Investor and Analyst Day June 23, 2011 Nasdaq: LGND Exhibit 99.1 |
Investor and Analyst Day John Higgins President and Chief Executive Officer 2 |
3 Safe Harbor Statement • The following presentation contains forward-looking statements regarding Ligand’s prospects, plans and strategies, drug development programs and collaborations. Forward- looking statements include financial projections, expectations regarding research and development programs, and other statements including words such as “will,” “should,” “could,” “plan,” etc. Actual events or results may differ from Ligand’s expectations. For example, expense reductions and drug development programs may not be realized. In addition there can be no assurance that Ligand will achieve its guidance in 2011. • The forward-looking statements made in the presentation are subject to several risk factors, including, but not limited to, Ligand’s reliance on collaborative partners for milestone and royalty payments, regulatory hurdles facing Ligand's, CyDex's and partner's product candidates, uncertainty regarding Ligand's, CyDex's and partner's product development costs, the possibility that Ligand's, CyDex's and partner's drug candidates might not be proved to be safe and efficacious and commercial performance of Ligand's and/or its partner's products. Additional risks may apply to forward-looking statements made in this presentation. • The risk factors facing Ligand are explained in greater detail in Ligand’s filings with the SEC, including the most recently filed annual reports on Form 10-K and quarterly reports on Form 10-Q, as well as other public filings. • While forward-looking statements reflect our good faith beliefs (or those of the indicated third parties), they are not guarantees of future performance. We disclaim any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. |
4 Investor and Analyst Day Agenda Welcome and Company Overview John Higgins Captisol ® Technology Matt Foehr Melphalan Program Rick White Promacta Highlights Rob McKay Thrombocytopenia in Hep C Nezam H. Afdhal, M.D. Chief of Hepatology, Director of Liver Center, Beth Israel Deaconess Medical Center Financial Highlights John Sharp Small Group Workshops • Captisol – Powerful Enabling Technology • “Shots on Goal” Portfolio Questions and Answers / Reception |
5 Small-Group Workshops 1. Captisol ® – Powerful Enabling Technology Matt Foehr – Executive Vice President, Chief Operating Officer JD Pipkin – Senior Director, New Product Development Vince Antle – Senior Director, Technical Operations and Quality Assurance 2. “Shots-on-Goal” Portfolio Rob McKay – Senior Director, Business Development and Investor Relations Syed Kazmi – VP, Business Development and Strategic Planning Rick White – VP, Business Development and Marketing Room 3 2 |
6 Ligand’s Business Model Ligand's focus is to build a large portfolio of high quality pharmaceutical assets that can drive substantial cash flow and profitability. We operate the business with an emphasis on focused drug development and partnerships, with a disciplined and highly selective cost structure. |
7 Revenue Outlook Robust Pipeline Captisol ® – Enabling Technology High Quality Partners The Foundation of the Ligand Opportunity |
8 Ligand is Doing Great • Significant expansion (doubling of portfolio to over 60 programs) in past 6 months as a result of Cydex acquisition • A number of positive news events by partners in 2011 • Important new additions to senior management and Board of Directors • Most revenue generating assets ever on lowest cost structure • Positive clinical data announced in the past three months • Promacta ® is a “now” story • Directors have personally purchased over $1.2 million of Ligand stock (131,125 shares) over the past 6 months. Directors now own 10% of Ligand. • Over past year, daily trading volume has increased by ~30% |
9 Ligand’s Potential Downside Individual project set-backs Slower growth Partners drop programs Risk Reward The Investment Proposition: Risk vs. Reward Ligand’s Potential Upside Potential blockbuster product approved/ in-development Near-term profitability Well funded/financially disciplined More royalty partnerships than any peer co Attractive fully-owned pipeline Substantial calendar of news flow Large NOLs We believe the upside reward is substantially greater than the downside risk |
10 Ligand’s Potential Upside List presented last summer (2010) Updated Outlook Potential blockbuster product approved/ in development Data for Promacta ® expected over next 6 months Near-term profitability Projected to turn profitable by year-end 2011 Well funded/financially disciplined Lowest cost structure in company’s history More royalty partnerships than any peer co Large portfolio of assets, doubled in over last 12 months Attractive fully-owned pipeline SARM, diabetes, JAK 3, and melphalan programs Substantial calendar of news flow Continued news flow Large NOLs Continue to be ready to use following profitability |
11 Potential Significant Revenue Expansion Over Next Several Years *Plus license fees Illustrative Growth 2015 2012 "Shots on Goal" Vision Turning into Reality Promacta Avinza Conbriza Promacta Nexterone Avinza Carfilzomib Conbriza Aprela Nexterone CXCR2 Carfilzomib Clopidogrel >$30 million revenue* Melphalan Carbamazepine Merck Captisol ® Program >$200 million revenue* |
12 Worldwide Quarterly Promacta ® Revenue Growth $0.0 $2.0 $4.0 $6.0 $8.0 $10.0 $12.0 $14.0 $16.0 $18.0 $20.0 4Q08 1Q09 2Q09 3Q09 4Q09 1Q10 2Q10 3Q10 4Q10 1Q11 New markets and new indications should help accelerate revenue growth Ligand and GSK reports Ligand expects to receive royalties for another 14 years |
13 Over 50 Partnered Programs 17% 9% 30% 39% 5% • Over half of the partnered portfolio is Phase II or later • Portfolio is highly diversified across many partners, stages of development and therapeutic areas • Merck, GSK and Pfizer are our partners with the most programs Marketed / Approved Phase III / NDA Phase II Phase I PreClin Ligand Portfolio: Partnered Programs |
14 19% 12% 7% 26% 35% • Programs are highly diversified across more than 10 therapeutic areas • The therapeutic areas most represented in the portfolio are oncology, inflammation, neurology and metabolic disease Ligand Portfolio: Total Portfolio Snapshot Total Portfolio (Over 60 programs) Marketed / Approved Phase III / NDA Phase II Phase I PreClin |
15 Ligand's Internal Pipeline Focus |
16 Timing* Projected Event 3Q11 Carfilzomib NDA filing Platform Captisol Partnership 4Q11 Promacta Phase III HepC Results Aprela NDA filing SARM program update 1Q12 Initiate pivotal Melphalan study Top Line IL-9 Phase II Results Clopidogrel 505(b)(2) study initiation 2Q12 Merck CXCR2/COPD Study Completion Carfilzomib NDA Approval Promacta sNDA filing for HepC *Ligand internal estimates Ligand Portfolio: Potential Upcoming News Flow |
18 • High return late-stage internal development programs • New opportunities New Shots • High quality relationships • Significant expansion of “shots on goal” Deals • Powerful enabling technology meeting key needs Captisol Captisol ® ® CyDex Acquisition: What has it brought to Ligand? |
19 Captisol ® : The Need |
20 Patented, chemically-modified cyclodextrin Increase drug solubility, reduce site reactions Versatile across molecule families and sizes Safe, inactive, inert Over 100 clinical studies Type V Drug Master File Captisol ® : Enabling New Drugs |
21 • Strong manufacturing technology and IP estate • Hovione Partnership 50 metric ton capacity for Captisol ® , ability to double Exclusive relationship with built-in site redundancy • Intellectual Property 8 patent families covering technology, 12 patent families for products Formulation and process-based patent portfolio providing protection through 2029 Trade secrets, Drug Master File Continuing internal innovation Captisol ® : Enabling New Drugs |
22 Captisol ® : The Value |
23 Approved or pending products Broader platform relationships with partners who can leverage Captisol ® in more ways Internal Captisol- enabled ® development programs with potential for high returns Captisol ® : The Value |
24 • Reformulation can bring meaningful innovation to established medicines • Late-stage internal development can create significant value in exchange for relatively modest investment • 505(b)(2) pathway leverages existing data Lower development costs Shorter timelines Smaller infrastructure requirements Captisol-enabled ® Internal Development Programs |
25 • High dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation for multiple myeloma • Orphan Drug Status Market exclusivity, PDUFA fee waiver • Phase II dosing now completed Interim results presented at ASCO • Pivotal trial projected to begin early 2012 Captisol-enabled ® PG-Free Melphalan |
27 Continuing need for new and innovative therapies Multiple Myeloma Second most common hematologic cancer 50,000 patients in the U.S., 20,000 diagnosed annually Area of growing industry interest Transplant remains a centerpiece in managing disease progression |
28 Multiple Myeloma: Disease Treatment and Progression |
29 Deep Freeze Thawing and infusion of patient stem cells Autologous Stem Cells Autologous Stem Cells Autologous Stem Cells High Dose Chemotherapy Cryopreservation of patient stem cells Mobilization and leukapheresis of patient stem cells Multiple Myeloma: Stem Cell Transplantation |
30 Captisol-enabled ® Melphalan for Injection Ligand Internal Development Asset One vial system Propylene glycol-free 24-hr infusion window Treatment Flexibility Alkeran ® Launched in 1993 GlaxoSmithKline Two vial system Propylene glycol diluent 60-min infusion window Per label limitations Melphalan Product Comparison |
31 Captisol-enabled ® Melphalan for Injection Ligand Internal Development Asset One vial system Propylene glycol-free 24-hr infusion window Treatment Flexibility Product Advantages: • Improved stability and use time in an all aqueous formulation • Longer administration durations, slower infusion rates • Elimination of two-vial system Physicians expected to: • Safely achieve higher dose intensity • Easily deliver concomitant meds in high- dose regimens • Modulate dose to patient tolerability • Higher dosage potential for improved response rates Melphalan Product Comparison |
32 • IMS Reports Sales of $85MM for Rolling 12 Month Period • Majority of the Current Usage as a High Dose Conditioning Agent Prior to Autologous Stem Cell Transplant in Multiple Myeloma Patients (currently off label) • Potential Label, and Orphan Designation, for Captisol-enabled ® Propylene Glycol-Free Melphalan Addresses this Market • Unmet Medical Need with the Current Standard of Care: Stability following reconstitution (60 minutes) Limits on Absolute Daily Dosing Limits on Duration of Infusion Potential Adverse Reactions Due to Co-Solvent (propylene glycol) Melphalan Market |
33 A Marketing and Sales effort could be relatively lean and efficient • Melphalan therapy is well understood and entrenched, with few influential bone-marrow-transplant hospitals “Ultra-niche” call universe • Benefits of Captisol-enabled ® Melphalan formulation are easily positioned • Effective promotion with lean sales organization achievable • Orphan Indication has favorable payer landscape (public and private) Compass/Defined Health survey, 2009 Captisol-enabled ® Melphalan: Opportunity |
34 Captisol-enabled ® Melphalan: Projected Timeline |
36 The Shots on Goal Model 8 Assets Currently Generating Commercial Revenue Over 50 Partnered Programs Over 60 Total Programs Over 25 Different Partners Over 10 Therapeutic Areas Minimizing Risk Through Portfolio Size and Diversification 10 Potential New Approvals in the Next 4 Years - - |
37 The Value Pyramid For Ligand Assets The Top of the Value Pyramid for Ligand is Promacta Avinza Carfilzomib Aprela Nexterone CXCR2 Viviant Over 50 Additional Programs from Preclinical to PIII • There are numerous programs in the Ligand portfolio today which add significant value to the business • But, Ligand’s royalty interest in the Promacta franchise at GSK is the most valuable single asset Ligand owns |
38 Promacta Background • What is Promacta Promacta is a once-daily oral medicine that activates the thrombopoietin (TPO) receptor Activation of the TPO receptor causes platelets to increase, relieving conditions of low platelets known as thrombocytopenia • History Ligand and GSK jointly discovered Promacta as part of a thrombopoietin (TPO) receptor agonist research collaboration started in 1995 GSK later licensed from Ligand the follow-on TPO receptor agonist LGD-4665 in 2008 |
39 Approved for ITP Marketed by GSK PIII HepC Data Release in 3Q/4Q11 Promacta Follow-On : GSK-5921 5-10%, blended 9% on $1B in Sales An Approved Drug in All Major Markets Promacta ® : The Foundation of the Ligand Growth Story Aspects Of The Promacta Franchise Make It An Ideal Foundation For Ligand’s Financial Growth Story Significant Royalty Interest Major Upcoming Catalyst Events Long Patent Protection Major Potential for Label Expansion Marketed by a Premier Pharma Company Life-Cycle Management Opportunity ITP HepC Oncology Others Patented until July 2025 |
40 Promacta Program Recent Developments (1 of 2) • New ITP Launches Around the World EU, Japan, South America • Increased ITP Sales World-wide ITP sales in 1Q2011 increased 109% over 1Q2010 The Promacta ITP Franchise Has Continued To Generate Positive News In The Past Year |
41 Promacta Program Recent Developments (2 of 2) • Full ITP Approval Granted by FDA GSK completed post-approval commitment of generating long-term safety data Label now includes efficacy and safety data from RAISE, 6-month ITP study Since 2008, GSK has been working with FDA. Studies submitted: • 6-month efficacy and safety data • 2-year safety data in chronic ITP • Updates from chronic liver disease (ELEVATE) trial The Promacta ITP Franchise Has Continued To Generate Positive News In The Past Year |
42 Idiopathic Thrombocytopenia Purpura (ITP) Phase I Phase II Phase III Approved Hepatitis C-Related Thrombocytopenia Oncology-Related Thrombocytopenia Clinical Studies 2 P-III Studies GSK Is Investing Significantly In The Growth Of The Promacta Franchise 11 PI and PII Studies Approved (Label Expansion Studies Ongoing) GSK Investment in Promacta Franchise Expansion |
43 Patients needed to potentially reach $1B in sales Thrombocytopenia Is Comprised Of Multiple Sub-Markets of Thrombocytopenia-Inducing Diseases, Similar to Anemia and Neutropenia Wall Street Research on GSK published Nov. 21, 2005 Thrombocytopenia: A Multibillion Dollar Platelet Potential |
44 Significant Revenue Growth Potential for Ligand Territory Expansion Indication Expansion • HepC • Oncology • Others + + Long IP Protection 2025 Expansion of the Promacta Franchise Translates Into Significant Revenue Growth for Ligand Promacta Royalty Illustrative Ligand Revenue Annual Sales Royalty <$100M 4.70% $100M-$200M 6.60% $200M-$400M 7.5% $400M-$1.5B 9.40% >1.5B 9.30% Annual Sales Blended Royalty Ligand Revenue $500M 7.1% $36M $1B 8.3% $83M $1.5B 8.6% $130M |
45 45 The Role for Eltrombopag (Promacta) in the Treatment of HepC-Related Thrombocytopenia N. Afdhal M.D Beth Israel Deaconess Liver Center Harvard Medical School |
46 46 Agenda Eltrombopag and thrombocytopenia Current status of HCV therapy The ENABLE 1 and ENABLE 2 P-III Studies ELEVATE Study – conclusions on Eltrombopag safety |
47 47 The Unmet Medical Need for Thrombocytopenia Thrombocytopenia is a major factor in patients being unable to achieve a desired clinical outcome in dozens of diseases Currently estimated to be nearly two million patients annually in the US who need to be treated for thrombocytopenia Current non-drug techniques used to increase platelets (i.e. platelet transfusion, splenectomy) are costly, risky, and inconvenient. The need for a more convenient and effective method for combating thrombocytopenia is clear |
48 48 Liver Disease–Associated Thrombocytopenia Platelet counts may be as low as 20,000–40,000/ L Prevalence of thrombocytopenia increases with severity of liver disease Degree of thrombocytopenia correlated with severity of liver disease Thrombocytopenia predictive of reduced 5-year survival Thrombocytopenia may develop or worsen with interferon-based therapy 4% in recent DAA trials Degree of Liver Damage Thrombocytopenia Prevalence Normal liver 2.3% Fatty liver 5.1% Chronic hepatitis 20.3% Advanced liver disease 31.8% |
49 49 Eltrombopag Thrombopoietin receptor agonist Oral, once-daily tablet Induces megakaryocyte proliferation and differentiation Increases platelet counts in patients with HCV¹ 1. McHutchison J, et al.N Engl J Med. 2007;357:2227–2236. |
50 50 Current Status of HCV therapy and the Role for Eltrombopag |
51 Thrombocytopenia, HepC, and Eltrombopag Nearly 10% of HepC patients in the US suffer from treatment-limiting thrombocytopenia These patients have significantly worse outcomes due to their underlying liver disease and inability to complete antiviral therapies Eltrombopag PII data demonstrates that this drug may be useful for these patients to overcome thrombocytopenia limitations and complete antiviral therapy Key question arising around the eltrombopag HepC opportunity How will new HepC therapies impact the need for eltrombopag? Is there a long-term safety concern for eltrombopag because of the ELEVATE study results? |
52 HCV Pipeline* by MOA and Stage of Development 3/2/2010 – selected compounds only. *Publicly available information via press release, corporate presentations, and assumptions based on patent filings. |
53 Target “Regimen” Outcomes Today’s Regimen 2015+ Target IFN + Ribavirin (R) G1-Naive • SVR = 40% • Duration = 48 weeks G2-3 Naïve • SVR = 75% • Duration = 24 weeks G1-Experienced • No meaningful option • Frequent dosing and poor tolerability New Triple / Quad Combo Regimens • Highest possible SVR • No / low resistance • Better tolerability • Shorter durations • Simplified delivery 1. IFN + R + DAA 2. IFN + DAA + DAA 3. IFN + R + DAA + DAA 4. DAA + DAA (+ DAA) IFN = Interferon R = Ribavirin DAA = Novel Direct Acting Antiviral agents Regimen 4. High risk / low probability / far away / no PoC |
54 SVR Rates in Telaprevir-Treated Patients Compared with Peginterferon/Ribavirin Alone Jacobson IM et al. Hepatology. 2010;52(Suppl 1):Abstract 211. Telaprevier 12 weeks + Peg/Riba 48 weeks Telaprevier 8 weeks + Peg/Riba 48 weeks Peg/Riba 48 weeks |
55 The Impact of New HepC Therapies on the Use of Eltrombopag in HepC Underlying thrombocytopenia is still an issue for many HepC patients The new protease inhibitors do not change that fact • New protease inhibitor therapies slightly increase the rate of thrombocytopenia Due to increased SVR seen with new cocktails, the need for eltrombopag should actually increase • Higher SVR rates may encourage doctors to treat more aggressively those patients with thrombocytopenia |
56 56 Eltrombopag Clinical Studies HepC Studies |
57 Eltrombopag PII HepC Study Design 4 wk 12 wk PEG-IFN + ribavirin + eltrombopag Pre-antiviral Eltrombopag 4 wk 4 wk 4 wk 12 wk + Eltrombopag 12 wk + Eltrombopag 12 wk + Eltrombopag INITIATE antiviral Rx if platelets >70–100 K/µL 30 mg 50 mg 75 mg PART 1 PART 2 4 wk 4 wk 4 wk 4 wk Follow-up |
PLACEBO 30 mg 50 mg 75 mg 0.0007 0.0003 < 0.0001 0% 74% 75% 95% 0% 20% 40% 60% 80% 100% McHutchison, NEJM 2007 58 Phase II: Primary Efficacy Endpoint Platelet count 100,000/uL at Week 4 |
59 59 PLACEBO 30 mg 50 mg 75 mg 6% 53% 36% 65% 0% 20% 40% 60% 80% 100% Phase II: Subjects Completing 12 Weeks of PEG-IFN Therapy |
Phase II: Median Platelet Count > 200K without thrombotic events 0 50 100 150 200 250 0 14 28 42 56 70 84 98 112 Placebo 30 mg 50 mg 75 mg INITIATION MAINTENANCE Study Day McHutchison, AASLD 2006 60 |
61 Treatment Group, n (%) PBO N=18 30mg N=14 50mg N=19 75mg N=23 Any AE 10 (56) 11 (79) 10 (53) 13 (57) Headache 3 (17) 5 (36) 3 (16) 4 (17) Dry mouth 1 (6) 2 (14) 2 (11) 2 (9) Pruritus 0 0 0 2 (9) Nausea 0 1 (7) 2 (11) 1 (4) Fatigue 0 0 2 (11) 1 (4) Upper abdominal pain 0 2 (14) 2 (11) 0 Insomnia 0 0 2 (11) 0 Arthralgia 0 2 (14) 1 (5) 0 No thromboembolic or elevated LFT events of concern Phase II: Adverse Events – Pre-Antiviral Phase |
62 62 Phase II: Conclusions Eltrombopag increased platelet counts in subjects in all dose groups A significant number of subjects achieved the primary endpoint (Week 4) in all dose groups compared to placebo Eltrombopag enabled 45/56 subjects to initiate IFN therapy – 31 subjects completed 12 weeks of IFN therapy Preliminary PK findings in general indicate exposure increases with dose with wide variability No safety signals of concern in this initial short term study Safety and efficacy data supports further investigation of eltrombopag in this patient population |
Two parallel global Phase III studies ENABLE 1 and 2 63 peginterferon alfa-2a (PEGASYS) plus ribavirin – ENABLE 1 peginterferon alfa-2b (PEG-Intron) plus ribavirin – ENABLE 2 ltrombopag to INitiate and Maintain Interferon ntiviral Treatment to Benefit Subjects with Hepatitis C related Liver DiseasE E A |
Pre-Antiviral Phase Open-label eltrombopag (2 – 9 weeks) Antiviral Phase Randomized (up to 48 weeks) platelets >90,000/uL (E1) or 100,000/uL (E2) 25mg>50mg>75mg>100mg • 2:1 randomization eltrombopag:placebo • Dose titration of eltrombopag allowed throughout • Primary endpoint = proportion of patients achieving SVR (6M off –Tx) • N=750 dosed/675 randomized study • 3 regions, 26 countries, >250 centres SVR SVR 6 months off-Tx Randomized Withdrawal Design open label eltrombopag Eltrombopag + PEG-IFN/Rib Placebo + PEG-IFN/Rib 64 |
65 65 Screening 45 Days Platelets <75K/µL Pre-Antiviral Treatment Phase Open-label eltrombopag dosed for up to 9wks until platelet count increases to enable initiation of antiviral therapy. Part 1 (2-9 Wks) Open-Label Platelets 90K/µL* Platelets 90K/µL* Platelets 90K/µL* *Platelets <90K/µL *Platelets <90K/µL *Platelets <90K/µL WD START *Platelets <90K/µL Platelets 90K/µL* *90K/µL (ENABLE 1) 100K/µL (ENABLE 2) 2:1 Randomisation (Eltrombopag:Placebo) Eltrombopag plus Antiviral Therapy Antiviral Treatment Phase Randomised either to maintain dose of eltrombopag from Part 1 or to matched placebo. Part 2 ( 48 Wks) Double-Blind Placebo plus Antiviral Therapy or a 24 Week FU Ocular/SVR a Post-last dose of investigational product. ENABLE 1 and 2 Study Design 25mg 2 Weeks 50mg 1-2 Weeks 75mg 1-2 Weeks 100mg 1-3 Weeks |
66 SVR rate defined as percentage of subjects with non-detectable HCV-RNA at 24 weeks post-completion of the planned treatment period Platelet count 90-100,000/ L in Part 1 Dose modifications Safety and tolerability Platelet counts PK RVR, EVR and ETR Health-related quality of life Safety modified to include risk of thrombotic events – both studies completed without DSMB concerns Endpoints |
Eltrombopag Safety Summary ELEVATE Study and Safety 67 |
68 Eltrombopag in Chronic Liver Disease Patients with Thrombocytopenia Undergoing an Elective Invasive Procedure: Results from ELEVATE, a Randomised Clinical Trial N. Afdhal, E. Giannini,² G.N. Tayyab, A. Mohsin, 4 J-W. Lee, 5 A. Andriulli, 6 L. Jeffers, 7 J. McHutchison, 8 F. Campbell, 9 N. Blackman, 10 D. Hyde, 9 A. Brainsky, 11 D. Theodore 12 1. Division of Gastroenterology/Liver Center, Beth Israel Deaconess Medical Center, Boston, MA, USA; 2. Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; 3. Department of Medicine, Gastroenterology and Hepatology, Post Graduate Medical Institute, and Lahore General Hospital, Lahore, Pakistan; 4. Department of Gastroenterology, Services Hospital Lahore, Services Institute of Medical Sciences, Lahore, Pakistan; 5. Department of Internal Medicine, Inha University Hospital and School of Medicine, Incheon, Korea; 6. Department of Internal Medicine, Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, San Giovanni Rotondo, Italy; 7. Center for Liver Diseases, University of Miami, Miller School of Medicine, Miami, FL, USA; 8. Division of Gastroenterology, Duke University Medical Center, Durham, NC, USA; 9. Clinical Development, GlaxoSmithKline, Stockley Park, Uxbridge, UK; 10. Biometrics and Epidemiology, GlaxoSmithKline, Collegeville, PA, USA; 11. Clinical Development, GlaxoSmithKline, Collegeville, PA, USA; 12. Clinical Development, GlaxoSmithKline, Research Triangle Park, NC, USA 1 3 |
Difference 53% (95% CI: 43, 62) p < 0.0001 0 10 20 30 40 50 60 80 100 Placebo (N = 147) Eltrombopag (N = 145) 70 90 72% 19% n = 28 n = 104 Primary Endpoint: Avoiding Platelet Transfusions with Elective Invasive Procedure 69 |
Placebo (N = 145) Eltrombopag (N = 143) n (%) n (%) Bleeding 25 (17) 19 (13) Thrombotic event 2 (1) 6 (4) Ocular (focus on cataracts / visual acuity decrease) 6 (4) 6 (4) Malignancies* 1 (<1) 1 (<1) Selected Adverse Events 70 * Basal cell carcinoma (Grade 2) reported for one patient receiving placebo and B cell lymphoma (Grade 4) reported for one patient receiving eltrombopag; neither was considered to be related to treatment by the investigator. |
71 71 Thrombotic event Temporal relationship to last dose Temporal relationship to procedure Platelet count at event (Gi/L) Procedure PV / SMV thrombosis +1 –6 days 417 Brain tumour resection PV thrombosis +5 +4 days 288 Oesophageal variceal ligation SMV thrombosis +8 +7 days 235 Dental extraction SMV / mesenteric thrombosis +9 +7 days 289 HCC ablation SPV thrombosis +14 +13 days 241 TACE PV thrombosis +38 +34 days 33 Oesophageal variceal ligation Acute MI +20 +19 days 83 Colon resection Non-occlusive PV and mesenteric thrombosis +128 +128 days Unknown Oesophagoduo- denoscopy PV, portal vein; SMV, superior mesenteric vein; SPV, spleno-portal vein; MI, myocardial infarction Eltrombopag Placebo Summary of Thrombotic Events |
72 72 Platelet count >200,000/µL YES NO 47 patients (16%) 241 patients (84%) YES = 5 (10.6%) NO = 42 (89.4%) YES = 3 (1.2%) NO = 238 (98.8%) TEs Thrombotic Events and Platelet Count |
73 73 ELEVATE Conclusions Eltrombopag 75 mg for 14 days – Reduced the need for platelet transfusions in CLD patients with thrombocytopenia undergoing elective invasive procedures – Increased platelets during treatment period and up to 2 weeks following treatment – Similar incidence of adverse events and serious adverse events – More thrombotic events in the eltrombopag group Relationship demonstrated for elevation of platelets Procedure with endovascular inflammation essential feature |
74 74 ENABLE studies are expected to confirm role of eltrombopag in HCV therapy in 2011 Eltrombopag is expected to be more widely used in HCV – increased SVR – increased treatment Long term safety of eltrombopag continues to be better understood and continued expansion of the eltrombopag franchise is warranted Eltrombopag Summary |
75 Financial Highlights John Sharp Vice President, Finance and Chief Financial Officer Ligand Pharmaceuticals Incorporated |
76 2011 Revenue Outlook • Total 2011 revenue currently projected to be $22 - $24 million – $11 - $12 million from Captisol sales – $8 million from royalties – $3 - $4 million from license and other • Potential for additional sources of revenue and cash in 2011 above these projections based on new license agreements 2011 Revenue Breakdown* License And Other Royalties Material Sales *Excludes revenue from new deals, if any ~15% ~35% ~50% |
77 Financial Guidance 2011 Guidance: • Revenue of $22 - $24 million • Operating expenses projected to be ~$20 million – Average gross margin on material sales of approximately 60% • Projecting turning profitable on an operating basis and having positive cash flow from operations by the 4 quarter of 2011 • Cash at year-end projected to be ~$20 million th |
78 Low Cost Structure $0.0 $10.0 $20.0 $30.0 $40.0 $50.0 $60.0 $70.0 $80.0 2007 2008 2009 2010 2011* G&A R&D * High end of expense guidance range • Ligand has significantly reduced expenses over the last several years • During the same period, the company closed 5 acquisitions while significantly expanding its asset base Pharmacopeia Acquisition Neurogen Acquisition Metabasis Acquisition CyDex Acquisition IL9 Account Acquisition |
79 Multiple Future Revenue Sources • 8 programs currently generating royalty revenues • Over 50 partnered programs • Numerous internal programs • Growing Captisol business |
80 Expected Revenue Growth *Excludes revenue from new deals, if any $0.0 $5.0 $10.0 $15.0 $20.0 $25.0 $30.0 $35.0 $40.0 $45.0 2011 Guidance* 2013 Illustrative License & Other Material Sales Royalty • Revenue could potentially double within two years on similar cost structure • Recurring and high-growth royalty revenue projected to drive the majority of revenue in 2013 * |
81 High Quality Revenue Future revenue drivers: – Increased royalties from multiple commercial products (Promacta,Conbriza, Carfilzomib, Nexterone, etc…) – Steadily increasing Captisol sales – Less dependence on “one-time” license/milestone events • Continued potential for additional sources of revenue and cash from new license agreements |
82 Value of Net Operating Loss Carryforwards (NOL) • Ligand has accumulated substantial NOL’s through our operating history and acquisitions • NOL’s should provide significant relief on taxable income if the company turns profitable • NOL’s as of December 31, 2010 = $438 million • Due to tax code, NOL’s are limited in the quantity and the timing in which they can be used, so we do not expect to get a full offset on taxable income immediately • Estimated net present value of NOL’s = ~$100M • In near-term, the NOL tax should reduce federal tax rate from 34% down to 2% (AMT) • Additionally, Ligand has ~$16 million of federal R&D Tax Credits |
Ligand Pharmaceuticals Incorporated 83 83 83 83 “Shots on Goal” Portfolio 2011 Ligand Analyst Day Workshop |
The “Shots on Goal” Model at Ligand • The low ROI for biopharma R&D suggests that sharing the cost and risk of R&D through partnering is a preferred route to meaningful ROI • Ligand has assembled the largest portfolio of partnered assets of any company in its biopharma peer group – Now over 50 assets fully funded by partners • A focus on assembling partnered assets allows Ligand to run a very lean cost structure without significantly high R&D costs • Coupled with our cost structure, this portfolio of assets gives Ligand a reasonable probability of becoming a sustainably profitable biopharma business 84 |
85 Industry Unique Partnered Asset Portfolio • Over 25 different partners • Over 10 different therapeutic areas • Over half of the portfolio is PII or later • Ligand estimates that partners spend over $150M per year on this portfolio • Significant quarterly news flow |
86 Portfolio Asset Highlights • PIII/NDA • Captisol-enabled proteasome inhibitor for multiple myeloma • Ligand eligible to receive milestones, royalties and material sales revenue • Potential 2012 launch • Beyond Promacta, there are multiple-late stage programs in the portfolio that offer Ligand opportunities for substantial future revenue growth Onyx Carfilzomib Merck CXCR2 Pfizer Aprela Merck Captisol Program • PII • Novel CXCR2 antagonist for COPD • Ligand eligible to receive milestones and royalties • Potential 2015 launch • PIII • Combination of Viviant and Premarin for menopausal symptoms • Ligand eligible to receive milestones and royalties • Potential 2013 launch • PII • Captisol-enabled undisclosed program • Ligand eligible to receive milestones and material sales revenue • Potential 2013 launch Over 40 Other Programs from Preclinical to Phase III Represent Another Potential Revenue Wave |
87 Quality Portfolio News Flow • New Territory Launches • New Product Launches • NDA Approvals • NDA Filings 3Q11 4Q11 1Q12 2Q12 3Q12 4Q12 The Size of the Portfolio Generates Regular, Meaningful, Quarterly News Flow • PIII Data Releases • PIII Trial Initiations • PII Data Releases Promacta Nexterone Viviant Aprela Carfilzomib CXCR2 IL-9 CDK Merck Captisol Clopidogrel Others |
88 Deep Partner Relationships • PII CXCR2 (COPD) • PII CDK Inhibitor (oncology) • PI BACE (Alzheimers) • Captisol Program • Promacta ITP • Promacta HepC • Promacta Oncology • LGD 4665/GSK 3521 • Viviant • Aprela • Marketed Captisol Products Ligand has Multiple Broad and Diverse Relationships With Premier Pharma Companies |
89 Ligand Business Development LIGAND REVENUE DRIVERS LIGAND PROPRIETARY PIPELINE LIGAND BUSINESS DEVELOPMENT Ligand business development is the core engine that drives the shots on goal model -Acquisitions – Licensing – Spin Offs - Alliance Management- |