collaboration arrangement with Roche; there were no such reimbursements during the comparable period in 2019.
We do not track fully-burdenedfully burdened research and development expenses on a project-by-project basis. We group our research and development expenses into three categories: 1)(1) development; 2)(2) drug discovery; and 3)(3) other. Our development group leads the development and implementation of our clinical and regulatory strategies and prioritizes disease indications in which our compounds are being or may be studied in clinical trials. Our drug discovery group utilizes a variety of technologies, including in-licensed technologies, to enable the rapid discovery, optimization and extensive characterization of lead compounds such that we are able to select development candidates with the best potential for further evaluation and advancement into clinical development.

Research and development expenses by category were as follows (in thousands):
Three Months Ended March 31,Three Months Ended March 31,Percent
2020 201920212020Change
Research and development expenses:   Research and development expenses:
Development:   Development:
Clinical trial costs$53,344
 $28,187
Clinical trial costs$60,691 $53,344 14 %
Personnel expenses20,288
 13,587
Personnel expenses28,884 20,288 42 %
Consulting and outside services3,244
 2,712
Consulting and outside services5,289 3,244 63 %
Other development costs4,741
 4,134
Other development costs7,284 4,741 54 %
Total development81,617
 48,620
Total development102,148 81,617 25 %
Drug discovery:   Drug discovery:
License and other collaboration costs5,013
 2,506
License and other collaboration costs28,438 5,013 467 %
Other drug discovery (1)
6,734
 4,534
Other drug discovery (1)
11,287 6,734 68 %
Total drug discovery11,747
 7,040
Total drug discovery39,725 11,747 238 %
Other (2)
8,513
 7,629
Other (2)
17,415 8,513 105 %
Total research and development expenses$101,877
 $63,289
Total research and development expenses$159,288 $101,877 56 %
____________________
(1)Primarily includes personnel expenses, consulting and outside services and laboratory supplies.
(2)Includes stock-based compensation, the allocation of general corporate costs to research and development, and development cost reimbursement received in connection with our December 2019 collaboration arrangement with Roche.
(1)    Primarily includes personnel expenses, consulting and outside services and laboratory supplies.
(2)    Includes stock-based compensation, the allocation of general corporate costs to research and development, and development cost reimbursements in connection with our collaboration arrangement with Roche executed in December 2019.
The increase in research and development expenses for the three months ended March 31, 2021, relative to the corresponding prior year period, was primarily related to increases in license and other collaboration costs, clinical trial costs, personnel expenses and stock-based compensation expense. License and other collaboration costs increased primarily due to increases in upfront license fees, program initiation fees and research funding commitments related to business development activities. Clinical trial costs, which include services performed by third-party contract research organizations and other vendors who support our clinical trials, increased primarily due to costs associated with the expanding clinical trial program for cabozantinib. Personnel expenses increased primarily due to increases in headcount to support our expanding discovery and development organization. Stock-based compensation expense increased primarily due to the performance-based restricted stock units (PSUs) granted in 2019 that became probable of achievement during the first quarter of 2021.
In addition to reviewing the three categories of research and development expenses described above, we principally consider qualitative factors in making decisions regarding our research and development programs. SuchThese factors include enrollment in clinical trials for our drug candidates, preliminary data from and final results offrom clinical trials, the potential indications for our drug candidates, the clinical and commercial potential for our drug candidates, and competitive dynamics. We also make our research and development decisions in the context of our overall business strategy.
We are focusing our development efforts primarily on cabozantinib to maximize the therapeutic and commercial potential of this compound and, as a result, we expectproject that a significant portion of our near-term research and development expenses to primarilywill relate to the continuedcontinuing clinical development program of cabozantinib. We expect to continue to incur significant development costs for cabozantinib, in future periods as we evaluate its potential in a broad development program comprisingwhich includes over 90100 ongoing or planned clinical trials across multiple indications. Notable company-sponsored studies resulting from this program include: COSMIC-021 and COSMIC-312, for which Roche is providing atezolizumab free of charge; COSMIC-313, for which BMS is providing nivolumab and ipilimumab free of charge; CONTACT-02 for which Roche is sharing the development costs and providing atezolizumab free of charge; and COSMIC-311. In addition, post-marketing commitments in connection with the approval
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Table of COMETRIQ in progressive, metastatic MTC led to the ongoing EXAMINER study in that indication.Contents
We are alsoremain committed to buildingexpanding our oncology product pipeline by discoveringthrough our drug discovery efforts, which encompass both small molecule and developing new cancer therapies for patients.biologics programs with multiple modalities and mechanisms of action. In this regard, we conduct internal drug discovery activities with the goal of identifying new product candidates to advance into clinical trials. We augment these internal drug discovery activities withIn addition, we will continue to engage in business development initiatives aimed at identifyingacquiring and in-licensing promising early-stage oncology platforms and assets and then further characterize and develop them utilizing our established preclinical and clinical development infrastructure.
Subject to the impact of the COVID-19 pandemic on our research and development efforts described under “—COVID-19 Update” above, we expectWe project our research and development expenses tomay continue to increase overfor the remainder of 2021 compared to 2020, as a resultprimarily driven by our ongoing clinical evaluation of cabozantinib, the expected initiation of new clinical trials and completionexpansion of numerous late-stageongoing clinical trials evaluating other product candidates in our pipeline, including XL092, XL102, and other potentially label-enabling cabozantinib trials.XB002, and anticipated business development activities.
The length of time required for clinical development of a particular product candidate and our development costs for that product candidate may be impacted by the scope and timing of enrollment in clinical trials for the product candidate, our decisions to develop a product candidate for additional indications and whether we pursue development of the product candidate or a particular indication with a collaborator or independently. For example, cabozantinib is being developed in multiple indications, and we do not yet know for how many of those indications we will ultimately pursue regulatory approval. In this regard, our decisions to pursue regulatory approval of cabozantinib for additional indications

depend on several variables outside of our control, including the strength of the data generated in our prior, ongoing and potential future clinical trials. Furthermore, the scope and number of clinical trials required to obtain regulatory approval for each pursued indication is subject to the input of the applicable regulatory authorities, and we have not yet sought such input for all potential indications that we may elect to pursue. Even after having given such input, applicable regulatory authorities may subsequently require additional clinical studies prior to granting regulatory approval based on new data generated by us or other companies, or for other reasons outside of our control. As a condition to any regulatory approval, we may also be subject to post-marketing development commitments, including additional clinical trial requirements. As a result of the uncertainties discussed above, we are unable to determine the duration of, or completetotal costs associated with the development of cabozantinib or any of our other research and development projects.
In any event, ourOur potential therapeutic products are subject to a lengthy and uncertain regulatory process that may not result in our receipt of the necessary regulatory approvals. Failure to receive the necessary regulatory approvals would prevent us from commercializing the product candidates affected, including cabozantinib in any additional indications. In addition, clinical trials of our potential product candidates may fail to demonstrate safety and efficacy, which could prevent or significantly delay regulatory approval. A discussion of the risks and uncertainties with respect to our research and development activities including completing the development of our product candidates, and the consequences to our business, financial position and growth prospects can be found in “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q.
Selling, General and Administrative Expenses
Selling, general and administrative expenses were as follows (dollars in thousands):
 Three Months Ended March 31,  Percentage Change
 2020 2019 
Selling, general and administrative expenses$62,940
 $60,138
 5%
Three Months Ended March 31,Percent Change
20212020
Selling, general and administrative expenses$102,351 $62,940 63 %
Selling, general and administrative expenses consist primarily of personnel expenses, stock-based compensation, marketing costs, and certain other administrative costs.
The increase in selling, general and administrative expenses for the three months ended March 31, 2020, as compared2021, relative to the comparablecorresponding prior year period, in 2019, was primarily related to the increases in personnel expenses, marketing costs, corporate giving and stock-based compensation expense, partially offset by a decrease in the Branded Prescription Drug Fee personnel expenses and occupancy costs, which were partially offset by decreases in marketing costs and corporate giving. The Branded Prescription Drug Fee increased $5.3 million for the three months ended March 31, 2020, as compared to the comparable period in 2019, primarily due to a change in estimate for such fees related to 2018 and 2019 salesin 2020 following our receipt of the 2020 preliminary fee notice from the Internal Revenue Service for the 2018 sales year.Service. Personnel expenses increased $4.5 million for the three months ended March 31, 2020, as compared to the comparable period in 2019, primarily due to an increaseincreases in administrative headcount to support our commercial and research and development organizations. OccupancyMarketing costs increased $1.1 million for the three months ended March 31, 2020, as compared to the comparable period in 2019, primarily due to anincreased marketing activities in support of the launch of the combination therapy of CABOMETYX and OPDIVO following approval by the FDA in January 2021. The increase in stock-based compensation expense was primarily due to PSUs granted in 2019 that became probable of achievement during the space leased for our corporate headquarters. Marketing costs decreased $4.0 million for the three months ended March 31, 2020, as compared to the comparable period in 2019. Corporate giving, consisting predominantlyfirst quarter of donations to independent patient support foundations, decreased $3.6 million for the three months ended March 31, 2020, as compared to the comparable period in 2019.2021.
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We expectproject our selling, general and administrative expenses may continue to increase modestly duringfor the remainder of 2021 relative to 2020 toin support of our overall organizational growth.continued commercial investment in CABOMETYX and the growth in the broader organization.
Non-operating Income
Items of non-operatingNon-operating income werewas as follows (dollars in thousands):
Three Months Ended March 31,  Percentage ChangeThree Months Ended March 31,Percent Change
2020 2019 20212020
Interest income$7,220
 $6,087
 19 %Interest income$2,682 $7,220 -63 %
Other income, net$6
 $25
 (76)%
Other income (expense), netOther income (expense), net(90)n/a
Non-operating incomeNon-operating income$2,592 $7,226 -64 %
The increasedecrease in interestnon-operating income for the three months ended March 31, 2020, as compared2021, relative to the comparablecorresponding prior year period, in 2019, was primarily the result of an increasethe decreases in our investment balances.

interest income due to lower interest rates.
Provision for (Benefit from) Income Taxes
The provision for (benefit from) income taxes and effective income tax rates were as follows (dollars in thousands):
Three Months Ended March 31,Percent Change
20212020
Provision for (benefit from) income taxes$(3,616)$11,423 n/a
 Three Months Ended March 31,  Percentage Change
 2020 2019 
Provision for income taxes$11,423
 $14,896
 (23)%
Effective income tax rate19.0% 16.4%  
The decrease in the provision forWe recorded a benefit from income taxes for the three months ended March 31, 2020,2021 as compareda result of a current period pre-tax loss, relative to the comparablecorresponding prior year period in 2019,which we reported pre-tax income. The effective tax rate for the three months ended March 31, 2021 differed from the U.S. federal statutory rate of 21% primarily due to excess tax benefits related to the exercise of certain stock options, in relation to the generation of a decrease insmall pre-tax income.loss during the period. The effective tax rate for the three months ended March 31, 2020 differed from the U.S. federal statutory tax rate of 21% primarily due to excess tax benefits related to the exercise of certain stock options during the period and the generation of researchfederal tax credits. The effective tax rate for the three months ended March 31, 2019 differed from the U.S. federal statutory rate of 21% primarily due to excess tax benefits related to the exercise of certain stock options during the period.
Liquidity and Capital Resources
As of March 31, 2020,2021, we had $1.4$1.6 billion in cash, cash equivalents, restricted cash equivalents and investments.investments, compared to $1.5 billion as of December 31, 2020. We anticipate that the aggregate of our current cash and cash equivalents, short-term investments available for operations, net product revenues and collaboration revenues will enable us to maintain our operations for a period of at least 12 months following the filing date of this report.
We expect toproject we may continue to spend significant amounts of cash to fund the continued development and commercialization of cabozantinib. In addition, we intend to continue to expand our oncology product pipeline through our internal drug discovery efforts, including additional research collaborations, in-licensing arrangements and the execution of strategic transactionsother business development activities that align with our oncology drug development, regulatory and commercial expertise. Financing these activities could materially impact our liquidity and capital resources and may require us to incur debt or raise additional funds through the issuance of equity. Furthermore, even though we believe we have sufficient funds for our current and future operating plans, we may choose to incur debt or raise additional funds through the issuance of equity due to market conditions or strategic considerations. However,
Letters of Credit
We have obtained standby letters of credit related to our lease obligations and certain other obligations with combined credit limits of $49.7 million and $1.6 million as of March 31, 2021 and December 31, 2020, respectively. As of March 31, 2021, none of our letters of credit have been drawn upon. All of the COVID-19 pandemic has caused volatility in the U.S. and global financial markets andletters of credit are fully collateralized by short-term investments.
In January 2021, we entered into a downturn in the U.S. and global economy, which may adversely impact our rates of return for our invested cash resources, the availability and coststandby letter of credit as wellguarantee of our obligation to fund our portion of the total tenant improvements related to our build-to-suit lease at our corporate campus. The letter of credit is secured by our short-term investments, which are recorded as restricted cash equivalents and are presented in other long-term assets in
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our ability to raise additional funds inCondensed Consolidated Balance Sheets and will be reduced as we fund our portion of the capital markets. Among other things,tenant improvements. As of March 31, 2021, restricted cash equivalents included $48.2 million of short-term investments as collateral under our inability to access additional funds could in the future inhibit our ability to engage in larger scale strategic transactions or investments.standby letter of credit.
Sources and Uses of Cash
Cash flow activities were as follows (in thousands):
 Three Months Ended March 31,
 2020 2019
Net cash provided by operating activities$56,074
 $161,593
Net cash provided by (used in) investing activities$32,620
 $(107,657)
Net cash provided by financing activities$2,145
 $5,226
 Three Months Ended March 31,
 20212020
Net cash provided by operating activities$39,544 $56,074 
Net cash provided by investing activities$62,255 $32,620 
Net cash (used in) provided by financing activities$(2,650)$2,145 
Operating Activities
Cash flows provided by operating activities represent the cash receipts and disbursements related to all of our activities other than investing and financing activities. Cash provided by operating activities is derived by adjusting our net income for: non-cash operating items such as deferred taxes, stock-based compensation, depreciation, non-cash lease expense and changes in operating assets and liabilities which reflect timing differences between the receipt and payment of cash associated with transactions and when they are recognized in our Condensed Consolidated Statements of Income, the most significant of which may include the timing of milestones payments from our collaboration partners.Income.
The most significant factors that contributed to the decrease in cashCash provided by operating activities for the three months ended March 31, 2020, as compared2021, decreased relative to the comparablecorresponding prior year period, in 2019, were a $48.0 million decrease in milestone payments received,primarily due to an increase in cash paid for operating expenses, as a result of a $43.2 million increase in operating expenses, and other netwhich was partially offset by favorable changes in operating assets and liabilities described above, which were partially offset by an increase in cash received on sales of our products.

liabilities.
Investing Activities
Cash provided by investing activities for the three months ended March 31, 2021 consisted of maturities and sales of investments of $407.4 million, partially offset by cash used in investment purchases of $331.6 million and purchases of property, equipment and other of $13.6 million.
Cash provided by investing activities for the three months ended March 31, 2020 was due toconsisted of cash provided by the maturities and sales of investments of $287.1 million, lesspartially offset by cash used in investment purchases of $251.5 million and purchases of property and equipment and other of $3.0 million.
Financing Activities
Cash used in investingfinancing activities for the three months ended March 31, 2019 was due2021 consisted of $5.4 million of withholding taxes paid related to investment purchasesnet share settlements of $239.9equity awards, partially offset by $2.8 million and property and equipment purchasesin proceeds from the issuance of $2.3 million, less cash provided by the maturities and sales of investments of $134.5 million.
Financing Activitiescommon stock under our equity incentive plans.
Cash provided by financing activities for the three months ended March 31, 2020 was a resultconsisted of $3.9 million in proceeds from the issuance of common stock under our equity incentive plans, offset by $1.8 million of taxes paid related to net share settlements.
Cash provided by financing activities for the three months ended March 31, 2019 was primarily a result of $6.8 million in proceeds from the issuance of common stock under our equity incentive plans, partially offset by $1.6$1.8 million of withholding taxes paid related to net share settlements.settlements of equity awards.
Contractual Obligations
There were no material changes outside of the ordinary course of business in our contractual obligations as of March 31, 20202021 from those disclosed in our Annual Report on Form 10-K for the year ended December 31, 2019.2020.
Off-Balance Sheet Arrangements
As of March 31, 2020,2021, we did not have any material off-balance-sheet arrangements, as defined by applicable SEC regulations.
Critical Accounting Policies and Estimates
The preparation of our Condensed Consolidated Financial Statements conforms to accounting principles generally accepted in the U.S. which requires management to make judgments, estimates and assumptions that affect the reported
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amounts of assets, liabilities, equity, revenues and expenses, and related disclosures. An accounting policy is considered to be critical if it requires an accounting estimate to be made based on assumptions about matters that are highly uncertain at the time the estimate is made, and if different estimates that reasonably could have been used, or changes in the accounting estimates that are reasonably likely to occur periodically, could materially impact our Condensed Consolidated Financial Statements. On an ongoing basis, management evaluates its estimates including, but not limited to: those related to revenue recognition, including determining the nature and timing of satisfaction of performance obligations, and determining the standalone selling price of performance obligations, and variable consideration such as rebates, chargebacks, sales returns and sales allowances as well as milestones included in collaboration arrangements; the amounts of revenues and expenses under our profit and loss sharing agreement; recoverability of inventory; the amounts of deferred tax assets and liabilities including the related valuation allowance; the accrual for certain liabilities including accrued clinical trial liabilities; and valuations of equity awards used to determine stock-based compensation, including certain awards with vesting subject to market or performance conditions.conditions; and the amounts of deferred tax assets and liabilities including the related valuation allowance. We base our estimates on historical experience and on various other market-specific and other relevant assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Our senior management has discussed the development, selection and disclosure of these estimates with the Audit Committee of our Board of Directors. Actual results could differ materially from those estimates.
We believe our critical accounting policies relating to revenue recognition, inventory, clinical trial accruals, stock-based compensation and income taxes reflect the moremost significant estimates and assumptions used in the preparation of our Condensed Consolidated Financial Statements.
There have been no significant changes in our critical accounting policies and estimates during the three months ended March 31, 2020,2021, as compared to the critical accounting policies and estimates disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report on Form 10-K for the year ended December 31, 2019 filed with2020 submitted to the SEC on February 25, 2020.

10, 2021.
Recent Accounting Pronouncements
For a description of the expected impact of recent accounting pronouncements, see “Note 1. Organization and Summary of Significant Accounting Policies” in the “Notes to Condensed Consolidated Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q.
Item 3. Quantitative and Qualitative Disclosures About Market Risk
Our market risks as of March 31, 20202021 have not changed significantly from those described in Item 7A of our Annual Report on Form 10-K for the year ended December 31, 2019.2020.
Item 4. Controls and Procedures.
Evaluation of disclosure controls and procedures. Based on the evaluation of our disclosure controls and procedures (as defined in Rules 13a-15(e) or 15d-15(e) of the Securities Exchange Act of 1934, as amended, or the Exchange Act) required by Rules 13a-15(b) or 15d-15(b) of the Exchange Act, our Chief Executive Officer and Chief Financial Officer have concluded that as of the end of the period covered by this report, our disclosure controls and procedures were effective at the reasonable assurance level.
Limitations on the effectiveness of controls. A control system, no matter how well-conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are met. Because of inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that all control issues, if any, within an organization have been detected. Accordingly, our disclosure controls and procedures are designed to provide reasonable, not absolute, assurance that the objectives of our disclosure control system are met and, as set forth above, our principal executive officer and principal financial officer have concluded, based on their evaluation as of the end of the period covered by this report, that our disclosure controls and procedures were effective to provide reasonable assurance that the objectives of our disclosure control system were met.
Changes in internal control over financial reporting. There were no changes in our internal control over financial reporting that occurred during our most recent fiscal quarter that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

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PART II. OTHER INFORMATION
Item 1. Legal Proceedings
In September 2019, we received a notice letter regarding an ANDA submitted to the FDA by MSN, requesting approval to market a generic version of CABOMETYX tablets. MSN’s initial notice letter included a Paragraph IV certification with respect to our U.S. Patent Nos. 8,877,776, 9,724,342, 10,034,873 and 10,039,757, which are listed in the Orange Book. MSN’s initial notice letter did not provide a Paragraph IV certification against U.S. Patent No. 7,579,473, the composition of matter patent, or U.S. Patent No. 8,497,284, a method of use patent. On October 29, 2019, we filed a complaint for patent infringement against MSN asserting U.S. Patent No. 8,877,776 in the United States District Court for the District of Delaware for patent infringement against MSN asserting U.S. Patent No. 8,877,776 arising from MSN’s ANDA filing with the FDA. Our complaint does not allege infringement of U.S. Patent Nos. 9,724,342, 10,034,873 and 10,039,757. In our complaint, we are seeking, among other relief, an order that the effective date of any FDA approval of the ANDA would be a date no earlier than the expiration of U.S. Patent No. 8,877,776 on October 8, 2030 and equitable relief enjoining MSN from infringing this patent. On November 20, 2019, MSN filed its response to the complaint, alleging that U.S. Patent No. 8,877,776 is invalid and not infringed. A date for a bench trial in this case has been scheduled for April 2022.
On May 5, 2020, we received notice from MSN that it had amended its ANDA to assert additional Paragraph IV certifications. The ANDA now requests approval to market a generic version of CABOMETYX tablets prior to expiration of the two previously-unassertedpreviously unasserted CABOMETYX patents: U.S. Patent No. 7,579,473 and U.S. Patent No. 8,497,284. WeOn May 11, 2020, we filed a complaint in the United States District Court for the District of Delaware for patent infringement against MSN asserting U.S. Patent No. 7,579,473 and U.S. Patent No. 8,497,284 arising from MSN’s amended ANDA filing with the FDA. Neither of our complaints alleges infringement of U.S. Patent Nos. 9,724,342, 10,034,873 and 10,039,757. On May 22, 2020, MSN filed its response to the complaint, alleging that each of U.S. Patent No. 7,579,473 and U.S. Patent No. 8,497,284 is invalid and not infringed. On March 23, 2021, MSN filed its First Amended Answer and Counterclaims (amending its prior filing from May 22, 2020), seeking, among other things, a declaratory judgment that U.S. Patent No. 9,809,549 is invalid and would not be infringed by MSN if its generic version of CABOMETYX tablets were approved by the FDA. On April 7, 2021, we filed our response to MSN’s First Amended Answer and Counterclaims, denying, among other things, that U.S. Patent No. 9,809,549 is invalid or would not be infringed. In our complaints, we are seeking, among other relief, an order that the effective date of any FDA approval of the ANDA would be a date no earlier than the expiration of all of U.S. Patent No. 7,579,473, U.S. Patent No. 8,497,284 and U.S. Patent No. 8,877,776, the latest of which expires on October 8, 2030, and equitable relief enjoining MSN from infringing these patents. These lawsuits against MSN have not yet responded to this additional Paragraph IV certification notice letter, but are well prepared to do sobeen consolidated, and will vigorously defend our cabozantinib intellectual property estatea bench trial has been scheduled for May 2022.
We may also from time to time become a party or subject to various other legal proceedings and claims, either asserted or unasserted, which arise in the ordinary course of business. Some of these proceedings have involved, and may involve in the future, claims that are subject to substantial uncertainties and unascertainable damages.
Item 1A. Risk Factors
In addition to the risks discussed elsewhere in this report, the following are important factors that make an investment in our securities speculative or risky, and that could cause actual results or events to differ materially from those contained in any forward-looking statements made by us or on our behalf. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties not currently known to us or that we deem immaterial also may impair our business operations. If any of the following risks or such other risks actually occur, our business and the value of your investment in our company could be harmed.
Risk Factor Summary
Our ability to grow our company is critically dependent upon the commercial success of CABOMETYX in its approved indications and the further clinical development, regulatory approval and commercial success of the cabozantinib franchise in additional indications.
If we are unable to obtain or maintain coverage and reimbursement for our products from third-party payers, our business will suffer.
Pricing for pharmaceutical products in the U.S. has come under increasing attention and scrutiny by federal and state governments, legislative bodies and enforcement agencies. This may result in actions that have the effect of reducing our revenue or harming our business or reputation.
Lengthy regulatory pricing and reimbursement procedures and cost control initiatives imposed by governments outside the U.S. could delay the marketing of and/or result in downward pressure on the price of our approved products, resulting in a decrease in revenue.
Legislation and regulatory action designed to reduce barriers to the development, approval and adoption of generic drugs in the U.S., and the entrance of generic competitors, could limit the revenue we derive from our products, which could have a material adverse impact on our business, financial condition and results of operations.
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We are subject to healthcare laws, regulations and enforcement, as well as laws and regulations relating to privacy, data collection and processing of personal data; our failure to comply with those laws could have a material adverse impact on our business, financial condition and results of operations.
Clinical testing of cabozantinib for new indications, or of new product candidates, is a lengthy, costly, complex and uncertain process that may fail ultimately to demonstrate safety and efficacy data for those products sufficiently differentiated to compete in our highly competitive market environment.
The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy and uncertain and may not result in regulatory approvals for additional cabozantinib indications or our other product candidates, which could have a material adverse impact on our business, financial condition and results of operations.
We may be unable to expand our development pipeline, which could limit our growth and revenue potential.
Our profitability could be negatively impacted if expenses associated with our extensive clinical development, business development and commercialization activities, both for the cabozantinib franchise and our earlier-stage product candidates, grow more quickly than the revenues we generate.
Our clinical, regulatory and commercial collaborations with major companies make us reliant on those companies for their continued performance and investments, which subjects us to a number of risks. For example, we rely on Ipsen and Takeda for the commercial success of CABOMETYX in its approved indications outside of the U.S., and are unable to control the amount or timing of resources expended by these collaboration partners in the commercialization of CABOMETYX in its approved indications outside of the U.S. In addition, our growth potential is dependent in part upon companies with which we have entered into research collaborations, in-licensing arrangements and similar business development relationships.
Data breaches, cyber-attacks and other failures in our information technology operations and infrastructure could compromise our intellectual property or other sensitive information, damage our operations and cause significant harm to our business and reputation.
If we are unable to adequately protect our intellectual property, third parties may be able to use our technology, which could adversely affect our ability to compete in the market.
If the COVID-19 pandemic is further prolonged or becomes more severe, our business operations and corresponding financial results could suffer, which could have a material adverse impact on our financial condition and prospects for growth.
The loss of key personnel or the inability to retain and, where necessary, attract additional personnel could impair our ability to operate and expand our operations.
Risks Related to the Commercialization of Our Business and IndustryProducts
Our ability to grow our company is critically dependent upon the commercial success of CABOMETYX in its approved indications and the further clinical development, regulatory approval and commercial success of the cabozantinib franchise in additional indications.
We anticipate that for the foreseeable future, our ability to maintain or meaningfully increase cash flow to fund our business operations and growth will depend upon the continued commercial success of CABOMETYX, both alone and in combination with other therapies, as a treatment for advanced RCC and previously treated HCC,the highly competitive indications for which it is approved, and possibly for other indications for which cabozantinib has been or is currently being evaluated in potentially label-enabling clinical trials, if warranted by the data generated from suchthese trials. In this regard, part of our strategy is to pursue additional indications for the cabozantinib franchise to increase the number of cancer patients who could benefit from this medicine. However, we cannot be certain that the clinical trials we and our collaboration partners are currently conducting, or may conduct in the future, will demonstrate adequate safety and efficacy in these additional indications to receive regulatory approval in the major commercial markets where CABOMETYX is approved. Even if we and our collaboration partners receive the required regulatory approvals to market cabozantinib for additional indications, we and our collaboration partners may not be able to commercialize CABOMETYX effectively and successfully in these additional indications. If revenue from CABOMETYX decreases or remains flat, or if we are unable to expand the labeled indications in major commercial markets where CABOMETYX is approved, or if we or our collaboration partners fail to achieve anticipated product royalties and collaboration milestones, whether as a result of the COVID-19 pandemic or otherwise, we may need to reduce our operating expenses, access other sources of cash or otherwise modify our business plans, which could have a material adverse impact on our business, financial condition and results of operations.

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If the current public health pandemic related to COVID-19 continues and grows in severity, our business operations and corresponding financial results could suffer, which could have a material adverse impact on our financial condition and prospects for growth.
Our business could be materially and adversely affected by the ongoing COVID-19 pandemic, a disease caused by a novel strainTable of coronavirus, SARS-CoV-2, which has been spreading globally since December 2019. Thus far, the COVID-19 pandemic has had a relatively modest impact on our business operations, in particular on our clinical trial and drug discovery activities. For example, to varying degrees and at different rates across our clinical trials being conducted in regions impacted by COVID-19, we have seen a decline in screening and enrollment activity, delays in new site activations, and restrictions on access to treatment sites that is necessary to monitor clinical study progress and initiation. Should the aggressive spread of the COVID-19 pandemic continue indefinitely, the impact on our clinical development operations could grow more severe. We anticipate that a prolonged global public health crisis could limit our ability to identify and work with clinical investigators at clinical trial sites globally to enroll, initiate and maintain treatment per protocol of patients for our ongoing COSMIC-311, COSMIC-312, COSMIC-313 and COSMIC-021 clinical trials. Disruptions to medical and administrative operations at clinical trial sites and the implementation of crisis management initiatives may reduce personnel and other resources necessary to conduct our clinical trials, which could delay our ability to execute on our clinical trial plans or require certain of our clinical trials to be temporarily suspended. Moreover, quarantines and travel restrictions have and may continue to impede patient movement or interrupt healthcare services, which we anticipate over time, could also interfere with and potentially negatively impact clinical trial results. In addition, new and increased costs connected with our efforts to mitigate the effect of the COVID-19 pandemic on our clinical trials could cause the expenses we incur in administering those clinical trials to increase considerably. Specifically, with respect to our clinical trials evaluating cabozantinib in combination with therapies that must be administered via professional intravenous infusion, such as COSMIC-312, COSMIC-313 and COSMIC-021, limited patient movement or interrupted healthcare services at medical institutions may delay or prevent on-site infusion of the therapies being evaluated in combination with cabozantinib. If a sizable portion of patients in our combination studies are unable or unwilling to receive all components of the combination therapy being tested in accordance with the applicable clinical trial protocol, those studies could be delayed, suspended or prevented from producing statistically significant results.Depending upon how long the COVID-19 pandemic continues and its severity, we could also experience delays in the commencement of new clinical trials of cabozantinib, including our three planned phase 3 pivotal trials evaluating cabozantinib in combination with atezolizumab in mCRPC, NSCLC and RCC, or our earlier-stage investigative product candidates. The COVID-19 pandemic could also impede our internal clinical operations and delay our planning and preparation timelines for new clinical trials, as well as adversely affect our ability to obtain regulatory approval for clinical protocols and increase the operating expenses connected with these new clinical trials.Contents
In addition, we have suspended internal drug discovery work in our laboratories temporarily while we observe the shelter in place orders issued by the State of California and Alameda County, and we have also experienced some delays with respect to the portion of drug discovery work outsourced to third-party contractors in regions impacted by COVID-19. While our outsourced drug discovery activities have since resumed and we are exploring various strategies to resume internal drug discovery work in our laboratories, should the COVID-19 pandemic continue and grow in severity, we could experience further delays or scaling back of activities. Prior to the COVID-19 pandemic, we had largely outsourced preclinical development work to third-party contractors, and although to date that work has continued without substantial delay or interference due to the COVID-19 pandemic, the ongoing effects of the crisis could impede these third parties from meeting their contractual obligations to us in the future. Should the COVID-19 pandemic continue and grows in severity, we may ultimately be unable to achieve our drug discovery and preclinical development objectives within the previously disclosed timelines, which could have a material adverse impact on our prospects for growth.
Although as of the date of this Quarterly Report, we have substantial safety stock inventories for both our commercial drug substance and drug products and, to our knowledge, we have not yet experienced production delays or seen significant impairment to our supply chain as a result of the COVID-19 pandemic, our third-party contract manufacturers and suppliers may experience delays, facility closures and other hardships due to COVID-19, which could potentially impact our supply chain and cause delays or disruption in our commercial or clinical supply of our products or product candidates. These potential delays or disruptions to our supply chain could be exacerbated if the COVID-19 pandemic persists for an extended period of time and begins to impact essential distribution systems such as FedEx and postal delivery, which could substantially increase delivery times and costs, or otherwise adversely affect our ability to provide our products to customers and clinical trial sites and generate product revenues.
As of the date of this Quarterly Report, we have taken temporary precautions to help minimize the risk of transmission of the virus, including: requiring Alameda-based employees to work remotely since March 16, 2020, with rare exceptions to maintain critical operational activities; suspending all non-essential business travel for our employees; and

restricting our commercial field employees and medical science liaisons from engaging in personal in-office promotional activities with healthcare professionals. Over a longer period, all of these measures could negatively affect our business operations and prospects in both foreseeable and unforeseeable ways. For instance, requiring all employees to work remotely has already limited our internal drug discovery activities, which if continued, would eventually cause substantial delays and otherwise negatively impact the effectiveness of these programs and delay our ability to execute on our long-term business plans. In addition, obstacles and changes to standard sales and marketing practices resulting from the COVID-19 pandemic, including the shift from in-person to telephonic and virtual interactions with healthcare professionals, could negatively impact the flow of important information regarding our medicines and ultimately diminish sales of our marketed products. Further, extended periods of remote work could impede the focused attention of management or reduce the productivity of teams that would otherwise be working closely together. The COVID-19 pandemic has also caused volatility in the U.S. and global financial markets and a downturn in the U.S. and global economy, which may adversely impact our rates of return for our invested cash resources, the availability and cost of credit, as well as our ability to raise additional funds in the capital markets. Among other things, our inability to access additional funds could in the future inhibit our ability to engage in larger scale strategic transactions or investments.
While we expect the COVID-19 pandemic to continue to have varying degrees of adverse impact on our business operations and, potentially in the future, our financial results, the extent of such adverse impact arising from the COVID-19 pandemic to our business and our financial results, as well as to the value of and market for our common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the U.S. and in other countries, and the effectiveness of actions taken globally to contain and treat the disease. These effects could materially and adversely affect our business, financial condition, results of operations and growth prospects, as further explained in the risks and uncertainties described elsewhere in this ‘‘Risk Factors’’ section. In addition, to the extent the ongoing COVID-19 pandemic adversely affects our business and financial results, it may also have the effect of exacerbating many of these other risks and uncertainties inherent to our business.
We rely on Ipsen and Takeda for the commercial success of CABOMETYX in its approved indications outside of the U.S., and are unable to control the amount or timing of resources expended by these collaboration partners in the commercialization of CABOMETYX in its approved indications outside of the U.S.
We rely heavily upon the regulatory, commercial, medical affairs, market access and other expertise and resources of our collaboration partners, Ipsen and Takeda, for commercialization of CABOMETYX in their respective territories outside of the U.S. We cannot control the amount and timing of resources that our collaboration partners dedicate to the commercialization of CABOMETYX, or to its marketing and distribution, and our ability to generate revenues from the commercialization of CABOMETYX by our collaboration partners depends on their ability to obtain and maintain regulatory approvals for, achieve market acceptance of, and to otherwise effectively market, CABOMETYX in its approved indications in their respective territories. Further, the operations of our collaboration partners, and ultimately their foreign sales of CABOMETYX, could be adversely affected by the degree and effectiveness of their respective corporate responses to the COVID-19 pandemic, as well as by the imposition of governmental price or other controls, political and economic instability, trade restrictions or barriers and changes in tariffs, escalating global trade and political tensions, or otherwise. If our collaboration partners are unable or unwilling to invest the resources necessary to commercialize CABOMETYX successfully in the EU, Japan and other international territories where it has been approved, this could reduce the amount of revenue we are due to receive under these collaboration agreements, thus resulting in harm to our business and operations.
Our ability to grow revenues from sales of CABOMETYX will depend upon the degree of market acceptance among physicians, patients, healthcare payers, and the medical community.
Our ability to increase or maintain revenues from sales of CABOMETYX for its approved indications is, and if approved for additional indications will be, highly dependent upon the extent of market acceptance of CABOMETYX among physicians, patients, government healthcare payers such as Medicare and Medicaid, commercial healthcare plans and the medical community. Market acceptance for CABOMETYX could depend on numerous factors, including the effectiveness and safety profile, or the perceived effectiveness and safety profile, of CABOMETYX compared to competing products, the strength of CABOMETYX sales and marketing efforts the impact to healthcare systems resulting from the COVID-19 pandemic and changes in pricing and reimbursement for CABOMETYX. For example, with respect to the FDA approval of CABOMETYX in combination with OPDIVO as a first-line treatment of patients with advanced RCC, we cannot predict whether our commercialization efforts will lead to increased adoption of this combination by healthcare professionals, who may continue to treat first-line RCC patients with competing product combinations and reserve CABOMETYX for later in their treatment plan. If CABOMETYX does not continue to be prescribed broadly for the treatment of its approved RCC and HCC indications, our product revenues could flatten or decrease, which could have a material adverse impact on our business, financial condition and results of operations.

Our competitors may develop products, combination therapies and technologies that impair the relative value of our marketed products and any future product candidates.
The biotechnology, biopharmaceutical and pharmaceutical industries are competitive and are characterized by rapidconstant technological change and diverse offerings of products, particularly in the area of novel oncology therapies. Many of our competitors have greater capital resources, larger research and development staff and facilities, deeper regulatory expertise and more extensive product manufacturing and commercial capabilities than we do, which may afford them a competitive advantage. Further, our competitors may be more effective at in-licensing and developing new commercial products that could render our products, and those of our collaboration partners, obsolete and noncompetitive. We face, and will continue to face, intense competition from biotechnology, biopharmaceutical and pharmaceutical companies, as well as academic research institutions, clinical reference laboratories and government agencies that are pursuing scientific and clinical research activities similar to ours.
Furthermore, the specific indications for which CABOMETYX is currently or may be approved, based on the results from clinical trials currently evaluating cabozantinib, are highly competitive. Several novel therapies and combinations of therapies have been approved, are in advanced stages of clinical development or are under expedited regulatory review in these indications, and these other therapies are currently competing or are expected to compete with CABOMETYX. WeGiven the shifting landscape of therapeutic strategy following the advent of ICIs, we believe our future success will depend upon our ability to maintain a competitive positionachieve positive clinical trial results for therapies combining cabozantinib with respect to the shifting landscape of therapeutic strategy following the advent of ICIs.ICIs across multiple indications, and if approved, successfully commercialize such combination therapies. While we have adaptedhad success in adapting our cabozantinib development strategy for the cabozantinib franchise to address the useexpanding role of therapies that combine ICIs with other targeted agents, including the FDA approval of CABOMETYX in indications for which CABOMETYXcombination with OPDIVO as a first-line treatment of patients with advanced RCC, it is approved, we cannot ensure that our ongoing or planneduncertain whether current and future clinical trials, including those evaluating cabozantinib in combination with an ICI in HCC, NSCLC and mCRPC, will show efficacy in comparisonlead to regulatory approvals, or whether physicians will prescribe regimens containing cabozantinib instead of competing product combinations. Moreover, the complexities of such a development strategy have required and are likely to continue to require collaboration with some of our competitors.
If we are unable to maintain or increase our internal sales, marketing, market access and product distribution capabilities for our products, we may be unable to maximize product revenues, which could have a material adverse impact on our business, financial condition and results of operations.
Maintaining our sales, marketing, market access and product distribution capabilities requires significant resources, and there are numerous risks involved with maintaining and continuously improving such a commercial organization, including our potential inability to successfully recruit, train, retain and incentivize adequate numbers of qualified and effective sales and marketing personnel. We are competing for talent with numerous commercial- and pre-commercial-stageprecommercial-stage, oncology-focused biotechnology companies seeking to build out and maintain their commercial organizations, as well as other large pharmaceutical and biotechnology organizations that have extensive, well-funded and more experienced sales and marketing operations, and we may be unable to maintain or adequately scale our commercial organization as a result of such competition. Also, to the extent that the commercial opportunities for CABOMETYX grow over time, we may not properly scale the size and experience of our commercialization teams to market and sell CABOMETYX successfully in an expanded number of indications. If we are unable to maintain or scale our commercial
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function appropriately, or should we have to maintainrevert back to primarily telephonic and virtual interactions in lieu of in-person meetings with healthcare professionals for an extended period of time as a result of the COVID-19 pandemic, we may not be able to maximize product revenues, which could have a material adverse impact on our business, financial condition and results of operations.
If we are unable to enter into or maintain agreements with third parties to store, distribute and commercialize our products, we may be unable to maximize product revenues, which could have a material adverse impact on our business, financial condition and results of operations.
Our ability to commercialize our products successfully will depend, in part, on the adequacy of our distribution of those products to eligible patients. We currently rely on third-party providers for storage and distribution and on collaboration partners for ongoing commercialization and distribution of CABOMETYX and COMETRIQ in their respective territories outside of the U.S., as well as for access and distribution activities for the approved products under named patient use programs (or similar programs).
Our current and anticipated future dependence upon the activities, support, and legal and regulatory compliance of third parties may adversely affect our ability to supply CABOMETYX and COMETRIQ on a timely and competitive basis. The services provided by these third parties may not be effective or timely, which risks may be increased as a result of the COVID-19 pandemic. In such cases, we may be unable to maintain, improve or renew our arrangements with these third parties or enter into new, alternative arrangements with other service providers, on acceptable terms or at all. If we are unable to contract successfully for effective third-party services on acceptable terms, our commercialization efforts and

those of our collaboration partners may be delayed or otherwise adversely affected, which could have a material adverse impact on our business, financial condition and results of operations.
If we are unable to obtain or maintain coverage and reimbursement for our products from third-party payers, our business will suffer.
Our ability to commercialize our products successfully is highly dependent on the extent to which health insurance coverage and reimbursement is, and will be, available from third-party payers, including governmental payers, such as Medicare and Medicaid, and private health insurers. Third-party payers continue to scrutinize and manage access to pharmaceutical products and services and may limit reimbursement for newly approved products and indications. Patients are generally not capable of paying for CABOMETYX or COMETRIQ themselves and rely on third-party payers to pay for, or subsidize, the costs of their medications, among other medical costs. Accordingly, market acceptance of CABOMETYX and COMETRIQ is dependent on the extent to which coverage and reimbursement is available from third-party payers. These entities could refuse, limit or condition coverage for our products, such as by using tiered reimbursement or pressing for new forms of contracting. If third-party payers do not provide coverage or reimbursement for CABOMETYX or COMETRIQ, our revenues and results of operations will suffer. In addition, even if third-party payers provide some coverage or reimbursement for CABOMETYX or COMETRIQ, the availability of such coverage or reimbursement for prescription drugs under private health insurance and managed care plans, which often varies based on the type of contract or plan purchased, may not be sufficient for patients to afford CABOMETYX or COMETRIQ.
We are subject to healthcare laws, regulations and enforcement; our failure to comply with those laws could have a material adverse impact on our business, financial condition and results of operations.
We are subject to federal and state healthcare laws and regulations, which laws and regulations are enforced by the federal government and the states in which we conduct our business. Should our compliance controls prove ineffective at preventing or mitigating the risk and impact of improper business conduct or inaccurate reporting, we could be subject to enforcement of the following, including, without limitation:
the federal Anti-Kickback Statute, which governs our business activities, including our marketing practices, medical educational programs, pricing policies, and relationships with healthcare providers or other entities;
the federal Food, Drug, and Cosmetic Act (FDCA) and its implementing regulations, which prohibit, among other things, the introduction or delivery for introduction into interstate commerce of any drug that is adulterated or misbranded;
federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payers that are false or fraudulent, or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;
federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and its implementing regulations, which impose certain requirements relating to the privacy, security and transmission of individually identifiable health information on covered entities and business associates that access such information on behalf of a covered entity;
state law equivalents of each of the above federal laws;
the Open Payments program of the Patient Protection and Affordable Care Act, as amended by the Healthcare and Education Reconciliation Act (PPACA), which was created under the Physician Payments Sunshine Act and its implementing regulations and requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the government information related to certain payments and other transfers of value to physicians (as defined by such law) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;
state and local laws and regulations that require drug manufacturers to file reports relating to marketing activities, payments and other remuneration and items of value provided to healthcare professionals and entities, as well as state and local laws requiring the registration of pharmaceutical sales representatives; and

state pharmaceutical price and price reporting laws and regulations that require us to provide notice of price increases or the introduction of new high-cost products, and/or file complex ancillary reports concerning prices and pricing and discount practices.
In addition, we may be subject to the Foreign Corrupt Practices Act, a U.S. law which regulates certain financial relationships with foreign government officials (which could include, for example, medical professionals employed by national healthcare programs) and its foreign equivalents, as well as federal and state consumer protection and unfair competition laws.
These federal and state healthcare laws and regulations govern pharmaceutical marketing practices, including off-label promotion. If our operations are found, or even alleged, to be in violation of the laws described above or any other governmental regulations that apply to us, we, or our officers or employees, may be subject to significant penalties, including administrative civil and criminal penalties, damages, fines, regulatory penalties, the curtailment or restructuring of our operations, exclusion from participation in Medicare, Medicaid and other federal and state healthcare programs, imprisonment, reputational harm, additional reporting requirements and oversight, any of which would adversely affect our ability to sell our products and operate our business and also adversely affect our financial results. Of particular concern are suits filed under the civil False Claims Act, known as “qui tam” actions, which can be brought by any individual on behalf of the government. Under the False Claims Act, these individuals, commonly known as relators or “whistleblowers,” may potentially share in amounts paid by the entity to the government in fines or settlement. When an entity is determined to have violated the civil False Claims Act, or settles a lawsuit brought pursuant to the False Claims Act to avoid further prosecution, it may be required to pay up to three times the actual damages sustained by the government, plus civil penalties for each separate false claim. Defending against any such actions can be costly, time-consuming and may require significant financial and personnel resources. Therefore, if any such action is brought against us, our business may be impaired, even if we are ultimately successful in our defense.
Current healthcare laws and regulations in the U.S. and future legislative or regulatory reforms to the U.S. healthcare system may affect our ability to commercialize our marketed products profitably.
Federal and state governments in the U.S. are considering legislative and regulatory proposals to change the U.S. healthcare system in ways that could affect our ability to continue to commercialize CABOMETYX and COMETRIQ profitably. Similarly, among policy makers and payers, there is significant interest in promoting such changes with the stated goals of containing healthcare costs, improving quality and expanding patient access. The pharmaceuticallife sciences industry and specifically the market for the sale, insurance coverage and distribution of pharmaceuticals has been a particular focus of these efforts and would likely be significantly affected by any major legislative or regulatory initiatives.
We face related uncertainties as a result ofFor instance, efforts to repeal, substantially modify or invalidate some or all of the provisions of the PPACA. Notably, in December 2018, a Texas U.S. District Court Judge ruled that the PPACA is unconstitutional in its entirety because the penalty enforcing the “individual mandate” was repealed by Congress as part of the Tax CutsPatient Protection and JobsAffordable Care Act of 2017. Then,2010, as amended (PPACA), some of which have been successful, create considerable uncertainties for all businesses involved in December 2019, the U.S. Court of Appeals for the 5th Circuit upheld this District Court ruling that the individual mandate was unconstitutional and remanded the case backhealthcare, including our own. Although such efforts have not significantly impacted our business to the District Court to determine whether the remaining provisions of the PPACA are invalid as well. While the U.S. Supreme Court has agreed to review an appeal of the 5th Circuit’s decision in 2020, it is unclear how this decision, future decisions, subsequent appeals and other efforts will impact the PPACA. Additionally, the 2020 federal spending package permanently repealed, effective January 1, 2020, the PPACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device taxes, and, effective January 1, 2021, also eliminates the health insurer tax. Theredate, there is no assurance that the repeal, modification or modificationinvalidation of some or all of the provisions of the PPACA in the future, will not have a material adverse impact on our business, financial condition and results of operations, and we cannot predict how future federal or state legislative or administrative changes relating to healthcare reform will affect our business.
In addition, there are pending federal and state-level legislative proposals that would significantly expand government-provided health insurance coverage, ranging from establishing a single-payer, national health insurance system to more limited “buy-in” options to existing public health insurance programs, each of which could have a significant impact on the healthcare industry. It is also possible that additional governmental actions will be taken in response to address the ongoing COVID-19 pandemic, and that such actions would have a significant impact on these public health insurance programs. While we cannot predict how future legislation (or enacted legislation that has yet to be implemented) will affect our business, such proposals could have the potential to impact access to and sales of our products.

As a result of these developments and trends, third-party payers are increasingly attempting to contain healthcare costs by limiting coverage and the level of reimbursement of new drugs. Insurers are also pursuing means of contracting for pharmaceutical “value” or “outcomes.” These entities could refuse, limit or condition coverage for our products, such as by using tiered reimbursement or pressing for new forms of value-based contracting, which could adversely affect product sales. Furthermore, the expansion of the 340B Drug Discount Program through the PPACA has increased the number of purchasers who are eligible for significant discounts on branded drugs, including our marketed products. Due to the volatilitygeneral uncertainty in the current regulatory and market dynamics,healthcare policy environment, and specifically regarding positions that the Biden Administration may take with respect to these issues, we are unable to predict the impact of any legislative, regulatory, third-party payer or policy actions, including potential cost containment and healthcare reform measures. If enacted, we and any third parties we may engage may be unable to adapt to any changes implemented as a result of such measures, couldand we may have difficulties in sustaining profitability or otherwise experience a material adverse impact on our business, financial condition and results of operations.
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Pricing for pharmaceutical products in the U.S. has come under increasing attention and scrutiny by federal and state governments, legislative bodies and enforcement agencies. These activitiesThis may result in actions that have the effect of reducing our revenue or harming our business or reputation.
There have been several recentcontinue to be U.S. Congressional inquiries, hearings and proposed and enacted federal legislation and rules, as well as executive orders, designed to, among other things: reduce or limit the prices of drugs and make them more affordable for patients;patients (including, for example, by tying the prices that Medicare reimburses for physician-administered drugs to the prices of drugs in other countries); reform the structure and financing of Medicare Part D pharmaceutical benefits, including through increasing manufacturer contributions to offset Medicare beneficiary costs; bring more transparency to drug pricing rationale and methodologies; enable the government to negotiate prices under Medicare; revise rules associated with the calculation of average manufacturer price and best price under Medicaid, which affect the amount of rebates that we pay on prescription drugs under Medicaid and to covered entities under the 340B Drug Discount Program; eliminate the Anti-Kickback Statute (AKS) discount safe harbor protection for manufacturer rebate arrangements with Medicare Part D plan sponsors; create new AKS safe harbors applicable to certain point-of-sale discounts to patients and fixed fee administrative fee payment arrangements with pharmacy benefit managers; and facilitate the importation of certain lower-cost drugs from other countries. While we cannot know the final form or timing of any such legislative, regulatory and/or administrative measures, some of the pending and enacted legislative proposals or executive rulemaking, such as those incorporating International Pricing Index or Most-Favored-Nation models, if enacted,implemented without successful legal challenges, would likely have a significant and far-reaching impact on the biopharmaceutical industry and therefore also likely have a material adverse impact on our business, financial condition and results of operations.
In connection with its evaluation of proposals concerning the pricing of, and access to, pharmaceutical products, many companies in our industry have received governmental requests for documents and information relating to drug pricing and patient support programs. We could receive a similar request, which would require us to incur significant expense and divert the attention of management. Additionally, to the extent there are findings, or even allegations, of improper conduct on the part of the company, these findings could further harm our business, reputation and/or prospects.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including restrictions on pricing or reimbursement at the state government level, limitations on discounts to patients, marketing cost disclosure and transparency measures, and, in some cases, policies to encourage importation from other countries (subject to federal approval) and bulk purchasing, including the National Medicaid Pooling Initiative.
For example, California adopted SB-17, which requires, among other provisions, pharmaceutical manufacturers to provide advance notice of price increases above a defined threshold to certain purchasers and related reports to In particular, the government. Such obligationsobligation to provide notices of price increases to purchasers under laws such as California’s SB-17 may influence customer ordering patterns for CABOMETYX and COMETRIQ, which in turn may increase the volatility of our revenues as a reflection of changes in inventory volumes. Furthermore, adoption of these drug pricing transparency regulations, and our associated compliance obligations, may increase our general and administrative costs and/or diminish our revenues as a resultrevenues. Implementation of the imposition of caps on pricing and price increases. Therefore, the implementation of these federal and/or state cost-containment measures or other healthcare reforms may result in fluctuations in our results of operations and limit our ability to generate product revenue or commercialize our products.products, and in the case of drug pricing transparency regulations, may result in fluctuations in our results of operations.
Lengthy regulatory pricing and reimbursement procedures and cost control initiatives imposed by governments outside the U.S. could delay the marketing of and/or result in downward pressure on the price of our approved products, resulting in a decrease in revenue.
Outside the U.S., particularlyincluding major markets in the EU and Japan, the pricing and reimbursement of prescription pharmaceuticals is generally subject to governmental control. In EUthese countries, pricing and reimbursement negotiations with governmental authorities or payers can take six to 12 months or longer after the initial marketing authorization is granted for a product, or after the marketing authorization for a new indication is granted. This can substantially delay broad availability of the product. To obtain reimbursement and/or pricing approval in some countries, our collaboration partnerpartners Ipsen and Takeda may also be required to conduct a study or otherwise provide data that seeks to establish the cost effectiveness of CABOMETYX compared with other available established therapies. The conduct of such a study could also result in delays in the commercialization of CABOMETYX. Additionally,

cost-control initiatives, increasingly based on affordability, could decrease the price we and Ipsen might establish for CABOMETYX, or the indications for which we are able to obtain reimbursement, which would result in lower license revenues to us.
A significantLegislation and prolonged economic downturn, whether globally or just withinregulatory action designed to reduce barriers to the development, approval and adoption of generic drugs in the U.S., and the entrance of generic competitors, could limit the revenue we derive from our products, which could have a substantialmaterial adverse impact on our revenuesbusiness, financial condition and financial condition.results of operations.
Our revenues are substantially dependentUnder the Federal Food, Drug, and Cosmetic Act (FDCA), the FDA can approve an ANDA for a generic version of a branded drug without the applicant undertaking the human clinical testing necessary to obtain approval to market a new drug. The FDA can also approve a New Drug Application (NDA) under section 505(b)(2) of the FDCA that relies in part on the net pricing that we ultimately realizeagency’s findings of safety and/or effectiveness for a previously approved drug, where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use. Both the ANDA and 505(b)(2) NDA processes are discussed in paymentmore detail in “Item 1.
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Business—Government Regulation—FDA Review and Approval” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2020 submitted to the SEC on February 10, 2021. In either case, if an ANDA or 505(b)(2) NDA applicant submits an application referencing one of our marketed products prior to the expiry of one or more our Orange Book-listed patents for the applicable product, we may litigate with the potential generic competitor to protect our patent rights, which would result in substantial costs, divert the attention of management, and commercial third-party payerscould have an adverse impact on our stock price. For example, MSN and Teva have separately submitted ANDAs to the FDA requesting approval to market their respective generic versions of CABOMETYX tablets. For a more detailed discussion of the litigation matter involving MSN, see “Legal Proceedings” in Part II, Item 1 of this Quarterly Report on Form 10-Q. It is possible that MSN, Teva or other companies, following FDA approval of an ANDA or 505(b)(2) NDA, could introduce generic or otherwise competitor versions of our marketed products before our patents expire if they do not receiveinfringe our patents or if it is determined that our patents are invalid or unenforceable, and we expect that generic cabozantinib products would be offered at a significantly lower price compared to our marketed cabozantinib products. Therefore, regardless of the same degree of discounts and allowances that we provide to government payers. Inregulatory approach, the eventintroduction of a significantgeneric version of cabozantinib could significantly decrease our revenues derived from the U.S. sales of CABOMETYX and prolonged economic downturn,thereby materially harm our business, financial condition and results of operations.
The U.S. federal government has also taken numerous legislative and regulatory actions to expedite the numberdevelopment and approval of patients enrolled in commercial health insurance programsgeneric drugs and biosimilars. The FDA Reauthorization Act of 2017 includes, inter alia, measures to expedite the development and approval of generic products, where generic competition is likely to decrease, particularlylacking even in the U.S. where workforce reductions could cause widespread lossabsence of exclusivities or listed patents. In addition, the FDA has also released a Drug Competition Action Plan, which proposes actions to broaden access to generic drugs and lower consumers’ healthcare costs by, among other things, improving the efficiency of the private health insurance coverage typicallygeneric drug approval process and supporting the development of complex generic drugs, and the FDA has taken and continues to take steps to implement this plan. Moreover, both Congress and the FDA are considering various legislative and regulatory proposals focused on drug competition, including legislation focused on drug patenting and provision of drug to generic applicants for testing. For example, the Further Consolidated Appropriations Act, 2020, which incorporated the framework from the Creating and Restoring Equal Access To Equivalent Samples (CREATES) legislation, was signed into law as part of the 2019 year-end federal spending package. The legislation purports to promote competition in the market for drugs and biological products by facilitating the timely entry of lower-cost generic and biosimilar versions of those drugs and biological products, including by allowing ANDA, 505(b)(2) NDA or biosimilar developers to obtain access to branded drug and biological product samples. While the full impact of these provisions is unclear at this time, its provisions do have the potential to facilitate the development and future approval of generic versions of our products, introducing generic competition that could have a material adverse impact on our business, financial condition and results of operations.
Risks Related to Healthcare Regulatory and Other Legal Compliance Matters
We are subject to healthcare laws, regulations and enforcement; our failure to comply with those laws could have a material adverse impact on our business, financial condition and results of operations.
We are subject to federal and state healthcare laws and regulations, which laws and regulations are enforced by the federal government and the states in which we conduct our business. Should our compliance controls prove ineffective at preventing or mitigating the risk and impact of improper business conduct or inaccurate reporting, we could be subject to enforcement of the following, including, without limitation:
the federal AKS;
the FDCA and its implementing regulations;
federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalty laws;
federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and its implementing regulations, as amended;
state law equivalents of each of the above federal laws;
the Open Payments program of the PPACA;
state and local laws and regulations that require drug manufacturers to file reports relating to marketing activities, payments and other remuneration and items of value provided by employers,to healthcare professionals and a commensurate shiftentities; and
state and federal pharmaceutical price and price reporting laws and regulations.
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In addition, we may be subject to the circumstance of lacking health insurance coverage altogether. The COVID-19 pandemic, among other catalysts, has already causedForeign Corrupt Practices Act, a downturn in the U.S. law which regulates certain financial relationships with foreign government officials (which could include, for example, medical professionals employed by national healthcare programs) and global economy and significant levels of unemployment, and the duration and severity of this economic downturn are not yet known. Depending on the scale and ultimate duration of the COVID-19 pandemic,its foreign equivalents, as well as other factors, we could experience a substantial decreasefederal and state consumer protection and unfair competition laws.
These federal and state healthcare laws and regulations govern drug marketing practices, including off-label promotion. If our operations are found, or even alleged, to be in revenues as a resultviolation of the increase in gross-to-net discounting appliedlaws described above or other governmental regulations that apply to us, we, or our officers or employees, may be subject to significant penalties, including administrative civil and criminal penalties, damages, fines, regulatory penalties, the pricecurtailment or restructuring of our products due to a substantial shiftoperations, exclusion from private health insurance coverage to government insurance coverage,participation in Medicare, Medicaid and also a significant increase in demand for our patient assistance and/or free drug program, all orother federal and state healthcare programs, imprisonment, reputational harm, additional reporting requirements and oversight, any of which would adversely affect our product revenues.ability to sell our products and operate our business and also adversely affect our financial results. Furthermore, responding to any such allegation and/or defending against any such enforcement actions can be time-consuming and would require significant financial and personnel resources. Therefore, if any state or the federal government initiates an enforcement action against us, our business may be impaired, and even if we are ultimately successful in our defense, litigating these actions could result in substantial costs and divert the attention of management.
Enhanced governmental and private scrutiny over, or investigations or litigation involving, pharmaceutical manufacturer patient assistance programs and donations to patient assistance programs offeredfoundations created by charitable foundationsorganizations could negatively impact our business practices, harm our reputation, divert the attention of management and increase our expenses.
To help patients afford our products, we have a patient assistance program and also occasionally make donations to independent charitable foundations that help financially needy patients. These types of programs designed to assist patients with affording pharmaceuticals have become the subject of Congressional interest and enhanced government scrutiny. The U.S. Department of Health and Human Services Office of Inspector General established specific guidelines permitting pharmaceutical manufacturers to make donations to charitable organizations that provide co-pay assistance to Medicare patients, provided that manufacturers meet certain specified compliance requirements. In the event we make such donations but are deemedfound not to have complied with these guidelines and other laws or regulations respecting the operation of these programs, we could be subject to significant damages, fines, penalties or other criminal, civil or administrative sanctions or enforcement actions. We also rely on a third-party hub provider and exercise oversight to monitor patient assistance program activities. Hub providers are generally hired by manufacturers to assist patients with insurance coverage, financial assistance and treatment support after the patients receive a prescription from their healthcare provider.professional. For manufacturers of specialty drugspharmaceuticals (including our marketed products), the ability to have a single point of contact for their therapies helps ensure efficient medication distribution to patients. Accordingly, our hub activities are also subject to scrutiny and may create risk for us if not conducted appropriately. A variety of entities, including independent charitable foundations and pharmaceutical manufacturers, but not including our company, have received subpoenas from the U.S. Department of Justice and other enforcement authorities seeking information related to their patient assistance programs and support. RegardlessShould we or our hub providers receive a subpoena or other process, regardless of whether we are ultimately found to have complied with the regulations governing patient assistance programs, this type of government investigation could negatively impact our business practices, harm our reputation, divert the attention of management and increase our expenses.
We are subject to laws and regulations relating to privacy, data protection and the collection and processing of personal data. Failure to maintain compliance with these regulations could create additional liabilities for us.
The legislative and regulatory landscape for privacy and data protection continues to evolve globally and in the U.S. For example, the California Consumer Privacy Act of 2018 (CCPA) went into operation on January 1,in 2020 and affords California residents expanded privacy rights and protections, including civil penalties for violations and statutory damages under a private right of action for data security breaches. These protections will be expanded by California Privacy Rights Act of 2020 (CPRA), which will be operational in most key respects on January 1, 2023. Similar legislative proposals are being advanced in other states and Congress is also considering federal privacy legislation. In addition, most healthcare providers are subject to privacy and security requirements under HIPAA. Although we are not directly subjectconsidered to be a covered entity or business associate under HIPAA, we could be subject to criminal penalties if we knowingly encourage, assist or otherwise facilitate a HIPAA-covered entity (or its business associate) to use or disclose individually identifiable health information in a manner not authorized or permitted by HIPAA. Other countries also have, or are developing, laws governing the collection, use and transmission of personal information. For example, the EU General Data Protection Regulation 2016/679 (GDPR) regulates the processing of personal data of individuals within the EU, even if, under certain circumstances, that processing occurs outside the EU, and also restrictsplaces restrictions on transfers of such data to countries

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outside of the EU, including the U.S. Should we fail to provide adequate privacy or data security protections or maintain compliance with these laws and regulations, including the CCPA, CPRA and GDPR, we could be subject to sanctions or other penalties, litigation or an increase in our cost of doing business.
LegislationRisks Related to Growth of Our Product Portfolio and regulatory action designed to facilitate the development, approvalResearch and adoption of generic drugs in the U.S., and the entrance of generic competitors, could limit the commercial potential of our products, which could have a material adverse impact on our business, financial condition and results of operations.
Under the FDCA, the FDA can approve an ANDA for a generic version of a branded drug without the applicant undertaking the human clinical testing necessary to obtain approval to market a new drug. The FDA can also approve a New Drug Application (NDA) under section 505(b)(2) of the FDCA that relies in whole or in part on the agency’s findings of safety and/or effectiveness for a previously approved drug. Both the ANDA and 505(b)(2) processes are discussed in more detail under “Item 1. Business—Government Regulation—FDA Review and Approval” in our Annual Report on Form 10-K for the year ended December 31, 2019 filed with the SEC on February 25, 2020. In either case, if an ANDA or 505(b)(2) applicant submits an application referencing one of our marketed products prior to the expiry of one or more our Orange Book-listed patents for the applicable product, we may litigate with the potential generic competitor to protect our patent rights, which would result in substantial costs and divert the attention of management, and could have an adverse impact on our stock price. For example, we received Paragraph IV certification notice letters from MSN concerning the ANDA that it had filed with the FDA seeking approval to market a generic version of CABOMETYX tablets. It is possible that MSN or other companies, following FDA approval of an ANDA or 505(b)(2) NDA, could introduce generic versions of our marketed products before our patents expire if they do not infringe our patents or if it is determined that our patents are invalid or unenforceable, and we expect that generic cabozantinib products would be offered at a significantly lower price compared to our marketed cabozantinib products. Therefore, regardless of the regulatory approach, the introduction of a generic version of cabozantinib could significantly decrease our revenues and thereby materially harm our business, financial condition and results of operations.
The U.S. federal government has also taken numerous legislative and regulatory actions to expedite the development and approval of generic drugs and biosimilars. In August 2017, President Trump signed the FDA Reauthorization Act of 2017, which reauthorized the FDA user fee programs for prescription drugs, generic drugs, medical devices, and biosimilars, under which applicants for such products partially pay for the FDA’s pre-market review of their product candidates and pay other specified fees. The legislation also includes, inter alia, measures to expedite the development and approval of generic products, where generic competition is lacking even in the absence of exclusivities or listed patents. In addition, the FDA has also released a Drug Competition Action Plan, which proposes actions to broaden access to generic drugs and lower consumers’ healthcare costs by, among other things, improving the efficiency of the generic drug approval process and supporting the development of complex generic drugs, and the FDA has taken steps to implement this plan. Moreover, both Congress and the FDA are considering various legislative and regulatory proposals focused on drug competition, including legislation focused on drug patenting and provision of drug to generic applicants for testing. For example, the Creating and Restoring Equal Access To Equivalent Samples (CREATES) Act of 2019, signed into law as part of the 2019 year-end federal spending package, purports to promote competition in the market for drugs and biological products by facilitating the timely entry of lower-cost generic and biosimilar versions of those drugs and biological products, including by allowing generic manufacturers access to branded drug samples. While we cannot predict the specific outcome or impact on our business of such regulatory actions or legislation, they do have the potential to facilitate the development and future approval of generic versions of our products, or otherwise limit or reduce the term for our market exclusivity, which could have a material adverse impact on our business, financial condition and results of operations.Development
Clinical testing of cabozantinib for new indications, or of new potential product candidates, is a lengthy, costly, complex and uncertain process andthat may fail ultimately to demonstrate safety and efficacy.efficacy data for those products sufficiently differentiated to compete in our highly competitive market environment.
Clinical trials are inherently risky and may reveal that cabozantinib, despite its approval for certain indications, or a new product candidate, is ineffective or has an unacceptable safety profile with respect to an intended use. Such results may significantly decrease the likelihood of regulatory approval of that product for a particular indication. Moreover, the results of preliminary studies do not necessarily predict clinical or commercial success, and late-stage or other potentially label-enabling clinical trials may fail to confirm the results observed in early-stage trials or preliminary studies. Although we have established timelines for manufacturing and clinical development of cabozantinib and our other product candidates based on existing knowledge of our compounds in development and industry metrics, we may not be able to meet those timelines.

We may experience numerous unforeseen events, during or as a result of clinical investigations, that could delay or prevent commercialization of cabozantinib (or of other product candidates) in new indications, and in some cases, as described in the risk factor entitled,titled,If the current public healthCOVID-19 pandemic related to COVID-19 continues and grows in severity,is further prolonged or becomes more severe, our business operations and corresponding financial results could suffer, which could have a material adverse impact on our financial condition and prospects for growth,” the COVID-19 pandemic has already increased and may further increase the potential for such developments to occur. These may include:
lack of acceptable efficacy or a tolerable safety profile;
negative or inconclusive clinical trial results that require us to conduct further testing or to abandon projects;
discovery or commercialization by our competitors of other compounds or therapies that show significantly improved safety or efficacy compared to cabozantinib or our other product candidates;
our inability to identify and maintain a sufficient number of trial sites;
lower-than-anticipated patient registration or enrollment in our clinical testing;
additional complexities posed by clinical trials evaluating cabozantinib or our other product candidates in combination with other therapies, including the failure by our collaboration partners to provide us with an adequate and timely supply of product that complies with the applicable quality and regulatory requirements for a combination trial;
failure of our third-party contract research organizations or investigators to satisfy their contractual obligations, including deviating from any trial protocols; and
withholding of authorization from regulators or institutional review boards to commence or conduct clinical trials or delays, suspensions or terminations of clinical research for various reasons, including noncompliance with regulatory requirements or a determination by these regulators and institutional review boards that participating patients are being exposed to unacceptable health risks.
If there are further delays in or termination of the clinical testing of cabozantinib or our other product candidates due to any of the events described above or otherwise, including as a result of the COVID-19 pandemic, our expenses could increase and our ability to generate revenues could be impaired, either of which could adversely impact our financial results. Furthermore, we rely on our collaboration partners to fund a significant portion of our clinical development programs. Should one or all of our collaboration partners decline to support future planned clinical trials, we will be entirely responsible for financing the further development of the cabozantinib franchise or our other product candidates and, as a result, we may be unable to execute our current business plans, which could have a material adverse impact on our business, financial condition and results of operations.
We may not be able to pursue the further development of the cabozantinib franchise or our other product candidates or meet current or future requirements of the FDA or regulatory authorities in other jurisdictions in accordance with our stated timelines or at all. Our planned clinical trials may not begin on time, or at all, may not be completed on schedule, or at all, may not be sufficient for registration of our product candidates or may not result in an approvable product. The duration and the cost of clinical trials vary significantly as a result of factors relating to the clinical trial, including, among others: characteristics of the product candidate under investigation; the number of patients who
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ultimately participate in the clinical trial; the duration of patient follow-up; the number of clinical sites included in the trials; and the length of time required to enroll eligible patients.
Any delay could limit our ability to generate revenues, cause us to incur additional expense and cause the market price of our common stock to decline significantly. Our partners under our collaboration agreements may experience similar risks with respect to the compounds we have out-licensed to them. If any of the events described above were to occur with such programs or compounds, the likelihood of receipt of milestones and royalties under such collaboration agreements could decrease.
The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy and uncertain and may not result in regulatory approvals for additional cabozantinib indications or our other product candidates, which could have a material adverse impact on our business, financial condition and results of operations.
The activities associated with the research, development and commercialization of the cabozantinib franchise and our other product candidates are subject to extensive regulation by the FDA and other regulatory agencies in the U.S., as well as by comparable authorities in other countries.territories. The processes of obtaining regulatory approvals in the U.S. and other foreign jurisdictions is expensive and often takes many years, if approval is obtained at all, and they can vary substantially based upon the type, complexity and novelty of the product candidates involved. For example, before an NDA or supplemental New Drug Application (sNDA)sNDA can be submitted to the FDA, or a marketing authorization application to the EMA or any

application or submission to regulatory authorities in other jurisdictions, the product candidate must undergo extensive clinical trials, which can take many years and require substantial expenditures.
Any clinical trial may fail to produce results satisfactory to the FDA or regulatory authorities in other jurisdictions. The FDA has substantial discretion in the approval process and may refuse to approve any NDA or sNDA or decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. For example, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent regulatory approval of cabozantinib for any individual additional indications. In addition, we may encounter delays or rejections based upon changes in policy, which could cause delays in the approval or rejection of an application for cabozantinib or for our other product candidates.
Even if the FDA or a comparable authority in another jurisdiction approves cabozantinib for one or more new indications, such approval may be limited, imposing significant restrictions on the indicated uses, conditions for use, labeling, distribution, and/or production of the product and could impose requirements for post-approval studies, including additional research and clinical trials, all of which may result in significant expense and limit our and our collaboration partners’ ability to commercialize cabozantinib in one or more new indications. For example, based on the regulatory feedback from the FDA, and if supported by the clinical data from COSMIC-021, we intend to file withsubmit an sNDA to the FDA forseeking accelerated approval of cabozantinib in an mCRPC indication as early asin 2021. We expect that as a condition of any potential approval under the FDA's accelerated approval, pathway, the FDA will require us to perform confirmatory post-marketing clinical trials to confirm the clinical benefit, if any, of cabozantinib in combination with Roche’s atezolizumab in patients with locally advanced or metastatic solid tumors, such as mCRPC. Failure to complete any post-marketing requirements of the FDA in connection with a specific approval in accordance with the timelines and conditions set forth by the FDA could significantly increase costs or delay, limit or ultimately restrict the commercialization of cabozantinib in any additional indications. Further, these regulatorythat indication. Regulatory agencies could also impose various administrative, civil or criminal sanctions for failure to comply successfully with regulatory requirements, including withdrawal of product approval.
In addition, on March 27, 2020, Congress Further, current or any future laws or executive orders enacted the Coronavirus Aid, Relief, and Economic Security Act (CARES Act)or executed in response to the COVID-19 pandemic. Amongst other provisions, the CARES Act made a number of changes to the FDCA aimed at preventing drug shortages. While we are still evaluating these and other CARES Act changes, these changes could impact our business. For example, in light of the COVID-19 pandemic the FDA has issued a number of guidance documents describing the agency’s expectations for how drug manufacturers should comply with various FDA requirements during the pandemic, including with respect to conducting clinical trials and reporting post-marketing adverse events. These and any further guidance documents issued by FDA that impact the requirements to which we are subject, as well as any equivalent federal or state legislative or regulatory initiatives, or similar measures outside of the United States, could have a material adverse impact on our business, financial condition, and results of operations.
We may be unable to expand our development pipeline, which could limit our growth and revenue potential.
Our business is focused on the discovery, development and commercialization of new medicines for difficult-to-treat cancers. In this regard, we have invested in substantial technical, financial and human resources toward internal drug discovery activities with the goal of identifying new product candidates to advance into clinical trials. Notwithstanding suchthis investment, the COVID-19 pandemic has caused temporary suspensions of internal drug discovery in our laboratories and other limitations to our programs described in the risk factor entitled, “If the current public health pandemic related to COVID-19 continues and grows in severity, our business operations and corresponding financial results could suffer, which could have a material adverse impact on our financial condition and prospects for growth.” Even assuming we successfully return to normal drug discovery and preclinical development operations in the future, many programs that may have initially shownshow promise will ultimately fail to yield product candidates for multiple reasons. For example, product candidates may, on further study, be shown to have inadequate efficacy, harmful side effects, suboptimal pharmaceutical profiles or other characteristics suggesting that they are unlikely to be commercially viable products.
Apart from our internal drug discovery efforts, our strategy to expand our development pipeline is also dependent on our ability to successfully identify and acquire or in-license relevant product candidates.candidates and technologies. However, the in-licensing and acquisition of product candidates and technologies is a highly competitive area, and many other companies are pursuing the same or similar product candidates and technologies to those that we may consider attractive. In particular, larger companies with more capital resources and more extensive clinical development and commercialization
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capabilities may have a competitive advantage over us. Furthermore, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We may also be unable to in-license or acquire additional product candidates and technologies on acceptable terms that would allow us to realize an appropriate return on our investment. If our internal drug discovery or business development efforts do not result in

suitable product candidates, our business and prospects for growth could suffer. Even if we succeed in our efforts to obtain rights to suitable product candidates and technologies, the competitive business environment may result in higher acquisition or licensing costs, and our investment in these potential products and technologies will remain subject to the inherent risks associated with the development and commercialization of new medicines. In certain circumstances, we may also be reliant on the licensor for the continued development of the in-licensed technology and their efforts to safeguard their underlying intellectual property.
With respect to acquisitions, we may not be able to integrate the target company successfully into our existing business, maintain the key business relationships of the target company, or retain key personnel of anthe acquired business. Furthermore, we could assume unknown or contingent liabilities or otherwise incur unanticipated expenses. Any acquisitions or investments made by us also could result in our spending significant amounts, issuing dilutive securities, assuming or incurring significant debt obligations and contingent liabilities, incurring large one-time expenses and acquiring intangible assets that could result in significant future amortization expense and significant write-offs, any of which could harm our financial condition and results of operations.
Increasing use of social media could give rise to liability If our drug discovery efforts, including research collaborations, in-licensing arrangements and other business development activities, do not result in harm to our business.
We and our employees are increasingly utilizing social media tools and our website as a means of communication. For example, we use Facebook and Twitter to communicate with the medical community and the investing public, although we do not intend to disclose material, nonpublic information through these means. Despite our efforts to monitor social media communications, there is risk that the unauthorized use of social media by us or our employees to communicate about our products or business, or any inadvertent disclosure of material, nonpublic information through these means, may result in violations of applicable laws and regulations, which may give rise to liability and result in harm to our business. In addition, there is also risk of inappropriate disclosure of sensitive information, which could result in significant legal and financial exposure and reputational damages that could potentially have a material adverse impact onsuitable product candidates, our business financial condition and results of operations. Furthermore, negative posts or comments about us or our products on social mediaprospects for growth could seriously damage our reputation, brand image and goodwill.suffer.
Risks Related to OurFinancial Matters and Capital Requirements Accounting and Financial Results
Our profitability could be negatively impacted byif expenses associated with our extensive clinical development, business development and commercialization activities, both for the cabozantinib franchise and pipeline expansion efforts relative toour earlier-stage product candidates, grow more quickly than the revenues we generate.
Although we reported net income of $48.6$1.6 million for the three months ended March 31, 20202021 and $321.0$111.8 million for the year ended December 31, 2019, respectively,2020, we may not be able to maintain or increase profitability on a quarterly or annual basis, and we are unable to predict the extent of future profits or losses. The amount of our net profits or losses will depend, in part, on: the level of sales of CABOMETYX and COMETRIQ in the U.S.; our achievement of clinical, regulatory and commercial milestones, if any, under our collaboration agreements with Ipsen and Takeda;agreements; the amount of royalties from sales of CABOMETYX and COMETRIQ outside of the U.S. under our collaboration agreements with Ipsen and Takeda;agreements; other collaboration revenues; and the level of our expenses, including forthose associated with our extensive drug discovery, clinical development, business development and commercialization activities, both for the cabozantinib franchise and our earlier-stage product candidates. For example, we reported a net loss for any pipeline expansion efforts.the quarter ended September 30, 2020, primarily due to substantial increases in clinical trial costs, license and other collaboration costs, and personnel expenses relative to the prior fiscal quarters, and it is possible that we may experience net losses in future fiscal quarters or fiscal years, whether due to increases in costs and expenses or otherwise. We expect to continue to spend substantial amounts to fund the continued development of the cabozantinib franchise for additional indications and the commercialization of our approved products. In addition, we intend to continue to expand our oncology product pipeline through our internal drug discovery efforts, including research collaborations, in-licensing arrangements and the execution of additional partnerships throughother business development activities or strategic transactions that align with our oncology drug development, regulatory and commercial expertise, which efforts could involve substantial costs. To offset these costs in the future, we will need to generate substantial revenues. If these costs exceed our current expectations, or we fail to achieve anticipated revenue targets, the market value of our common stock may decline.
Our financial outlook may not be realized.
From time to time, in press releases and otherwise, we may publish estimates, forecasts or other forward-looking statements regarding our future financial or operating results, including estimated revenues, expenses and earnings. Any forecast of our future performance reflects various assumptions. These assumptions are subject to significant risks and uncertainties, and as a matter of course, any number of them may prove to be incorrect. Further, the achievement of any forecast depends on numerous assumptions and other factors (including those described in this discussion), many of which are beyond our control. Moreover, should the COVID-19 pandemic continue to spread and grow in severity, the impact on our profitability is difficult to predict. As a result, we cannot be certain that our performance will be consistent with any management estimates or forecasts or that the variation from such estimates or forecasts will not be material and adverse. Current and potential stockholders are cautioned not to base their entire analysis of our business and prospects upon

isolated estimates or forecasts, but instead are encouraged to utilize our entire publicly available mix of historical and forward-looking information, as well as other available information regarding us, our products, the competitive landscape for our products, our commercialization, development and regulatory efforts, as well as those of our collaboration partners, and the biotechnology and pharmaceutical industry generally when evaluating our prospective financial or operating results.
If additional capital is not available to us when we need it, we may be unable to expand our product offerings and maintain business growth.
As of both March 31, 2020 and December 31, 2019, we had $1.4 billion in cash and investments. Our business operations grew substantially during 2019. In order to maintain business growth in 2020, we plan to continue to execute on our U.S. commercialization plans for CABOMETYX, while reinvesting in our product pipeline through the continued development of cabozantinib and our other product candidates, internal discovery activities, and the execution of strategic transactions. Our ability to achieve these business objectives will depend on many factors including but not limited to:
the commercial success of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products;
costs associated with maintaining our expanded sales, marketing, market access, medical affairs and product distribution capabilities for CABOMETYX and COMETRIQ;
the achievement of stated regulatory and commercial milestones and royalties paid under our collaboration agreements with Ipsen and Takeda;
the commercial success of and revenues generated by products marketed under our collaboration and license agreements;
future clinical trial results;
the impact of the COVID-19 pandemic on our ability to conduct critical business operations, including internal drug discovery activities, clinical trials and commercial operations;
the level of our investments in the expansion of our pipeline through internal drug discovery and business development activities;
the number and size of clinical trials we conduct and the cost of drug supply for such clinical trials evaluating our products with other therapeutic agents;
trends and developments in the pricing of oncologic therapeutics in the U.S. and abroad, especially in the EU;
scientific developments in the market for oncologic therapeutics and the timing of regulatory approvals for competing oncologic therapies; and
the filing, maintenance, prosecution, defense and enforcement of patent claims and other intellectual property rights.
Our commitment of cash resources to CABOMETYX and the reinvestment in our product pipeline through the continued development of the cabozantinib franchise and increasing internal drug discovery activities, as well as through the execution of strategicbusiness development transactions, could require us to obtain additional capital. We may seek such additional capital through some or all of the following methods: corporate collaborations; licensing arrangements; and public or private debt or equity financings. Our ability to obtain additional capital may depend on prevailing economic conditions and financial, business and other factors beyond our control. Disruptions in the U.S. and global financial markets, including disruptions that have resulted and may continue to result from the COVID-19 pandemic and the related downturn in the U.S. and global economy, as well as future potential U.S. federal government shutdowns, rising interest rate environments, increased or changed tariffs and trade restrictions or otherwise, may adversely impact the availability and cost of credit, as well as our ability to raise additional funds in the capital markets. Economic and capital markets conditions have been, and continue to be, volatile. Continued instability in these market conditions may limit our ability to access the capital necessary
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to fund and grow our business. In particular, our inability to access additional funds, whether due to the effects of the COVID-19 pandemic or otherwise, could in the future inhibit our ability to engage in larger scalelarger-scale strategic transactions or investments. We do not know whether additional capital will be available when needed, or that, if available, we will obtain additional capital on terms favorable to us or our stockholders. If we are unable to raise additional funds when we need them, we may be unable to expand our product offerings and maintain business growth, which could have a material adverse impact on our business, financial condition and results of operations.

Our financial results are impacted by management’s selection of accounting methods, certain assumptions and estimates and future changes in accounting standards.
Our accounting policies and methods are fundamental to how we record and report our financial condition and results of operations. Our management must exercise judgment in selecting and applying many of these accounting policies and methods so they comply with generally accepted accounting principles and reflect management’s judgment of the most appropriate manner to report our financial condition and results of operations. In some cases, management must select the accounting policy or method to apply from two or more alternatives, any of which may be reasonable under the circumstances, yet may result in our reporting materially different results than would have been reported under a different alternative.
Certain accounting policies are critical to the presentation of our financial condition and results of operations. We believe our critical accounting policies relating to revenue recognition, clinical trial accruals, inventory, stock-based compensation and income taxes reflect the more significant estimates and judgments used in the preparation of our Consolidated Financial Statements. Although we base our estimates and judgments on historical experience, our interpretation of existing accounting literature and on various other assumptions that we believe to be reasonable under the circumstances, if our assumptions prove to be materially incorrect, actual results may differ materially from these estimates.
In addition, future changes in financial accounting standards may cause adverse, unexpected revenue fluctuations and affect our financial position or results of operations. New pronouncements from the Financial Accounting Standards Board and varying interpretations of pronouncements have occurred with frequency in the past and are expected to occur again in the future and, as a result, we may be required to make changes in our accounting policies. Those changes could adversely affect our reported revenues and expenses, our other results of operations or our current financial position.
Our effective tax rate may fluctuate, and we may incur obligations in tax jurisdictions in excess of accrued amounts.
We are subject to income tax in the U.S. as well as numerous U.S. states and territories, municipalities, and other local jurisdictions. As a result, our effective tax rate is derived from various factors including the mix of earnings and applicable tax rates in the various places that we operate, the accounting for stock options and stock-based awards, and research and development spending. In preparing our financial statements, we estimate the amount of tax that will become payable in each jurisdiction. Our effective tax rate, however, may be different than experienced in the past due to numerous factors, including changes in tax laws, changes in the mix of our earnings from state to state, the results of examinations and audits of our tax filings, or our inability to secure or sustain acceptable agreements with tax authorities. Any of these factors could cause our effective tax rate to fluctuate.
Our ability to use net operating losses and tax credits to offset future taxable income may be subject to limitations.
As of December 31, 2019, we had federal and state net operating loss carryforwards of approximately $675 million. The federal and state net operating loss carryforwards will begin to expire, if not utilized, beginning in 2035 for federal income tax purposes and 2020 for state income tax purposes. These net operating loss carryforwards could expire unused and be unavailable to offset future income tax liabilities. Under the Internal Revenue Code (the Code) and similar state provisions, certain substantial changes in our ownership could result in an annual limitation on the amount of net operating loss carryforwards that can be utilized in future years to offset future taxable income. The annual limitation may result in the expiration of net operating losses and credit carryforwards before utilization. Based on our review and analysis, we concluded, as of December 31, 2019, that an ownership change, as defined under Section 382, had not occurred. However, if there is an ownership change under Section 382 of the Code in the future, we may not be able to utilize a material portion of our net operating losses. Furthermore, our ability to utilize our net operating losses is conditioned upon our maintaining profitability and generating U.S. federal taxable income.
The United Kingdom’s (UK’s) withdrawal from the EU may have a negative effect on global economic conditions, financial markets and our business.
Following the ratification of the Withdrawal Agreement by the European Parliament and UK Parliament, the UK left the EU on January 31, 2020 (commonly referred to as “Brexit”). The Withdrawal Agreement provides for a transition period until December 31, 2020, during which the UK remains in the single market and customs union and the free movement of people will continue, in order to ensure frictionless trade and business continuity until a long-term relationship is agreed. At

the end of transition, the UK’s relationship with the EU will be determined by the new agreements it has entered into on trade and other areas of cooperation. The new agreements must be reached before the transition period ends. If not, the UK would have to rely on previous international conventions for security cooperation and would trade with the EU on World Trade Organization terms. The exception is Northern Ireland, whose trade in goods with the EU would be covered by the provisions in the Northern Ireland Protocol. As a result of the COVID-19 pandemic, planned negotiating rounds for the UK’s future relationship with the EU have not been progressing at a pace that would facilitate a final agreement on trade and cooperation between the UK and the EU prior to December 31, 2020. Under these circumstances, it is uncertain whether the UK and EU would agree to extend the transition period beyond December 31, 2020. Given the lack of comparable precedent, it is unclear what financial, trade, regulatory and legal implications Brexit will have and how it might affect us. For example, we rely on third-party contract manufacturing organization facilities located in the UK, responsible for packaging, labeling, storing and subsequently distributing supplies of our product to the EU. Any tariffs, differing regulatory requirements and other restrictions on the free movement of goods between the UK and the EU that ultimately result from Brexit may have an adverse impact on this part of our supply chain. Trade restrictions, changes to the regulatory approval or drug cost reimbursement systems, and additional administrative costs may impede the ability of our collaboration partner Ipsen to market our products in Europe. Furthermore, the initial announcement of Brexit caused significant volatility in global stock markets and currency exchange rate fluctuations; therefore, the Brexit transition may continue to adversely affect European and global economic and market conditions, which may cause third-party payers, including governmental organizations, to closely monitor their costs and reduce their spending budgets, and which could contribute to instability in the global financial and foreign exchange markets. Any of these effects of Brexit could have a material adverse impact on our business, financial condition and results of operations.
Risks Related to Our Relationships with Third Parties
We rely on Ipsen and Takeda for the commercial success of CABOMETYX in its approved indications outside of the U.S., and are dependentunable to control the amount or timing of resources expended by these collaboration partners in the commercialization of CABOMETYX in its approved indications outside of the U.S.
We rely upon the regulatory, commercial, medical affairs, market access and other expertise and resources of our collaboration partners, Ipsen and Takeda, for commercialization of CABOMETYX in their respective territories outside of the U.S. We cannot control the amount and timing of resources that our collaboration partners dedicate to the commercialization of CABOMETYX, or to its marketing and distribution, and our ability to generate revenues from the commercialization of CABOMETYX by our collaboration partners depends on their ability to obtain and maintain regulatory approvals for, achieve market acceptance of, and to otherwise effectively market, CABOMETYX in its approved indications in their respective territories. Further, the operations of our collaboration partners, and ultimately their sales of CABOMETYX in their respective territories outside of the U.S., could be adversely affected by the degree and effectiveness of their respective corporate responses to the COVID-19 pandemic, as well as by the imposition of governmental price or other controls, political and economic instability, trade restrictions or barriers and changes in tariffs, escalating global trade and political tensions, or other factors. If our collaboration partners are unable or unwilling to invest the resources necessary to commercialize CABOMETYX successfully in the EU, Japan and other international territories where it has been approved, this could reduce the amount of revenue we are due to receive under these collaboration agreements, thus resulting in harm to our business and operations.
Our clinical, regulatory and commercial collaborations with major companies make us reliant on those companies for their continued performance and investments, which subjectsubjects us to a number of risks.
We have established clinical and commercial collaborations with leading biotechnology, biopharmaceutical and pharmaceutical companies, including, Ipsen, Takeda, Roche and Genentech, BMS, Merck KGgA, Pfizer and Daiichi Sankyo, for the development and ultimate commercialization of our products. Ourproducts, and our dependence on our relationships withthese collaboration partners for the development and commercialization of compounds subjects us to a number of risks, including:including, but not limited to:
our collaboration partners’ decision to terminate our collaboration, or their failure to comply with the terms of our collaboration agreements and related ancillary agreements, either intentionally or as a result of negligent performance;
our inability to control the amount and timing of resources that our collaboration partners or potential future collaboration partners will devote to the development or commercialization of drug candidates or to their marketing and distribution;our products;
the possibility that our collaboration partners may stop or delay clinical trials, fail to supply us on a timely basis with the product required for a combination trial (including as a result of the COVID-19 pandemic), or deliver product that fails to meet appropriate quality and regulatory standards and results in a market recall or withdrawal, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a drug candidate, repeat or conduct new clinical trials or require a new formulation of a drug candidate for clinical testing;standards;
disputes that may arise between us and our collaboration partners that result in the delay or termination of the research, development or commercialization of our drug candidates, or that diminish or delay receipt of the economic benefits we are entitled to receive under the collaboration, or that result in costly litigation or arbitration;
the possibility that our collaboration partners may experience financial difficulties, including, without limitation, difficulties arising from the impact of the COVID-19 pandemic;pandemic that prevent them from fulfilling their obligations under our agreements;
our collaboration partners’ lack of success in their effortsinability to obtain regulatory approvals in a timely manner, or at all;
our collaboration partners’ failure to comply with legal and regulatory requirements relevant to the authorization, marketing, distribution and supply of our marketed products in the territories outside the U.S. where they are approved; and
our collaboration partners’ failure to properly maintain or defend our intellectual property rights or their use of our intellectual property rights or proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property rights or expose us to potential litigation;litigation.
our collaboration partners’ failure to comply with the terms
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Table of our collaboration agreements and related ancillary agreements;Contents
our collaboration partners’ failure to comply with applicable healthcare laws, as well as established guidelines, laws and regulations related to Good Manufacturing Practice, Good Clinical Practice, Good Distribution Practice and Good Pharmacovigilance Practice;
the possibility that our collaboration partners could independently move forward with competing drug candidates, developed either independently or in collaboration with others, including our competitors;

our inability to enter into additional collaboration arrangements with third parties in an area or field of exclusivity;
the possibility that future collaboration partners may require us to relinquish some important rights, such as marketing and distribution rights; and
the possibility that collaborations may be terminated or allowed to expire, which would delay, and may increase the cost of, development of our drug candidates.
If any of these risks materialize, we may not receive collaboration revenues or otherwise realize anticipated benefits from such collaborations, and our product development efforts and prospects for growth could be delayed or disrupted, all of which could have a material adverse impact on our business, financial condition and results of operations.
Our growth potential is dependent in part upon companies with which we have entered into research collaborations, in-licensing arrangements and similar business development relationships.
To expand our early-stage product pipeline, we have augmented our drug discovery activities with multiple research collaborations and in-licensing arrangements with other companies. Our dependence on our relationships with these research and in-licensing partners subjects us to numerous risks, including, but not limited to:
our research and in-licensing partners’ decision to terminate our relationship, or their failure to comply with the terms of our agreements, either intentionally or as a result of negligent performance;
disputes that may arise between us and our research and in-licensing partners that result in the delay or termination of research activities with respect to any in-licensed assets or supporting technology platforms;
the possibility that our research and in-licensing partners may experience financial difficulties, including, without limitation, difficulties arising from the impact of the COVID-19 pandemic, which prevent them from fulfilling their obligations under our agreements;
our research and in-licensing partners’ failure to properly maintain or defend their intellectual property rights or their use of third-party intellectual property rights or proprietary information in such a way as to invite litigation that could jeopardize or invalidate our license to develop these assets or utilize technology platforms
laws, regulations or practices imposed by countries outside the U.S. that could impact or inhibit scientific research or the development of healthcare products by foreign competitors or disadvantage healthcare products made by foreign competitors, or general political or economic instability in those countries, any of which could complicate, interfere with or impede our relationships with our ex-U.S. research, development and in-licensing partners; and
our research and in-licensing partners’ failure to comply with applicable healthcare laws, as well as established guidelines, laws and regulations related to Good Manufacturing Practice and Good Laboratory Practice.
If any of these risks materialize, we may not be able to expand our product pipeline or otherwise realize a return on the resources we will have invested to develop these early-stage assets, which could have a material adverse impact on our financial condition and prospects for growth.
If third parties upon which we rely to perform clinical trials for cabozantinib in new indications or for new potential product candidates do not perform as contractually required or expected, we may not be able to obtain regulatory approval for or commercialize cabozantinib or other product candidates beyond currently approved indications.
We do not have the ability to conduct clinical trials for cabozantinib or for new potential product candidates independently, so we rely on independent third parties for the performance of these trials, such as the U.S. federal government (including NCI-CTEP, a department of the National Institutes of Health, with whom we have our CRADA), third-party contract research organizations, medical institutions, clinical investigators and contract laboratories to conduct our clinical trials. If these third parties do not successfully carry out their contractual duties or regulatory obligations or meet expected deadlines, whether as a result of the COVID-19 pandemic or otherwise, or if the third parties must be replaced or if the quality or accuracy of the data they generate or provide is compromised due to their failure to adhere to our clinical trial or data security protocols or regulatory requirements or for other reasons, our preclinical development activities or clinical trials may be extended, delayed, suspended or terminated, and we may not be able to obtain regulatory approval for or commercialize cabozantinib or other product candidates beyond currently approved indications. In addition, due to the complexity of our research initiatives, we may be unable to engage with third-party contract research organizations that have the necessary experience and sophistication to furtherhelp advance our internal drug discovery efforts, which would impede our ability to identify, develop and commercialize our potential product candidates.
We lack internalour own manufacturing and distribution capabilities necessary for us to produce materials required for certain preclinical activities and to produce and distribute our products for clinical development or for commercial sale, and relyour reliance on third parties to do so, whichfor these services subjects us to various risks.
We do not own or operate manufacturing facilities, distribution facilities or resources for chemistry, manufacturing and control development activities, preclinical, clinical or commercial production and distribution offor our products.current products and new product candidates. Instead, we have multiple contractual agreements in place withrely on various third-party contract manufacturing organizations that,to conduct these operations on our behalf, manufacture clinical and commercial supplies of CABOMETYX and COMETRIQ.behalf. As our operations continue to expand through our clinical development and commercial progress,grow in these areas, we continue to appropriately expand our supply chain
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through secondary third-party contract manufacturers, distributors and suppliers.
To establish and manage our supply chain requires a significant financial commitment, the creation of numerous third-party contractual relationships and continued oversight of these third parties to fulfill compliance with applicable regulatory requirements. Although we maintain significant resources to directly and effectively oversee the activities and relationships with the companies in our supply chain, we do not have direct control over their operations.
Our third-party contract manufacturers may not be able to produce material on a timely basis or manufacture material with the required quality standards, or in the quantity required to meet our preclinical, clinical development and commercial needs and applicable regulatory requirements, including as a result of the COVID-19 pandemic. Although as of the date of this Quarterly Report, we have substantial safety stock inventories for both our commercial drug substance and drug products and, to our knowledge, have not yet experienced production delays or seen significant impairment to our supply chain as a result of the COVID-19 pandemic, our third-party contract manufacturers, distributors and suppliers maycould experience operational delays due to facility closures and other hardships due toas a result of the COVID-19 pandemic, which could potentially impact our supply chain and causeby potentially causing delays to or disruptiondisruptions in the supply of our commercial or clinical supply of our products or product candidates. If our third-party contract manufacturers, distributors and suppliers do not continue to supply us with our products or product candidates in a timely fashion and in compliance with applicable quality and regulatory requirements, or if they otherwise fail or refuse to comply with their obligations to us under our supplymanufacturing, distribution and manufacturingsupply arrangements, we may not have adequate remedies for any breach. Furthermore, their failure to supply us could impair or preclude our ability to meet ourmeeting commercial or clinical product supply requirements or our supply needs for clinical trials, including those being conducted in collaboration withus or our partners, which could delay our product development and future commercialization efforts and have a material adverse impact on our business, financial condition and results of

operations. In addition, through our third-party contract manufacturers and data service providers, we continue to provide serialized commercial products as required to comply with the Drug Supply Chain Security Act (DSCSA). If our third-party contract manufacturers or data service providers fail to support our efforts to continue to comply with DSCSA and any future federal or state electronic pedigree requirements, we may face legal penalties or be restricted from selling our products.
As part of our collaboration agreements with Ipsen and Takeda, we are responsible for the supply of CABOMETYX and COMETRIQ for global development and commercial purposes. Failure to meet our supply obligations under these collaboration agreements could impair our partners’ ability to successfully develop and commercialize CABOMETYX and COMETRIQ and generate revenues to which we are entitled under the collaborations.
If third-party scientific advisors and contractors we rely on to assist with our drug discovery efforts do not perform as expected, the expansion of our product pipeline may be delayed.
We work with scientific advisors at academic and other institutions, as well as third-party contractors in various locations throughout the world, that assist us in our research and development efforts, including in internal drug discovery and preclinical development strategy. These third parties are not our employees and may have other commitments or contractual obligations that limit their availability to us. Although these third-party scientific advisors and contractors generally agree not to do competing work, if a conflict of interest between their work for us and their work for another entity arises, we may lose their services. There has also been increased scrutiny surrounding the disclosures of payments made to medical researchers from companies in the pharmaceutical industry, and it is possible that the academic and other institutions that employ these medical researchers may prevent us from engaging them as scientific advisors and contractors or otherwise limit our access to these experts, or that the scientific advisors themselves may now be more reluctant to work with industry partners. Even if these scientific advisors and contractors with whom we have engaged intend to meet their contractual obligations, their ability to perform services may be impacted by external factors, as we experienced in the early stages of the COVID-19 pandemic. If we have or may continue to experience additional delays in the receipt of services, lose work performed by these scientific advisors and contractors or are unable to engage them in the first place, our discovery and development efforts with respect to the matters on which they were working or would work in the future may be significantly delayed or otherwise adversely affected.
Risks Related to Our Information Technology Data Privacy and Intellectual Property
Data breaches, cyber attackscyber-attacks and other failures in our information technology operations and infrastructure could compromise our intellectual property or other sensitive information, damage our operations and cause significant harm to our business and reputation.
In the ordinary course of our business, we and our third-party service providers, such as contract research organizations, collect, maintain and transmit sensitive data on our networks and systems, including our intellectual property and proprietary or confidential business information (such as research data and personal information) and confidential information with respect to our customers, clinical trial patients and our collaboration partners. We have also outsourced significant elements of our information technology infrastructure to third parties and, as a result, such third parties may or could have access to our confidential information. The secure maintenance of this information is critical to our business and reputation, and while we have enhanced and are continuing to enhance our cybersecurity efforts commensurate with the growth and complexity of our business, our systems and those of third-party service providers may be vulnerable to a cyber attack. Such
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cyber-attack. The level of vulnerabilities that exist under normal conditions may be furtherhave been exacerbated by the fact that, during the COVID-19 pandemic, the portion of our workforce is operating remotely as we comply with shelter in place ordershas increased, at least temporarily, and the recent rise in COVID-19some phishing attacks targetingare specifically designed to target remote workers. In addition, we are heavily dependent on the functioning of our information technology infrastructure to carry out our business processes, such as external and internal communications or access to clinical data and other key business information. Accordingly, both inadvertent disruptions to this infrastructure and cyber attackscyber-attacks could cause us to incur significant remediation or litigation costs, result in product development delays, disrupt critical business operations, expend key information technology resources and divert the attention of management.
Numerous companies have been subject to a wide variety of security incidents, cyber attacks (including through use of ransomware) and other attempts to gain unauthorized access or otherwise compromise information technology systems. In fact, althoughAlthough the aggregate impact of cyber attackscyber-attacks on our operations and financial condition has not been material to date, we and our third-party vendorsservice providers have frequently been the target of threats of this nature and expect them to continue. These threats can come from a variety of sources, ranging in sophistication from an individual hacker to a state-sponsored attack, and such threats can also vary in motive (including corporate espionage). Cyber attacks continue to become more prevalent and much harder to detect and defend against, and it is often difficult to anticipate or immediately detect such incidents and the damage caused by such incidents. TheseAny data breaches and anybreach and/or unauthorized access or

disclosure of our information or intellectual property could compromise our intellectual property and expose our sensitive business information (oror sensitive business information of our collaboration partners, which may lead to significant liability for us).us. A data security breach could also lead to public exposure of personal information of our clinical trial patients, employees or others. Any such event that leadsothers and result in harm to unauthorized access, use or disclosure of personal information, including personal information regarding our patients or employees, could harm our reputation and business, compel us to comply with federal and/or state breach notification laws and foreign law equivalents (includingincluding the GDPR),GDPR, subject us to investigations and mandatory corrective action, or otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information, which could disrupt our business, result in increased costs or loss of revenue, and/or result in significant financial exposure. Furthermore, the costs of maintaining or upgrading our cybersecurity systems (including the recruitment and retention of experienced information technology professionals, who are in high demand) at the level necessary to keep up with our expanding operations and prevent against potential attacks are increasing, and despite our best efforts, our network security and data recovery measures and those of our vendorsthird-party service providers may still not be adequate to protect against such security breaches and disruptions, which could cause material harm to our business, financial condition and results of operations.
If we are unable to adequately protect our intellectual property, third parties may be able to use our technology, which could adversely affect our ability to compete in the market.
Our success will depend in part upon our ability to obtain patents and maintain adequate protection of the intellectual property related to our technologies and products. The patent positions of biopharmaceutical companies, including our patent position, are generally uncertain and involve complex legal and factual questions. We will be able to protect our intellectual property rights from unauthorized use by third parties only to the extent that our technologies are covered by valid and enforceable patents or are effectively maintained as trade secrets. We will continue to apply for patents covering our technologies and products as, where and when we deem lawful and appropriate. However, these applications may be challenged or may fail to result in issued patents. Our issued patents have been and may in the future be challenged by third parties as invalid or unenforceable under U.S. or foreign laws, or they may be infringed by third parties, and we are from time to time involved in the defense and enforcement of our patents or other intellectual property rights in a court of law, U.S. Patent and Trademark Office inter partes review or reexamination proceeding, foreign opposition proceeding or related legal and administrative proceeding in the U.S. and elsewhere. The costs of defending our patents or enforcing our proprietary rights in post-issuance administrative proceedings and litigation can be substantial and the outcome can be uncertain. An adverse outcome may allow third parties to use our intellectual property without a license and/or allow third parties to introduce generic and other competing products, any of which would negatively impact our business. Third parties may also attempt to invalidate or design around our patents, or assert that they are invalid or otherwise unenforceable, and seek to introduce generic versions of cabozantinib. For example, we received Paragraph IV certification notice letters from MSN and Teva concerning the ANDArespective ANDAs that iteach had filed with the FDA seeking approval to market atheir respective generic versionversions of CABOMETYX tablets. Should MSN, Teva or any other third parties receive FDA approval of an ANDA or a 505(b)(2) NDA with respect to cabozantinib, it is possible that such company or companies could introduce generic versions of our marketed products before our patents expire if they do not infringe our patents or if it is determined that our patents are invalid or unenforceable, and the resulting generic competition could have a material adverse impact on our business, financial condition and results of operations.
In addition, because patent applications can take many years to issue, third parties may have pending applications, unknown to us, which may later result in issued patents that cover the production, manufacture, commercialization or use of our product candidates. Our existing patents and any future patents we obtain may not be sufficiently broad to prevent others from practicing our technologies or from developing competing products. Furthermore, others may independently develop similar or alternative technologies or design around our patents. In addition, our patents may be challenged or invalidated or may fail to provide us with any competitive advantages, if, for example, others were the first to invent or to file patent applications for closely related inventions.
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The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the U.S., and many companies have encountered significant problems in protecting and defending such rights in foreign jurisdictions. Many countries, including certain countries in Europe, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties (for example, the patent owner has failed to “work” the invention in that country or the third party has patented improvements). In addition, many countries limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of the patent. Initiatives seeking compulsory licensing of life-saving drugs are also becoming increasingly prevalent in developing countries either through direct legislation or international initiatives. Governments in those developing countries could require that we grant compulsory licenses to allow competitors

to manufacture and sell their own versions of our products or product candidates, thereby reducing our product sales. Moreover, the legal systems of certain countries, particularly certain developing countries, do not favor the aggressive enforcement of patent and other intellectual property protection, which makes it difficult to stop infringement. We rely on trade secret protection for some of our confidential and proprietary information. We have taken security measures to protect our proprietary information and trade secrets, but these measures may not provide adequate protection. While we seek to protect our proprietary information by entering into confidentiality agreements with employees, partners and consultants, we cannot provide assurance that our proprietary information will not be disclosed, or that we can meaningfully protect our trade secrets. In addition, our competitors may independently develop substantially equivalent proprietary information or may otherwise gain access to our trade secrets.
Litigation or third-party claims of intellectual property infringement could require us to spend substantial time and money and adversely affect our ability to develop and commercialize products.
Our commercial success depends in part upon our ability to avoid infringing patents and proprietary rights of third parties and not to breach any licenses that we have entered into with regard to our technologies and the technologies of third parties. Other parties have filed, and in the future are likely to file, patent applications covering products and technologies that we have developed or intend to develop. If patents covering technologies required by our operations are issued to others, we may have to obtain licenses from third parties, which may not be available on commercially reasonable terms, or at all, and may require us to pay substantial royalties, grant a cross-license to some of our patents to another patent holder or redesign the formulation of a product candidate so that we do not infringe third-party patents, which may be impossible to accomplish or could require substantial time and expense.
In addition, we may be subject to claims that our employees or independent contractors have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers, or that they used or sought to use patent inventions belonging to their former employers. Furthermore, third parties may obtain patents that relate to our technologies and claim that use of such technologies infringes on their patents or otherwise employs their proprietary technology without authorization. Regardless of their merit, such claims could require us to incur substantial costs and divert the attention of management and key technical personnel in defending ourselves against any such claims or enforcing our own patents. In the event that aof any third party’s successful claim of patent infringement is brought against us,or misappropriation of trade secrets, we may lose valuable intellectual property rights or personnel, which could impede or prevent the achievement of our product development goals, or we may be required to pay damages and obtain one or more licenses from these third parties, subjecting us to substantial royalty payment obligations. We may not be able to obtain these licenses on commercially reasonable terms, or at all. Defense of any lawsuit or failure to obtain any of these licenses could adversely affect our ability to develop and commercialize products.
We may be subjectRisks Related to damages resulting from claims that we,Our Operations, Managing Our Growth and Employee Matters
If the COVID-19 pandemic is further prolonged or becomes more severe, our employees or independent contractors have wrongfully used or disclosed alleged trade secrets of their former employers.
Many of our employeesbusiness operations and independent contractors were previously employed at universities or other biotechnology, biopharmaceutical or pharmaceutical companies, including our competitors or potential competitors. We may be subject to claims that we or these employees or independent contractors have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers, or used or sought to use patent inventions belonging to their former employers. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigationcorresponding financial results could result in substantial costs and divert the attention of management. If we fail in defending such claims, in addition to paying damages, we may lose valuable intellectual property rights or personnel. A loss of key research personnel and/or their work product could hamper or prevent our ability to develop or commercialize certain product candidates,suffer, which could have a material adverse impact on our financial condition and prospects for growth.
To date, the COVID-19 pandemic has had a modest impact on our business operations, in particular on our clinical trial, drug discovery and commercial activities. For example, to varying degrees and at different rates across our clinical trials, we experienced declines in screening and enrollment activity during the early days of the COVID-19 pandemic, as well as delays in new site activations and restrictions on access to treatment sites that is necessary to monitor clinical study progress and initiation. However, as the COVID-19 pandemic continues to surge or continues to have a significant presence in various parts of the world, the impact on our clinical development operations could continue or grow more severe. We anticipate that a further prolonged, or more severe, global public health crisis could limit our ability to identify and work with clinical investigators at clinical trial sites globally to enroll, initiate and maintain treatment per protocol of patients for our ongoing clinical trials. Disruptions to medical and administrative operations at clinical trial sites and the implementation
47

of crisis management initiatives have and may continue to reduce personnel and other resources necessary to conduct our clinical trials, which could delay our clinical trial plans or require certain trials to be temporarily suspended. Moreover, quarantines and travel restrictions have impeded and may continue to impede patient movement or interrupt healthcare services, which we anticipate over time, could also interfere with and potentially negatively impact clinical trial execution, and ultimately results. In addition, increased costs connected with our efforts to mitigate the adverse impacts resulting from the COVID-19 pandemic on our clinical trials could cause the expenses we incur in conducting those clinical trials to increase considerably. Specifically, with respect to our clinical trials evaluating cabozantinib in combination with therapies that must be administered via professional intravenous infusion, such as COSMIC-312, COSMIC-313, COSMIC-021, CONTACT-01, CONTACT-02, CONTACT-03, or our early-stage trials evaluating XL092, XL102 and other product candidates to the extent they may incorporate additional therapies that must be administered via professional intravenous infusion, limited patient movement or interrupted healthcare services at medical institutions have delayed in some instances, and may continue to delay or prevent, on-site infusion of the therapies being evaluated in combination with cabozantinib. If a sizable portion of patients in our combination studies are unable or unwilling to receive all components of the combination therapy being tested in accordance with the applicable clinical trial protocol, it could cause those studies to be delayed, suspended or prevented from producing statistically significant results.Depending upon the duration and severity of the COVID-19 pandemic, we could also experience delays in the commencement of new clinical trials of cabozantinib, or our earlier-stage investigative product candidates. The COVID-19 pandemic could also impede clinical operations and delay our planning and preparation timelines for new clinical trials, as well as adversely affect our ability to obtain regulatory approval for clinical protocols and increase the operating expenses associated with these new clinical trials.
In addition, the COVID-19 pandemic caused us to suspend drug discovery work in our laboratories temporarily while we observed the shelter in place orders issued by the State of California and Alameda County. We also experienced some modest delays with respect to the portion of drug discovery work outsourced to third-party contractors in regions first impacted by COVID-19. While both drug discovery work in our laboratories and outsourced drug discovery activities have since partially resumed, we may be unable to maximize the potential of these programs due to reduced staffing and the imposition of increased safety protocols, and should the COVID-19 pandemic continue to grow in severity, we may have to further scale back or suspend activities in the future. For example, as a result of spikes or surges in infection, positivity or hospitalization rates, or emergence of new SARS-CoV-2 variants, we may choose or be required to suspend work in our laboratories, which will once again impede our drug discovery efforts. With respect to the preclinical development work and drug discovery activities outsourced to third-party contractors, the COVID-19 pandemic could again impede these third parties from providing timely deliverables to us in the future. In addition, should we experience delays in the construction of new laboratory facilities due to the COVID-19 pandemic, our ability to expand our drug discovery activities may be impaired. Should the COVID-19 pandemic be further prolonged or grow in severity, we may ultimately be unable to achieve our drug discovery and preclinical development objectives within the previously disclosed timelines, which could have a material adverse impact on our prospects for growth.
While we believe that our commercial business has, to date, only experienced a modest impact related to the COVID-19 pandemic, it remains possible that over a longer period, changes to our standard sales and marketing practices, including any shifts from in-person back to primarily telephonic and virtual interactions with healthcare professionals, could negatively impact the flow of important information regarding our medicines, which along with obstacles to patient access to healthcare professionals, could diminish sales of our marketed products.
Although as of the date of this Quarterly Report on Form 10-Q, we continue to maintain substantial safety stock inventories for our drug substance and drug products and have not experienced production delays or seen significant impairment to our supply chain as a result of the COVID-19 pandemic, our third-party contract manufacturers and suppliers could experience operational delays due to facility closures and other hardships as a result of the COVID-19 pandemic, which could impact our supply chain by potentially causing delays to or disruptions in the supply of our commercial or clinical products or product candidates. These delays or disruptions could be further exacerbated if the COVID-19 pandemic begins to impact essential distribution systems, which could substantially increase delivery times and costs, or otherwise adversely affect our ability to provide our products to customers and clinical trial sites and generate product revenues.
In response to the COVID-19 pandemic, we have taken numerous temporary precautions to help mitigate the risk of transmission of the virus, including: reducing the number of our employees working on-site at our Alameda headquarters under enhanced safety and social distancing protocols; suspending all non-essential business travel for our employees; and partially limiting the circumstances under which our field employees may engage in in-person promotional activities with healthcare professionals. Over a longer period, these measures could delay our research and development programs, reduce engagements with potential prescribers for our products, and impede our ability to execute on our long-term
48

business plans. Further, extended periods of remote work could impede the focused attention of management or reduce the productivity of teams that would otherwise be working closely together.
In addition, as a result of broad economic shifts during and as a consequence of efforts to address unemployment and other negative economic effects of the COVID-19 pandemic, we may experience further reductions in the net price of our products. For example, there may be a substantial shift from private health insurance coverage to government insurance coverage, or additional downward pressure on the prices government purchasers will pay for our products due to significant increases in government debt incurred in connection with relief efforts, as well as significant increases in demand for our patient assistance and/or free drug program or other impacts that may not be foreseeable, all or any of which would adversely affect our product revenues.
While we expect the COVID-19 pandemic to continue to have varying degrees of adverse impact on our business operations and, potentially in the future, our financial results, the extent of such adverse impact will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic and resulting disruptions to normal business and personal activities in the U.S. and in other countries, and the effectiveness of actions taken globally to contain and treat the disease, including the rate at which vaccinations are made available and the percentage of the population that becomes vaccinated. These continuing or future effects could materially and adversely affect our business, financial condition, and results of operations.
Risks Related to Employeesoperations and Locationgrowth prospects, and exacerbate the other risks and uncertainties described elsewhere in this ‘‘Risk Factors’’ section.
If we are unable to manage our growth, there could be a material adverse impact on our business, financial condition and results of operations, and our prospects may be adversely affected.
We have experienced and expect to continue to experience growth in the number of our employees and in the scope of our operations.operations, in particular as we continue to expand the cabozantinib franchise into new indications and grow our pipeline of product candidates. This growth places significant demands on our management and resources, and our current and planned personnel and operating practices may not be adequate to support our growth. To effectively manage our growth, we must continue to improve existing, and implement new, facilities, operational and financial systems, and procedures and controls, as well as expand, train and manage our growing employee base, and there can be no assurance that we will effectively manage our growth without experiencing operating inefficiencies or control deficiencies. We expect that we may needplan to increase our management personnel to oversee our expanding operations, and recruiting and retaining qualified individuals is difficult. If we are unable to manage our growth effectively, including as a result of the COVID-19 pandemic or otherwise, or we are unsuccessful in recruiting qualified

management personnel, there could be a material adverse impact on our business, financial condition and results of operations.
The loss of key personnel or the inability to retain and, where necessary, attract additional personnel could impair our ability to operate and expand our operations.
We are highly dependent upon the principal members of our management, as well as clinical, commercial and scientific staff, the loss of whose services might adversely impact the achievement of our objectives. Also, we may not have sufficient personnel to execute our business plans. Retaining and, where necessary, recruiting qualified clinical, commercial, scientific and pharmaceutical operations personnel will be critical to support activities related to advancing the development program for the cabozantinib franchise and our other product candidates, successfully executing upon our commercialization plan for the cabozantinib franchise and our internal proprietary research and development efforts. Competition is intense for experienced clinical, commercial, scientific and pharmaceutical operations personnel, and we may be unable to retain or recruit such personnel with the expertise or experience necessary to allow us to successfully develop and commercialize our products. Similarly, the COVID-19 pandemic could negatively impact the health of key personnel or make it difficult to recruit qualified personnel for critical positions. Further, all of our employees are employed “at will” and, therefore, may leave our employment at any time.
Our operations might be interrupted by the occurrence of a natural disaster or other catastrophic event.
Our headquarters in Alameda, California is located in the San Francisco Bay Area, and therefore our facilities are vulnerable to damage from earthquakes. Our earthquake insurance may not cover all of the damage we may suffer in the event of an earthquake. We are also vulnerable to damage from other types of disasters, including fires and floods, which have become a significant danger in California during recent years, as well as power loss, communications failures, aircraft disasters (due to the proximity of our headquarters to a major international airport), terrorism and similar events, and any insurance we may maintain may be inadequate to cover our losses. If any disaster were to occur, our ability to operate our business at our facilities could be seriously, or potentially completely, impaired, causing significant delays in our programs and making it difficult for us to recover due to the unique nature of our research activities. Accordingly, an earthquake or other disaster could have a material adverse impact on our business, financial condition and results of operations.
Facility security breaches may disrupt our operations, subject us to liability and harm our operating results.
Any break-in or trespass at our facilities that results in the misappropriation, theft, sabotage or any other type of security breach with respect to our proprietary and confidential information, including research or clinical data, or that results in damage to our research and development equipment and assets, or that results in physical or psychological harm to any of our employees, could subject us to liability or otherwise have a material adverse impact on our business, financial condition and results of operations.
Risks Related to Environmental and Product Liability
We use hazardous chemicals and biological materials in our business. Any claims relating to improper handling, storage or disposal of these materials could be time consuming and costly.
Our research and development processes involve the controlled use of hazardous materials, including chemicals and biological materials, and our operations can produce hazardous waste products. We cannot eliminate the risk of accidental contamination or discharge, or any resultant injury from these materials, and we may face liability under applicable laws for any injury or contamination that results from our use or the use by our collaboration partners or other
49

third parties of these materials, and such liability may exceed our insurance coverage and our total assets. In addition, we may be required to indemnify our collaboration partners against all damages and other liabilities arising out of our development activities or products produced in connection with our collaborations with them. Moreover, our continued compliance with environmental laws and regulations may be expensive, and current or future environmental regulations may impair our research, development and production efforts.
We face potential product liability exposure far in excess of our limited insurance coverage.
We may be held liable if any product we or our collaboration partners develop or commercialize causes injury or is found otherwise unsuitable during product testing, manufacturing, marketing or sale. Regardless of merit or eventual outcome, product liability claims could result in decreased demand for our products and product candidates, injury to our reputation, withdrawal of patients from our clinical trials, product recall, substantial monetary awards to third parties and

the inability to commercialize any products that we may develop in the future. These claims might be made directly by consumers, healthcare providers, pharmaceutical companies or others selling or testing our products. We have obtainedmaintain limited product liability insurance coverage for our clinical trials and commercial activities for cabozantinib in the amount of $20.0 million per occurrence and $20.0 million in the aggregate.cabozantinib. However, our insurance may not reimburse us or may not be sufficient to reimburse us for expenses or losses we may suffer. Moreover, if insurance coverage becomes more expensive, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. On occasion, juries have awarded large judgments in class action lawsuits for claims based on drugs that had unanticipated side effects. In addition, the biotechnology, biopharmaceutical and pharmaceutical industries, in general, have been subject to significant medical malpractice litigation. A successful product liability claim or series of claims brought against us could harm our reputation and business and would decrease our cash reserves.
Risks Related to Our Common Stock
Our stock price has been and may in the future be highly volatile.
The trading price of our common stock has been highly volatile, and we believe the trading price of our common stock willit may remain highly volatile and mayor fluctuate substantially due to factors such as the following, many of which we cannot control:
the announcement of FDA or other regulatory approval or non-approval, or delays in the FDA or other regulatory review process with respect to cabozantinib, our collaboration partners’ product candidates being developed in combination with cabozantinib, or our competitors’ product candidates;
the commercial performance of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products, including royalties paid under our collaboration and license agreements;
adverse or inconclusive results or announcements related to our or our collaboration partners’ clinical trials or delays in those clinical trials;
the timing of achievement of our clinical, regulatory, partnering, commercial and other milestones for the cabozantinib franchise or any of our other programs or product candidates;
our ability to make future investments in the expansion of our pipeline through internal drug discovery, including future research collaborations, in-licensing arrangements and other business development activities;
our ability to obtain the materials and services, including an adequate product supply for any approved drug product, from our third-party vendors or do so at acceptable prices;
the timing and amount of expenses incurred for clinical development and manufacturing of cabozantinib;
actions taken by regulatory agencies, both in the U.S. and abroad, with respect to cabozantinib or our clinical trials for cabozantinib;
unanticipated regulatory actions taken by the FDA as a result of changing FDA standards and practices concerning the review of product candidates, including approvals at earlier stages of clinical development or with lesser developed data sets and expedited reviews;
the announcement of new products or clinical trial data by our competitors;
the announcement of regulatory applications, such as MSN’s ANDA,and Teva’s respective ANDAs, seeking approval of generic versions of our marketed products;
quarterly variations in our or our competitors’ results of operations;
changes in our relationships with our collaboration partners, including the termination or modification of our agreements, or other events or conflicts that may affect our collaboration partners’ timing and willingness to develop, or if approved, commercialize our products and product candidates out-licensed to them;
the announcement of an in-licensed product candidate or strategic acquisition;
litigation, including intellectual property infringement and product liability lawsuits, involving us;
the impairment
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changes in earnings estimates or recommendations by securities analysts, or financial guidance from our management team, and any failure to achieve the operating results projected by securities analysts or by our management team;
the entry into new financing arrangements;
developments in the biotechnology, biopharmaceutical or pharmaceutical industry;

sales of large blocks of our common stock or sales of our common stock by our executive officers, directors and significant stockholders;
additions and departures of key personnel or board members;
the disposition of any of our technologies or compounds; and
significant fluctuations in interest rates or foreign currency exchange rates; and
general market, economic and political conditions and other factors, including factors unrelated to our operating performance or the operating performance of our competitors, such as the impact of the COVID-19 pandemic on financial markets.
These and other factors could have material adverse impact on the market price of our common stock. In addition, the stock markets in general, and the markets for biotechnology and pharmaceutical stocks in particular, have historically experienced significant volatility that has often been unrelated or disproportionate to the operating performance of particular companies. Likewise, as a result of significant changes in U.S. or global political and economic conditions, including the effects of the COVID-19 pandemic, policies governing foreign trade and healthcare spending and delivery, or future potential U.S. federal government shutdowns, the financial markets could continue to experience significant volatility that could also continue to negatively impact the markets for biotechnology and pharmaceutical stocks. These broad market fluctuations have adversely affected and may in the future adversely affect the trading price of our common stock. Excessive volatility may continue for an extended period of time following the date of this report.
In the past, following periods of volatility in the market price of a company’s securities, securities class action litigation has often been instituted. A securities class action suit against us could result in substantial costs and divert the attention of management, which could have a material adverse impact on our business, financial condition and results of operations.
Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent or deter attempts by our stockholders to replace or remove our current management, which could cause the market price of our common stock to decline.
Provisions in our corporate charter and bylaws may discourage, delay or prevent an acquisition of us, a change in control, or attempts by our stockholders to replace or remove members of our current Board of Directors. Because our Board of Directors is responsible for appointing the members of our management team, these provisions could in turn affect any attempt by our stockholders to replace current members of our management team. These provisions include:
a prohibition on actions by our stockholders by written consent;
the ability of our Board of Directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our Board of Directors; and
advance notice requirements for director nominations and stockholder proposals.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.
Item 2. Unregistered Sales of Equity Securities and Use of Proceeds    
Not applicable.
Item 3. Defaults Upon Senior Securities
Not applicable.
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Item 4. Mine Safety Disclosures
Not applicable.

Item 5. Other Information
Not applicable.
Item 6. Exhibits
Exhibit
Number
 Exhibit Description Incorporation by Reference 
Filed
Herewith
Form File Number 
Exhibit/
Appendix
Reference
 Filing Date 
3.1  10-K 000-30235 3.1 3/10/2010  
3.2  10-K 000-30235 3.2 3/10/2010  
3.3  8-K 000-30235 3.1 5/25/2012  
3.4  8-K 000-30235 3.1 10/15/2014  
3.5  8-K 000-30235 3.2 10/15/2014  
3.6  8-K 000-30235 3.1 5/23/2019  
3.7  8-K 000-30235 3.1 2/20/2020  
4.1  
S-1,
as amended
 333-96335 4.1 4/7/2000  
10.1  10-K 000-30235 10.37 2/25/2020  
10.2  10-K 000-30235 10.39 2/25/2020  
10.3  10-K 000-30235 10.29 2/25/2020  
10.4          X
31.1          X
31.2          X
32.1‡          X

Exhibit
Number
Exhibit DescriptionIncorporation by Reference
Filed
Herewith
FormFile Number
Exhibit/
Appendix
Reference
Filing Date
3.110-K000-302353.13/10/2010
3.210-K000-302353.23/10/2010
3.38-K000-302353.15/25/2012
3.48-K000-302353.110/15/2014
3.58-K000-302353.210/15/2014
3.68-K000-302353.15/23/2019
3.78-K000-302353.13/3/2021
4.1S-1,
as amended
333-963354.14/7/2000
10.1*X
10.2*X
10.3*X
10.4*X
52

Exhibit
Number
Exhibit DescriptionIncorporation by Reference
Filed
Herewith
FormFile Number
Exhibit/
Appendix
Reference
Filing Date
101.INS10.5*X
10.6*X
31.1X
31.2X
32.1‡X
101.INSXBRL Instance DocumentThe XBRL instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document.
101.SCH
Inline XBRL Taxonomy Extension Schema Document
X
101.CAL
Inline XBRL Taxonomy Extension Calculation Linkbase Document
X
101.DEF
Inline XBRL Taxonomy Extension Definition Linkbase Document
X
101.LAB
Inline XBRL Taxonomy Extension Labels Linkbase Document
X
101.PRE
Inline XBRL Taxonomy Extension Presentation Linkbase Document
X
104Cover Page Interactive Data FileFormatted as Inline XBRL and contained in Exhibit 101.
*Portions of this exhibit have been omitted as being immaterial and would be competitively harmful if publicly disclosed.
This certification accompanies this Quarterly Report on Form 10-Q, is not deemed filed with the SEC and is not to be incorporated by reference into any filing of Exelixis, Inc. under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended (whether made before or after the date of this Quarterly Report on Form 10-Q), irrespective of any general incorporation language contained in such filing.

53

SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized. 
EXELIXIS, INC.
May 5, 20206, 2021By:
/s/ CHRISTOPHER J. SENNER
DateChristopher J. Senner
DateChristopher J. Senner
Executive Vice President and Chief Financial Officer
(Duly Authorized Officer and Principal Financial and Accounting Officer)

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