UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 14A INFORMATION

PROXY STATEMENT PURSUANT TO SECTION 14(a) OF THE

SECURITIES EXCHANGE ACT OF 1934 

ALPINE IMMUNE SCIENCES, INC.

NOTICE OF 20222023 ANNUAL MEETING OF STOCKHOLDERS

To our Stockholders:

The record date for the 20222023 Annual Meeting is April 20, 2022.2023. If you held our common stock at the close of business on that date, you are entitled to vote at the meeting. For ten days prior to the annual meeting, a complete list of stockholders of record entitled to vote at the annual meeting will be available for examination by any stockholder for any purpose relevant to the annual meeting. If you would like to view the list, please contact our corporate secretary to schedule an appointment by calling (206) 788-4545 or writing to Alpine Immune Sciences, Inc., 188 East Blaine Street, Suite 200, Seattle, Washington 98102. The stockholder list will also be available online during the annual meeting at www.virtualshareholdermeeting.com/ALPN2022. Additional information regarding voting rights and the matters to be voted upon is presented in our proxy statement.

We are mailing to our stockholders a Notice of Internet Availability of Proxy Materials, or the Notice, containing instructions on how to access our proxy statement for our annual meeting and our annual report to stockholders over the Internet. The Notice provides instructions on how to vote online or by telephone and includes instructions on how to receive a paper copy of proxy materials by mail. The Notice, our proxy statement and our annual report can be accessed directly at the following Internet address: www.proxyvote.com, using the control number located on your proxy card.

We appreciate your continued support and look forward to you joining our virtual meeting or receiving your proxy.

ALPINE IMMUNE SCIENCES, INC.

FOR 20222023 ANNUAL MEETING OF STOCKHOLDERS

This proxy statement and the enclosed form of proxy are furnished in connection with solicitation of proxies by our board of directors for use at the 20222023 annual meeting of stockholders and adjournment, postponement or other delay thereof, or the Annual Meeting, to be held on Thursday,Tuesday, June 16, 2022 including any postponements, adjournments or continuations thereof.13, 2023. The Annual Meeting will be held virtually via live webcast on the Internet at www.virtualshareholdermeeting.com/ALPN2022ALPN2023 on June 16, 202213, 2023 at 1:30 p.m. Pacific Time. On or about April 29, 2022,May 1, 2023, we expect to mail to our stockholders a Notice of Internet Availability of Proxy Materials, or the Notice, containing instructions on how to access our proxy statement for our Annual Meeting and our annual report to stockholders.

GENERAL INFORMATION

The information provided in the “question and answer” format below is for your convenience only and is merely a summary of the information contained in this proxy statement. You should read this entire proxy statement carefully. Information contained on, or that can be accessed through, our website is not intended to be incorporated by reference into this proxy statement and references to our website address in this proxy statement are inactive textual references only.

You will be voting on:

Our board of directors recommends that you vote your shares:

Only holders of our common stock as of the close of business on April 20, 2022,2023, the record date, are entitled to receive notice of and to vote at the Annual Meeting. In deciding all matters at the Annual Meeting, each stockholder will be entitled to one vote for each share of our common stock owned as of the record date. We do not have cumulative voting rights for the election of directors. As of the record date, there were 30,316,06647,965,835 shares of our common stock outstanding and entitled to vote, and there were 2725 stockholders of record, which number does not include approximately 4,0184,060 beneficial owners of shares held in the name of a bank or brokerage firm. We do not have any outstanding shares of preferred stock.

Many of our stockholders hold their shares as beneficial owners through a brokerage firm or other nominee rather than directly in their own name. As summarized below, there are some distinctions between shares held of record and those owned beneficially through a broker or other nominee.

You can contact our transfer agent using the following information:

You may vote by following the instructions set forth in the Notice or on your proxy card or, if you are a beneficial owner, by following the procedures provided by your broker or other nominee. You may access the notice, proxy materials and our annual report to stockholders at www.proxyvote.com.

Yes. You can change your vote or revoke your proxy any time before the Annual Meeting by:

A proxy is your legal designation of another person to vote the stock that you own at the Annual Meeting. The person you designate is your “proxy,” and you give your proxy authority to vote your shares by voting by telephone or over the Internet, or if you requested to receive a printed copy of the proxy materials, by submitting the proxy card.

Proxies are solicited by and on behalf of our board of directors, and our board has designated Mitchell H. Gold and Paul Rickey to serve as proxies for the Annual Meeting. When proxies are properly dated, executed and returned, the shares represented by such proxies will be voted at the Annual Meeting in accordance with the instruction of the stockholder.

If no specific instructions are given, however, the shares will be voted in accordance with the recommendations of our board of directors as described above.

If any matters not described in the proxy statement are properly presented at the Annual Meeting, the proxy holders will use their own judgment to determine how to vote your shares.

If the Annual Meeting is adjourned, the proxy holders can vote your shares on the new meeting date as well, unless you have properly revoked your proxy instructions, as described above.

In accordance with the rules of the U.S. Securities and Exchange Commission, or SEC, we have elected to furnish our proxy materials, including this proxy statement and our annual report to our stockholders, primarily via the Internet. On or about April 29, 2022,May 1, 2023, we expect to mail to our stockholders the Notice, thatwhich contains instructions on how to access our proxy materials on the Internet, how to vote at the meeting,Annual Meeting, and how to request printed copies of the proxy materials and annual report.

Stockholders may request to receive all future proxy materials in printed form by mail or electronically by e-mail by following the instructions contained in the Notice. We encourage stockholders to take advantage of the availability of the proxy materials on the Internet to help reduce our costs and the environmental impact of our annual meetings.

A quorum is the minimum number of shares required to be present in person, or by remote communication, if applicable, or represented by proxy at the Annual Meeting for the meeting to be properly held and business to be conducted at the meeting in accordance with our bylaws and Delaware law. If there is no quorum at the Annual Meeting, either the chairperson of the meeting or a majority in voting power of the stockholders entitled to vote who are present in person, or by remote communication, if applicable, or represented by proxy at the meeting may adjourn the meeting to another date. The presence, in person, or by remote communication, if applicable, or represented by proxy, of the holders of a majority in voting power of all issued and outstanding shares of common stock entitled to vote at the Annual Meeting will constitute a quorum at the meeting.

A proxy submitted by a stockholder may indicate that all or a portion of the shares represented by the proxy are not being voted, which is referred to as stockholder withholding, with respect to a particular matter. Similarly, a broker may not be permitted to vote stock, referred to as a broker non-vote, held in street name on a particular matter in the absence of instructions from the beneficial owner of the stock. The shares subject to a proxy that are not being voted on a particular matter because of either stockholder withholding or broker non-vote will count for purposes of determining the presence of a quorum. Abstentions are also counted in the determination of a quorum.

If you are a beneficial owner, your broker or other nominee holder of record is permitted to vote your shares on the ratification of the appointment of Ernst & Young LLP as our independent registered public accounting firm, even if the record holder does not receive voting instructions from you. However, your broker or other nominee holder of record does not have discretionary authority to vote on any of the other proposals at the Annual Meeting, all of which are considered non-routine matters, without instructions from you, in which case a broker non-vote will occur and your shares will not be voted on these

proposals. Accordingly, if you are a beneficial owner, it is particularly important that you provide your instructions for voting your shares on Proposals No. 1, 3 and 34 to your broker or other nominee.

Abstentions are not considered votes cast and thus, will not have an effect on Proposals 1, 2 or 3. Abstentions will have the foregoing Proposals.same effect as a vote "AGAINST" Proposal 4.

With regard to Proposals 1, 2 and 3, broker non-votes, if any, will not be counted as votes cast and will have no effect on the result of the vote. Ratification of the selection of our independent registered public accounting firm is considered a routine matter on which a broker or other nominee has discretionary authorityWith regard to vote. As a result,Proposal 4, broker non-votes, for Proposal 2 are not expected; however, if any, broker non-votes occur, they will not be counted as votes cast and will have nothe same effect onas a vote "AGAINST" the result of the vote.proposal.

The board of directors is soliciting proxies for use at the Annual Meeting. All expenses associated with this solicitation, including the cost of preparing, assembling, printing, filing, mailing and otherwise distributing the Notice or proxy materials and soliciting votes for use at the Annual Meeting will be borne by us. If you chooseWe have hired Saratoga Proxy Consulting, LLC to accesshelp us solicit proxies. We expect to pay Saratoga Proxy Consulting, LLC a base fee of $10,000 plus reimbursement of reasonable out-of-pocket expenses. Proxy solicitations will be made primarily through the proxy materials or vote over the Internet, you are responsible for Internet access charges youmail, but may incur. If you choose to votebe supplemented by telephone, you are responsible for any telephone charges you may incur.facsimile and internet. In addition to the mailing of the Notice or proxy materials, the solicitation of proxies or votes may be made in person, by telephone, or by electronic communication by our directors, officers and employees, who will not receive any additional compensation for such solicitation activities.

Proxy instructions, ballots, and voting tabulations that identify individual stockholders are handled in a manner that protects your voting privacy. Your vote will not be disclosed either within Alpine Immune Sciences, Inc. or to third parties, except as necessary to meet applicable legal requirements, to allow for the tabulation of votes and certification of the vote, or to facilitate a successful proxy solicitation.

We will announce preliminary voting results at the Annual Meeting. We will also disclose voting results on a Current Report on Form 8-K that we will file with the SEC within four business days after the meeting. If final voting results are not

available to us in time to file a Form 8-K, we will file a Form 8-K to publish preliminary results and will provide the final results in an amendment to the Form 8-K as soon as they become available.

We are continuously exploring technologies and services that will best permit our stockholders to engage with us and exercise their vote, and we have decided to conduct the Annual Meeting via virtual live webcast because we believe it better achieves these aims than holding a live in-person meeting. We believe that a virtual annual meeting of stockholders provides all of the rights and opportunities for stockholders to participate as they would at an in-person meeting, but offers a greater level of flexibility and access for many of our stockholders who may not be able to attend an annual meeting of stockholders in person, particularly in light of the ongoing COVID-19 pandemic and potential restrictions and guidance on public gatherings.person. In addition, compared with the cost and inefficiency associated with holding an in-person meeting, a virtual meeting via live webcast offers an attractive alternative. We believe our stockholders’ opportunity to participate in the annual meeting virtually

If you want to submit a question during the Annual Meeting, log into www.virtualshareholdermeeting.com/ALPN2022,ALPN2023, type your question into the “Ask a Question” field, and click “Submit.” Stockholders are permitted to submit questions during the Annual Meeting via the virtual meeting website, with a limit of one question per stockholder. We will answer as many questions submitted in accordance with the meeting rules of conduct as possible in the time allotted for the meeting. Only questions that are relevant to an agenda item to be voted on by stockholders will be answered. Our virtual meeting website will also contain instructions for accessing technical support to assist in the event a stockholder encounters any difficulties accessing the virtual meeting. The questions received during the meeting and our answers will be available as soon as practicable after the Annual Meeting on https://ir.alpineimmunesciences.com. The questions and answers will remain available on https://ir.alpineimmunesciences.com for one week after posting.

We have adopted a procedure approved by the SEC called “householding” to limit duplicate copies of our proxy materials being printed and delivered to stockholders sharing the same household. Under this householding procedure, we send only a single copy of the Notice and, if applicable, the proxy materials to multiple stockholders of record who share the same address unless one of those stockholders notifies us that the stockholder would like a separate copy of the Notice or proxy materials. This householding procedure reduces our printing costs, mailing costs, and fees. Stockholders who participate in householding will continue to be able to access and receive separate proxy cards. Upon written or oral request, we will deliver promptly a separate copy of the Notice and, if applicable, the proxy materials to any stockholder at a shared address to which we delivered a single copy of any of these documents. To receive a separate copy, or, if you are receiving multiple copies, to request that Alpine Immune Sciences, Inc. only send a single copy, of the Notice and, if applicable, the proxy materials, stockholders may contact us by telephone at (206) 788-4545 or at the following address:

Attention: Legal

Stockholders who hold shares in street name may contact their brokerage firm, bank, broker-dealer or other similar organization to request information about householding.

Stockholder Proposals

Stockholders may present proper proposals for inclusion in our proxy statement and for consideration at the next annual meeting of stockholders by submitting their proposals in writing to our corporate secretary in a timely manner. For a stockholder proposal to be considered for inclusion in our proxy statement for our 20232024 annual meeting of stockholders, our corporate secretary must receive the written proposal at our principal executive offices not later than December 30, 2022.29, 2023. In

addition, stockholder proposals must comply with the requirements of Rule 14a-8 of the Securities Exchange Act of 1934, or the Exchange Act, regarding the inclusion of stockholder proposals in company-sponsored proxy materials. Proposals should be addressed to:

Attention: Corporate Secretary

Our bylaws provide that the only business that may be conducted at an annual meeting is business that is (1) specified in a notice of meeting given by or at the direction of the board of directors, (2) if not specified in the notice of meeting, otherwise properly brought before the meeting by or at the direction of our board of directors or the chairperson of the board of directors, or (3) otherwise properly brought before the meeting by a stockholder present in person (a) who is a beneficial owner of our

If we hold our 20232024 annual meeting of stockholders more than 3025 days before or more than 6025 days after the one-year anniversary date of the 20222023 Annual Meeting, then notice of a stockholder proposal that is not intended to be included in our proxy statement must be received no earlier than 8:00 a.m. Eastern Time on the 120th day prior to such annual meeting and no later than the close of business5:00 p.m. Eastern Time on the later of the following two dates:

If, after complying with the provisions above, a stockholder, or such stockholder’s qualified representative, as applicable, does not appear at the annual meeting to present the stockholder’s proposal, we are not required to present the proposal for a vote at such meeting.

Recommendation and Nomination of Director Candidates

Availability of Bylaws

A copy of our bylaws may be obtained by accessing our filings on the SEC’s website at www.sec.gov. You may also contact our corporate secretary at our principal executive offices for a copy of the relevant bylaw provisions regarding the requirements for making stockholder proposals and nominating director candidates.

Our annual meetingThe Annual Meeting will be held on Thursday,Tuesday, June 16, 202213, 2023, at 1:30 p.m. Pacific Time. This year’s annual meetingThe Annual Meeting will be a virtual meeting via live webcast on the Internet. You will be able to attend the 2022 Annual Meeting, vote and submit your questions during the meeting by visiting www.virtualshareholdermeeting.com/ALPN2022.ALPN2023. In order to vote or submit a question during the 2022 Annual Meeting, you will need to follow the instructions posted at www.proxyvote.com and www.virtualshareholdermeeting.com/ALPN2022ALPN2023 and will need the control number included on your Notice or proxy card. If you do not have a control number, you will be able to listen to the meeting only. Youonly, and you will not be able to vote or submit your questions during the meeting.

ELECTION OF DIRECTORS

Our business and affairs are managed under the direction of our board of directors, which is currently composed of eight members. Seven of our directors are “independent” under the Nasdaq listing standards. Our board of directors is divided into three staggered classes of directors. At each annual meeting of stockholders, a class of directors will be elected for a three-year term to succeed the same class whose term is then expiring.

Each director’s term continues until his or her successor is duly elected and qualified or until his or her death, resignation or removal. Any increase or decrease in the number of directors will be distributed among the three classes so that, as nearly as possible, each class will consist of one-third of the directors. This classification of our board of directors may have the effect of delaying or preventing changes in control of our company.

The following table sets forth the names and certain other information for each of the nominees for election as a director and for each of the continuing members of the board of directors as of April 20, 2022. 2023.

We believe that Dr. Gold possesses specific attributes that qualify him to serve as a member of our board of directors, including more than 20 years of experience in senior executive management roles with both early stage and public biopharmaceutical companies.

We believe that Dr. Cui’s venture capital and management experience in the pharmaceuticals industry provides him with the qualifications and skills necessary to serve as a member of our board of directors. Dr. Cui was appointed to the Board pursuant to the terms of the securities purchase agreement relating to our January 2019 private placement.

We believe that Mr. Conway’s experience and expertise in the pharmaceutical industry, pharmaceutical development and clinical trials, and corporate finance, governance, accounting and public company compliance give him the qualifications and skills to serve on our board of directors.

We believe that Dr. Topper’s experience overseeing Frazier Life Sciences’ investments in biotechnology, his experience in senior management positions, and his significant knowledge of industry, medical and scientific matters, provide Dr. Topper with the qualifications and skills to serve on our board of directors.

We believe Mr. Peetz’ experience in senior management positions in both business and finance and his experience supporting various corporate and financing transactions provide him with the qualifications and skills to serve on our board of directors.

Our board of directors has undertaken a review of its composition, the composition of its committees and the independence of current directors and considered whether any such director has a material relationship with us that could compromise his or her ability to exercise independent judgment in carrying out his or her responsibilities. Based upon

During the fiscal year ended December 31, 2021,2022, our board of directors held fiveeight meetings. No director attended fewer than 75% of the total number of meetings of the board of directors and the committees of which they were a member.

In order to promote open discussion among independent directors, our board of directors has a policy of holding regular executive sessions of non-management directors during each regularly scheduled board meeting and an executive session including only independent directors at least once each year (and at such other times as requested by an independent director). The chair of the nominating and corporate governance committee presides at executive sessions of independent directors.

Pursuant to our corporate governance guidelines, absent unusual circumstances, each director is expected to attend the annual meeting of stockholders. TwoThree of our directors attended our 20212022 annual meeting of stockholders.

Our board of directors has three standing committees — an audit committee, a compensation committee, and a nominating and corporate governance committee, each of which has the composition and responsibilities described below. The nominating and corporate governance committee and the board of directors evaluate committee membership at least annually. Our board of directors may from time to time establish other committees.

The responsibilities of the audit committee include, but are not limited to, the following:

Since December 2020, the audit committee has consisted of three directors: Messrs. Conway (chairman) and Peetz and Ms. Hernday. Our board of directors has determined that Mr. Conway is an “audit committee financial expert” as defined in the SEC rules and made a qualitative assessment of Mr. Conway’s level of knowledge and experience based on several factors, including his prior experience, business acumen and independence. Our board of directors has concluded that the composition of the audit committee meets the requirements for independence under the rules and regulations of Nasdaq and the SEC.

The audit committee met fivefour times during 2021.2022. The audit committee also meets periodically with our outside auditors without management present, at such times as it deems appropriate. Our board of directors has adopted a written charter for the audit committee in compliance with the applicable rules of the SEC and the Nasdaq listing standards and which is available on our website at https://ir.alpineimmunesciences.com/governance.

The compensation committee acts on behalf of the board of directors to review, adopt and oversee our compensation strategy, policies, plans and programs, and its responsibilities include the following:

Since December 2020, the compensation committee has consisted of three directors: Drs. Topper (chairman), Cui and Thompson. Our board of directors has affirmatively determined that all members of the compensation committee are independent, as independence is currently defined in the Nasdaq listing standards. The compensation committee met fivethree times during the 20212022 fiscal year. The compensation committee has adopted a written charter that is available to stockholders on our website at https://ir.alpineimmunesciences.com/governance.

The purpose of our nominating and corporate governance committee will beis to assist our board of directors in discharging its responsibilities relating to:

The nominating and corporate governance committee consists of three directors; Drs. Thompson (chairman) and Cui and Mr. Conway. All members of the nominating and corporate governance committee in 20212022 were independent (as currently defined in the Nasdaq listing standards). The nominating and corporate governance committee met three timesdid not formally meet during 2021.2022, but members of the committee did discuss matters within the purview of the committee and acted by written consent as needed. Our board of directors has adopted a written charter for the nominating and corporate governance committee that is available to stockholders on our website at http://www.alpineimmunesciences.com.

The nominating and corporate governance committee selects as candidates for appointment or nomination to the board of directors individuals of high personal and professional integrity and ability who can contribute to the board of directors’ effectiveness in serving the interests of our stockholders. Director nominees are expected to have considerable management experience that would be relevant to our current and expected future business directions, a track record of accomplishment and a commitment to ethical business practices. The nominating and corporate governance committee also considers diversity in professional experience and skill sets in identifying nominees for director. Our board of directors, along with the nominating and corporate governance committee, utilizes its own resources to identify qualified candidates that meet these criteria to join our board of directors and, may, in the future, use anfrom time to time, uses executive recruiting firmfirms to assist in the identification and evaluation of such qualified candidates. For these services, anretained executive recruiting firm may befirms are paid a fee.

Our board of directors also believes that the board should be a diverse body. In evaluating candidates for director nominations, the nominating and corporate governance committee considers all aspects of each candidate’s qualifications and competencies in light of our needs, with a view towards creating a board of directors with diverse experiences and perspectives, including diversity with respect to race, gender, geography and areas of expertise.

The nominating and corporate governance committee has not established a procedure for considering director candidates recommended by our stockholders, but intends to evaluate candidates nominated by stockholders in the same manner as other

Stockholders may nominate candidates for director in accordance with the advance notice and other procedures contained in our amended and restated bylaws.

The responsibilities of the nominating and corporate governance committee relating to corporate governance include, but are not limited to, the following:

Additional responsibilities of the nominating and corporate governance committee include, but are not limited to, the following:

Our board of directors has adopted a process for identifying and evaluating director nominees. Before recommending an individual to the board of directors for board membership, the nominating and corporate governance committee confers with its members, other directors and our management team for potential candidates for the board. The nominating and corporate governance committee also uses its network of contacts to identify potential candidates and, if it deems appropriate, may also engage a professional search firm. The nominating and corporate governance committee will consider stockholders’ recommendations for nominees to serve as director if notice is timely received by our corporate secretary. Candidates nominated by stockholders will be evaluated in the same manner as other candidates. The nominating and corporate governance committee keeps the board of directors apprised of its discussions with potential nominees, and the names of potential nominees received from its current directors, management, and stockholders, if the stockholder notice of nomination is timely made.

We seek to align board composition with our strategic direction so that members of our board of directors bring skills, experience and backgrounds that are relevant to the key strategic and operational issues that they will oversee and approve. Although the board of directors has not adopted a fixed set of minimum qualifications for candidates for board membership, the nominating and corporate governance committee generally considers several factors in its evaluation of a potential member, which include integrity, character, independent judgment, breadth of experience, insight, knowledge and business acumen. Leadership skills and executive experience, expertise in the pharmaceutical, biotechnology or related industries, familiarity with issues affecting global businesses, financial and accounting knowledge, prior experience in our core markets, expertise in capital markets, strategic planning and marketing expertise, among others, may also be among the relevant selection criteria. In

addition, we strive to maintain a board of directors that reflects a diversity of experience and personal background. These criteria will vary over time depending on the needs of the board of directors. Accordingly, the board of directors may adopt new criteria and amend or abandon existing criteria as and when it determines such action to be appropriate.

In the case of incumbent directors whose terms of office are set to expire, the nominating and corporate governance committee reviews these directors’ overall contributions to the company and the board of directors during their terms, including level of attendance, level of participation and contribution to the board of directors’ responsibilities and actions, and any relationships and transactions that might impair the directors’ independence. In the case of new director candidates, the nominating and corporate governance committee also determines whether the nominee is independent for Nasdaq and SEC purposes, which determination is based upon applicable Nasdaq listing standards, applicable SEC rules and regulations and the advice of counsel, if necessary. The nominating and corporate governance committee conducts any appropriate and necessary inquiries into the backgrounds and qualifications of possible candidates after considering the function and needs of the board of

The nominating and corporate governance committee will evaluate stockholder recommendations of candidates for directors in accordance with its charter, our bylaws and the regular nominee criteria described above. Recommendations must include certain information, including the full name of the proposed nominee, a description of the proposed nominee’s business experience for at least the previous five years, complete biographical information, a description of the proposed nominee’s qualifications as a director, a representation that the recommending stockholder is a beneficial or record owner of our stock, other information that would be required to be disclosed in a proxy statement filed by us in connection with an annual meeting of stockholders, and any other information we may require to verify the independence of the proposed nominee. Any such submission must be accompanied by the written consent of the proposed nominee to be named as a nominee and to serve as a director if elected. Eligible stockholders wishing to recommend a director candidate for nomination should contact our corporate secretary in writing.

In 2021,2022, the nominating and corporate governance committee did not pay any feesretained Klein Hersh to assistconduct a search to identify a new candidate to serve on our board. The search resulted in the processappointment of identifyingJörn Drappa, M.D., Ph.D. as a director in July 2022. The nominating and corporate governance committee may in the future engage additional third-party search firms in those situations where particular qualifications are required or evaluating director candidates.where existing contacts are not sufficient to identify an appropriate candidate.

In addition, our president and chief executive officer and other executive officers regularly report to the non-executive directors and the audit, the compensation and the nominating and corporate governance committees to ensure effective and efficient oversight of our activities and to assist in proper risk management and the ongoing evaluation of management controls. We believe that the leadership structure of our board of directors provides appropriate risk oversight of our activities.

Each non-employee director is eligible to receive the following cash annual retainer, which will be paid quarterly in arrears on a prorated basis.

RATIFICATION OF APPOINTMENT OF

The audit committee of the board of directors has appointed Ernst & Young LLP, or EY, independent registered public accountants, to audit our financial statements for the year ending December 31, 2022.2023.

During the year ended December 31, 2021,2022, EY served as our independent registered public accounting firm.

Notwithstanding its selection and even if our stockholders ratify the selection, our audit committee, in its discretion, may appoint another independent registered public accounting firm at any time during the year if the audit committee believes that such a change would be in the best interests of our company and stockholders. At the 20222023 Annual Meeting, the stockholders are being asked to ratify the appointment of EY as our independent registered public accounting firm for the year ending December 31, 2022.2023. Our audit committee is submitting the selection of EY to our stockholders because we value our stockholders’ views on our independent registered public accounting firm and as a matter of good corporate governance.

Representatives of EY will be present at the 20222023 Annual Meeting, and they will have an opportunity to make statements and will be available to respond to appropriate questions from stockholders.

If the stockholders do not ratify the appointment of EY, the audit committee may reconsider the appointment.

THE BOARD OF DIRECTORS RECOMMENDS A VOTE “FOR” PROPOSAL #2

The audit committee of the board of directors is currently comprised of three independent directors and operates under a written charter, which is reviewed on an annual basis and amended as necessary by the board of directors upon recommendation by the audit committee.

During the fiscal year ended December 31, 2021,2022, the audit committee has consisted of: Messrs. Conway (chairman) and Peetz and Ms. Hernday (effective December 10, 2020).Hernday. Our board of directors has determined that Mr. Conway is an “audit committee financial expert” as defined in the SEC rules and made a qualitative assessment of Mr. Conway’s level of knowledge and experience based on several factors, including his prior experience, business acumen and independence. Our board of directors has concluded that the composition of the audit committee meets the requirements for independence under the rules and regulations of Nasdaq and the SEC.

The audit committee appoints an accounting firm as our independent registered public accounting firm. The independent registered public accounting firm is responsible for performing an independent audit of our financial statements in accordance with generally accepted auditing standards and issuing a report thereon. Management is responsible for our internal controls and the financial reporting process. The audit committee is responsible for monitoring and overseeing these processes.

The audit committee met fivefour times during 2021.2022. The meetings were designed to provide information to the audit committee necessary for it to conduct its oversight function of the external financial reporting activities and audit process of our company, and to facilitate and encourage communication between the audit committee, management and our independent registered public accounting firm, Ernst & Young LLP. Management represented to the audit committee that our financial statements were prepared in accordance with generally accepted accounting principles. The audit committee reviewed and discussed the audited financial statements for fiscal year 20212022 with management and the independent registered public accounting firm. The audit committee also instructed the independent registered public accounting firm that the audit committee expects to be advised if there are any subjects that require special attention.

The audit committee discussed with the independent registered public accounting firm the matters required to be discussed by the applicable requirements of the Public Company Accounting Oversight Board (“PCAOB”) and the SEC.

The audit committee has also received the written disclosures and the letter from the independent registered public accounting firm, Ernst & Young LLP, required by applicable requirements of the PCAOB regarding the independent registered public accounting firm’s communications with the audit committee concerning independence, and has discussed with Ernst & Young LLP that firm’s independence.

Respectfully submitted,

THE AUDIT COMMITTEE OF

THE BOARD OF DIRECTORS OF ALPINE IMMUNE SCIENCES, INC.

Robert Conway, Chairman

Natasha Hernday

Christopher Peetz

ADVISORY VOTE ON COMPENSATION OF NAMED EXECUTIVE OFFICERS (“SAY-ON-PAY”)

Pursuant to Section 14A of the Exchange Act and in accordance with SEC rules, we are providing our stockholders with the opportunity to vote at the Annual Meeting on this advisory or non-binding proposal regarding the compensation of our named executive officers (commonly referred to as “say-on-pay”).

This say-on-pay proposal gives our stockholders the opportunity to express their views on the compensation of our named executive officers as a whole. This vote is not intended to address any specific item of compensation or any specific named executive officer, but rather the overall compensation of all of our named executive officers and the policies and practices described in this proxy statement. Because the vote on this proposal is advisory in nature, it will not affect any compensation already paid or awarded to our named executive officers and will not be binding on us, the board of directors or the compensation committee. The say-on-pay vote will, however, provide information to us regarding investor sentiment about our executive compensation policies and practices, which the compensation committee will be able to consider when determining executive compensation for the remainder of the current fiscal year and beyond. Our board of directors and our compensation committee value the opinions of our stockholders. To the extent there is any significant vote against the compensation of our named executive officers as disclosed in this proxy statement, we will endeavor to communicate with stockholders to better understand the concerns that influenced the vote and consider our stockholders’ concerns, and our compensation committee will evaluate whether any actions are necessary to address those concerns. The company currently holds a say-on-pay vote every year and the next say-on-pay vote will occur at our 2024 annual meeting.

We are asking our stockholders to approve the compensation of our named executive officers as described in this proxy statement by voting in favor of the following non-binding resolution:

“RESOLVED, that the stockholders of Alpine Immune Sciences, Inc. approve, on an advisory basis, the compensation of Alpine Immune Sciences, Inc.’s named executive officers, as disclosed in the Alpine Immune Sciences, Inc.’s proxy statement for the 20222023 annual meeting of stockholders pursuant to the executive compensation disclosure rules of the Securities and Exchange Commission, the compensation tables and related narrative disclosures.”

EXECUTIVE OFFICERS

The names of our executive officers, their ages, their positions, and other biographical information as of April 20, 2022,21, 2023, are set forth below. Executive officers are elected by our board of directors to hold office until their successors are elected and qualified. There are no family relationships among our directors or executive officers. 

EXECUTIVE COMPENSATION

Our compensation committee is responsible for the executive compensation programs for our executive officers and reports to our board of directors on its discussions, decisions and other actions. The compensation committee is authorized to retain the services of one or more executive compensation advisors, as it sees fit, in connection with the establishment of our compensation programs and related policies. Beginning in 2017, the compensation committee retained AON Radford, or AON, a compensation consultant, to provide it with information, recommendations and other advice relating to executive compensation on an ongoing basis. Accordingly, RadfordAON now serves at the discretion of the compensation committee. The compensation committee engaged RadfordAON to assist in developing a group of peer companies to help us determine the appropriate level of overall compensation for our executive officers, as well as assess each separate element of compensation, with a goal of ensuring that the compensation we offer to our executive officers is competitive and fair.

The following table provides information regarding the compensation of our named executive officers:

We entered into amended and restated executive employment agreements with each of Drs. Gold and Peng, and Mr. Rickey effective January 1, 2018. In January 2021, the compensation committee approved adjusted salaries for Drs. Gold and Peng and Mr. Rickey of $523,000, $485,000, and $400,000 respectively. In March 2021, the compensation committee approved an adjusted salary for Dr. Peng of $500,000. In January 2022, the compensation committee approved adjusted salaries for Drs. Gold and Peng, and Mr. Rickey of $544,000, $525,000 and $416,000, respectively. In January 2023, the compensation committee approved adjusted salaries for Drs. Gold and Peng, and Mr. Rickey of $599,000, $546,000 and $437,000, respectively. Additionally, Drs. Gold and Peng, and Mr. Rickey are eligible to earn cash bonuses of up to 50%, 50% and 40%, respectively, of their base salary under our Executive Incentive Compensation Plan described below. These agreements also provide for certain severance benefits upon the termination of employment or a change in control of the company pursuant to our Change in Control and Severance Policy, or the Severance Policy.

Pursuant to the Severance Policy, if we terminate the employment of any of Dr. Gold, Dr. Peng or Mr. Rickey, each an Eligible Employee, other than for cause, death or disability, or the Eligible Employee resigns for good reason on or within 12 months following a change of control, then, subject to the Eligible Employee signing and not revoking a separation agreement and release of claims and continuing to adhere to the Eligible Employee’s non-competition, non-disclosure and invention assignment agreement, the Severance Conditions, such Eligible Employee will be eligible to receive the following severance benefits, less applicable tax withholdings:

Further, under the Severance Policy, if we terminate an Eligible Employee’s employment other than for cause, death or disability or such Eligible Employee resigns for good reason at any time other than during the period lasting from the date of a change of control or within 12 months thereafter, then, subject to the Severance Conditions, such Eligible Employee will be eligible to receive the following severance benefits, less applicable tax withholdings:

RELATED PARTY TRANSACTIONS

In addition to the compensation arrangements, including employment, termination of employment and change-in-control arrangements discussed, when required, elsewhere in this report, the following is a description of each transaction since January 1, 20202021 and each currently proposed transaction in which:

Our board of directors has adopted a written policy governing the review and approval of related party transactions. The audit committee of our board of directors has the primary responsibility for reviewing and approving or disapproving related party transactions, as designated in the audit committee charter. In addition, our Code of Business Conduct and Ethics requires that each of our employees and directors inform his or her superior or the chairman of the audit committee, respectively, of any material transaction or relationship that comes to his or her attention that could reasonably be expected to create a conflict of interest. Further, at least annually, each director and executive officer will complete a detailed questionnaire that asks questions about any business relationship that may give rise to a conflict of interest and all transactions in which we are involved and in which an executive officer, a director or a related person has a direct or indirect material interest.

Dr. Gold is an executive officer, and Dr. Venkatesan was an executive officer until August 2018. Each of Drs. Venkatesan and Gold is also a member of our board of directors and, in theirhis individual capacities,capacity, a limited partner of Alpine Immunosciences, L.P., Delaware limited partnership, which is a holder of more than 5% of our outstanding capital stock.partnership. In addition, each of Drs. Venkatesan andDr. Gold, in theirhis individual capacities, is a Managing Partner of Alpine BioVentures, GP, LLC, a Delaware limited liability company, which is the general partner of Alpine Immunosciences, L.P.

Dr. James N. Topper is a member of our board of directors and, in his individual capacity, is a managing member of FHM Life Sciences VIII, LLC, a Delaware limited liability company. FHM Life Sciences VIII, LLC is the general partner of FHM Life Sciences VIII, LP, a Delaware limited partnership. FHM Life Sciences VIII, LP is the general partner of Frazier Life Sciences VIII, L.P., a Delaware limited partnership, which is a holder of more than 5% of our outstanding capital stock.partnership. Dr. Topper is also, in his individual capacity, a member of FHMLSP, L.L.C., a Delaware limited liability company, the general partner of FHMLSP, L.P., a Delaware limited partnership, which is the general partner of Frazier Life Sciences Public Fund L.P., a Delaware limited partnership. Frazier Life Sciences Public Fund L.P. is a holder of our common stock.

Mr. Peetz is a member of our board of directors and, in his individual capacity, is an Entrepreneur-in-Residence at Frazier Healthcare Partners, which is an affiliate of the Frazier Life Sciences VIII, L.P.entities described above.

Dr. Peter Thompson is a member of our board of directors and, in his individual capacity, is an employee of OrbiMed Advisors LLC. OrbiMed Advisors LLC is the managing member of OrbiMed Capital GP VI LLC. OrbiMed Capital GP VI LLC is the general partner of OrbiMed Private Investments VI, LP, which is a holder of more than 5% of our outstanding capital stock.LP.

Dr. Xiangmin Cui is a member of our board of directors and, in his individual capacity, is the manager of Decheng Capital Management III (Cayman), LLC, which in turn is the general partner of Decheng Capital China Life Sciences USD Fund III, L.P. Decheng Capital China Life Sciences USD Fund III, L.P. is a holder of more than 5% of our outstanding capital stock.

We have entered into indemnification agreements with each of our directors and with each of our executive officers. Pursuant to the indemnification agreements, we have agreed to indemnify and hold harmless these directors and officers to the

made a party or participant by reason of his or her service as a current or former director, officer, employee or agent of Alpine Immune Sciences. The agreements also provide for the advancement of expenses to the directors and executive officers subject to specified conditions. There are certain exceptions to our obligation to indemnify the directors and officers, including any intentional misconduct or act where the director or officer did not in good faith believe he or she was acting in our best interests, with respect to “short-swing” profit claims under Section 16(b) of the 1934 Act and, with certain exceptions, with respect to proceedings that he or she initiates.

None of our current or former directors or executive officers is indebted to us, nor are any of these individuals indebted to another entity which indebtedness is the subject of a guarantee, support agreement, letter of credit or other similar arrangement or understanding provided by us.

In September 2021, we entered into a securities purchase agreement for a private placement with a select group of institutional investors, pursuant to which we sold 6,489,357 shares of our common stock and prefunded warrants to purchase 3,191,487 shares of common stock. The purchase price for each share of common stock and for each prefunded warrant was $9.40 per share, for an aggregate purchase price of approximately $91.0 million.

The following table summarizes the purchases in September 2021 of our securities by our 5% stockholders at the time of the September 2021 private placement:

Additionally, as part of the September 2021 private placement, Frazier Life Sciences Public Fund L.P., an entity for which Dr. Topper shares voting control with others, acquired prefunded warrants to purchase 1,702,127 shares of common stock. The aggregate purchase price for such prefunded warrants was $16,000,000.

In September 2021, we also entered into an exchange agreement with Frazier Life Sciences VIII, L.P. (the “Exchanging Stockholder”), pursuant to which we exchanged an aggregate of 1,200,000 shares of common stock held by the Exchanging Stockholder for prefunded warrants (the “Exchange Warrants”) to purchase an aggregate of 1,200,000 shares of common stock.

We also entered into a registration rights agreement with the investors in the September 2021 private placement. The registration rights agreement required us to register the resale of the shares of common stock issued and issuable upon the exercise of prefunded warrants issued in the September 2021 private placement. We filed a registration statement on Form S-3 on November 10, 2021 covering the resale of such shares, which registration statement was declared effective by the Securities and Exchange Commission on November 19, 2021.

We have granted stock options and/or restricted stock units to our named executive officers, other executive officers and our directors.

OTHER MATTERS

None of our directors are a party to any agreement or arrangement that would require disclosure pursuant to Nasdaq Rule 5250(b)(3).

The board of directors does not know of any other matters to be presented at the 2022 Annual Meeting. If any additional matters are properly presented at the 2022 Annual Meeting, the persons named in the enclosed proxy card will have discretion to vote shares they represent in accordance with their own judgment on such matters.

It is important that your shares be represented at the 2022 Annual Meeting, regardless of the number of shares that you hold. You are, therefore, urged to vote by telephone or by using the Internet as instructed on the enclosed proxy card or execute and return, at your earliest convenience, the enclosed proxy card in the envelope that has also been provided.