As filed with the Securities and Exchange Commission on April 21, 2025.

Registration No. 333-           

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Form S-4

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

ALUMIS INC.

(Exact name of registrant as specified in its charter)

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280 East Grand Avenue

South San Francisco, CA 94080

(650) 231-6625

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Martin Babler

President and Chief Executive Officer

Alumis Inc.

280 East Grand Avenue

South San Francisco, CA 94080

(650) 231-6625

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies to:

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Approximate date of commencement of proposed sale of the securities to the public: As soon as practicable after this registration statement becomes effective and upon completion of the transactions, including all conditions to the merger described in the enclosed joint proxy statement/prospectus have been satisfied or waived.

If the securities being registered on this Form are being offered in connection with the formation of a holding company and there is compliance with General Instruction G, check the following box. ☐

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or 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:

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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 7(a)(2)(B) of the Securities Act. ☐

If applicable, place an X in the box to designate the appropriate rule provision relied upon in conducting this transaction:

Exchange Act Rule 13e-4(i) (Cross-Border Issuer Tender Offer) ☐

Exchange Act Rule 14d-1(d) (Cross-Border Third-Party Tender Offer) ☐

EXPLANATORY NOTE AND STATEMENT PURSUANT TO RULE 429

Pursuant to Rule 429 under the Securities Act of 1933, as amended (the “Securities Act”), the prospectus contained in this registration statement will be used as a combined prospectus in connection with this registration statement and the registration statement on Form S-4, No. 333-286178, which was originally filed on March 27, 2025, and became effective on April 4, 2025 (the “Prior Registration Statement”). This registration statement is a new registration statement and also constitutes a post-effective amendment to the Prior Registration Statement. Such post-effective amendment will become effective concurrently with the effectiveness of this registration statement in accordance with Section 8(c) of the Securities Act.

The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act, or until this registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to Section 8(a), may determine.

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PRELIMINARY JOINT PROXY STATEMENT/PROSPECTUS — SUBJECT TO COMPLETION 
DATED APRIL 21, 2025

MERGER PROPOSAL — YOUR VOTE IS VERY IMPORTANT

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Dear stockholders of Alumis Inc. and stockholders of ACELYRIN, Inc.:

As previously announced, the board of directors of Alumis Inc. (“Alumis”) and the board of directors of ACELYRIN, Inc. (“ACELYRIN”), each with Alan Colowick and Patrick Machado recused, have approved the merger of ACELYRIN and Alumis. Alumis, ACELYRIN and Arrow Merger Sub, Inc (“Merger Sub”), entered into an Agreement and Plan of Merger, dated as of February 6, 2025, which was amended on April 20, 2025 (as amended, the “Merger Agreement”), pursuant to which Merger Sub will merge with and into ACELYRIN, with ACELYRIN continuing as a direct wholly owned subsidiary of Alumis (the “Merger”).

If the transaction is completed, ACELYRIN stockholders will have the right to receive, for each issued and outstanding share of common stock, par value $0.00001 per share, of ACELYRIN (“ACELYRIN common stock”) held by such stockholder immediately prior to the effective time of the Merger, 0.4814 shares of common stock, par value $0.0001 per share, of Alumis (“Alumis common stock”), without interest (the number of shares of Alumis common stock issued in exchange for each share of ACELYRIN common stock, the “Exchange Ratio”), with cash paid in lieu of fractional shares. Alumis stockholders will continue to own their existing shares of Alumis common stock. The Exchange Ratio is fixed and will not reflect changes in the market price of ACELYRIN common stock or Alumis common stock between the date of signing of the Merger Agreement and consummation of the Merger. We urge Alumis stockholders and ACELYRIN stockholders to obtain current stock price quotations for Alumis common stock and ACELYRIN common stock.

Immediately following the Merger, Alumis stockholders as of immediately prior to the Merger are expected to collectively own approximately 52% of the combined company and ACELYRIN stockholders as of immediately prior to the Merger are expected to collectively own approximately 48% of the combined company, in each case, calculated on a fully diluted basis as of January 31, 2025. Alumis common stock and ACELYRIN common stock are both currently traded on the Nasdaq Global Select Market under the symbols “ALMS” and “SLRN,” respectively. Upon completion of the Merger, the ACELYRIN common stock will cease to be traded on the Nasdaq Global Select Market.

At the special meeting of Alumis stockholders to be held virtually on May 13, 2025, Alumis stockholders will be asked to vote on (i) a proposal to approve the issuance of shares of Alumis common stock to ACELYRIN stockholders, which is a condition to completion of the Merger (the “Alumis stock issuance proposal”), and (ii) a proposal to approve the adjournment from time to time of the Alumis virtual special meeting, if necessary, to solicit additional proxies if there are not sufficient votes to approve the issuance of shares of Alumis common stock in the Merger (the “Alumis adjournment proposal”).

At the special meeting of ACELYRIN stockholders to be held virtually on May 13, 2025, ACELYRIN stockholders will be asked to vote on (i) a proposal to adopt the Merger Agreement (the “ACELYRIN merger proposal”) and (ii) a proposal to approve the adjournment from time to time of the ACELYRIN virtual special meeting, if necessary, to solicit additional proxies if there are not sufficient votes to adopt the Merger Agreement (the “ACELYRIN adjournment proposal”).

Only holders of record of Alumis common stock on April 1, 2025 (including shares of Alumis common stock held through a bank, broker or other nominee that is a stockholder of record of Alumis) and holders of record of ACELYRIN common stock on April 1, 2025 (including shares of ACELYRIN common stock held through a bank, broker or other nominee that is a stockholder of record of ACELYRIN) are entitled to attend and vote at the virtual special meeting of Alumis stockholders or the virtual special meeting of ACELYRIN stockholders, respectively, or any adjournment or postponement thereof.

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We cannot complete the Merger unless the ACELYRIN stockholders and the Alumis stockholders approve the respective proposals related to the Merger. Your vote is very important, regardless of the number of shares you own. Whether or not you expect to attend the Alumis virtual special meeting or ACELYRIN virtual special meeting, as applicable, please vote your shares as promptly as possible by (1) accessing the internet website specified on your proxy card, (2) calling the toll-free number specified on your proxy card, or (3) signing and returning all proxy cards that you receive in the postage- paid envelope provided, so that your shares may be represented and voted at the Alumis virtual special meeting or the ACELYRIN virtual special meeting, as applicable. If you are an Alumis stockholder, please note that a failure to vote your shares may result in a failure to establish a quorum for the Alumis virtual special meeting. If you are an ACELYRIN stockholder, please note that a failure to vote your shares is the equivalent of a vote against the Merger.

The Alumis board of directors, with Alan Colowick and Patrick Machado recused, recommends that Alumis stockholders vote “FOR” the Alumis stock issuance proposal and, if necessary, “FOR” the Alumis adjournment proposal. The ACELYRIN board of directors, with Alan Colowick and Patrick Machado recused, recommends that ACELYRIN stockholders vote “FOR” the ACELYRIN merger proposal and, if necessary, “FOR” the ACELYRIN adjournment proposal.

The obligations of Alumis and ACELYRIN to complete the Merger are subject to the satisfaction or waiver of several conditions set forth in the Merger Agreement. More information about Alumis, ACELYRIN and the Merger is contained in this joint proxy statement/prospectus. Alumis and ACELYRIN encourage you to read this entire joint proxy statement/prospectus carefully, including the section titled “Risk Factors” beginning on page 34 of this joint proxy statement/prospectus.

We look forward to the successful Merger of Alumis and ACELYRIN.

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NEITHER THE U.S. SECURITIES AND EXCHANGE COMMISSION NOR ANY STATE SECURITIES COMMISSION HAS APPROVED OR DISAPPROVED OF THE SECURITIES TO BE ISSUED UNDER THIS JOINT PROXY STATEMENT/PROSPECTUS OR DETERMINED THAT THIS JOINT PROXY STATEMENT/PROSPECTUS IS ACCURATE OR COMPLETE. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.

This joint proxy statement/prospectus is dated        , 2025 and is first being mailed to the stockholders of Alumis and stockholders of ACELYRIN on or about        , 2025.

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ABOUT THIS JOINT PROXY STATEMENT/PROSPECTUS

This joint proxy statement/prospectus, which forms part of a registration statement on Form S-4 filed with the Securities and Exchange Commission (the “SEC”), by Alumis, constitutes a prospectus of Alumis under Section 5 of the Securities Act of 1933, as amended (the “Securities Act”), with respect to the shares of Alumis voting common stock (referred to as “Alumis common stock” in this joint proxy statement/prospectus) proposed to be issued to ACELYRIN stockholders pursuant to the Merger Agreement. This document also constitutes a joint proxy statement under Section 14(a) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). It also includes a notice of meeting with respect to the special meeting of Alumis stockholders, at which Alumis stockholders will be asked to vote upon the Alumis stock issuance proposal, and a notice of meeting with respect to the special meeting of ACELYRIN stockholders, at which ACELYRIN stockholders will be asked to vote on the ACELYRIN merger proposal.

Alumis has supplied all information contained in this joint proxy statement/prospectus relating to Alumis and Merger Sub. ACELYRIN has supplied all information contained in or incorporated by reference into this joint proxy statement/prospectus relating to ACELYRIN. Alumis and ACELYRIN have both contributed information relating to the proposed transactions.

Before casting your vote, you should carefully review all the information contained or incorporated by reference into this joint proxy statement/prospectus. Neither Alumis nor ACELYRIN has authorized anyone to provide you with information that is different from that contained in, or incorporated by reference into, this joint proxy statement/prospectus. This joint proxy statement/prospectus is dated         , 2025. You should not assume that the information contained in, or incorporated by reference into, this joint proxy statement/prospectus is accurate as of any date other than the date on the front cover of those documents. Neither our mailing of this joint proxy statement/prospectus to Alumis stockholders or ACELYRIN stockholders nor the issuance by Alumis of Alumis common stock in connection with the Merger will create any implication to the contrary.

In deciding how to vote with respect to any of the proposals discussed herein, you must make your own independent examination of the merits and risks of the proposal. You should not construe anything included in this joint proxy statement/prospectus as investment, legal, business or tax advice, and should consult with your own advisors if you have questions concerning any of the matters described herein.

This joint proxy statement/prospectus does not constitute an offer to sell, or a solicitation of an offer to buy, any securities, or the solicitation of a proxy, in any jurisdiction in which or from any person to whom it is unlawful to make any such offer or solicitation in such jurisdiction. As permitted by SEC rules, this joint proxy statement/prospectus does not contain all of the information you can find in Alumis’ registration statement or its exhibits. For further information pertaining to Alumis and the shares of Alumis common stock to be issued in connection with the Merger, reference is made to that registration statement and its exhibits. Statements contained in this document or in any document incorporated into this document by reference as to the contents of any contract or other document referred to in this document or in other documents that are incorporated by reference into this document are not necessarily complete and, in each instance, reference is made to the copy of the applicable contract or other document filed as an exhibit to the registration statement or otherwise filed with the SEC. Each statement contained in this document is qualified in its entirety by reference to the underlying documents. You are encouraged to read the entire registration statement. You may obtain copies of the registration statement on Form S-4 including documents incorporated by reference into the registration statement (and any amendments to those documents) by following the instructions under the section titled “Where You Can Find More Information.”

All references in this joint proxy statement/prospectus to “ACELYRIN” refer to ACELYRIN, Inc., a Delaware corporation (except that in connection with the description of its operations or business under the sections titled “Cautionary Note Regarding Forward-Looking Statements” and “Risk Factors,” such term refers to the consolidated operations of ACELYRIN and its wholly owned subsidiary); all references in this joint proxy statement/prospectus to “Alumis” refer to Alumis Inc., a Delaware corporation; all references to “Merger Sub” refer to Arrow Merger Sub, Inc, a Delaware corporation and a wholly owned subsidiary of Alumis, formed for the purpose of effecting the Merger. Unless otherwise indicated or as the context requires, all references to the “Merger Agreement” refer to the Agreement and Plan of Merger, dated as of February 6, 2025, as amended on April 20, 2025, by and among Alumis, ACELYRIN and Merger Sub, a copy of which is included as Annexes A-1 and A-2 to this joint proxy statement/prospectus.

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TRADEMARKS AND SERVICE MARKS

Alumis and ACELYRIN own or have rights to various trademarks, logos, service marks and trade names that each uses in connection with the operation of its business. Alumis and ACELYRIN each also own or have the rights to copyrights that protect the content of their respective products. Solely for convenience, the trademarks, service marks, trade names and copyrights referred to in this joint proxy statement/prospectus are listed without the ™, ^® and ^© symbols, but such references do not constitute a waiver of any rights that might be associated with the respective trademarks, service marks, trade names and copyrights included or referred to in this joint proxy statement/prospectus.

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ADDITIONAL INFORMATION

This joint proxy statement/prospectus incorporates important business and financial information about ACELYRIN from other documents that are not included in or delivered with this joint proxy statement/ prospectus. For a listing of documents incorporated by reference into this joint proxy statement/prospectus, please see the section titled “Where You Can Find More Information.” This information is available to you without charge upon your request.

You can obtain the documents incorporated by reference into this joint proxy statement/prospectus by requesting them in writing or by telephone from ACELYRIN at the following addresses and telephone numbers:

ACELYRIN, Inc.

4149 Liberty Canyon Road

Agoura Hills, California 91301

(805) 730-0360

Attn: Investor Relations

Investors may also consult Alumis’ or ACELYRIN’s website for more information concerning the Merger described in this joint proxy statement/prospectus. Alumis’ website is www.alumis.com. ACELYRIN’s website is www.acelyrin.com. Information included on these websites is not incorporated by reference into this joint proxy statement/prospectus.

In addition, if you have questions about the Merger or the accompanying joint proxy statement/prospectus, would like additional copies of the joint proxy statement/prospectus, or need to obtain proxy cards or other information related to the proxy solicitation, for Alumis stockholders, please call Mackenzie Partners, Inc., the proxy solicitor for Alumis, toll-free at (800) 322-3885 or email proxy@mackenziepartners.com, or, for ACELYRIN stockholders, please call Sodali & Co, the proxy solicitor for ACELYRIN, toll-free at (800) 662-5200 or email SLRN@investor.sodali.com. You will not be charged for any of these documents that you request.

If you would like to request any documents, please do so no later than five business days before the date of the relevant special meeting in order to receive timely delivery of such documents before such special meeting. Therefore, if you would like to request documents from Alumis, please do so by May 6, 2025 and if you would like to request documents from ACELYRIN, please do so by May 6, 2025 in order to receive such documents before the Alumis and ACELYRIN virtual special meetings, respectively.

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280 East Grand Avenue

South San Francisco, California 94080

(650) 231-6625

NOTICE OF SPECIAL MEETING OF STOCKHOLDERS TO BE HELD ON MAY 13, 2025

Virtual Meeting Only — No Physical Meeting Location

Dear Alumis stockholders:

We are pleased to invite you to attend the special meeting of the Alumis stockholders, which will be held on May 13, 2025, at 9:00 a.m. (Pacific Time) (the “Alumis virtual special meeting”). The Alumis virtual special meeting will be conducted via live webcast at www.virtualshareholdermeeting.com/ALMS2025SM for the following purposes:

Alumis will transact no other business at the special meeting except such business as may properly be brought before the special meeting or any adjournment or postponement thereof. Please refer to the attached joint proxy statement/prospectus for further information with respect to the business to be transacted at the Alumis virtual special meeting.

In order to attend the Alumis virtual special meeting, as well as vote and submit your questions during the live webcast of the meeting, you will need to visit www.virtualshareholdermeeting.com/ALMS2025SM and enter the 16-digit Control Number shown on your proxy card. Please be sure to follow the instructions found on your proxy card and/or voting authorization form.

At a meeting of the board of directors of Alumis with Alan Colowick and Patrick Machado recused (the “Alumis Board”) held on April 20, 2025, the Alumis Board, acting on the unanimous recommendation of a special committee, consisting solely of independent and disinterested directors of Alumis (the “Alumis Special Committee”), determined that the Merger Agreement and the transactions contemplated thereby, including the Merger, are advisable, fair to and in the best interests of Alumis and its stockholders, approved the Merger Agreement, the execution of the Merger Agreement and the consummation of the transactions contemplated thereby, including the issuance of shares of Alumis common stock to the ACELYRIN stockholders, and resolved to recommend that the Alumis stockholders vote to approve the Alumis stock issuance proposal.

The Alumis Board, acting on the unanimous recommendation of the Alumis Special Committee, recommends that Alumis stockholders vote “FOR” the Alumis stock issuance proposal and “FOR” the Alumis adjournment proposal.

Holders of record of shares of Alumis common stock, at the close of business on April 1, 2025 (the “Alumis record date”), are entitled to notice of, and may vote at, the Alumis virtual special meeting and any adjournment of the special meeting. A list of Alumis stockholders entitled to vote at the Alumis virtual special meeting will be available for inspection at Alumis’ principal executive offices, located at 280 East Grand Avenue, South San Francisco, California 94080, at least 10 days prior to the date of the Alumis virtual special meeting and continuing through the date thereof for any purpose germane to the Alumis virtual special meeting, between the hours of 9:00 a.m. and 4:30 p.m., local time.

Approval of the Alumis stock issuance proposal requires the affirmative vote of the holders of shares of Alumis common stock representing a majority of the votes cast on such matter at the Alumis virtual special meeting (provided that a quorum exists).

Approval of the Alumis adjournment proposal requires the affirmative vote of the holders of shares of Alumis common stock representing a majority of the votes cast on such matter at the Alumis virtual special meeting (whether or not a quorum is present).

Important Notice Regarding the Availability of Proxy Materials for the Special Meeting to Be Held on May 13, 2025 starting at 9:00 a.m. (Pacific Time) via live webcast at www.virtualshareholdermeeting.com/ALMS2025SM

The proxy statement is available at www.virtualshareholdermeeting.com/ALMS2025SM

Your vote is important. Whether or not you expect to attend the Alumis virtual special meeting virtually, we urge you to vote your shares as promptly as possible by (1) accessing the internet website specified on your proxy card; (2) calling the toll-free number specified on your proxy card; or (3) signing and returning the enclosed proxy card in the postage-paid envelope provided, so that your shares may be represented and voted at the Alumis virtual special meeting. If your shares are held in “street name” through a bank, broker or other fiduciary, please follow the instructions on the voting instruction card furnished by the record holder. In lieu of receiving a proxy card, participants in certain benefit plans of Alumis and certain participating Alumis subsidiaries have been furnished with voting instruction cards, which are described in greater detail in the accompanying joint proxy statement/prospectus. If your shares are registered directly in your name with our transfer agent, Equiniti Trust Company, LLC, you are considered, with respect to those shares, the stockholder of record. In such case, these proxy materials are being sent directly to you.

If you have any questions or need assistance voting your shares, please call our proxy solicitor, Mackenzie Partners, Inc., toll-free at (800) 322-3885.

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We are pleased to invite you to attend the Alumis virtual special meeting, conducted via live webcast, at www.virtualshareholdermeeting.com/ALMS2025SM. You will not be able to attend the special meeting in person. Whether or not you expect to attend the virtual special meeting, please complete, date, sign and return the proxy card that may be delivered to you or vote over the telephone or the internet as instructed in these materials, as promptly as possible in order to ensure your representation at the virtual special meeting. Even if you have voted by proxy, you may still vote if you attend the virtual special meeting. Please note, however, that if your shares are held of record by a broker, bank or other nominee and you wish to vote at the special meeting, you may be instructed to obtain a legal proxy form from your broker, bank or other nominee and to submit a copy in advance of the special meeting.

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4149 Liberty Canyon Road

Agoura Hills, California 91301

(805) 730-0360

NOTICE OF SPECIAL MEETING OF STOCKHOLDERS TO BE HELD ON MAY 13, 2025

Virtual Meeting Only — No Physical Meeting Location

Dear ACELYRIN stockholders:

We are pleased to invite you to attend the special meeting of the ACELYRIN stockholders, which will be held on May 13, 2025, at 9:00 a.m. (Pacific Time) (the “ACELYRIN virtual special meeting”). The ACELYRIN virtual special meeting will be conducted via live webcast at www.virtualshareholdermeeting.com/SLRN2025SM for the following purposes:

ACELYRIN will transact no other business at the special meeting except such business as may properly be brought before the special meeting or any adjournment or postponement thereof. Please refer to the attached joint proxy statement/prospectus for further information with respect to the business to be transacted at the ACELYRIN virtual special meeting.

In order to attend the ACELYRIN virtual special meeting, as well as vote and submit your questions during the live webcast of the meeting, you will need to visit www.virtualshareholdermeeting.com/SLRN2025SM and enter the 16-digit Control Number shown on your proxy card. Please be sure to follow instructions found on your proxy card and/or voting authorization form.

At a meeting of the board of directors of ACELYRIN with Alan Colowick and Patrick Machado recused (the “ACELYRIN Board”) held on February 6, 2025, the ACELYRIN Board, acting on the unanimous recommendation of a transaction committee, consisting solely of independent and disinterested directors of ACELYRIN (the “ACELYRIN Transaction Committee”), determined that the Merger Agreement and the transactions contemplated thereby, including the Merger, are advisable, fair to and in the best interests of ACELYRIN and its stockholders, approved the Merger Agreement and the Merger, the execution of the Merger Agreement and the consummation of the transactions contemplated thereby and resolved to recommend that ACELYRIN’s stockholders adopt the Merger Agreement. At a meeting of the ACELYRIN Board with Alan Colowick and Patrick Machado recused held on April 20, 2025, the ACELYRIN Board, acting on the unanimous recommendation of the ACELYRIN Transaction Committee (other than Mr. Cozadd, who was unable to attend due to a scheduling conflict), determined that the amendment to the Merger Agreement and the transactions contemplated thereby are advisable, fair to and in the best interests of ACELYRIN and its stockholders, approved the amendment to the Merger Agreement, the execution of the amendment to the Merger Agreement and the consummation of the transactions contemplated thereby and resolved to recommend that ACELYRIN’s stockholders adopt the amendment to the Merger Agreement.

The ACELYRIN Board, acting on the unanimous recommendation of the ACELYRIN Transaction Committee, recommends that ACELYRIN stockholders vote “FOR” the ACELYRIN merger proposal and “FOR” the ACELYRIN adjournment proposal.

Holders of record of shares of ACELYRIN common stock, at the close of business on April 1, 2025 (the “ACELYRIN record date”) are entitled to notice of, and may vote at, the ACELYRIN virtual special meeting and any adjournment thereof. A list of ACELYRIN stockholders entitled to vote at the ACELYRIN virtual special meeting will be available for inspection at ACELYRIN’s principal executive offices, located at 4149 Liberty Canyon Road, Agoura Hills, California 91301, for a period of 10 days ending on the date before the date of the ACELYRIN virtual special meeting date for any purpose germane to the ACELYRIN virtual special meeting, during ordinary business hours.

Approval of the ACELYRIN merger proposal requires the affirmative vote of holders of ACELYRIN common stock representing a majority of the outstanding shares of ACELYRIN common stock entitled to vote on such matter at the ACELYRIN virtual special meeting. Approval of the ACELYRIN adjournment proposal requires the affirmative vote of holders of ACELYRIN common stock representing a majority of votes cast on such matter at the ACELYRIN virtual special meeting (whether or not a quorum is present).

Your vote is important. Whether or not you expect to attend the ACELYRIN virtual special meeting virtually, we urge you to vote your shares as promptly as possible by (1) accessing the internet website specified on your proxy card; (2) calling the toll-free number specified on your proxy card; or (3) signing and returning the enclosed proxy card in the postage-paid envelope provided, so that your shares may be represented and voted at the ACELYRIN virtual special meeting. If your shares are held in “street name” through a bank, broker or other fiduciary, please follow the instructions on the voting instruction card furnished by the record holder. In lieu of receiving a proxy card, participants in certain benefit plans of ACELYRIN and certain participating ACELYRIN subsidiaries have been furnished with voting instruction cards, which are described in greater detail in the accompanying joint proxy statement/prospectus. If your shares are registered directly in your name with our transfer agent, Computershare Trust Company, N.A., you are considered, with respect to those shares, the stockholder of record. In such case, these proxy materials are being sent directly to you.

If you have any questions or need assistance voting your shares, please contact our proxy solicitor, Sodali & Co, at (800) 662-5200 or by email at SLRN@investor.sodali.com.

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We are pleased to invite you to attend the ACELYRIN virtual special meeting, conducted via live webcast, at www.virtualshareholdermeeting.com/SLRN2025SM. You will not be able to attend the special meeting in person. Whether or not you expect to attend the virtual special meeting, please complete, date, sign and return the proxy card that may be delivered to you or vote over the telephone or the internet as instructed in these materials, as promptly as possible in order to ensure your representation at the virtual special meeting. Even if you have voted by proxy, you may still vote if you attend the virtual special meeting. Please note, however, that if your shares are held of record by a broker, bank or other nominee and you wish to vote at the special meeting, you may be instructed to obtain a legal proxy form from your broker, bank or other nominee and to submit a copy in advance of the special meeting.

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TABLE OF CONTENTS

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QUESTIONS AND ANSWERS ABOUT THE MERGER AND THE VIRTUAL SPECIAL MEETINGS

The following are brief answers to certain questions that Alumis stockholders and ACELYRIN stockholders may have regarding the Merger, the Merger Agreement, the issuance of shares of Alumis common stock in connection with the Merger, the Alumis virtual special meeting, the ACELYRIN virtual special meeting, and other matters to be considered at the Alumis virtual special meeting and at the ACELYRIN virtual special meeting. Alumis and ACELYRIN urge you to carefully read the remainder of this joint proxy statement/ prospectus and additional important information contained in the annexes and exhibits to, and the documents incorporated by reference into, this joint proxy statement/prospectus because the information in this section may not provide all of the information that might be important to you in determining how to vote. See the section titled “Where You Can Find More Information.”

Under the terms of the Merger Agreement, Merger Sub will merge with and into ACELYRIN, with ACELYRIN continuing as a direct, wholly owned subsidiary of Alumis. If the Merger is completed, holders of ACELYRIN common stock (other than shares held by (i) ACELYRIN, including in treasury, (ii) ACELYRIN’s subsidiaries, (iii) Alumis or (iv) Alumis’ subsidiaries, if any) (“ACELYRIN stockholders”) will have the right to receive for each share of ACELYRIN common stock held by such ACELYRIN stockholder 0.4814 shares of Alumis common stock, without interest (the number of shares of Alumis common stock in exchange for each share of ACELYRIN common stock, the “Exchange Ratio”). The Exchange Ratio will not reflect changes in the market price of ACELYRIN common stock or Alumis common stock between the date of signing of the Merger Agreement and consummation of the Merger.

Alumis is holding a virtual special meeting of stockholders in order to obtain the stockholder approval necessary to approve the Alumis stock issuance proposal. Alumis stockholders will also be asked to approve the adjournment from time to time of the Alumis virtual special meeting if necessary to solicit additional proxies if there are not sufficient votes at the time of the Alumis virtual special meeting, or any adjournment or postponement thereof, to approve the stock issuance. It is important that Alumis stockholders vote on each of these matters, regardless of the number of shares owned.

ACELYRIN is holding a virtual special meeting of stockholders to obtain the stockholder approval necessary to approve the ACELYRIN merger proposal. In addition, ACELYRIN stockholders will also be asked to approve the adjournment from time to time of the ACELYRIN virtual special meeting if necessary to solicit additional proxies if there are not sufficient votes to approve the ACELYRIN merger proposal at the time of the ACELYRIN virtual special meeting or any adjournment or postponement thereof. It is important that ACELYRIN stockholders vote their ACELYRIN common stock on each of these matters, regardless of the number of shares owned.

Your vote is important. We encourage you to vote as soon as possible.

Q:Who is soliciting my proxy?

Q:When and where will the meetings be held?

The ACELYRIN virtual special meeting will be held virtually on May 13, 2025, at 9:00 a.m. (Pacific Time). There will be no physical meeting location. In order to attend the ACELYRIN virtual special meeting, as well as vote and submit your questions during the live webcast of the meeting, you will need to visit www.virtualshareholdermeeting.com/SLRN2025SM and enter the 16-digit Control Number shown on your proxy card. Please be sure to follow instructions found on your proxy card and/or voting authorization form.

Q:What will ACELYRIN stockholders receive in the Merger?

We encourage you to obtain current market quotations of Alumis common stock and ACELYRIN common stock before voting.

Alumis stockholders will continue to own their existing shares of Alumis common stock. Alumis common stock and ACELYRIN common stock are both currently traded on the Nasdaq Global Select Market (“Nasdaq”) under the symbols “ALMS” and “SLRN,” respectively.

Q:After applying the Exchange Ratio, how will fractional shares be handled?

Q:How does the Exchange Ratio affect the ownership of Alumis after completion of the Merger?

Q:How do ACELYRIN stockholders vote?

A:

Stockholder of Record; Shares Registered in Your Name

If you are a stockholder of record of ACELYRIN, you may vote at the ACELYRIN virtual special meeting, vote by proxy over the telephone, vote by proxy through the internet or vote by proxy using the proxy card that may be delivered to you. Whether or not you plan to attend the ACELYRIN virtual special meeting, we urge you to vote by proxy to ensure your vote is counted. You may still attend the virtual special meeting and vote even if you have already voted by proxy.

Beneficial Owner: Shares Registered in the Name of Broker or Bank

If you are a beneficial owner of shares registered in the name of your brokerage firm, bank or other agent, you should have received a voting instruction form with the proxy card delivered to you from that organization rather than from ACELYRIN.

Simply complete and mail the voting instruction form to ensure that your vote is counted. Alternatively, you may vote by telephone or over the internet as instructed by your broker, bank or other agent. To vote at the ACELYRIN virtual special meeting, you will need to visit www.virtualshareholdermeeting.com/SLRN2025SM. You may be instructed to obtain a legal proxy from your broker, bank or other nominee and to submit a copy in advance of the ACELYRIN virtual special meeting. Further instruction will be provided to you as part of your registration process.

If you are a stockholder of record, internet proxy voting allows you to vote your shares online, with procedures designed to ensure the authenticity and correctness of your proxy vote instructions. However, please be aware that you must bear any costs associated with your internet access, such as usage charges from internet access providers and telephone companies.

Q:How do Alumis stockholders vote?

A:

Stockholder of Record; Shares Registered in Your Name

If you are a stockholder of record of Alumis, you may vote at the Alumis virtual special meeting, vote by proxy over the telephone, vote by proxy through the internet or vote by proxy using the proxy card that may be delivered to you. Whether or not you plan to attend the Alumis virtual special meeting, we urge you to vote by proxy to ensure your vote is counted. You may still attend the virtual special meeting and vote even if you have already voted by proxy.

Stockholders will be able to attend the Alumis virtual special meeting platform beginning at 9:00 a.m. (Pacific Time) on May 13, 2025, by visiting www.virtualshareholdermeeting.com/ALMS2025SM.

Beneficial Owner: Shares Registered in the Name of Broker or Bank

If you are a beneficial owner of shares registered in the name of your brokerage firm, bank or other agent, you should have received a voting instruction form with the proxy card delivered to you from that organization rather than from Alumis. Simply complete and mail the voting instruction form to ensure that your vote is counted. Alternatively, you may vote by telephone or over the internet as instructed by your broker, bank or other agent. To vote at the Alumis virtual special meeting, you will need to visit www.virtualshareholdermeeting.com/ALMS2025SM. You may be instructed to obtain a legal proxy from your broker, bank or other nominee and to submit a copy in advance of the Alumis virtual special meeting. Further instruction will be provided to you as part of your registration process.

If you are a stockholder of record, internet proxy voting allows you to vote your shares online, with procedures designed to ensure the authenticity and correctness of your proxy vote instructions. However, please be aware that you must bear

any costs associated with your internet access, such as usage charges from internet access providers and telephone companies.

Q:What are the voting deadlines?

If you are an ACELYRIN stockholder, the deadline for submitting a proxy using the internet or the telephone is 11:59 p.m. (Eastern Time) on May 12, 2025. If you received your special meeting materials by mail, you may complete, sign and date the proxy card or voting instruction card and return it in the prepaid envelope. All holders of ACELYRIN common stock as of the close of business on the record date may vote virtually at the ACELYRIN virtual special meeting. For detailed information, see the section titled “The ACELYRIN Virtual Special Meeting.”

Q:What vote is required to approve each proposal at the Alumis virtual special meeting?

Alumis Adjournment Proposal. Approval of the Alumis adjournment proposal requires the affirmative vote of the holders of Alumis common stock representing a majority of the votes cast at the Alumis virtual special meeting (whether or not a quorum is present). Failure to vote virtually or by proxy at the special meeting, abstentions, and broker non-votes (if any) will have no effect on the outcome of the Alumis adjournment proposal. Shares of Alumis common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon.

Q:What vote is required to approve each proposal at the ACELYRIN virtual special meeting?

ACELYRIN Adjournment Proposal. Approval of the ACELYRIN adjournment proposal requires the affirmative vote of the holders of ACELYRIN common stock representing a majority of the votes cast at the ACELYRIN virtual special meeting (whether or not a quorum is present). Failure to vote virtually or by proxy at the special meeting, abstentions, and broker non-votes (if any) will have no effect on the outcome of the ACELYRIN adjournment proposal. Shares of ACELYRIN common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon.

Q:How does the ACELYRIN Board recommend that ACELYRIN stockholders vote?

Committee (other than Mr. Cozadd, who was unable to attend due to a scheduling conflict), (i) determined that the amendment to the Merger Agreement and the transactions contemplated thereby are advisable, fair to and in the best interests of ACELYRIN and its stockholders, (ii) approved the amendment to the Merger Agreement, the execution of the amendment to the Merger Agreement and the consummation of the transactions contemplated thereby and (iii) resolved to recommend that ACELYRIN’s stockholders adopt the amendment to the Merger Agreement. The ACELYRIN Board recommends that ACELYRIN stockholders vote “FOR” the ACELYRIN merger proposal and “FOR” the ACELYRIN adjournment proposal.

To assist the ACELYRIN Board in reviewing potential business combinations, on September 7, 2023, the ACELYRIN Board established the ACELYRIN Transaction Committee, consisting entirely of independent and disinterested directors of ACELYRIN, with exclusive authority to, among other things, evaluate the risks and merits of, and assist the officers of ACELYRIN with the negotiation of the terms of, any proposed transaction involving ACELYRIN that would require ACELYRIN Board or committee approval, and to make recommendations to the ACELYRIN Board with respect to any such transaction. On January 23, 2025, the ACELYRIN Board expanded the authority of the ACELYRIN Transaction Committee to, among other things, (i) address the potential conflicts that may arise in the negotiation of the combination, (ii) oversee the process for evaluation and negotiation of any transaction with Alumis or any alternative to that transaction, (iii) make recommendations to the ACELYRIN Board regarding the Alumis transaction (it being understood that the ACELYRIN Board must approve any potential transaction) and (iv) engage legal counsel and financial advisors to assist with the transaction as it deems appropriate.

On February 6, 2025, after extensive consultation with, and acting with the advice of, legal and financial advisors, the ACELYRIN Transaction Committee unanimously (i) determined that the terms of the Merger Agreement, ACELYRIN Voting Agreements and the transactions contemplated by the Merger Agreement, including the Merger were advisable, fair to and in the best interests of ACELYRIN and its stockholders, (ii) recommended that the ACELYRIN Board approve and declare advisable the Merger Agreement, the ACELYRIN Voting Agreements and the transactions contemplated by the Merger Agreement, in each case on the terms and subject to the conditions set forth in the Merger Agreement and ACELYRIN Voting Agreements, as applicable, (iii) recommended that the ACELYRIN Board authorize and approve the execution, delivery and performance by ACELYRIN of the Merger Agreement and the Voting Agreement and the consummation by ACELYRIN of the transactions contemplated by the Merger Agreement and (iv) recommended that the ACELYRIN Board recommend that ACELYRIN’s stockholders adopt the Merger Agreement and direct that the Merger Agreement be submitted to a vote at a meeting of the stockholders of ACELYRIN.

On April 20, 2025, after extensive consultation with, and acting with the advice of, legal and financial advisors, the ACELYRIN Transaction Committee unanimously (other than Mr. Cozadd, who was unable to attend due to a scheduling conflict) (i) determined that the terms of the amendment to the Merger Agreement and the transactions contemplated thereby were advisable, fair to and in the best interests of ACELYRIN and its stockholders, (ii) recommended that the ACELYRIN Board approve and declare advisable the amendment to the Merger Agreement and the transactions contemplated thereby, (iii) recommended that the ACELYRIN Board authorize and approve the execution, delivery and performance by ACELYRIN of the amendment to the Merger Agreement and the consummation by ACELYRIN of the transactions contemplated thereby and (iv) recommended that the ACELYRIN Board recommend that ACELYRIN’s stockholders adopt the amendment to the Merger Agreement and direct that the amendment to the Merger Agreement be submitted to a vote at a meeting of the stockholders of ACELYRIN.

Q:How does the Alumis Board recommend that Alumis stockholders vote?

to approve the Alumis stock issuance proposal. The Alumis Board recommends that Alumis stockholders vote “FOR” the Alumis stock issuance proposal and “FOR” Alumis adjournment proposal.

Q:Why did the Alumis Board form a special committee and what was the role of the Alumis Special Committee?

To address the potential conflicts of interest that may arise in the negotiation of a potential transaction with ACELYRIN, Dr. Colowick and Mr. Machado recused themselves from any Alumis Board or committee discussions about a potential transaction with ACELYRIN or potential strategic alternatives. Further, on January 12, 2025, the Alumis Board (as referred to hereinafter, with Dr. Colowick and Mr. Machado recused) established special committee of the Alumis Board, consisting entirely of independent and disinterested directors of Alumis (the “Alumis Special Committee”), with exclusive authority to, among other things, (i) review and to evaluate the terms and conditions, and determine the advisability, of a potential buy-side strategic transaction or a proposal for a potential buy-side strategic transaction (“potential transaction”) and any alternatives thereto that the Special Committee deems appropriate, (ii) establish, approve, modify, monitor and direct the process and procedures related to the review and evaluation of a potential transaction and any alternatives thereto, including, the authority to determine not to proceed with any such process, procedures, review or evaluation, or to recommend any of the foregoing to the Alumis Board, (iii) make or accept, reject, negotiate or seek to modify the price, structure, form, terms and conditions of a potential transaction, the form, terms and conditions of any definitive agreements in connection therewith and review and comment on any and all materials to be filed with the SEC, if any, and other governmental and non-governmental persons and entities, (iv) determine whether a potential transaction or any alternative thereto negotiated by the Alumis Special Committee is fair to, and in the best interests of, Alumis and its stockholders and (v) with respect to any actions required to be taken by the Alumis Board with respect to a potential transaction or any alternative thereto, recommend to the Alumis Board what action, if any, should be taken by the Alumis Board (it being understood that the Alumis Board must also approve any potential transaction).

On April 20, 2025, after extensive consultation with, and acting with the advice of, legal and financial advisors, the Alumis Special Committee unanimously (i) determined that the Merger Agreement and the transactions contemplated thereby, including the Merger, are advisable, fair to and in the best interests of Alumis and its stockholders, (ii) recommended to the Alumis Board that it approve the Merger and the transactions contemplated by the Merger Agreement, including the Alumis stock issuance, and (iii) recommended to the Alumis Board that it submit, and recommend the approval of the Alumis stock issuance proposal, to Alumis’ stockholders.

Q:How many votes do I have?

ACELYRIN. You are entitled to one vote for each share of ACELYRIN common stock that you owned as of the ACELYRIN record date. As of the close of business on April 1, 2025, there were 100,907,206 outstanding shares of ACELYRIN common stock. As of that date, 10% of the outstanding shares of ACELYRIN common stock were beneficially owned by the directors and executive officers of ACELYRIN.

Q:What will happen if I fail to vote or I abstain from voting?

Your failure to cast a vote virtually will also make it more difficult to meet the quorum requirement for the Alumis virtual special meeting.

ACELYRIN. If you are an ACELYRIN stockholder, failure to vote virtually or by proxy at the ACELYRIN virtual special meeting, abstentions, and broker non-votes (if any) will have the same effect as a vote against the ACELYRIN merger proposal and will have no effect on the ACELYRIN adjournment proposal. Shares of ACELYRIN common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon.

Q:What are “broker non-votes”?

Q:What constitutes a quorum?

ACELYRIN. The holders of a majority of the voting power of ACELYRIN’s outstanding shares of common stock entitled to vote as of the close of business on the ACELYRIN record date must be virtually present or represented by proxy to constitute a quorum to conduct the ACELYRIN virtual special meeting. All shares of ACELYRIN common stock represented at the ACELYRIN virtual special meeting, including abstentions and broker non-votes will be treated as present for purposes of determining the presence or absence of a quorum to conduct the ACELYRIN virtual special meeting.

Q:What is the difference between a stockholder of record and a “street name” holder?

Q:If I am a beneficial owner of shares held in street name, how do I vote?

Please follow the voting instructions provided by your broker or nominee. Please note that you may not vote shares held in street name by returning a proxy card directly to Alumis or ACELYRIN or by voting virtually at your special meeting. Further, brokers who hold shares of Alumis common stock or ACELYRIN common stock on behalf of their customers may not give a proxy to Alumis or ACELYRIN to vote those shares without specific instructions from their customers.

Q:What will happen if I return my proxy card without indicating how to vote?

determining the presence of a quorum for the Alumis virtual special meeting and will be voted “FOR” the Alumis stock issuance proposal and “FOR” the Alumis adjournment proposal.

If you are an ACELYRIN stockholder of record and you sign and return your proxy card without indicating how to vote on any particular proposal, the shares of ACELYRIN common stock represented by your proxy will be counted as present for purposes of determining the presence of a quorum for the ACELYRIN virtual special meeting and will be voted “FOR” the ACELYRIN merger proposal and “FOR” the ACELYRIN adjournment proposal.

Q:Can I change my vote after I have returned a proxy or voting instruction card?

If you choose either of the first two methods, you must provide your notice of revocation or your new proxy to the Secretary of Alumis or corporate secretary of ACELYRIN, as applicable, prior to your shares being voted. If your shares are held in street name by your broker or nominee, you should contact them to change your vote.

Q:What should I do if I receive more than one set of voting materials?

Q:Is there a list of stockholders entitled to vote at the Alumis and ACELYRIN virtual special meetings?

The names of stockholders of record entitled to vote at the ACELYRIN virtual special meeting will be available for inspection at ACELYRIN’s principal executive offices, located at 4149 Liberty Canyon Road, Agoura Hills, California 91301, for a period of 10 days ending on the day before the date of the ACELYRIN virtual special meeting date for any purpose germane to the ACELYRIN virtual special meeting, during ordinary business hours.

you will retain your right to vote at the ACELYRIN virtual special meeting, but will have transferred the right to receive the merger consideration in the Merger. In order to receive the merger consideration, you must hold your shares through the Effective Time.

Treatment of Restricted Stock Unit Awards. At the Effective Time, each ACELYRIN restricted stock unit (“RSU”) that is outstanding and unvested immediately prior to such time, will be converted into an RSU with respect to a number of shares of Alumis common stock, referred to as a converted RSU, equal to the product of (a) the number of shares of ACELYRIN common stock subject to such ACELYRIN RSU immediately prior to the Merger and (b) the Exchange Ratio (with any fractional shares rounded down to the nearest whole share). Except for the change to the number and type of shares, each converted RSU will be subject to the same terms and conditions, including accelerated vesting upon certain qualifying terminations of service, as were applicable to such ACELYRIN RSU immediately prior to the Merger. Any withholding obligations arising in connection with the settlement of such converted RSU will be satisfied through a net settlement mechanism.

At the Effective Time, each ACELYRIN RSU that is outstanding and vested immediately prior to such time (including any ACELYRIN RSU that becomes vested as a result of the Merger), will be converted into a right to receive the number of shares of Alumis common stock equal to the product of (a) the number of shares of ACELYRIN common stock subject to such ACELYRIN RSU immediately prior to the Merger and (b) the Exchange Ratio (with any fractional shares rounded down to the nearest whole share). Any withholding obligations arising in connection with such settlement will be satisfied through a net settlement mechanism.

Treatment of Performance Restricted Stock Unit Awards. At the Effective Time, each ACELYRIN performance RSU that is outstanding and unvested immediately prior to such time, will have any performance-based conditions deemed met at 100% of the target level of performance and will be converted into an RSU with respect to a number of shares of Alumis common stock, referred to as a converted performance RSU, equal to the product of (a) the target number of shares of ACELYRIN common stock subject to such ACELYRIN performance RSU immediately prior to the Merger and (b) the Exchange Ratio (with any fractional shares rounded down to the nearest whole share). Each converted performance RSU will not have any vesting conditions based on performance metrics and will vest in three equal installments on May 15 of calendar years 2025, 2026 and 2027, unless the closing of the Merger occurs after May 15, 2025, in which case the converted performance RSU will vest in two equal installments on May 15 of calendar years 2026 and 2027, subject to the holder of the converted performance RSU remaining in service with Alumis or any of its subsidiaries on such date. Except for the change to the number and type of shares and the vesting, each converted performance RSU will be subject to the same terms and conditions as were applicable to such ACELYRIN performance RSU immediately prior to the Merger, including accelerated vesting upon certain qualifying terminations of service. Any withholding obligations arising in connection with the settlement of such converted performance RSU will be satisfied through a net settlement mechanism.

Treatment of the Employee Stock Purchase Plan. Following the date of the Merger Agreement, ACELYRIN has taken actions with respect to the ACELYRIN Employee Stock Purchase Plan (the “ACELYRIN ESPP”) to provide that with respect to the current purchase period, (i) no employee who is not a participant in the ACELYRIN ESPP as of the date of the Merger Agreement may become a participant in the ACELYRIN ESPP, and (ii) no employee participating in the current purchase period may increase his or her payroll contribution rate pursuant to the ACELYRIN ESPP from the rate in effect immediately prior to the date of the Merger Agreement, except as required by applicable law. In addition, (A) if any current purchase period is still in effect at the Effective Time, then the last day of such current purchase period will be accelerated to a specified trading day occurring within 10 business days prior to the date on which the Merger is expected to close; (B) if the current purchase period terminates prior to the Effective Time, then the ACELYRIN ESPP will be suspended and there will be no new offering periods following the current purchase period and (C) in all events, subject to the consummation of the Merger, ACELYRIN will terminate the ACELYRIN ESPP immediately prior to the Effective Time.

Q:How will the rights of ACELYRIN stockholders change after the Merger?

The rights of Alumis stockholders will remain the same as prior to the Merger.

TAX MATTERS ARE COMPLICATED, AND THE TAX CONSEQUENCES OF THE MERGER WILL DEPEND ON THE FACTS OF YOUR OWN SITUATION. YOU SHOULD CONSULT YOUR TAX ADVISOR AS TO THE SPECIFIC TAX CONSEQUENCES OF THE MERGER TO YOU IN YOUR PARTICULAR CIRCUMSTANCES.

Q:Are there any risks that I should consider in deciding how to vote?

Q:What happens if the Merger is not completed?

Q:Does ACELYRIN have to pay anything to Alumis if the Merger Agreement is terminated?

Q:Does Alumis have to pay anything to ACELYRIN if the Merger Agreement is terminated?

Q:Is the completion of the Merger subject to a financing condition?

Q:How will I know when the other conditions to completion of the Merger have been satisfied or waived?

Q:When do you expect the Merger to be completed?

Q:What do I need to do now?

Q:Do I need to do anything with my ACELYRIN common stock certificates now?

If you are an Alumis stockholder, you are not required to take any action with respect to your Alumis stock certificates.

Q:Do I need to do anything with my ACELYRIN common stock held in book-entry form now?

Q:Are stockholders entitled to appraisal rights?

Under Delaware law, the Alumis stockholders are not entitled to appraisal rights in connection with the Alumis stock issuance proposal.

Q:How can I contact Alumis’ or ACELYRIN’s transfer agent?

Q:Who should I contact if I have any questions about the proxy materials or about voting?

Q:Who is the exchange agent in the Merger?

A:Equiniti Trust Company, LLC will be the exchange agent for the Merger.

Q:Where can I find more information about Alumis and ACELYRIN?

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SUMMARY

This summary highlights selected information contained elsewhere in this joint proxy statement/prospectus and may not contain all the information that is important to you with respect to the Merger and the related matters being considered at the applicable special meeting. Alumis and ACELYRIN urge you to carefully read the remainder of this joint proxy statement/prospectus, including the annexes and exhibits attached to and the documents incorporated by reference into this joint proxy statement/prospectus. For a description of, and instructions as to how to obtain, this information, see the section titled “Where You Can Find More Information.” Certain items in this summary include a page reference directing you to a more complete description of that item.

Parties to the Merger (see page 134)

Alumis Inc.

280 East Grand Avenue

South San Francisco, CA 94080

(650) 231-6625

Alumis was incubated by Foresite Labs, LLC (“Foresite Labs”) and incorporated on January 29, 2021 as a Delaware corporation under the name FL2021-001, Inc. FL2021-001, Inc.’s name was changed to Esker Therapeutics, Inc. in March 2021 and to Alumis Inc. in January 2022.

Alumis is a clinical stage biopharmaceutical company with an initial focus on developing its two Tyrosine Kinase 2 (“TYK2”) inhibitors: ESK-001, a second-generation inhibitor that Alumis is developing to maximize target inhibition and optimize tolerability, and A-005, a central nervous system (“CNS”) penetrant molecule. ESK-001 has demonstrated significant therapeutic effect in Alumis’ Phase 2 program in patients with PsO, which Alumis defines as moderate-to-severe plaque psoriasis (“PsO”), and is currently being evaluated in an additional Phase 2 clinical trial in patients with systemic lupus erythematosus (“SLE”), for which Alumis expects to report results in 2026. With the favorable results in its Phase 2 clinical trial in PsO, Alumis has initiated its Phase 3 ONWARD clinical program, which consists of two parallel Phase 3 clinical trials of ESK-001 in this indication and for which Alumis expects to report topline results in the first quarter of 2026. These parallel Phase 3 clinical trials also include one long-term extension (“LTE”) study, ONWARD3. In addition, the open label extension (“OLE”) of Alumis’ Phase 2 clinical trial in PsO remains ongoing. TYK2 genetic mutations are associated with a strong protective effect in multiple sclerosis (“MS”), motivating Alumis to develop its second product candidate, A-005, as a CNS-penetrant, allosteric TYK2 inhibitor for neuroinflammatory and neurodegenerative diseases. In April 2024, Alumis initiated its Phase 1 program of A-005 in healthy volunteers and reported its initial results in December 2024.

Since its inception, Alumis has devoted substantially all of its efforts to organizing the company, hiring personnel, business planning, acquiring and developing its product candidates, performing research and development, conducting preclinical studies and clinical trials, establishing and protecting its intellectual property portfolio, raising capital and providing general and administrative support for these activities. Alumis does not have any products approved for sale and has not generated any revenue from product sales. Alumis expects to continue to incur significant and increasing expenses and increasing substantial losses for the foreseeable future as it continues its development of and seek regulatory approvals for its product candidates and commercialize any approved products, seek to expand its product pipeline and invest in the organization. Alumis’ ability to achieve and sustain profitability will depend on its ability to successfully develop, obtain regulatory approval for and commercialize its product candidates. There can be no assurance that Alumis will ever earn revenue or achieve profitability, or if achieved, that the revenue or profitability will be sustained on a continuing basis. Alumis has incurred significant operating losses and negative cash flows since inception.

See the sections titled “Description of Alumis’ Business” and “Alumis’ Management’s Discussion and Analysis of Financial Condition and Results of Operation,” as well as the consolidated financial statements of Alumis included in this joint proxy statement/prospectus, for further business and financial information about Alumis.

Arrow Merger Sub, Inc.

280 East Grand Avenue

South San Francisco, CA 94080

(650) 231-6625

Arrow Merger Sub, Inc., a direct wholly owned subsidiary of Alumis, is a Delaware corporation formed on January 31, 2025, for the purposes of effecting the Merger. Upon completion of the Merger, Merger Sub will be merged with and into ACELYRIN, with ACELYRIN continuing as a direct wholly owned subsidiary of Alumis.

Merger Sub has not conducted any activities other than those incidental to its formation and the matters contemplated by the Merger Agreement.

ACELYRIN, Inc.

4149 Liberty Canyon Road

Agoura Hills, CA 91301

(805) 730-0360

ACELYRIN is a late-stage clinical biopharma company focused on identifying, acquiring, and accelerating the development and commercialization of transformative medicines.

ACELYRIN’s lead product candidate is lonigutamab, a subcutaneously delivered, monoclonal antibody targeting IGF-1R for the treatment of Thyroid Eye Disease (“TED”), TED is a potentially vision- threatening progressive autoimmune ocular disease in which the eye muscles, eyelids, tear glands and fatty tissues behind the eye become inflamed. Recurrent inflammation, scarring and fibrosis lead to pathological changes in the tissues surrounding the eyeball. Initial TED symptoms include redness, irritation, and discomfort of the eyes and eyelids, pain and headaches. As the fat and muscle tissues surrounding the eye continue to swell, disabling symptoms include double vision and corneal erosions due to eye bulging and the subsequent inability to close the eyelids. Elevated ocular pressure can occur with compression of the retinal nerve, leading to blindness, or optic neuropathy. The most obvious feature of TED is the protrusion of the eye outward from the eye socket, or proptosis.

ACELYRIN’s Common Stock is listed on Nasdaq under the symbol “SLRN.”

This joint proxy statement/prospectus incorporates important business and financial information about ACELYRIN from other documents that are not included in or delivered with this joint proxy statement/ prospectus. For a list of the documents that are incorporated by reference, see the section titled “Where You Can Find More Information.”

Risk Factors; Risk Factors Summary (see page 34)

Both Alumis and ACELYRIN are subject to various risks associated with their businesses and their industries. In addition, the Merger, including the possibility that the Merger may not be completed, poses a number of risks to each company and its respective stockholders. Before voting at the Alumis virtual special meeting or the ACELYRIN virtual special meeting, you should carefully consider all of the information contained in or as incorporated by reference into this joint proxy statement/prospectus, as well as the specific factors under the section titled “Risk Factors.”

Some of the more significant risks include the following:

Risk Factors Relating to the Merger (see page 34)

Risk Factors Relating to the Combined Company (see page 39)

Risk Factors Relating to Alumis (see page 44)

For purposes of this subsection only, “Alumis,” “the Company,” “we,” “us” or “our” refer to Alumis, unless the context otherwise requires.

The Merger (see page 134)

A copy of the Merger Agreement is attached as Annexes A-1 and A-2 to this joint proxy statement/prospectus. Alumis and ACELYRIN encourage you to read the entire Merger Agreement carefully because it is the principal document governing the Merger. For more information on the Merger Agreement, see the section titled “The Merger Agreement.”

Effects of the Merger; Merger Consideration (see page 115)

If the conditions set forth in the Merger Agreement are satisfied or waived, Merger Sub will merge with and into ACELYRIN. ACELYRIN will survive the Merger and will continue as a wholly owned subsidiary of Alumis.

In the Merger, each share of ACELYRIN common stock issued and outstanding immediately prior to the Effective Time will be automatically converted at the Effective Time into the right to receive the Exchange Ratio, with cash paid in lieu of fractional shares. The Exchange Ratio will not reflect changes in the market price of ACELYRIN common stock and will not reflect changes in the market price of Alumis common stock. Alumis stockholders will not receive any merger consideration and will continue to hold their existing shares of Alumis common stock.

Treatment of ACELYRIN Equity Awards (see page 127)

For a description of the treatment of ACELYRIN equity awards, see the section titled “The Merger Agreement — Treatment of ACELYRIN Equity Awards.”

Certain Material U.S. Federal Income Tax Consequences of the Merger (see page 181)

The Merger is intended to qualify, and the parties have agreed to report the Merger for tax purposes, as a “reorganization” within the meaning of Section 368(a) of the Internal Revenue Code of 1986, as amended (the “Code”), as described in this joint proxy statement/prospectus. No assurance can be given that the Merger will so qualify, that the Internal Revenue Service (the “IRS”) will not challenge such qualification or that a court will not sustain such a challenge. The closing of the Merger is not conditioned upon achieving, or receiving a ruling from the IRS or opinion of counsel with respect to, such qualification; however, ACELYRIN has obtained a tax opinion from its counsel, Fenwick & West LLP.

If the Merger qualifies as a “reorganization,” a U.S. holder (as defined in the section titled “Certain Material U.S. Federal Income Tax Consequences” of this joint proxy statement/prospectus) of ACELYRIN common stock generally will not recognize any gain or loss for U.S. federal income tax purposes upon the exchange of ACELYRIN common stock for Alumis common stock in the Merger, except with respect to cash received by such holder in lieu of fractional shares of Alumis common stock.

It is the opinion of Fenwick & West LLP, counsel to ACELYRIN, that it is more likely than not that the Merger qualifies as a “reorganization.” Such opinion of counsel is based on, among other things, certain factual representations made by ACELYRIN and Alumis and certain assumptions, all of which must be consistent with the state of facts existing at the time of the Merger. If any of these representations and assumptions are, or become, inaccurate or incomplete, such opinion may be invalid. Further, an opinion of counsel represents counsel’s best legal judgment and is not binding on the IRS or the courts, which may not agree with the conclusions set forth in such opinion.

If the Merger does not qualify as a “reorganization” within the meaning of Section 368(a) of the Code, the exchange of ACELYRIN common stock for Alumis common stock in the Merger will be a taxable transaction for U.S. federal income tax purposes. See the section titled “Certain Material U.S. Federal Income Tax Consequences” of this joint proxy statement/prospectus for a more complete description of certain material U.S. federal income tax consequences of the Merger. Please consult your tax advisors as to the specific tax consequences to you of the Merger, including the consequences if the Merger does not qualify as a “reorganization.”

Alumis’ Reasons for the Merger; Recommendation of the Alumis Board (see page 150)

At a meeting of the Alumis Board held on April 20, 2025, the Alumis Board, acting on the unanimous recommendation of the Alumis Special Committee, determined that the Merger Agreement and the transactions contemplated thereby, including the Merger, are advisable, fair to and in the best interests of Alumis and its stockholders, and approved the Merger Agreement, the execution of the Merger Agreement and the consummation of the transactions contemplated thereby, including the issuance of shares of Alumis common stock to the ACELYRIN stockholders and resolved to recommend that the Alumis stockholders vote to approve the Alumis stock issuance proposal.

For the factors considered by the Alumis Special Committee and Alumis Board in reaching its decision to approve the Merger Agreement, see the section titled “The Merger — Alumis’ Reasons for the Merger; Recommendation of the Alumis Board.”

The Alumis Board recommends that Alumis stockholders vote “FOR” the proposal to issue shares of Alumis common stock in connection with the Merger and “FOR” the Alumis adjournment proposal.

ACELYRIN’s Reasons for the Merger; Recommendation of the ACELYRIN Board (see page 155)

At a meeting of the ACELYRIN Board held on February 6, 2025, the ACELYRIN Board, after consideration and consultation with its senior management and its financial and legal advisors, determined that the Merger Agreement and the transactions contemplated thereby, including the Merger, are advisable, fair to and in the best interests of ACELYRIN and its stockholders, and approved the Merger Agreement and the Merger, the execution of the Merger Agreement and the consummation of the transactions contemplated thereby and declared advisable and resolved to recommend that ACELYRIN’s stockholders adopt the Merger Agreement. At a meeting of the ACELYRIN Board, held on April 20, 2025, the ACELYRIN Board, after consideration and consultation with its senior management and its financial and legal advisors, determined that the amendment to the Merger Agreement and the transactions contemplated thereby are advisable, fair to and in the best interests of ACELYRIN and its stockholders, approved the amendment to the Merger Agreement, the execution of the amendment to the Merger Agreement and the consummation of the

transactions contemplated thereby and resolved to recommend that ACELYRIN’s stockholders adopt the amendment to the Merger Agreement.

For the factors considered by the ACELYRIN Board in reaching its decision to approve the Merger Agreement, see the section titled “The Merger — ACELYRIN’s Reasons for the Merger; Recommendation of the ACELYRIN Board.”

The ACELYRIN Board recommends that ACELYRIN stockholders vote “FOR” the ACELYRIN merger proposal and “FOR” the ACELYRIN adjournment proposal.

Opinion of Alumis’ Financial Advisor (see page 162)

The Alumis Special Committee retained Morgan Stanley & Co. LLC (“Morgan Stanley”) as its financial advisor in connection with the Merger. On April 20, 2025, Morgan Stanley rendered its oral opinion to the Alumis Special Committee, which was subsequently confirmed in writing by delivery of Morgan Stanley’s written opinion to the Alumis Special Committee, dated April 20, 2025, to the effect that, as of the date of such opinion and based upon and subject to the various qualifications, assumptions, limitations and other matters set forth in Morgan Stanley’s written opinion, the Exchange Ratio pursuant to the Merger Agreement was fair, from a financial point of view, to Alumis.

The full text of Morgan Stanley’s written opinion, dated April 20, 2025, which sets forth the qualifications, assumptions, limitations and other matters considered by Morgan Stanley in connection with the opinion, is attached as Annex D to this joint proxy statement/prospectus. The summary of Morgan Stanley’s opinion contained in this joint proxy statement/prospectus is qualified in its entirety by reference to the full text of the opinion. Alumis’ stockholders are encouraged to read the Morgan Stanley opinion carefully in its entirety. Morgan Stanley provided its opinion for the information of the Alumis Special Committee, in connection with its consideration of the Merger. Morgan Stanley’s opinion addressed only the fairness from a financial point of view to Alumis of the Exchange Ratio pursuant to the Merger Agreement as of the date of such opinion. Morgan Stanley’s opinion did not address any other term or aspect of the Merger Agreement or the transactions contemplated thereby or any term or aspect of any other agreement or instrument contemplated by the Merger Agreement or entered into or amended in connection therewith. Morgan Stanley’s opinion did not in any manner address the prices at which Alumis’ common stock will trade following consummation of the Merger or at any time, and Morgan Stanley expressed no opinion or recommendation as to how the stockholders of Alumis and ACELYRIN should vote at the stockholders’ meetings to be held in connection with the Merger or in connection with any other matter.

For a description of the opinion that the Alumis Special Committee received from Morgan Stanley, see the section titled “The Merger — Opinion of Alumis’ Financial Advisor.”

Opinion of ACELYRIN’s Financial Advisor (see page 169)

ACELYRIN retained Guggenheim Securities, LLC (“Guggenheim Securities”) as its financial advisor in connection with ACELYRIN’s exploration of strategic and financial alternatives. In connection with the Merger, Guggenheim Securities delivered its oral opinion, subsequently confirmed in writing, to the ACELYRIN Board that, as of February 6, 2025 and based on and subject to the matters considered, the procedures followed, the assumptions made and various limitations of and qualifications to the review undertaken, the number of shares of Alumis common stock proposed to be issued in exchange for each share of ACELYRIN common stock as set forth in the Agreement and Plan of Merger, dated February 6, 2025, prior to giving effect to the April 20, 2025 amendment (0.4274, the “Original Exchange Ratio”) was fair, from a financial point of view, to the stockholders of ACELYRIN.

The full text of Guggenheim Securities’ opinion, which is attached as Annex E to this joint proxy statement/ prospectus and which you should read carefully and in its entirety, is subject to the assumptions made, procedures followed, matters considered and limitations, qualifications and other conditions contained in such opinion and necessarily based on economic, business, capital markets and other conditions, and the information made available to Guggenheim Securities, as of the date of such opinion.

In rendering its opinion, Guggenheim Securities did not express any view or opinion as to (i) the prices at which the shares of common stock or other securities or financial instruments of or relating to ACELYRIN or Alumis may trade or otherwise be transferable at any time, (ii) the potential effects of volatility in the credit, financial or equity markets on ACELYRIN or Alumis, their respective securities or other financial instruments or the Merger or (iii) the impact of the Merger on the solvency or viability of ACELYRIN, Alumis or Merger Sub or the ability of ACELYRIN, Alumis or Merger Sub to pay their respective obligations when they come due. Guggenheim Securities has no responsibility for updating or revising its opinion based on facts, circumstances or events occurring after the date of rendering the opinion. Guggenheim Securities did not opine on the fairness of the Exchange Ratio, from a financial point of view, to the stockholders of ACELYRIN.

Guggenheim Securities’ opinion was provided to the ACELYRIN Board (in its capacity as such) for its information and assistance in connection with its evaluation of the Original Exchange Ratio. Guggenheim Securities’ opinion and any materials provided in connection therewith did not constitute a recommendation to the ACELYRIN Board with respect to the Merger, nor does Guggenheim Securities’ opinion or the summary of its underlying financial analyses elsewhere in this joint proxy statement/prospectus constitute advice or a recommendation to any stockholder of ACELYRIN or Alumis as to how to vote or act in connection with the Merger or otherwise. Guggenheim Securities’ opinion addresses only the fairness, from a financial point of view and as of the date of such opinion, of the Original Exchange Ratio to the stockholders of ACELYRIN to the extent expressly specified in such opinion and does not address any other term, aspect or implication of the Merger (including, without limitation, the form or structure of the Merger or the Merger Agreement) or any other agreement, transaction document or instrument contemplated by the Merger Agreement or to be entered into or amended in connection with the Merger.

This summary is qualified in its entirety by reference to the full text of such opinion. For a description of the opinion that the ACELYRIN Board received from Guggenheim Securities, see the section titled “The Merger — Opinion of ACELYRIN’s Financial Advisor.”

Voting Agreements (see page 245)

In connection with the execution of the Merger Agreement, Alumis entered into Voting and Support Agreements (the “Alumis Voting Agreements”) with certain of ACELYRIN’s stockholders, including certain entities affiliated with Westlake Village BioPartners, certain entities affiliated with AyurMaya Capital Management, certain entities affiliated with Access Industries, Beth Seidenberg, Dan Becker and Mina Kim (collectively, the “ACELYRIN Specified Stockholders”). Pursuant to the Alumis Voting Agreements, the ACELYRIN Specified Stockholders have agreed, among other things, to (i) vote or cause to be voted all of their shares of ACELYRIN common stock in favor of (A) the adoption of the Merger Agreement and approval of the transactions contemplated thereby, (B) any other proposals presented by ACELYRIN to its stockholders to effect or facilitate the transactions contemplated by the Merger Agreement and (C) any proposal to adjourn or postpone any meeting of the holders of shares of ACELYRIN common stock at which the matters described in clause (A) are submitted for the consideration and vote of the holders of shares of ACELYRIN common stock to a later date if there are not sufficient votes for approval of such matters on the date on which the meeting is held; and (ii) against (A) any ACELYRIN acquisition proposal or any of the transactions contemplated thereby, (B) any action, proposal, transaction or agreement which could reasonably be expected to result in a breach of any covenant, representation or warranty, or any other obligation or agreement of ACELYRIN under the Merger Agreement or of such ACELYRIN Specified Stockholder under its Alumis Voting Agreement and (C) any action, proposal, transaction, or agreement that could reasonably be expected to impede, interfere with, delay, discourage, adversely affect, or inhibit the timely consummation of the transactions contemplated by the Merger Agreement. A copy of the form of Alumis Voting Agreement is included as Annex B to this joint proxy statement/prospectus.

The shares of ACELYRIN common stock owned by the ACELYRIN Specified Stockholders represented approximately 24% of the outstanding shares of ACELYRIN common stock as of January 31, 2025.

In connection with the execution of the Merger Agreement, ACELYRIN entered into Voting and Support Agreements (the “ACELYRIN Voting Agreements”) with certain of Alumis’ stockholders, including certain entities affiliated with Foresite Capital management, certain entities affiliated with AyurMaya Capital Management, certain entities affiliated with Samsara BioCapital and Martin Babler (collectively, the “Alumis Specified Stockholders”). Pursuant to the ACELYRIN Voting Agreements, the Alumis Specified Stockholders have agreed, among other things, to (i) vote or cause to be voted all of their shares of Alumis common stock in favor of (A) the Alumis stock issuance proposal, (B) any other proposals presented by Alumis to its stockholders in connection with the transactions contemplated by the Merger Agreement, and (C) any proposal to adjourn or postpone any meeting of the holders of Alumis common stock at which the matters described in clause (A) are submitted for the consideration and vote of the holders of

Alumis common stock to a later date if there are not sufficient votes for approval of such matters on the date on which the meeting is held or to constitute a quorum; and (ii) against (A) any Alumis acquisition proposal or any of the transactions contemplated thereby, (B) any action, proposal, transaction or agreement which could reasonably be expected to result in a breach of any covenant, representation or warranty, or any other obligation or agreement of ACELYRIN under the Merger Agreement or of such Alumis Specified Stockholder under its ACELYRIN Voting Agreement and (C) any action, proposal, transaction, or agreement that could reasonably be expected to impede, interfere with, delay, discourage, adversely affect, or inhibit the timely consummation of the transactions contemplated by the Merger Agreement. A copy of the form of ACELYRIN Voting Agreement is included as Annex C to this joint proxy statement/prospectus.

The shares of Alumis common stock owned by the Alumis Specified Stockholders represented approximately 62% of the outstanding Alumis common stock as of January 31, 2025.

The Merger Agreement (see page 115)

The terms and conditions of the Merger are contained in the Merger Agreement, which is attached to this joint proxy statement/prospectus as Annexes A – 1 and A - 2. You should read the Merger Agreement carefully, as it is the legal document that governs the Merger.

Conditions to Completion of the Merger (see page 129)

As more fully described in this joint proxy statement/prospectus and in the Merger Agreement, the completion of the Merger depends on a number of conditions being satisfied or, where legally permissible, waived, including:

The respective obligation of each party to close is also conditioned on the satisfaction or waiver of the following conditions (among other things): (i) the other party’s representations and warranties being true and correct (subject to certain materiality and material adverse effect qualifications), (ii) the other party having performed in all material respects its obligations under the Merger Agreement and (iii) no material adverse effect on the other party having occurred.

Termination of the Merger Agreement (see page 131)

At any time before the Effective Time, whether before or after Alumis’ or ACELYRIN’s respective stockholder votes, the parties may terminate the Merger Agreement by mutual written consent.

At any time before the Effective Time, either party may terminate the Merger Agreement:

At any time before the Effective Time, ACELYRIN may terminate the Merger Agreement if, (a) prior to the time the Alumis stockholder approval is obtained, (i) the Alumis Board effects a change in recommendation in relation to the stock issuance proposal contained in this joint proxy/prospectus statement mailed to its stockholders, (ii) Alumis failed to include the Alumis Board recommendation in this joint proxy statement/prospectus, (iii) Alumis Board failed to publicly reaffirm its recommendation to approve the Alumis stock issuance proposal within 10 business days after ACELYRIN so requests in writing following the public disclosure of any acquisition proposal with any person other than ACELYRIN, (iv) a tender offer or exchange offer for outstanding shares of Alumis capital stock has been commenced (other than by ACELYRIN or an affiliate of ACELYRIN) and Alumis Board shall have recommended that the stockholders of Alumis tender their shares in such tender or exchange offer or, within 10 business days after the commencement of such tender or exchange offer, the Alumis Board will have failed to recommend against acceptance of such offer; or (v) Alumis materially breaches or fails to perform its non-solicitation obligations pursuant to the Merger Agreement (clauses (i) through (v) collectively, an “Alumis triggering event”); (b) prior to or after the time the ACELYRIN stockholder approval is obtained, Alumis or Merger Sub breaches any representation, warranty, covenant or agreement made by Alumis or Merger Sub under the Merger Agreement (subject to certain procedures and materiality exceptions) such that the closing condition related to the correctness of certain representations and warranties or performance of covenants or agreements of Alumis are not met; or (c) prior to the time the ACELYRIN stockholder approval is obtained, subject to compliance with certain terms and conditions, the ACELYRIN Board authorizes ACELYRIN to enter into an alternative acquisition agreement with respect to a superior proposal and ACELYRIN pays to Alumis the required termination fee.

At any time before the Effective Time, Alumis may terminate the Merger Agreement if, (a) prior to the time the ACELYRIN stockholder approval is obtained, (i) the ACELYRIN Board effects a change in recommendation in relation to the ACELYRIN merger proposal, (ii) ACELYRIN fails to include the ACELYRIN merger proposal in this joint proxy statement/prospectus, (iii) the ACELYRIN Board has failed to publicly reaffirm its recommendation to approve ACELYRIN merger proposal within 10 business days after Alumis so requests in writing following the public disclosure of any acquisition proposal with any person other than Alumis, (iv) a tender offer or exchange offer for outstanding ACELYRIN common stock has been commenced (other than by Alumis or an Affiliate of Alumis) and the ACELYRIN Board shall have recommended that the stockholders of ACELYRIN tender their shares in such tender or exchange offer or, within 10 business days after the commencement of such tender or exchange offer, the ACELYRIN Board shall have failed to recommend against acceptance of such offer, or (v) ACELYRIN materially breaches or fails to perform the non-solicitation provisions of the Merger Agreement (clauses (i) through (v), collectively, an “ACELYRIN triggering event”); (b) prior to or after the time the Alumis stockholder approval is obtained, ACELYRIN breaches any representation, warranty, covenant or agreement made by ACELYRIN under the Merger Agreement (subject to certain procedures and materiality exceptions) such that the closing condition related to the correctness of certain representations and warranties or performance of covenants or agreements of ACELYRIN are not met; or (c) prior to the time the Alumis stockholder approval is obtained, the Alumis Board authorizes Alumis to enter into an alternative acquisition agreement with respect to a superior proposal and Alumis pays to ACELYRIN the required termination fee.

Termination Fees (see page 132)

If the Merger Agreement is terminated (i) by Alumis following an ACELYRIN triggering event or (ii) by ACELYRIN to enter into a superior proposal, then ACELYRIN will, within two business days after such termination in the case of clause (i) or concurrently with such termination in the case of clause (ii), pay Alumis a fee equal to $10.0 million.

Further, if (i) the Merger Agreement is terminated (x) by Alumis or ACELYRIN due to a failure to close the Merger by July 7, 2025 or failure to obtain the ACELYRIN stockholder approval or (y) by Alumis due to a breach of the Merger Agreement by ACELYRIN, (ii) prior to such termination referred to in clause (i) of this sentence, but after the date of the Merger Agreement, a bona fide acquisition proposal with respect to ACELYRIN will have been announced or publicly disclosed to ACELYRIN or its stockholders and not publicly withdrawn and (iii) within 12 months after the date of such termination, ACELYRIN consummates an acquisition proposal with respect to ACELYRIN or enters into an agreement contemplating an acquisition proposal with respect to ACELYRIN that is subsequently consummated, then ACELYRIN will pay Alumis a fee equal to $10.0 million, concurrently with such consummation, provided that solely for purposes of this provision, the term “acquisition proposal” will have the meaning assigned to such term with respect to ACELYRIN in the section titled “The Merger Agreement — No Solicitation of Alternative Proposals,” except that the references to “15% or more” will be deemed to be references to “50% or more.”

If the Merger Agreement is terminated (i) by ACELYRIN following an Alumis triggering event or (ii)by Alumis to enter into a superior proposal, then Alumis will, within two business days after such termination in the case of clause (i) or concurrently with such termination in the case of clause (ii), pay ACELYRIN a fee equal to $10.0 million.

Further, if (i) the Merger Agreement is terminated (x) by Alumis or ACELYRIN due to a failure to close the Merger by July 7, 2025 or failure to obtain the Alumis stockholder approval or (y) by ACELYRIN due to a breach of the Merger Agreement by Alumis, (ii) prior to such termination referred to in clause (i) of this sentence, but after the date of the Merger Agreement, a bona fide acquisition proposal with respect to Alumis will have been publicly made or publicly disclosed to Alumis or its stockholders and not publicly withdrawn and (iii) within 12 months after the date of such termination, Alumis consummates an acquisition proposal with respect to Alumis or enters into an agreement contemplating an acquisition proposal with respect to Alumis that is subsequently consummated, then Alumis will pay ACELYRIN a fee equal to $10.0 million, concurrently with such consummation, provided that solely for purposes of this provision, the term “acquisition proposal” will have the meaning assigned to such term with respect to Alumis in the section titled “The Merger Agreement — No Solicitation of Alternative Proposals,” except that the references to “15% or more” will be deemed to be references to “50% or more.”

In no event will ACELYRIN or Alumis be required to pay a termination fee on more than one occasion.

Regulatory Matters (see page 179)

Neither Alumis nor ACELYRIN is aware of any material regulatory approvals or actions that are required for completion of the Merger. It is presently contemplated that if any such additional regulatory approvals or actions are required, those approvals or actions will be sought. There can be no assurance, however, that any additional approvals or actions will be obtained.

Accounting Treatment (see page 179)

Alumis prepares its consolidated financial statements in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”). Based on the Alumis preliminary analysis, the Merger will be accounted for as a business combination using the acquisition method of accounting. Please see the section titled “The Merger — Accounting Treatment.”

Appraisal Rights (see page 262)

Under Delaware law, the ACELYRIN stockholders are not entitled to appraisal rights in connection with the Merger or any other transaction contemplated by the Merger Agreement.

Under Delaware law, the Alumis stockholders are not entitled to appraisal rights in connection with the issuance of shares of Alumis common stock in the Merger pursuant to the terms of the Merger Agreement. Please see the section titled “The Merger — Appraisal Rights.”

Alumis’ and ACELYRIN’s Executive Officers and Directors Have Interests in the Merger That Differ from the Interests of Alumis Stockholders and ACELYRIN Stockholders (see page 178)

In considering the information contained in this joint proxy statement/prospectus, you should be aware that certain of Alumis’ and ACELYRIN’s directors and executive officers may be deemed to have interests in the Merger that are in addition to, or different from, the interests of other Alumis or ACELYRIN stockholders generally. Each of the Alumis Board and the ACELYRIN Board was aware of these interests and considered them, among other matters, in approving the Merger and the Merger Agreement and in making the recommendation that you adopt the Merger Agreement. These potential interests include:

For additional details about these interests, see the section titled “The Merger — Interests of Alumis and ACELYRIN Directors and Executive Officers in the Merger.”

Board of Directors and Management Following the Merger (see page 226)

In connection with the Merger, two additional directors of ACELYRIN will join the Alumis Board. For a description of the Alumis Board and management following the Merger, see the section titled “Management of Alumis Following the Merger.”

Rights of ACELYRIN Stockholders Will Change as a Result of the Merger (see page 256)

As a result of the Merger, ACELYRIN stockholders will become holders of shares of Alumis common stock, and their rights will be governed by the Amended and Restated Certificate of Incorporation of Alumis and Alumis’ Amended and Restated Bylaws (instead of the Amended and Restated Certificate of Incorporation of ACELYRIN and ACELYRIN’s Amended and Restated Bylaws) and the General Corporation Law of Delaware (the “DGCL”). Following the Merger, former ACELYRIN stockholders will have

different rights as holders of Alumis common stock than they had as ACELYRIN stockholders due to differences in the organizational documents of Alumis and ACELYRIN. For additional information on stockholder rights, see the section titled “Description of Capital Stock and Comparison of Rights of Alumis Stockholders and ACELYRIN Stockholders.”

The Alumis Virtual Special Meeting (see page 102)

The Alumis virtual special meeting will be held by live webcast at 9:00 a.m. (Pacific Time), on May 13, 2025. There will be no physical meeting location. In order to attend the Alumis virtual special meeting, as well as vote and submit your questions during the live webcast of the meeting, you will need to visit www.virtualshareholdermeeting.com/ALMS2025SM and enter the 16-digit Control Number shown on your proxy card. At the Alumis virtual special meeting, Alumis stockholders will be asked to consider and vote upon the following proposals:

Only holders of record of shares of Alumis common stock at the close of business on April 1, 2025, the Alumis record date, will be entitled to notice of, and to vote at, the Alumis virtual special meeting and any postponements or adjournments thereof. Holders of Alumis common stock at the close of business on the Alumis record date may cast one vote for each share of Alumis common stock so held, including (i) shares held directly in the name of the holder of record and (ii) shares held on behalf of the holder as the beneficial owner in street name through a broker, bank, or other nominee. On the Alumis record date, there were outstanding a total of 47,222,419 shares of common stock entitled to vote at the Alumis virtual special meeting.

Approval of the Alumis stock issuance proposal requires the affirmative vote of the holders of shares of Alumis common stock representing a majority of the votes cast on such matter at the Alumis virtual special meeting (provided that a quorum exists). Approval of the Alumis adjournment proposal requires the affirmative vote of the holders of shares of Alumis common stock representing a majority of the votes cast on such matter at the Alumis virtual special meeting (whether or not a quorum is present).

The ACELYRIN Virtual Special Meeting (see page 108)

The ACELYRIN virtual special meeting will be held by live webcast at 9:00 a.m. (Pacific Time), on May 13, 2025. There will be no physical meeting location. In order to attend the ACELYRIN virtual special meeting, as well as vote and submit your questions during the live webcast of the meeting, you will need to visit www.virtualshareholdermeeting.com/SLRN2025SM and enter the 16-digit Control Number shown on your proxy card. At the ACELYRIN virtual special meeting, ACELYRIN stockholders will be asked to consider and vote upon the following proposals:

Only holders of record of shares of ACELYRIN common stock at the close of business on April 1, 2025, the ACELYRIN record date, will be entitled to notice of, and to vote at, the ACELYRIN virtual special meeting and any postponements or adjournments thereof. Holders of ACELYRIN common stock at the close of business on the ACELYRIN record date may cast one vote for each share of ACELYRIN common stock so held, including (i) shares held directly in the name of the holder of record and (ii) shares held on behalf of the holder as the beneficial owner in street name through a broker, bank, or other nominee. On the ACELYRIN record date, there were outstanding a total of 100,907,206 shares of ACELYRIN common stock entitled to vote at the ACELYRIN virtual special meeting.

Completion of the Merger is conditioned on the approval of the ACELYRIN merger proposal. Approval of the ACELYRIN merger proposal requires the affirmative vote of the holders of ACELYRIN’s common stock representing a majority of the outstanding shares of ACELYRIN common stock entitled to vote on such matter at the ACELYRIN virtual special meeting. Approval of the ACELYRIN adjournment proposal requires the affirmative vote of the holders of shares of ACELYRIN common stock representing a majority of the votes cast on such matter at the ACELYRIN virtual special meeting (whether or not a quorum is present).

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UNAUDITED PRO FORMA CONDENSED COMBINED FINANCIAL INFORMATION

The following unaudited pro forma condensed combined financial information presents the combination of the historical consolidated financial statements of Alumis and ACELYRIN, adjusted to give effect to the transactions contemplated by the Merger Agreement. The Merger Agreement contemplates, among other things, the merger of Merger Sub with and into ACELYRIN, with ACELYRIN as the surviving entity and continuing as a direct, wholly owned subsidiary of Alumis. The Merger is anticipated to qualify as a tax-free reorganization for U.S. federal income tax purposes. As consideration for net assets acquired, subject to the terms and conditions of the Merger Agreement, and at the Effective Time, Alumis will (i) issue shares of its common stock in exchange for ACELYRIN issued and outstanding common stock shares and will pay cash for any fractional shares, (ii) assume options of ACELYRIN optionholders with an exercise price of $18.00 or less outstanding and unexercised immediately prior to the Effective Time, which will be exercisable in Alumis’ common stock, (iii) assume RSUs outstanding and unvested immediately prior to the Effective Time, and (iv) assume performance RSUs outstanding and unvested immediately prior to the Effective Time, which will be convertible into Alumis RSUs awards subject only to a service vesting condition.

Outstanding shares, options, RSUs and performance RSUs will be exchanged at the Exchange Ratio of 0.4814-for-one. ACELYRIN’s outstanding and unexercised options with exercise prices more than $18.00 will be cancelled. Exercise prices for the assumed options will be determined as the product of the original exercise prices multiplied by the reciprocal of the Exchange Ratio. Converted ACELYRIN options and RSUs will continue to vest in accordance with their original terms. Performance RSUs will be deemed to have 100% satisfied their performance conditions and will vest in three equal installments on May 15 of calendar years 2025, 2026 and 2027, unless the closing of the Merger occurs after May 15, 2025, in which case the converted performance RSUs will vest in two equal installments on May 15 of calendar years 2026 and 2027, subject to the holder of the converted performance RSUs remaining in service with Alumis or any of its subsidiaries on such date.

The following unaudited pro forma condensed combined balance sheet and the unaudited pro forma condensed combined statement of operations give effect to the Merger assuming that it closed on December 31, 2024 and January 1, 2024, respectively, and are based upon and derived from:

The pro forma adjustments are preliminary and are based upon available information and certain assumptions, as described in the accompanying notes to the unaudited pro forma condensed combined financial information, which Alumis believes are reasonable under the circumstances. Actual results and valuations may differ materially from the assumptions within the unaudited pro forma condensed combined financial information.

The unaudited pro forma condensed combined financial information has been prepared in accordance with the regulations of the SEC and is not necessarily indicative of the financial position or results of operations to be expected in future periods or the results that actually would have been realized had Alumis and ACELYRIN been a combined company during the specified periods. The unaudited pro forma condensed combined financial information also does not give effect to the potential impact of current financial conditions, any anticipated synergies, operating efficiencies or cost savings that may result from the Merger or any integration costs. The unaudited pro forma condensed combined financial information also does not include any future integration costs.

The assumptions and estimates underlying the adjustments to the unaudited pro forma condensed combined financial information are described in the accompanying notes, which should be read together with the unaudited pro forma condensed combined financial information as well as the historical consolidated financial statements and accompanying notes of Alumis, which are included elsewhere in this joint proxy statement/prospectus, and the historical consolidated financial statements and accompanying notes of ACELYRIN, which are incorporated by reference in this joint proxy statement/prospectus.

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UNAUDITED PRO FORMA CONDENSED COMBINED BALANCE SHEET

As of December 31, 2024

(in thousands)

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See the accompanying “Notes to Unaudited Pro Forma Condensed Combined Financial Information.”

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UNAUDITED PRO FORMA CONDENSED COMBINED STATEMENT OF OPERATIONS

For the Year Ended December 31, 2024

(in thousands, except share and per share data)

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