Dear stockholders of Equillium, Inc. and stockholders of Metacrine, Inc.:

As previously announced, the board of directors of Equillium, Inc., or Equillium, and the board of directors of Metacrine, Inc., or Metacrine, have approved an acquisition of Metacrine by Equillium. Equillium, Metacrine, Equillium Acquisition Sub, Inc., or Acquisition Sub I, Triumph Acquisition Sub, Inc., or Acquisition Sub II, and Triumph Merger Sub, Inc., or Merger Sub, entered into an Agreement and Plan of Merger, dated as of September 6, 2022, as amended on October 26, 2022, pursuant to which Merger Sub will merge with and into Metacrine, with Metacrine continuing as an indirect wholly owned subsidiary of Equillium, or the Merger.

If the transaction is completed, Metacrine stockholders will have the right to receive for each share of Metacrine common stock held by such stockholder (i) a portion of a share of Equillium common stock equal to the exchange ratio, or the Exchange Ratio, determined by dividing (x) (a) 125% of Metacrine’s net cash as of the closing of the Merger, or the Upfront Merger Consideration, by (b) the price per share of Equillium common stock determined based on the 10 day trading volume weighted average price per share of Equillium common stock calculated 10 trading days prior to the closing date of the Merger, provided that in no event will the price per share of Equillium common stock be less than $2.70 or greater than $4.50, or the Equillium Stock Price, by (y) the aggregate fully diluted shares of Metacrine, or Metacrine’s Closing Capitalization, plus (ii) any cash payable in lieu of fractional shares of Equillium’s common stock. The Exchange Ratio will not reflect changes in the market price of Metacrine common stock and will not reflect changes in the market price of Equillium common stock, except that the Exchange Ratio will reflect the 10-day trading volume weighted average price per share of Equillium common stock calculated 10 trading days prior to the closing date of the Merger, or the Closing Date.

For illustrative purposes only, we have provided the below assumptions and sensitivity analysis to inform your decision. Assuming (1) an Upfront Merger    Consideration of $33.75 million, which is based on Metacrine’s current forecasts of net cash as of December 23, 2022, the assumed closing date, or the Assumed Upfront Merger Consideration, (2) an Equillium Stock Price of $2.70, which reflects the lowest trading price per share of Equillium common stock to be calculated for purposes of the Exchange Ratio, or the Floor Price, and the applicable per share price that would be used to determine the Exchange Ratio based on applying the 10-day trading volume weighted average price per share of Equillium common stock calculated 10 trading days prior to November 8, 2022, the last trading day before November 9, 2022, and (3) Metacrine’s Closing Capitalization is 44,378,697, the aggregate fully diluted shares of Metacrine as of November 9, 2022, or the Assumed Metacrine Closing Capitalization, the Exchange Ratio would equal 0.282.

Assuming (1) the Upfront Merger Consideration equals the Assumed Upfront Merger Consideration and (2) the Metacrine Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $0.25 increase to the Floor Price would decrease the Exchange Ratio to 0.258. Assuming (1) the Upfront Merger Consideration equals the Assumed Upfront Merger Consideration, (2) an Equillium Stock Price of $4.50, which reflects the highest trading price per share of Equillium common stock to be calculated for purposes of the Exchange Ratio, or the Ceiling Price, and (3) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, the Exchange Ratio would equal 0.169. Assuming (1) the Upfront Merger Consideration equals the Assumed Upfront Merger Consideration and (2) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $0.25 decrease to the Ceiling Price would increase the Exchange Ratio to 0.179. Assuming (1) the Equillium Stock Price remains constant and (2) the Metacrine Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $1,000,000 increase or decrease in the Upfront Merger Consideration would increase or decrease, respectively, the Exchange Ratio by approximately 0.008.

We encourage you to obtain current market quotations of Equillium common stock and Metacrine common stock before voting.

Based on the Assumed Upfront Merger Consideration, Equillium estimates that it may issue between 7.5 and 12.5 million shares of its common stock to Metacrine equityholders in connection with the Closing. Upon completion of the Merger and based on the Assumed Upfront Merger Consideration and 34,352,084 shares of Equillium common stock outstanding as of November 9, 2022, we estimate that current Equillium stockholders will own between 82.08% and 73.32% of the outstanding common stock of the combined company and former Metacrine equityholders will own between 17.92% and 26.68% of the outstanding common stock of the combined company. If the actual facts are different from these assumptions (which they are likely to be), the percentage ownership retained by Equillium’s stockholders in the combined company will be different. The foregoing numbers are based on assumptions and illustrative and the actual percentage ownership in the combined company retained by Equillium’s stockholders at Closing will be calculated based on the actual numbers. Equillium common stock and Metacrine common stock are both traded on Nasdaq under the symbols “EQ” and “MTCR”, respectively. Upon completion of the Merger, Metacrine common stock will cease to be traded on Nasdaq.

At the special meeting of Equillium stockholders to be held virtually on December 20, 2022, Equillium stockholders will be asked to vote on (i) a proposal to approve the issuance of shares of Equillium common stock to Metacrine stockholders, which is a condition to completion of the Merger, or the Equillium stock issuance proposal, and (ii) a proposal to approve the adjournment from time to time of the Equillium virtual special meeting, if necessary, to solicit additional proxies if there are not sufficient votes to approve the issuance of shares of Equillium common stock in the Merger, which we refer to as the Equillium adjournment proposal.

At the special meeting of Metacrine stockholders to be held virtually on December 20, 2022, Metacrine stockholders will be asked to vote on (i) a proposal to adopt the Merger Agreement, or the Metacrine merger proposal and (ii) a proposal to approve the adjournment from time to time of the Metacrine virtual special meeting, if necessary, to solicit additional proxies if there are not sufficient votes to adopt the Merger Agreement, or the Metacrine adjournment proposal.

Only holders of record of Equillium common stock on November 9, 2022 (including shares of Equillium common stock held through a bank, broker or other nominee that is a stockholder of record of Equillum) and holders of record of Metacrine common stock on November 9, 2022 (including shares of Metacrine common stock held through a bank, broker or other nominee that is a stockholder of record of Metacrine) are entitled to attend and vote at the virtual special meeting of Equillium stockholders or the virtual special meeting of Metacrine stockholders, respectively, or any adjournment or postponement thereof.

We cannot complete the Merger unless the Metacrine stockholders and the Equillium 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 Equillium virtual special meeting or Metacrine 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 Equillium or the Metacrine virtual special meeting, as applicable. If you are a Metacrine stockholder, please note that a failure to vote your shares is the equivalent of a vote against the Merger. If you are an Equillium stockholder, please note that a failure to vote your shares may result in a failure to establish a quorum for the Equillium virtual special meeting.

The Equillium board of directors, or the Equillium Board, recommends that Equillium stockholders vote “FOR” the Equillium stock issuance proposal and, if necessary, “FOR” the Equillium adjournment proposal. The Metacrine board of directors, or the Metacrine Board, recommends that Metacrine stockholders vote “FOR” the Metacrine merger proposal and, if necessary, “FOR” the Metacrine adjournment proposal.

The obligations of Equillium and Metacrine to complete the Merger are subject to the satisfaction or waiver of several conditions set forth in the Merger Agreement. More information about Equillium, Metacrine and the Merger is contained in this joint proxy statement/prospectus. Equillium and Metacrine encourage you to read this entire joint proxy statement/prospectus carefully, including the section entitled “Risk Factors” beginning on page 30.

We look forward to the successful Merger of Equillium and Metacrine.

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 November 10, 2022 and is first being mailed to the stockholders of Equillium and stockholders of Metacrine on or about November 10, 2022.

of Merger, dated as of September 6, 2022, among Equillium, Metacrine, Acquisition Sub I, Acquisition Sub II and Merger Sub, as amended on October 26, 2022, a copy of which is included as Annex A to this joint proxy statement/prospectus.

Equillium and Metacrine own or have rights to various trademarks, logos, service marks and trade names that each uses in connection with the operation of its business. Equillium and Metacrine 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.

This joint proxy statement/prospectus incorporates important business and financial information about Equillium and Metacrine 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 entitled “Where You Can Find More Information” beginning on page 141 of this joint proxy statement/prospectus. 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 the appropriate company at the following addresses and telephone numbers:

Investors may also consult Equillium’s or Metacrine’s website for more information concerning the Merger described in this joint proxy statement/prospectus. Equillium’s website is www.Equilliumbio.com. Metacrine’s website is www.Metacrine.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 Metacrine stockholders, please call Morrow Sodali, LLC, the proxy solicitor for Metacrine, toll-free at (800) 662-5200, or, for Equillium stockholders, please call Equillium at (858) 240-1200 or email ir@equilliumbio.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 Equillium, please do so by December 13, 2022 and if you would like to request documents from Metacrine, please do so by December 13, 2022 in order to receive such documents before the Equillium and Metacrine virtual special meetings, respectively.

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

Your vote is important. Whether or not you expect to attend the Equillium 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 Equillium 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 Equillium and certain participating Equillium 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, American Stock Transfer & Trust Company, LLC, you are considered, with respect to those shares, the shareholder of record. In such case, these proxy materials are being sent directly to you.

We are pleased to invite you to attend the Equillium virtual special meeting, conducted via live webcast, at www.virtualshareholdermeeting.com/EQ2022SM. 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.

We are pleased to invite you to attend the special meeting of the Metacrine stockholders, which will be held on December 20, 2022, at 12:00p.m. (Eastern Time), or the Metacrine virtual special meeting. The Metacrine virtual special meeting will be conducted via live webcast at www.virtualshareholdermeeting.com/MTCR2022SM for the following purposes:

Metacrine 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 Metacrine virtual special meeting.

In order to attend the Metacrine 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/MTCR2022SM 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.

Pursuant to an action by unanimous written consent of the Metacrine Board dated September 5, 2022, the Metacrine Board determined that the Merger Agreement and the transactions contemplated thereby are in the best interests of Metacrine 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 recommended that Metacrine’s stockholders adopt the Merger Agreement.

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

Holders of record of shares of Metacrine common stock, at the close of business on November 9, 2022, or the Metacrine record date, are entitled to notice of, and may vote at, the special meeting and any adjournment of the special meeting. A list of Metacrine stockholders entitled to vote at the Metacrine virtual special meeting will be available for inspection at Metacrine’s principal executive offices, located at 4225 Executive Square, Suite 600, San Diego, California 92037, at least 10 days prior to the date of the Metacrine virtual special meeting and continuing through the date thereof for any purpose germane to the Metacrine virtual special meeting, between the hours of 9:00 a.m. and 4:30 p.m., local time.

Approval of the Metacrine merger proposal requires the affirmative vote of holders of Metacrine common stock representing a majority of the outstanding shares of Metacrine common stock entitled to vote on such

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

Your vote is important. Whether or not you expect to attend the Metacrine 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 Metacrine 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 Metacrine and certain participating Metacrine 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, American Stock Transfer & Trust Company, LLC, you are considered, with respect to those shares, the shareholder 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, Morrow Sodali, LLC, toll-free at (800) 662-5200.

We are pleased to invite you to attend the Metacrine virtual special meeting, conducted via live webcast, at www.virtualshareholdermeeting.com/MTCR2022SM. 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.

The following are brief answers to certain questions that Equillium stockholders and Metacrine stockholders may have regarding the merger, the merger agreement, the issuance of shares of Equillium common stock in connection with the merger, the Equillium virtual special meeting, the Metacrine virtual special meeting, and other matters to be considered at the Equillium virtual special meeting and at the Metacrine virtual special meeting. Equillium and Metacrine 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 “Where You Can Find More Information” beginning on page 141 in this joint proxy statement/ prospectus.

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 Metacrine. 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 Metacrine virtual special meeting, you will need to visit www.virtualshareholdermeeting.com/MTCR2022SM. 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 Metacrine virtual special meeting. Further instruction will be provided to you as part of your registration process.

Internet proxy voting may be provided to allow 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.

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 Equillium. 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 Equillium virtual special meeting, you will need to visit www.virtualshareholdermeeting.com/EQ2022SM. 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 Equillium virtual special meeting. Further instruction will be provided to you as part of your registration process.

Internet proxy voting may be provided to allow 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.

The following unaudited pro forma condensed combined financial information is presented to illustrate the estimated effects of the proposed Merger.

The unaudited pro forma condensed combined balance sheet information as of June 30, 2022 is based upon and derived from the historical financial information of Equillium and Metacrine and gives effect to the Merger as if such acquisition had occurred on June 30, 2022. The unaudited pro forma condensed combined statements of operations and comprehensive loss for the year ended December 31, 2021 and the six months ended June 30, 2022 are also based upon and derived from the historical financial information of Equillium and Metacrine and give effect to the Merger as if it occurred on January 1, 2021. In addition, the unaudited pro forma condensed combined statements of operations and comprehensive loss for the year ended December 31, 2021 and the six months ended June 30, 2022 are also based upon and derived from the historical financial information of Bioniz, Inc., or Bioniz, which was acquired by Equillium on February 14, 2022 and give effect to the Bioniz acquisition as if it occurred on January 1, 2021, or the Bioniz Acquisition and together with the Merger, the Acquisitions.

The unaudited pro forma condensed combined financial information should be read in conjunction with:

Additional information about the basis of presentation of this information is provided in Note 1 hereto.

The unaudited pro forma condensed combined financial information is provided for informational purposes only and is not necessarily indicative of the operating results or financial position that would have occurred if the Acquisitions had been completed as of the dates set forth above, nor is it indicative of the future results or financial position of the combined company. In connection with the pro forma financial information, Equillium allocated the purchase price using its best estimates of fair value. Accordingly, the pro forma Merger price adjustments are preliminary and subject to further adjustments as additional information becomes available and as additional analyses are performed. 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 statements of operations and comprehensive loss do not reflect certain amounts resulting from the Merger that were determined to be of a non-recurring nature.

The unaudited pro forma condensed combined financial information was prepared in accordance with Article 11 of Regulation S-X. Equillium has accounted for the Merger using the acquisition method of accounting, in accordance with FASB Accounting Standards Codification, or ASC, Topic 805 “Business Combinations”, or ASC 805. Equillium preliminarily determined that the Merger constitutes an acquisition of assets instead of a business combination as substantially all of the fair value of the gross assets acquired was concentrated in a group of similar identifiable assets, and therefore, the Merger was not considered a business combination.

After the closing of the Merger, Equillium will complete the valuations necessary to finalize the required purchase price allocation based upon the fair market values as of the actual closing date of the Merger, at which time the final allocation of the purchase price will be determined. The pro forma financial information contained in this joint proxy statement/prospectus is also based upon certain assumptions with respect to the amount of net

cash to be received from Metacrine at the closing of the Merger and the number of shares of Equillium common stock to be issued to Metacrine at closing of the Merger. Differences between preliminary estimates in the pro forma financial information presented herein and the final acquisition accounting will occur and could have a material impact on the pro forma financial information. In this regard, differences between those preliminary estimates and the actual net cash received from Metacrine at the closing of the Merger and the number of shares of Equillium common stock ultimately issued to Metacrine at closing of the Merger would result in changes to various components of the unaudited pro forma condensed combined balance sheet, including cash and cash equivalents, common stock and additional paid-in capital, and various components of the unaudited pro forma condensed combined statements of operations, including in-process research and development expense, net loss per share and weighted-average shares used in computing net loss per share.

The unaudited pro forma condensed combined financial information has been prepared by Equillium in accordance with SEC Regulation S-X Article 11 and is not necessarily indicative of the condensed combined financial position or results of operations that would have been realized had the Acquisitions been completed as of the dates indicated above, nor is it meant to be indicative of any anticipated combined financial position or future results of operations that Equillium will experience after the Merger is completed. In addition, the accompanying unaudited pro forma condensed combined statements of operations and comprehensive loss do not include any pro forma adjustments to reflect expected cost savings or restructuring actions which may be achievable or the impact of any non-recurring expenses and one-time transaction-related costs that may be incurred as a result of the Acquisitions.

Equillium, Metacrine, Acquisition Sub I, Acquisition Sub II and Merger Sub entered into the Merger Agreement dated September 6, 2022 and amended on October 26, 2022. Pursuant to the Merger Agreement, Merger Sub will be merged with and into Metacrine, and Metacrine will continue as the surviving corporation and an indirect, wholly owned subsidiary of Equillium. In connection with the Merger, all of the issued and outstanding shares of common stock of Metacrine, par value $0.0001 per share, or the Shares, will be cancelled and converted into the right to receive consideration per share consisting of (i) the Exchange Ratio, which is determined by dividing (x) (a) 125% of Metacrine’s net cash as of the closing of the Merger, or the Closing, by (b) the price per share of common stock of Equillium, par value $0.0001 per share, or Equillium common stock determined based on the 10-day trading volume weighted average price per share of Equillium common stock calculated 10 trading days prior to the Closing date, provided that the price per share of Equillium common stock shall be no less than $2.70 and no more than $4.50 by (y) the aggregate fully diluted shares of Metacrine, plus (ii) any cash payable in lieu of fractional shares of Equillium’s common stock. As defined in the Merger Agreement, net cash consists of Metacrine’s cash and cash equivalents, deposits, prepaid expenses, and short-term investments, adjusted by certain factors including the full payoff amount of Metacrine’s existing term debt having an outstanding principal of $15 million. Net cash is estimated to be approximately $27.0 million at Closing, assuming a Closing on December 23, 2022. In addition, Equillium has agreed to terms on an amended debt facility with Metacrine’s current lender, K2 HealthVentures LLC, whereby at the Closing Equillium would assume Metacrine’s existing loan, subject to certain modifications. Concurrent with the Closing, Equillium intends to retire its existing debt facility with Oxford Finance LLC and SVB, which has an outstanding principal balance of $10 million as of June 30, 2022.

Consummation of the Merger is subject to certain closing conditions, including Metacrine’s net cash being no less than $23 million, the absence of certain legal impediments, the effectiveness of a registration statement to which this joint proxy statement/prospectus is a part, adoption of the Merger Agreement by the holders of a majority of Metacrine’s outstanding common stock at Metacrine’s virtual special meeting, and approval of the issuance of shares of Equillium common stock in the Merger by the holders of shares of Equillium common stock representing a majority of the votes cast at Equillium’s virtual special meeting.

The historical consolidated financial information of Equillium has been adjusted in the accompanying unaudited pro forma condensed combined financial information to give effect to pro forma events that are (i) directly attributable to the Acquisitions, (ii) factually supportable, and (iii) with respect to the unaudited pro forma condensed combined statements of operations and comprehensive loss, are expected to have a continuing impact on the results of operations.

The unaudited pro forma condensed combined financial statements were prepared in accordance with the regulations of the SEC and are intended to show how the Acquisitions might have affected the historical financial statements. The unaudited pro forma condensed combined financial information set forth herein is based upon the consolidated financial statements of Equillium, Bioniz and Metacrine. The unaudited pro forma condensed combined financial information is presented as if the Merger had been completed on June 30, 2022 with respect to the unaudited pro forma condensed combined balance sheet as of June 30, 2022 and as of January 1, 2021 with respect to the unaudited pro forma condensed combined statements of operations and comprehensive loss for the year ended December 31, 2021 and the six month period ended June 30, 2022 for both the Acquisitions. The unaudited pro forma condensed combined financial statements have also been adjusted to give effect to pro forma events that are directly attributable to the Acquisitions, factually supportable and expected to have a continuing impact on the combined results.

Equillium’s combined financial information has been prepared in accordance with Generally Accepted Accounting Principles in the United States, or GAAP, as issued by the Financial Accounting Standards Board, or FASB. Metacrine’s and Bioniz’s financial information has been historically prepared in accordance with GAAP.

The unaudited pro forma condensed combined financial information is presented for informational purposes only and is not necessarily indicative of the combined financial position or results of operations had the Merger occurred as of the dates indicated, nor is it meant to be indicative of any anticipated combined financial position or future results of operations that the combined company will experience after the completion of the Merger. To the extent there are significant changes to the combined company’s business following completion of the Merger, the assumptions and estimates set forth in the unaudited pro forma condensed combined financial statements could change significantly.

Equillium determined the Merger constitutes an acquisition of assets instead of a business combination as substantially all of the fair value of the gross assets acquired was concentrated in a group of similar identifiable assets, and therefore, the acquisition was not considered a business. Asset acquisitions are accounted for by allocating the cost of the acquisition, including transaction costs, to the individual assets acquired and liabilities assumed on a relative fair value basis without recognition of goodwill.

Equillium determined the Merger meets the definition of an acquisition of a business as defined in Rule 8-04 of Regulation S-X of the SEC. The accompanying unaudited pro forma condensed combined financial information was prepared for the purpose of complying with Rule 8-04 of Regulation S-X of the SEC and for inclusion in Equillium’s filings with the SEC.

Following the execution of the Merger Agreement, Equillium will conduct a review of accounting policies of Metacrine in an effort to determine if differences in accounting policies require restatement or reclassification of results of operations or reclassification of assets or liabilities to conform to Equillium’s accounting policies and classifications. Equillium may identify differences among the accounting policies of Equillium and Metacrine that, when conformed, could have a material impact on this unaudited pro forma condensed combined financial information. During the preparation of this unaudited pro forma condensed combined financial information, Equillium was not aware of any material differences between accounting policies of Equillium and Metacrine to conform to Equillium’s financial presentation, and accordingly, this unaudited pro forma condensed combined financial information does not assume any material differences in accounting policies among Equillium and Metacrine.

The calculation of the estimated preliminary purchase consideration is as follows:

In connection with the Merger, all of the issued and outstanding Shares will be cancelled and converted into the right to receive consideration per share consisting of (i) the Exchange Ratio, plus (ii) any cash payable in lieu of fractional shares of Equillium’s common stock.

Each of Metacrine’s stock options, or Options, that is outstanding as of immediately prior to the effectiveness of the Merger, or the Effective Time, will (i), if held by a continuing employee or service provider, be substituted automatically into an Equillium option award to purchase the number of shares of Equillium common stock equal to the number of Shares subject to the Option immediately prior to the Effective Time multiplied by the Exchange Ratio, and (ii) if the Option is held by a former employee, service provider or director of Metacrine, (x) to the extent unvested, be cancelled without the payment of any consideration and (y) to the extent vested, be cancelled and converted into a right to receive the number of shares of Equillium common stock equal to (1) the number of Shares subject to the Option immediately prior to the Effective time multiplied by the excess, if any, of Metacrine’s price per Share based on the 10 day trading volume weighted average price per Share calculated 10 trading days prior to the Closing date over the per share exercise price for the Shares underlying the Option immediately prior to the Effective Time, or the Metacrine Share Value, divided by (2) the Metacrine Share Value multiplied by the Exchange Ratio.

Each of Metacrine’s restricted stock unit awards, or the RSUs, that is outstanding as of immediately prior to the Effective Time will (i), if held by a continuing employee or service provider, whether vested or unvested, be substituted automatically into an Equillium restricted stock unit award with respect to a number of shares of Equillium common stock equal to the product obtained by multiplying the total number of Shares subject to the RSU immediately prior to the Effective Time by the Exchange Ratio, and (ii) if the RSU is held by a former employee, service provider or director of Metacrine, (x) to the extent unvested, be cancelled without the payment of any consideration and (y) to the extent vested, be cancelled and converted into a right to receive the number of shares of Equillium common stock equal to the product obtained by multiplying the total number of Shares subject to the RSU immediately prior to the Effective Time by the Exchange Ratio.

Each of Metacrine’s warrants, or the Warrants, that is outstanding and unexercised immediately prior to the Effective Time will be automatically substituted into a warrant to purchase the number of shares of Equillium common stock equal to the product obtained by multiplying the number of Shares subject to the Warrant immediately prior to the Effective Time by the Exchange Ratio. Each Warrant will have an exercise price per share of Equillium common stock equal to exercise price per Share immediately prior to the Effective Time divided by the Exchange Ratio.

For illustrative purposes only, we have calculated the potential number of shares Equillium would issue in connection with the closing of the Merger based on the assumptions and sensitivity analysis set forth herein.

Based on (1) the Estimated equity consideration of $33,346,709, or the Pro Forma Assumed Upfront Merger Consideration, and (2) an Equillium Stock Price equal to the Floor Price, Equillium would issue 12,350,633 shares of common stock.

Keeping the Pro Forma Assumed Upfront Merger Consideration constant, a $0.25 increase from the Floor Price would decrease the number of shares of common stock Equillium issues at the Closing by 1,046,664. Keeping the Equillium stock price constant, a $1 million increase or decrease in the Assumed Upfront Merger Consideration would increase or decrease, respectively, the number of shares of common stock to be issued by Equillium by 462,963 shares. Keeping the Pro Forma Assumed Upfront Merger Consideration constant, and

assuming an Equillium stock price equal to the Ceiling Price, Equillium would issue 7,410,380 shares. Keeping the Pro Forma Assumed Upfront Merger Consideration constant, a $0.25 decrease from the Ceiling Price would increase the number of shares of common stock Equillium issues at the Closing by 435,904.

The estimated fair value of the outstanding Options and RSUs are included in the consideration transferred in accordance with ASC 805. Because no Metacrine employees will be continuing following Closing, the outstanding Options and RSUs which are vested and in-the-money at the Effective Time will be exchanged into shares of common stock of Equillium based on the Exchange Ratio, those shares of common stock being an allocation of the total shares of common stock issued in the Merger as described above, with no incremental consideration attributed to such equity awards. There is no future service requirement. Any unvested Options or RSUs will be cancelled at the Effective Time.

Each Warrant that is outstanding and unexercised immediately prior to the Merger will be automatically substituted into a warrant to purchase the number of shares of Equillium common stock equal to the product obtained by multiplying the number of Shares subject to the Warrant immediately prior to the Merger by the Exchange Ratio. Each Warrant will have an exercise price per share of Equillium common stock equal to exercise price per Share immediately prior to the Effective Time divided by the Exchange Ratio. The fair value of the warrants to purchase common stock to be issued to the Metacrine debt holders will be allocated to the pro forma long-term notes payable balance.

The total estimated equity consideration was recorded to common stock at par ($0.0001 per share) and the remainder to additional paid-in capital.

Total estimated preliminary purchase consideration consists of the following:

The summary of the preliminary estimated purchase price allocation is as follows (in thousands):

The unaudited pro forma adjustments included in the unaudited pro forma condensed combined financial statements are based on preliminary estimates that may change significantly as additional information is obtained, are as follows:

The pro forma adjustment related to Merger costs of $4.6 million reflected in accumulated deficit consists of the estimated accrual to be incurred by Equillium and Metacrine in connection with the Merger which was not reflected in each of the historical consolidated balance sheets. Approximately $3.7 million of the estimated Merger costs is attributable to Metacrine, and approximately $0.9 million of the estimated Merger costs is attributable to Equillium.

These Merger-related costs are not expected to have a continuing impact on the results of the combined company. There were no material Merger-related costs included in the historical results of operations of Equillium or Metacrine requiring pro forma adjustment.

For illustrative purposes, the following table provides equivalent high and low price per share of Metacrine common stock on each of the specified dates. These equivalent high and low price per share amounts reflect the fluctuating value of Equillium common stock that Metacrine stockholders would receive in exchange for each share of Metacrine common stock if the Merger were completed on either of these dates and assuming an Exchange Ratio of 0.282.

The market value of the shares of Equillium common stock to be issued in exchange of shares of Metacrine common stock upon the completion of the Merger will not be known at the time of the Equillium and Metacrine virtual special meetings. The above tables show only historical comparisons. Because (1) the market prices of Equillium common stock and Metacrine common stock will likely fluctuate prior to the Merger, (2) the Equillium stock price used for the purposes of calculating the Exchange Ratio is determined based on the 10 day trading volume weighted average price per share of Equillium common stock calculated 10 trading days prior to the Closing date, provided that in no event will the price per share of Equillium common stock be less than $2.70 or greater than $4.50 and (3) Metacrine’s Closing net cash and aggregate fully diluted capitalization will not be known until shortly prior to the Closing, these comparisons may not provide meaningful information to (i) Equillium stockholders in determining whether to approve the issuance of shares of Equillium common stock to holders of Metacrine common stock in connection with the Merger pursuant to the Merger Agreement or (ii) Metacrine stockholders in determining whether to adopt the Merger Agreement. Equillium stockholders and Metacrine stockholders are encouraged to obtain current market quotations for shares of Equillium common stock and Metacrine common stock and to review carefully the other information contained in this joint proxy statement/prospectus or incorporated by reference in this joint proxy statement/prospectus in considering whether to approve the issuance of shares of Equillium common stock in connection with the Merger pursuant to the terms of the Merger Agreement, in the case of Equillium stockholders, and whether to adopt the Merger Agreement, in the case of Metacrine stockholders. See the section entitled “Where You Can Find More Information” beginning on page 141 of this joint proxy statement/prospectus.

As of 5:00 p.m. (Eastern Time) on the record date for the Equillium virtual special meeting, 34,352,084 shares of Equillium common stock, held by 49 holders of record, were outstanding and entitled to vote at the Equillium virtual special meeting. As of 5:00 p.m. (Eastern Time) on the record date for the Metacrine virtual special meeting, 42,569,515 shares of Metacrine common stock, held by 35 holders of record, were outstanding and entitled to vote at the Metacrine virtual special meeting.

In addition to the other information included and incorporated by reference into this joint proxy statement/prospectus, including the matters addressed in the section entitled “Cautionary Statement Regarding Forward-Looking Statements,” you should carefully consider the following risks before deciding whether to vote for the adoption and approval of the Merger Agreement, in the case of Metacrine stockholders, or for the issuance of shares of Equillium common stock in connection with the Merger, in the case of Equillium stockholders. In addition, you should read and consider the risks associated with each of the businesses of Equillium and Metacrine because these risks will also affect the combined company. These risks can be found in Equillium’s and Metacrine’s respective Quarterly Reports on Form 10-Q for the fiscal quarter ended June 30, 2022, both of which are filed with the SEC and incorporated by reference into this joint proxy statement/prospectus. You should also read and consider the other information in this joint proxy statement/prospectus and the other documents incorporated by reference into this joint proxy statement/prospectus. See the section entitled “Where You Can Find More Information,” beginning on page 141 of this joint proxy statement/prospectus.

The consummation of the Merger is subject to numerous conditions, including (1) the approval by the Metacrine stockholders of the Metacrine Merger proposals, (2) the approval by the Equillium stockholders of the Equillium Merger proposals, (3) the effectiveness of the Registration Statement on Form S-4 of which the joint proxy statement and prospectus forms a part, (4) Metacrine’s net cash at the Closing being no less than $23,000,000, and (5) other customary closing conditions. See the section “The Merger Agreement – Conditions to Completion of Merger.”

If the Merger is not completed for any reason, including the failure to complete the Merger by January 2, 2023 (or such later date to which such date may be extended in accordance with the terms of the Merger Agreement), the price of Equillium common stock and/or the price of the Metacrine common stock, par value $0.0001, or Metacrine common stock, may decline to the extent that the market price of Equillium common stock or Metacrine common stock, as applicable, reflects or previously reflected positive market assumptions that the Merger would be completed and the related benefits would be realized. In addition, Equillium and Metacrine have expended and will continue to expend significant management time and resources and have incurred and will continue to incur significant expenses due to legal, advisory, printing and financial services fees related to the Merger. These expenses must be paid regardless of whether the Merger is consummated. If the Merger is not consummated because the Merger Agreement is terminated, Equillium may be required under certain circumstances to pay Metacrine a termination fee of $1,750,000 or Metacrine may be required under certain circumstances to pay Equillium a termination fee of $1,250,000. There is no assurance that the Merger will be consummated. If the Merger is not timely completed, Equillium and Metacrine may have to materially alter their respective business plans, including pausing and/or terminating their current and planned clinical trials and the development of their respective product candidates.

In general, either party can refuse to complete the Merger if there is a material adverse change affecting the other party between the signing date of the Merger Agreement, and the Closing. However, certain types of changes do not permit either party to refuse to complete the Merger, even if such change could have a material adverse effect on Equillium and Metacrine, including, subject to certain exceptions, among others:

If one or more material adverse changes occur and Metacrine and Equillium still complete the Merger, the stock price of the combined company following the Closing may suffer. This in turn may reduce the value of the shares of Equillium common stock to the stockholders of the combined company. See “The Merger Agreement” beginning on page 57 for more information.

In connection with the Merger, all of the issued and outstanding shares of Metacrine common stock, will be cancelled and converted into the right to receive consideration per share consisting of (i) the exchange ratio, or the Exchange Ratio, determined by dividing (x) (a) 125% of Metacrine’s net cash as of the Closing, or the Upfront Merger Considerations, divided by (b) the price per share of Equillium common stock determined based on the 10 day trading volume weighted average price per share of Equillium common stock calculated 10 trading days prior to the Closing date, provided that in no event will the price per share of Equillium common stock, or the Equillium Stock Price, be less than $2.70 or greater than $4.50 by (y) the aggregate fully diluted shares of Metacrine, or Metacrine’s Closing Capitalization, plus (ii) any cash payable in lieu of fractional shares of Equillium common stock.

The Exchange Ratio is adjustable, as described above, and the price per share of Equillium common stock may be subject to change prior to, during and following the period during which the price per share of Equillium common stock is set for purposes of the Exchange Ratio. Changes in Metacrine’s net cash as of Closing and the price of Equillium common stock prior to the Merger, will each affect the market value of the Merger consideration that Metacrine stockholders actually receive upon the Closing. Stock price changes may result from a variety of factors (many of which are beyond Metacrine’s and Equillium’s control), including the following factors:

Under the Merger Agreement, there will be no adjustment to the Exchange Ratio for changes in the market price of Equillium common stock within 10 trading days of the Closing, and neither company is permitted to terminate the Merger Agreement or resolicit the vote of Equillium stockholders or Metacrine stockholders solely because of changes in the market price of either company’s stock. You are encouraged to obtain current market quotations for shares of Metacrine common stock and for shares of Equillium common stock before voting.

Because the Merger will be completed after the date of the respective special stockholder meetings, if the special stockholder meeting occurs prior to the finalization of the Closing net cash or more than 10 trading days prior to the Closing, at the time of the applicable special stockholder meeting, the Equillium or Metacrine stockholders may not know the Exchange Ratio or the exact market value of the Equillium common stock that Metacrine stockholders will receive upon completion of the Merger.

For illustrative purposes only, we have calculated the potential Exchange Ratio based on the assumptions and sensitivity analysis set forth herein. Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration, (2) an Equillium Stock Price equal to the Floor Price, and (3) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, the Exchange Ratio would equal 0.282. Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration and (2) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $0.25 increase to the Floor Price would decrease the Exchange Ratio to 0.258. Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration, (2) an Equillium Stock Price equal to the Ceiling Price, and (3) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, the Exchange Ratio would equal 0.169. Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration and (2) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $0.25 decrease to the Ceiling Price would increase the Exchange Ratio to 0.179. Assuming (1) the Equillium Stock Price remains constant and (2) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $1,000,000 increase or decrease in the Upfront Merger Consideration would increase or decrease, respectively, the Exchange Ratio by approximately 0.008.

We encourage you to obtain current market quotations of Equillium common stock, Metacrine common stock and consider the foregoing risk before voting. See the section “The Merger Agreement – Treatment of Metacrine Equity Awards and Warrants” beginning on page 70 for more information.

If the Merger is not completed, the ongoing businesses of Equillium and Metacrine may be adversely affected and Equillium and Metacrine will be subject to several risks, including the following:

In addition, if the Merger is not completed, Equillium or Metacrine could be subject to litigation related to any failure to complete the Merger or to perform their respective obligations under the Merger Agreement.

If the Merger is not completed, Equillium and Metacrine cannot assure their stockholders that these risks will not materialize and will not materially affect the business, financial results and stock prices of Equillium or Metacrine. See the section “The Merger Agreement – Termination of the Merger Agreement” beginning on page 57 for more information.

For purposes of the Merger Agreement, Metacrine cash is subject to certain reductions, including, without limitation, certain short and long term liabilities, unpaid expenses related to the Merger, the purchase of a six-year tail to Metacrine’s directors and officers liability insurance policy, and certain other unpaid obligations, including change of control payments, severance and similar payments payable to its current and former employees, the expected cost and expenses of Metacrine liability arising from legal proceedings, payments in order to terminate certain agreements, and payments (up to the unpaid deductible) under D&O insurance reasonably expected to be paid in connection with legal proceedings. In the event the amount of Metacrine’s net cash at the Closing is less than anticipated, Metacrine’s stockholders could hold a significantly smaller portion of the combined organization. Additionally, the Merger Agreement includes a closing condition that requires Metacrine deliver a minimum net cash of $23 million at the Closing. In the event that Metacrine’s net cash falls below this threshold, Equillium would not be obligated to, but may in its sole discretion elect to, consummate the Merger, which would further reduce Metacrine stockholders holding a smaller portion of the combined organization. See the section “The Merger Agreement – Representations and Warranties” beginning on page 60 for more information.

Equillium has the right to pursue certain strategic transactions and to issue and sell equity and convertible securities subject to certain limitations, the occurrence of which may impact Metacrine’s stockholders’ decisions to vote for the Metacrine merger proposals.

The Merger Agreement allows Equillium to issue, sell or agree to issue or sell shares of Equillium capital stock and/or other equity and convertible securities of Equillium that in the aggregate would not equal or exceed 20% of Equillium’s outstanding capital stock, calculated as of the date of the Merger Agreement, without Metacrine’s consent. Any such issuance or sale of Equillium equity or convertible securities may result in Metacrine stockholders holding a smaller portion of the combined organization. Additionally, in limited circumstances, Equillium may enter into and consummate a strategic transaction to exclusively license or sell, or grant an option to exclusively license or sell, certain of its assets, including Equillium’s rights to develop, manufacture and commercialize EQ001 (itolizumab) without Metacrine’s consent. Should such a transaction occur, it is likely to materially impact Equillium’s stock price and its current and future business plans. Metacrine stockholders should consider these possibilities or the lack of such possibilities, among other things disclosed in this joint proxy/prospectus, in determining whether to vote for the Metacrine merger proposals. See the section “The Merger Agreement – Conduct of Business” beginning on page 62 for more information.

Appraisal rights are statutory rights that, if applicable under law, enable stockholders to dissent from an extraordinary transaction, such as a merger, and to demand that the corporation pay the fair value for their shares as determined by a court in a judicial proceeding instead of receiving the consideration offered to stockholders in connection with the extraordinary transaction.

Under the DGCL § 262(b), stockholders do not have appraisal rights if the shares of stock they hold, as of the record date for determination of stockholders entitled to vote at the meeting of stockholders to act upon a merger, are either (i) listed on a national securities exchange or (ii) held of record by more than 2,000 holders. Notwithstanding the foregoing, appraisal rights are available if stockholders are required by the terms of the merger agreement to accept for their shares anything other than (a) shares of stock of the surviving corporation, (b) shares of stock of another corporation that will either be listed on a national securities exchange or held of record by more than 2,000 holders, (c) cash instead of fractional shares or (d) any combination of clauses (a) through (c).

Equillium stockholders will not be entitled to appraisal rights in the Merger with respect to their Equillium shares. Metacrine shares are listed on Nasdaq and are expected to continue to be so listed on the record date for the Metacrine virtual special meeting. Because holders of shares of Metacrine common stock will receive shares of Equillium common stock in the Merger and cash in lieu of fractional shares, holders of shares of Metacrine common stock will also not be entitled to appraisal rights in the Merger with respect to their shares of Metacrine common stock.

The Merger Agreement contains “no-shop” provisions that, subject to limited exceptions, restrict Metacrine’s and Equillium’s ability to solicit, encourage, facilitate or discuss competing third-party proposals to acquire all or a significant part of Equillium or Metacrine. In addition, the other party generally has an opportunity to offer to modify the terms of the proposed merger in response to any competing acquisition proposals that may be made before such board of directors may withdraw or qualify its recommendation regarding the proposals described herein. In specified circumstances, Equillium or Metacrine may be required to pay a termination fee to the other party due to the termination of the Merger Agreement.

These provisions could discourage a potential competing acquiror that might have an interest in acquiring all or a significant part of Equillium or Metacrine from considering or proposing that acquisition, even if it were prepared to pay consideration with a higher value than that market value proposed to be received or realized in the Merger, or might result in a potential competing acquiror proposing to pay a lower price than it might otherwise have proposed to pay because of the added expense of the termination fee or expenses that may become payable in certain circumstances.

If the Merger Agreement is terminated and either Equillium or Metacrine attempts to seek another business combination, there is no assurance that either Equillium or Metacrine, as applicable, may be able to negotiate a transaction with another party on terms comparable or better than the terms of the Merger. See the section “The Merger Agreement – No Solicitation of Alternative Proposals” beginning on page 65 for more information.

In connection with the Merger, some prospective partners of each of Equillium and Metacrine may delay or defer decisions or reduce their level of business with either or both of the companies, any of which could negatively affect the financials and business plans of Equillium and Metacrine, regardless of whether the Merger is completed. In addition, due to operating covenants in the Merger Agreement, each of Equillium and Metacrine may be unable, during the pendency of the Merger, to pursue strategic transactions, undertake significant capital projects, undertake certain significant financing transactions and otherwise pursue other actions without the consent of the other party or as otherwise discussed elsewhere in these risk factors, even if such actions would prove beneficial. Any of these effects could adversely affect Equillium’s or Metacrine’s respective business prior to the completion of the Merger. Moreover, the pursuit of the Merger and the preparation for the integration of the companies may place a significant burden on the management and personnel of both companies. The diversion of management's attention away from operating the companies in the ordinary course could adversely affect Equillium’s and Metacrine’s financial results and the advancement of their respective product candidates.

After the completion of the Merger, the current securityholders of Equillium and Metacrine will own a smaller percentage of the combined company than their ownership in their respective companies prior to the Merger.

The aggregate value for each share of Metacrine common stock will not be determined until shortly prior to the closing of the Merger. For illustrative purposes only, we have provided the below assumptions and sensitivity analysis to inform your decision.

Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration, (2) an Equillium Stock Price equal to the Floor Price, and (3) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, the Exchange Ratio would equal 0.282. Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration and (2) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $0.25 increase to the Floor Price would decrease the Exchange Ratio to 0.258. Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration, (2) an Equillium Stock Price equal to the Ceiling Price, and (3) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, the Exchange Ratio would equal 0.169. Assuming (1) an Upfront Merger Consideration equal to the Assumed Upfront Merger Consideration and (2) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $0.25 decrease to the Ceiling Price would increase the Exchange Ratio to 0.179. Assuming (1) the Equillium Stock Price remains constant and (2) Metacrine’s Closing Capitalization is equal to the Assumed Metacrine Closing Capitalization, a $1,000,000 increase or decrease in the Upfront Merger Consideration would increase or decrease, respectively, the Exchange Ratio by approximately 0.008. We encourage you to obtain current market quotations of Equillium common stock and Metacrine common stock before voting.

Based on the Assumed Upfront Merger Consideration, Equillium estimates that it may issue between 7.5 and 12.5 million shares of its common stock to Metacrine stockholders in connection with the Closing. Based on the Assumed Upfront Merger Consideration and 34,352,084 shares of Equillium common stock outstanding as of November 9, 2022, we estimate that current Equillium stockholders will own between 82.08% and 73.32% of the outstanding common stock of the combined company and former Metacrine equityholders will own between 17.92% and 26.68% of the outstanding common stock of the combined company.

Equillium stockholders and Metacrine stockholders currently have the right to vote for their respective directors and on certain other matters affecting their company. If and when the Merger occurs, each Equillium stockholder will remain a stockholder of Equillium with a percentage ownership of Equillium that will be smaller than the stockholder’s percentage of Equillium prior to the Merger (without considering such stockholder’s current ownership of Metacrine shares, if any). Correspondingly, each Metacrine stockholder who receives shares of Equillium common stock will become an Equillium stockholder with a percentage ownership of Equillium that will be smaller than the stockholder’s percentage ownership of Metacrine (without considering such stockholder’s current ownership of Equillium common stock). Equillium stockholders will have less voting power in Equillium than they currently have, and former Metacrine stockholders will have less voting power in Equillium than they now have in Metacrine. Each of Equillium and Metacrine’s pre-Merger stockholders, respectively, as a group, will be able to exercise less influence over the management and policies of the combined company following the consummation of the Merger than immediately prior to the consummation of the Merger. See the section “The Merger Agreement – Treatment of Metacrine Equity Awards and Warrants” beginning on page 70 for more information.

Upon completion of the Merger, holders of Metacrine common stock will become holders of Equillium common stock. Equillium’s business differs from that of Metacrine in certain respects, and, accordingly, the financial position or results of operations and/or cash flows of Equillium after the Merger, as well as the market price of shares of Equillium common stock, may be affected by factors different from those currently affecting the financial position or results of operations and/or cash flows of Metacrine. In addition, the stock market has experienced significant price and volume fluctuations in recent times which, if they continue to occur, could have a material adverse effect on the market for, or liquidity of, the Equillium common stock, regardless of Equillium's actual operating performance. As a result, the market price of shares of Equillium common stock may fluctuate significantly following completion of the Merger, and holders of Metacrine common stock could lose some or all of the value of their investment in Equillium common stock.

In considering whether to approve the proposals at the special meetings, Equillium and Metacrine stockholders should recognize that directors and executive officers of Equillium and Metacrine have interests in the Merger that may differ from, or that are in addition to, their interests as stockholders of Equillium and stockholders of Metacrine. The Equillium Board and the Metacrine Board were aware of these interests at the time each approved the Merger Agreement. These interests may cause Equillium's and Metacrine's directors and executive officers to view the Merger differently than you may view it as a stockholder. The interests include, among others, severance benefits, continued indemnification and the right to accelerated vesting. For example, Metacrine previously entered into severance and bonus agreements with certain members of management that provide them with cash severance payments, certain health insurance coverage and the acceleration of their outstanding equity awards in the event their employment is terminated in connection with a change of control of Metacrine.

The Equillium Board received a written opinion, or the VPA Opinion, dated September 6, 2022 from Vantage Point Advisors, Inc., its financial advisor, that the Merger transaction was fair, from a financial point of view, to the Equillium common stockholders, as of such date, and based on and subject to the qualifications, limitations and assumptions set forth in the VPA Opinion (including, without limitation, the accuracy and completeness of the audited and unaudited financial statements, forecasts and other information provided to it by the Equillium Board and the assurances from the Equillium Board that they were unaware of any facts or circumstances that would make the VPA Opinion incomplete or misleading). The VPA Opinion did not constitute a recommendation to the Equillium Board (or any member thereof) as to how it should vote with respect to the Merger transaction. The Metacrine Board received written opinions from MTS, an affiliate of its financial advisor MTS Health Partners, LP, or MTS Partners, dated September 2, 2022, or the September MTS Opinion, and October 19, 2022, or the October MTS Opinion and together with the September Opinion, the MTS Opinions, that as of such dates and based upon and subject to the assumptions made, procedures followed, matters considered and qualifications and limitations on the scope of review undertaken by MTS, as set forth in the MTS Opinions, the Exchange Ratio employed in the Merger pursuant to the Merger Agreement was fair to the holders of shares of Metacrine common stock (other than Excluded Shares), from a financial point of view. Changes in the operations or prospects of Equillium or Metacrine, general market and economic conditions and other factors that may be beyond the control of Equillium and Metacrine, and on which the above-described opinions were based, may alter the value of Equillium or Metacrine or the prices of shares of Equillium Common stock or Metacrine common stock by the time the Merger is completed. Except for the October MTS Opinion, Equillium and Metacrine have not obtained, and do not expect to request, updated opinions from their respective financial advisors. None of the above-listed opinions speak to any date other than the date of such opinion. See the sections “The Merger Agreement – Opinion of Equillium’s Financial Advisor” beginning on page 96, and “The Merger Agreement – Opinions of Metacrine’s Financial Advisor” beginning on page 103 for more information.

As of December 31, 2021, Metacrine had federal net operating loss carryforwards, which we refer to as NOLs, of approximately $164.5 million. In general, under Section 382 of the Code, a corporation that undergoes an “ownership change” is subject to limitations on its ability to utilize its pre-ownership change NOLs to offset future taxable income. As of December 31, 2021, Metacrine has not completed a Section 382 limitation study. If the Merger is completed, Metacrine's existing NOLs may be subject to limitations. In addition, if Equillium undergoes any subsequent ownership change, its ability to utilize NOLs would be limited.

U.S. holders of Metacrine common stock will recognize gains or losses for U.S. federal income tax purposes on each share of Metacrine common stock surrendered in the Merger in an amount equal to the difference between (1) the fair market value of the merger consideration received in exchange for such surrendered share upon completion

of the Merger and (2) the holder's basis in the share of Metacrine common stock surrendered. Any gain or loss recognized would be long-term capital gain or loss if the U.S. holder's holding period in a particular block of Metacrine common stock exceeds one year at the effective time of the Merger. Long-term capital gain of non-corporate U.S. holders (including individuals) is taxed at reduced U.S. federal income tax rates. See the section “Material U.S. Federal Income Tax Consequences” beginning on page 123 for more information.

Equillium expects to incur substantial costs and expenses in connection with completing the Merger and integrating Metacrine’s business. While Equillium has assumed that a certain level of transaction and integration costs and expenses would be incurred, there are a number of factors beyond its control that could affect the total amount or the timing of its integration costs and expenses, including any Metacrine liabilities that arise, or become known, following the Closing. Many of the costs and expenses that will be incurred, by their nature, are difficult to estimate accurately at the present time. Due to these factors, the transaction and integration costs and expenses could be greater or could be incurred over a longer period of time than Equillium currently expects.

In connection with the Closing, Equillium intends to enter into an arrangement with Metacrine’s current lender, K2 HealthVentures LLC, to amend and assume Metacrine’s current debt facility with an outstanding principal balance of $15 million, or the K2 Debt Arrangement. If Equillium and K2 HealthVentures LLC are able to consummate the K2 Debt Arrangement, Equillium would retire its existing debt facility with Oxford Finance LLC and Silicon Valley Bank, which currently has an outstanding principal amount of $10 million, or the Existing Debt Facility. After retiring the Existing Debt Facility and as a result of the Merger, Equillium anticipates adding approximately $35 million in cash to its balance sheet at the Closing. As a condition of the K2 Debt Arrangement, K2 HealthVentures LLC may require Equillium to provide additional warrant coverage, which, if issued and exercised, would dilute both Equillium and Metacrine stockholders’ ownership in the combined organization.

There are no assurances that Equillium and K2 HealthVentures LLC will be able to agree on terms mutually acceptable to each other with respect to the K2 Debt Arrangement. If Equillium and K2 HealthVentures LLC are unable to agree on acceptable terms for the K2 Debt Arrangement, Metacrine’s existing debt facility with K2 HealthVentures LLC will be retired at the Closing. If Metacrine’s existing debt facility is retired at the Closing, Equillium would expect to add approximately $27 million in cash to its balance sheet at the Closing and continue to maintain its Existing Debt Facility.

The restrictions and obligations contained in the K2 Debt Arrangement, if consummated, may differ from those under the Existing Debt Facility and Metacrine’s existing debt facility. Equillium anticipates the terms of the K2 Debt Arrangement will subject its business to the risks normally associated with debt financing, including the following risks:

If any of the above risks occurred, Equillium’s financial condition and results of operations could be materially adversely affected. See section “Description of the Merger” beginning on page 21 for more information.

The development of biotechnology product candidates is capital-intensive. As Equillium conducts non-clinical research and clinical development of its product candidates, Equillium will need substantial additional funds to maintain and expand its capabilities in a variety of areas including research, clinical development, regulatory affairs, product quality assurance, and pharmacovigilance. In addition, if Equillium obtains marketing approval for any of its product candidates, Equillium expects to incur significant commercialization expenses for marketing, sales, manufacturing and distribution. Some of those commercialization investments may be made at-risk in advance of receiving an approval. Because the outcome of any preclinical study or clinical trial is highly uncertain, we cannot reasonably estimate the actual amounts necessary to successfully complete the development and commercialization of our drug candidates. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.

Based on Equillium’s current operating plan, Equillium believes that its existing cash and cash equivalents, together with the cash proceeds from the Merger, will be sufficient to fund its operating expenses and capital expenditure requirements through at least calendar year 2023. In particular, Equillium expects the cash proceeds from the Merger, together with its existing cash and cash equivalents, will allow it to advance its clinical development plans through topline data from the EQUALISE study, interim data from its planned Phase 2 study of EQ101 in alopecia areata and interim data from its planned Phase 1 study of EQ102 in healthy volunteers as well as in subjects with celiac disease. Equillium’s operating plan may change as a result of many factors currently unknown to it, and Equillium may need to seek additional funding sooner than planned.

Until such time as Equillium can generate significant revenue from sales of its product candidates, if ever, Equillium expects to finance its cash needs through equity offerings, debt financings or other capital sources, including potentially grants, collaborations, licenses or other similar arrangements. Accordingly, Equillium will need to continue to rely on additional financing to achieve its business objectives. If Equillium is unable to raise additional capital when needed, its ability to grow and support its business and to respond to market challenges could be significantly limited, which could have a material adverse effect on its business, financial condition and results of operations. Any additional capital raising efforts may divert Equillium’s management from their day-to-day activities, which may adversely affect its ability to develop and, if approved, commercialize its current and any future drug candidates. Additional funding may not be available on acceptable terms, or at all.

The competitors of the combined company include major pharmaceutical and biotechnology companies, academic institutions, government agencies, public and private research institutions, and smaller or early stage companies, of which many are well-capitalized. The competitiveness of the combined company, is based on factors including the efficacy, safety and convenience of our product candidates, our combined ability to raise capital and enter into strategic transactions, and recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials. If the combined company is unable to compete based on such factors, the combined company's results of operations and business prospects could be harmed.

The combined company will have numerous product candidates and two discovery platforms and will need to prioritize its research programs and focus development of its product candidates on the potential treatment of certain indications. As a result, the combined company may forego or delay pursuit of opportunities with other indications or for any future product candidates that later prove to have greater commercial potential. The resource allocation decisions of the combined company may cause it to fail to capitalize on viable commercial products or profitable market opportunities. Such failure may result in the combine company being unable to

raise additional capital to continue to fund its existing programs and operations, and could lead to stockholders losing all or substantially all of their investment in Equillium.

The combined company will operate in an increasingly complex regulatory environment. Businesses in the countries in combined company will operate are subject to local, legal and political environments and regulations including with respect to employment, tax, statutory supervision and reporting and trade restriction. These regulations and environments are also subject to change.

Adjusting business operations to changing environments and regulations may be costly and could potentially render the particular business operations uneconomical, which may adversely affect the profitability of the combined company or lead to a change in the business operations.

Notwithstanding the best efforts of the combined company, it may not be in compliance with all regulations in the countries in which it operates at all times and may be subject to sanctions, penalties or fines as a result. These sanctions, penalties or fines may materially and adversely impact the profitability of the combined.

Equillium and Metacrine will continue to operate as separate companies prior to the Merger. Equillium and Metacrine have no prior history as a combined company. The historical financial statements of Metacrine may be different from those that would have resulted had Metacrine been operated as part of Equillium. The pro forma condensed combined financial information appearing elsewhere herein has been presented for informational purposes only and is not necessarily indicative of the financial position or results of operations that actually would have occurred had the Merger been completed as of the dates indicated, nor is it indicative of the future operating results or financial position of the combined company. The unaudited pro forma condensed combined financial information reflects adjustments, which are based upon preliminary estimates, to allocate the aggregate consideration to Metacrine assets and liabilities. The aggregate consideration allocation reflected in the pro forma condensed combined financial information included in this joint proxy statement/prospectus is preliminary, and the final allocation of the aggregate consideration will be based upon the actual aggregate consideration and the fair value of the assets and liabilities of Metacrine as of the date of the completion of the Merger. The unaudited pro forma condensed combined financial information does not reflect future events that may occur after the Merger, including the incurrence of costs related to the planned integration of Metacrine, any future non-recurring charges resulting from the Merger, or consider potential effects of future market conditions on expense efficiencies, if any. The unaudited pro forma financial information presented in this joint proxy statement/prospectus is based in part on certain assumptions regarding the Merger that Equillium believes are reasonable under the circumstances. Equillium cannot assure you that the assumptions will prove to be accurate over time.

While presented with numeric specificity, the Equillium and Metacrine prospective financial information provided in this document was prepared based on numerous variables and assumptions (including, but not limited to, those related to industry performance and competition and general business, economic, market and financial conditions, and additional matters specific to Equillium or Metacrine business, as applicable, including the possibility of consummating certain other strategic transactions) that are inherently subjective and uncertain and are largely beyond the control of the respective management of each. As a result, actual results may differ from the prospective financial information. Important factors that may affect actual results and cause these projected financial forecasts to not be achieved include, but are not limited to, risks and uncertainties relating to Equillium’s or Metacrine’s business, as applicable (including each company’s ability to achieve strategic goals, objectives and targets over applicable periods) and general industry, business, competitive and economic conditions.

Securities class action lawsuits and derivative lawsuits are often brought against public companies that have entered into merger agreements. Even if the lawsuits are without merit, defending against these claims could result in substantial costs and divert management time and resources. An adverse judgment could result in monetary damages, which could have a negative impact on Equillium’s and Metacrine’s respective liquidity and financial condition. Additionally, if a plaintiff is successful in obtaining an injunction prohibiting completion of the Merger, then that injunction may delay or prevent the Merger from being completed, which may adversely affect Equillium’s and Metacrine’s respective business, financial position and results of operations.

Equillium’s and Metacrine’s businesses are, and following completion of the transaction Equillium will continue to be, subject to the risks described above and in Equillium’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, as amended and as updated by subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K and Metacrine’s Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2022, as amended and as updated by subsequent Current Reports on Form 8-K, all of which are filed with the SEC and incorporated by reference into this joint proxy statement/prospectus. See “Where You Can Find More Information” beginning on page 141 for the location of information incorporated by reference in this joint proxy statement/prospectus.

This joint proxy statement/prospectus and the documents incorporated by reference into this joint proxy statement/prospectus contain forward-looking statements. These forward-looking statements are based on current expectations and beliefs and involve numerous risks and uncertainties that could cause actual results to differ materially from expectations. These forward-looking statements should not be relied upon as predictions of future events as it cannot be assured that the events or circumstances reflected in these statements will be achieved or will occur. You can identify forward-looking statements by the use of forward-looking terminology including “anticipates,” “believes,” “could,” “seeks,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “pro forma,” “should,” “will,” “would,” or the negative of these words and phrases or other variations of these words and phrases or comparable terminology. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. For example, forward-looking statements include, but are not limited to statements about:

For a discussion of the factors that may cause Equillium, Metacrine or the combined company’s actual results, performance or achievements following the Closing to differ materially from any future results, performance or achievements expressed or implied in such forward-looking statements, or for a discussion of risk associated with the ability of Equillium and Metacrine to complete the Merger and the effect of the Merger on the business of Equillium, Metacrine and the combined company following the completion of the Merger, see the section titled “Risk Factors” in this joint proxy statement/prospectus. Additional factors that could cause actual results to differ materially from those expressed in the forward-looking statements are discussed in reports filed with the SEC by Equillium and Metacrine. See the section titled “Where You Can Find More Information” in this joint proxy statement/prospectus. There can be no assurance that the Merger will be completed, or if it is completed, that it will close within the anticipated time period or that the expected benefits of the Merger will be realized.

If any of these risks or uncertainties materializes or any of these assumptions proves incorrect, the results of Equillium, Metacrine or the combined company following completion of the Merger could differ materially from the forward-looking statements. All forward-looking statements in this joint proxy statement/prospectus are current only as of the date on which the statements were made. Equillium and Metacrine do not undertake any obligation (and expressly disclaim any such obligation) to publicly update any forward-looking statement to reflect events or circumstances after the date on which any statement is made or to reflect the occurrence of unanticipated events, except as required by applicable law.

In addition, statements that “Equillium believes” or “Metacrine believes” and similar statements reflect Equillium’s or Metacrine’s beliefs and opinions on the relevant subject. These statements are based upon information available to Equillium or Metacrine, as the case may be, as of the date of this joint proxy statement/prospectus, and while Equillium or Metacrine, as the case may be, believes such information forms a reasonable basis for such statements, such information may be limited or incomplete, and such statements should not be read to indicate that such party has conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.

This joint proxy statement/prospectus is being mailed on or about November 10, 2022, to holders of record of Equillium common stock as of the close of business on November 9, 2022, and constitutes notice of the Equillium virtual special meeting in conformity with the requirements of the DGCL.

This joint proxy statement/prospectus is being provided to Equillium stockholders as part of a solicitation of proxies by the Equillium Board for use at the Equillium virtual special meeting and at any adjournments or postponements of the Equillium virtual special meeting. Equillium stockholders are encouraged to read the entire document carefully, including the annexes to and documents incorporated by reference into this document, for more detailed information regarding the Merger Agreement.

The Equillium virtual special meeting will be held via live webcast on December 20, 2022, starting at 12:00 p.m. (Eastern Time). There will be no physical meeting location. In order to attend the Equillium 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/EQ2022SM 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 the Equillium virtual special meeting, Equillium stockholders will be asked to consider and vote upon the following proposals:

At a meeting of the Equillium Board held on September 5, 2022, the Equillium Board determined that the Merger Agreement and the transactions contemplated thereby, including the issuance of shares of Equillium common stock to the Metacrine stockholders in connection with the Merger, are in the best interests of Equillium 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.

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

See also the section entitled “The Merger—Reasons for the Merger; Recommendation of the Merger by the Equillium Board” beginning on page 87.

Only holders of record of shares of Equillium common stock at the close of business on November 9, 2022, the record date for the Equillium virtual special meeting, will be entitled to notice of, and to vote at, the Equillium virtual special meeting and any postponements or adjournments thereof. Holders of Equillium common stock at the close of business on the Equillium record date may cast one vote for each share of Equillium common stock that you owned as of the Equillium record date, 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 Equillium record date, there were outstanding a total of 34,352,084 shares of Equillium common stock entitled to vote at the Equillium virtual special meeting.

The cost of proxy solicitation for the Equillium virtual special meeting, if any, and expenses for the filing, printing and mailing of this joint proxy statement/prospectus will be borne by Equillium. In addition to the use of the mail, proxies may be solicited by officers and directors and regular employees of Equillium, without additional remuneration, by personal interview, telephone, electronic communication or otherwise. Equillium will

also request brokerage firms, nominees, custodians and fiduciaries to forward proxy materials to the beneficial owners of shares held of record on the Equillium record date and will provide customary reimbursement to such firms for the cost of forwarding these materials. Equillium has not retained a proxy solicitor to assist in its solicitation of proxies.

The holders of a majority of the voting power of Equillium’s outstanding shares of common stock entitled to vote as of the close of business on the Equillium record date must be virtually present or represented by proxy to constitute a quorum to conduct the Equillium virtual special meeting. All shares of Equillium common stock represented at the Equillium virtual special meeting, including abstentions and broker non-votes (shares held by a broker or nominee that are represented at the meeting, but with respect to which the broker or nominee is not instructed by the beneficial owner of such shares to vote on the particular proposal), will be treated as present for purposes of determining the presence or absence of a quorum to conduct the Equillium virtual special meeting.

The chairperson of the Equillium virtual special meeting may, if necessary, adjourn the Equillium virtual special meeting for the purpose of soliciting additional proxies (whether or not a quorum exists).

If you are an Equillium stockholder, abstentions and broker “non-votes” have no effect on the outcome of the stock issuance proposal or the Equillium adjournment proposal. Shares of Equillium common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon. If you are an Equillium stockholder of record and you sign and return your proxy card without indicating how to vote on any particular proposal, the shares of Equillium common stock represented by your proxy will be counted as present for purposes of determining the presence of a quorum for the Equillium virtual special meeting and will be voted “FOR” that proposal. Your failure to cast a vote will also make it more difficult to meet the quorum requirement with respect to organizing the meeting.

On the Equillium record date, 25.5% of the outstanding Equillium common stock was held by Equillium directors and executive officers and their respective affiliates. Equillium currently expects that its directors and executive officers will vote their shares in favor of Equillium stock issuance proposal and the Equillium adjournment proposal.

All holders of Equillium common stock, including stockholders of record and stockholders who hold shares through banks, brokers or other nominees, are invited to virtually attend the Equillium virtual special meeting. Stockholders of record can vote at the special meeting. In order to attend the Equillium 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/EQ2022SM 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.

A proxy card is enclosed for use by Equillium stockholders of record. Equillium requests that its record stockholders sign the accompanying proxy and return it promptly in the enclosed postage-paid envelope. You may also vote your shares by telephone or through the Internet. Information and applicable deadlines for voting

by telephone or through the Internet are set forth on the enclosed proxy card. Shares of Equillium common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon. If you are an Equillium stockholder of record and you sign and return your proxy card without indicating how to vote on any particular proposal, the shares of Equillium common stock represented by your proxy will be counted as present for purposes of determining the presence of a quorum for the Equillium virtual special meeting and will be voted “FOR” that proposal.

At the date hereof, Equillium management has no knowledge of any business that will be presented for consideration at the special meeting and which would be required to be set forth in this joint proxy statement/prospectus other than the matters set forth in Equillium’s accompanying Notice of Special Meeting of Stockholders. In accordance with Equillium’s bylaws and Delaware law, business transacted at the Equillium virtual special meeting will be limited to those matters set forth in such notice. Nonetheless, if any other matter is properly presented at the Equillium virtual special meeting for consideration, it is intended that the persons named in the enclosed proxy and acting thereunder will vote in accordance with their best judgment on such matter.

Your vote is important. Whether or not you expect to attend the Equillium virtual special meeting in person, 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 Equillium virtual special meeting.

If you hold your shares of Equillium common stock in a stock brokerage account or if your shares are held by a bank or nominee (that is, in street name), you must provide the record holder of your shares with instructions on how to vote your shares if you wish them to be counted. Please follow the voting instructions provided by your broker, bank or nominee. Please note that you may not vote shares held in street name by returning a proxy card directly to Equillium or by voting at the Equillium virtual special meeting. Further, brokers who hold shares of Equillium common stock on behalf of their customers may not vote those shares without specific instructions from their customers.

If you hold your Equillium common stock in street name and you do not instruct your broker on how to vote any of your shares, your broker may not vote those shares. For a discussion of the consequences of such broker non-votes, see “The Equillium virtual special meeting—Abstentions and Broker Non-Votes” beginning on page 44 of this joint proxy statement/prospectus.

If you are a holder of shares of Equillium common stock as of the record date for the Equillium virtual special meeting, you have the power to revoke your proxy at any time before your proxy is voted at the Equillium virtual special meeting. You can revoke your proxy in one of four ways:

The latest dated completed proxy will be the one that counts. Written notices of revocation and other communications with respect to the revocation of any proxies should be addressed to:

If you are an Equillium stockholder whose shares of Equillium common stock are held in “street name” by a bank, broker, or other nominee, you may revoke your proxy or voting instructions and vote your shares in person at the Equillium virtual special meeting only in accordance with applicable rules and procedures as employed by your bank, broker, or other nominee. If your shares are held in “street name” in an account at a bank, broker, or other nominee, you must follow the directions you receive from your bank, broker, or other nominee in order to change or revoke your proxy or voting instructions and should contact your bank, broker, or other nominee to do so.

Although it is not currently expected, the Equillium virtual special meeting may be adjourned for the purpose of soliciting additional proxies if Equillium has not received sufficient proxies to constitute a quorum or sufficient votes for approval of the Equillium stock issuance proposal. Adjourning the Equillium virtual special meeting requires the affirmative vote of the holders of Equillium common stock representing a majority of the votes cast on such matter at the Equillium virtual special meeting (whether or not a quorum is present), or in the case that no Equillium stockholders are present at the Equillium virtual special meeting, any Equillium officer entitled to preside at or to act as secretary of the Equillium virtual special meeting may adjourn the Equillium virtual special meeting. Pursuant to the Equillium bylaws, notice need not be given of any such adjourned meeting if the time and place thereof are announced at the meeting at which adjournment is taken. If the adjournment is for more than 30 days or if after the adjournment a new record date is fixed for the adjourned meeting, a notice of the adjourned meeting shall be given to each stockholder of record entitled to vote at the Equillium virtual special meeting. At any adjourned meeting, any business may be transacted which might have been transacted at the original meeting. If the Equillium virtual special meeting is adjourned, stockholders who have already sent in their proxies will be allowed to revoke them at any time prior to their use. The Merger Agreement provides that the Equillium virtual special meeting will not be adjourned to a date that is more than 15 calendar days after the date for which the Equillium virtual special meeting was originally scheduled.

At any time prior to convening the Equillium virtual special meeting, the Equillium Board may postpone the Equillium virtual special meeting for any reason without the approval of the Equillium stockholders. The Merger Agreement provides that the Equillium virtual special meeting will not be postponed to a date that is more than 15 calendar days after the date for which the Equillium virtual special meeting was originally scheduled. Although it is not currently expected, the Equillium Board may postpone the Equillium virtual special meeting for the purpose of soliciting additional proxies if Equillium has not received sufficient proxies to constitute a quorum or sufficient votes for approval of the Equillium stock issuance proposal. If the Equillium virtual special meeting is postponed, stockholders who have already sent in their proxies will be allowed to revoke them at any time prior to their use.

A list of Equillium stockholders entitled to vote at the Equillium virtual special meeting will be available for inspection at Equillium’s principal executive offices, located at 2223 Avenida de la Playa, Suite 105, La Jolla, California 92037, at least 10 days prior to the date of the Equillium virtual special meeting and continuing through the date thereof for any purpose germane to the Equillium virtual special meeting, between the hours of 9:00 a.m. and 4:30 p.m., local time.

A representative of Equillium’s mailing and tabulating agent, Broadridge Financial Solutions, will tabulate the votes and Equillium’s corporate secretary will act as inspector of elections.

Equillium has adopted a procedure approved by the Securities and Exchange Commission called “householding.” Under this procedure, stockholders of record who have the same address and last name and who do not participate in electronic delivery of proxy materials will receive only one copy of the proxy materials,

unless one or more of these stockholders notifies Equillium that they wish to continue receiving individual copies. This procedure reduces Equillium’s printing costs and postage fees. Stockholders who wish to participate in householding will continue to receive separate proxy cards.

If you are eligible for householding, but you and other stockholders of record with whom you share an address currently receive multiple copies of the proxy materials, or if you hold stock in more than one account, and, in either case, you wish to receive only a single copy of the proxy materials for your household, please contact your broker.

If you participate in householding and wish to receive a separate copy of the proxy materials, or if you do not wish to continue to participate in householding and prefer to receive separate copies of the proxy materials in the future, please contact your broker or Equillium. Direct your written request to Equillium, Inc., Investor Relations, 2223 Avenida de la Playa, Suite 105, La Jolla, California 92037 or contact Investor Relations at (858) 240-1200 or by email at ir@equilliumbio.com.

Beneficial owners can request information about householding from their banks, brokers, or other holders of record.

If you need assistance in completing your proxy card or have questions regarding the Equillium virtual special meeting, please contact Investor Relations at (858) 240-1200 or email ir@equilliumbio.com.

Equillium stockholders are asked to approve the issuance of shares of Equillium common stock to Metacrine stockholders in connection with the Merger contemplated by the Merger Agreement. Equillium stockholders should carefully read this joint proxy statement/prospectus in its entirety, including the documents incorporated by reference and the Merger Agreement, for more detailed information concerning the Merger Agreement and the Equillium stock issuance proposal. For a detailed discussion of the terms of the Merger Agreement and the Merger, including the proposed Equillium stock issuance, see the information about the Merger and the Merger Agreement throughout this joint proxy statement/prospectus, including the information set forth in the section entitled “The Merger Agreement” beginning on page 57 of this joint proxy statement/prospectus. A copy of the Merger Agreement is attached as Annex A to this joint proxy statement/prospectus.

Approval of the Equillium stock issuance proposal is a condition to completion of the Merger. If the Equillium stock issuance proposal is not approved, the Merger will not occur. For a detailed discussion of the conditions of the Merger, see “The Merger Agreement—Conditions to Completion of the Merger” beginning on page 72 of this joint proxy statement/prospectus.

Approval of the Equillium stock issuance proposal requires the affirmative vote of the holders of shares of Equillium common stock representing a majority of the votes cast on such matter at the Equillium virtual special meeting (provided that a quorum exists). For the Equillium stock issuance proposal, abstentions and broker “non-votes” will have no effect on the outcome of the proposal. If an Equillium stockholder returns a signed proxy card without indicating voting preferences on such proxy card, the shares of Equillium common stock represented by that proxy will be counted as present for purposes of determining the presence of a quorum for the Equillium virtual special meeting and all of such shares will be voted as recommended by the Equillium Board.

At a meeting of the Equillium Board held on September 5, 2022, the Equillium Board determined that the Merger Agreement and the transactions contemplated thereby, including the issuance of shares of Equillium common stock to the Metacrine stockholders in connection with the Merger, were in the best interests of Equillium 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.

This proposal would permit the Equillium Board to adjourn from time to time the Equillium virtual special meeting, if necessary, to solicit additional proxies if there are not sufficient votes to approve the Equillium stock issuance proposal.

Pursuant to Equillium’s bylaws, notice need not be given of any such adjourned meeting if the time and place thereof are announced at the meeting at which the adjournment is taken. If the adjournment is for more than 30 days or if, after the adjournment, a new record date is fixed for the adjourned meeting, a notice of the adjourned meeting shall be given to the Equillium stockholders of record entitled to vote at the adjourned meeting. At any adjourned meeting, any business may be transacted which might have been transacted at the original meeting.

Approval of the Equillium adjournment proposal requires the affirmative vote of the holders of Equillium common stock representing a majority of the votes cast on such matter at the Equillium virtual special meeting (whether or not a quorum is present). For the Equillium adjournment proposal, abstentions and broker “non-votes” will have no effect on the outcome of the proposal. Shares of Equillium common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon. If an Equillium stockholder returns a signed proxy card without indicating voting preferences on such proxy card, the shares of Equillium common stock represented by that proxy will be counted as present for purposes of determining the presence of a quorum for the Equillium virtual special meeting and all of such shares will be voted as recommended by the Equillium Board.

This joint proxy statement/prospectus is being mailed on or about November 10, 2022, to holders of record of Metacrine common stock as of the close of business on November 9, 2022, and constitutes notice of the Metacrine virtual special meeting in conformity with the requirements of the DGCL.

This joint proxy statement/prospectus is being provided to Metacrine stockholders as part of a solicitation of proxies by the Metacrine board of directors for use at the Metacrine virtual special meeting and at any adjournments or postponements of the Metacrine virtual special meeting. Metacrine stockholders are encouraged to read the entire document carefully, including the annexes to and documents incorporated by reference into this document, for more detailed information regarding the Merger Agreement

The Metacrine virtual special meeting will be held via live webcast on December 20, 2022, starting at 12:00 p.m. (Eastern Time). There will be no physical meeting location. In order to attend the Metacrine 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/MTCR2022SM 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 the Metacrine virtual special meeting, Metacrine stockholders will be asked to consider and vote upon the following proposals:

Pursuant to an action by unanimous written consent of the Metacrine Board dated September 5, 2022, which was reaffirmed by the Metacrine Board on October 19, 2022, the Metacrine Board determined that the Merger Agreement and the transactions contemplated thereby are in the best interests of Metacrine 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 recommended that Metacrine’s stockholders adopt the Merger Agreement.

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

See also the section entitled “The Merger—Reasons for the Merger; Recommendation of the Merger by the Metacrine Board” beginning on page 88.

Only holders of record of shares of Metacrine common stock at the close of business on November 9, 2022, the record date for the Metacrine virtual special meeting, will be entitled to notice of, and to vote at, the Metacrine virtual special meeting and any postponements or adjournments thereof. Holders of Metacrine common stock at the close of business on the Metacrine record date may cast one vote for each share of Metacrine common stock that you owned as of the Metacrine record date, 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 Metacrine record date, there were outstanding a total of 42,569,515 shares of Metacrine common stock entitled to vote at the Metacrine virtual special meeting.

The cost of proxy solicitation for the Metacrine virtual special meeting will be borne by Metacrine. In addition to the use of the mail, proxies may be solicited by officers and directors and regular employees of Metacrine, without additional remuneration, by personal interview, telephone, electronic communication or

otherwise. Metacrine will also request brokerage firms, nominees, custodians and fiduciaries to forward proxy materials to the beneficial owners of shares held of record on the Metacrine record date and will provide customary reimbursement to such firms for the cost of forwarding these materials. Metacrine has retained Morrow Sodali, LLC to assist in its solicitation of proxies and has agreed to pay them a fee of $25,000 and potentially additional fees under certain circumstances, plus reasonable expenses, for these services.

The holders of a majority of the voting power of Metacrine’s outstanding shares of common stock entitled to vote as of the close of business on the Metacrine record date must be virtually present or represented by proxy to constitute a quorum to conduct the Metacrine virtual special meeting. All shares of Metacrine common stock represented virtually at the Metacrine virtual special meeting, including abstentions and broker non-votes (shares held by a broker or nominee that are represented at the meeting, but with respect to which the broker or nominee is not instructed by the beneficial owner of such shares to vote on the particular proposal), will be counted for purposes of determining the presence or absence of a quorum to conduct the Metacrine virtual special meeting.

If you are a Metacrine stockholder, failure to vote at the virtual special meeting or by proxy at the special meeting, abstentions, and broker non-votes (if any) will have the same effect as a vote against the Metacrine merger proposal. Assuming a quorum is present, (i) a failure to vote at the virtual special meeting or vote by proxy at the Metacrine virtual special meeting will have no effect on the outcome of the Metacrine adjournment proposal, (ii) abstentions will be treated as votes cast and, therefore, will have the same effect as a vote against the Metacrine adjournment proposal, and (iii) broker “non-votes” (if any) will have no effect on the outcome of the Metacrine adjournment proposal. Shares of Metacrine common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon. If you are a Metacrine stockholder of record and you sign and return your proxy card without indicating how to vote on any particular proposal, the shares of Metacrine common stock represented by your proxy will be counted as present for purposes of determining the presence of a quorum for the Metacrine virtual special meeting and will be voted “FOR” that proposal.

On the Metacrine record date, 8.4 % of the outstanding Metacrine common stock was held by Metacrine directors and executive officers and their respective affiliates. Metacrine currently expects that its directors and executive officers will vote their shares in favor of the Metacrine merger proposal and the Metacrine adjournment proposal.

All holders of Metacrine common stock, including stockholders of record and stockholders who hold shares through banks, brokers or other nominees, are invited to virtually attend the Metacrine virtual special meeting. Stockholders of record can vote at the special meeting. In order to attend the Metacrine 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/MTCR2022SM 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.

A proxy card is enclosed for use by Metacrine stockholders of record. Metacrine requests that its record stockholders sign the accompanying proxy and return it promptly in the enclosed postage-paid envelope. You may also vote your shares by telephone or through the Internet. Information and applicable deadlines for voting

by telephone or through the Internet are set forth on the enclosed proxy card. Shares of Metacrine common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon. If you are a Metacrine stockholder of record and you sign and return your proxy card without indicating how to vote on any particular proposal, the shares of Metacrine common stock represented by your proxy will be counted as present for purposes of determining the presence of a quorum for the Metacrine virtual special meeting and will be voted “FOR” that proposal.

At the date hereof, Metacrine management has no knowledge of any business that will be presented for consideration at the special meeting and which would be required to be set forth in this joint proxy statement/prospectus other than the matters set forth in Metacrine’s accompanying Notice of Special Meeting of Stockholders. In accordance with Metacrine’s bylaws and Delaware law, business transacted at the Metacrine virtual special meeting will be limited to those matters set forth in such notice. Nonetheless, if any other matter is properly presented at the Metacrine virtual special meeting for consideration, it is intended that the persons named in the enclosed proxy and acting thereunder will vote in accordance with their best judgment on such matter.

Your vote is important. Whether or not you expect to attend the Metacrine virtual special meeting in person, 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 Metacrine virtual special meeting.

If you hold your shares of Metacrine common stock in a stock brokerage account or if your shares are held by a bank or nominee (that is, in street name), you must provide the record holder of your shares with instructions on how to vote your shares if you wish them to be counted. Please follow the voting instructions provided by your broker, bank or nominee. Please note that you may not vote shares held in street name by returning a proxy card directly to Metacrine or by voting at the Metacrine virtual special meeting. Further, brokers who hold shares of Metacrine common stock on behalf of their customers may not vote those shares without specific instructions from their customers.

If you hold your Metacrine common stock in street name and you do not instruct your broker on how to vote any of your shares, your broker may not vote those shares. For a discussion of the consequences of such broker non-votes, see “The Metacrine virtual special meeting—Abstentions and Broker Non-Votes” beginning on page 51 of this joint proxy statement/prospectus.

If you are a holder of shares of Metacrine common stock as of the record date for the Metacrine virtual special meeting, you have the power to revoke your proxy at any time before your proxy is voted at the Metacrine virtual special meeting. You can revoke your proxy in one of four ways:

The latest dated completed proxy will be the one that counts. Written notices of revocation and other communications with respect to the revocation of any proxies should be addressed to:

If you are a Metacrine stockholder whose shares of common stock are held in “street name” by a bank, broker, or other nominee, you may revoke your proxy or voting instructions and vote your shares in person at the Metacrine virtual special meeting only in accordance with applicable rules and procedures as employed by your bank, broker, or other nominee. If your shares are held in “street name” in an account at a bank, broker, or other nominee, you must follow the directions you receive from your bank, broker, or other nominee in order to change or revoke your proxy or voting instructions and should contact your bank, broker, or other nominee to do so.

Although it is not currently expected, the Metacrine virtual special meeting may be adjourned for the purpose of soliciting additional proxies if Metacrine has not received sufficient proxies to constitute a quorum or sufficient votes for approval of the Metacrine merger proposal. Adjourning the Metacrine virtual special meeting requires the affirmative vote of the holders of Metacrine common stock representing a majority of the votes cast on such matter at the Metacrine virtual special meeting (whether or not a quorum is present), or in the case that no Metacrine stockholders are present at the Metacrine virtual special meeting, any Metacrine officer entitled to preside at or to act as secretary of the Metacrine virtual special meeting may adjourn the Metacrine virtual special meeting. Pursuant to the Metacrine bylaws, notice need not be given of any such adjourned meeting if the time and place thereof are announced at the meeting at which adjournment is taken. If the adjournment is for more than 30 days or if after the adjournment a new record date is fixed for the adjourned meeting, a notice of the adjourned meeting shall be given to each stockholder of record entitled to vote at the Metacrine virtual special meeting. At any adjourned meeting, any business may be transacted which might have been transacted at the original meeting. If the Metacrine virtual special meeting is adjourned, stockholders who have already sent in their proxies will be allowed to revoke them at any time prior to their use. The Merger Agreement provides that the Metacrine virtual special meeting will not be adjourned to a date that is more than 15 calendar days after the date for which the Metacrine virtual special meeting was originally scheduled.

At any time prior to convening the Metacrine virtual special meeting, the Metacrine Board may postpone the Metacrine virtual special meeting for any reason without the approval of the Metacrine stockholders. The Merger Agreement provides that the Metacrine virtual special meeting will not be postponed to a date that is more than 15 calendar days after the date for which the Metacrine virtual special meeting was originally scheduled. Although it is not currently expected, the Metacrine Board may postpone the Metacrine virtual special meeting for the purpose of soliciting additional proxies if Metacrine has not received sufficient proxies to constitute a quorum or sufficient votes for approval of the Metacrine merger proposal. If the Metacrine virtual special meeting is postponed, stockholders who have already sent in their proxies will be allowed to revoke them at any time prior to their use.

A list of Metacrine stockholders entitled to vote at the Metacrine virtual special meeting will be available for inspection at Metacrine’s principal executive offices, located at 4225 Executive Square, Suite 600, San Diego, CA 92037, at least 10 days prior to the date of the Metacrine virtual special meeting and continuing through the date thereof for any purpose germane to the Metacrine virtual special meeting, between the hours of 9:00 a.m. and 4:30 p.m., local time.

A representative of Metacrine’s mailing and tabulating agent, Broadridge Financial Solutions, will tabulate the votes and Metacrine’s corporate secretary will act as inspector of elections.

Metacrine has adopted a procedure approved by the Securities and Exchange Commission called “householding.” Under this procedure, stockholders of record who have the same address and last name and who do not participate in electronic delivery of proxy materials will receive only one copy of the proxy materials, unless one or more of these stockholders notifies Metacrine that they wish to continue receiving individual copies. This procedure reduces Metacrine’s printing costs and postage fees. Stockholders who wish to participate in householding will continue to receive separate proxy cards.

If you are eligible for householding, but you and other stockholders of record with whom you share an address currently receive multiple copies of the proxy materials, or if you hold stock in more than one account, and, in either case, you wish to receive only a single copy of the proxy materials for your household, please contact your broker.

If you participate in householding and wish to receive a separate copy of the proxy materials, or if you do not wish to continue to participate in householding and prefer to receive separate copies of the proxy materials in the future, please contact your broker or Metacrine. Direct your written request to Metacrine, Inc., Investor Relations, 4225 Executive Square, Suite 600, San Diego, CA 92037 or contact Investor Relations at (858) 369-7800 or by email at investors@metacrine.com.

Beneficial owners can request information about householding from their banks, brokers, or other holders of record.

If you need assistance in completing your proxy card or have questions regarding the Metacrine virtual special meeting, please contact Morrow Sodali, LLC, the proxy solicitor for Metacrine, by telephone toll-free at (800) 662-5200.

Metacrine stockholders are asked to approve the adoption of the Merger Agreement. Metacrine stockholders should carefully read this joint proxy statement/prospectus in its entirety, including the documents incorporated by reference and the Merger Agreement, for more detailed information concerning the Merger Agreement and the Metacrine merger proposal. For a detailed discussion of the terms of the Merger Agreement and the Merger, see the information about the Merger and the Merger Agreement throughout this joint proxy statement/prospectus, including the information set forth in the section entitled “The Merger Agreement” beginning on page 57 of this joint proxy statement/prospectus. A copy of the Merger Agreement is attached as Annex A to this joint proxy statement/prospectus.

Approval of the Metacrine merger proposal is a condition to completion of the Merger. If the Metacrine merger proposal is not approved, the Merger will not occur. For a detailed discussion of the conditions of the Merger, see “The Merger Agreement—Conditions to Completion of the Merger” beginning on page 72 of this joint proxy statement/prospectus.

Approval of the Metacrine merger proposal requires the affirmative vote of a majority of the outstanding shares of Metacrine's common stock. Failure to vote at the virtual special meeting or vote by proxy at the special meeting, abstentions, and broker non-votes (if any) will have the same effect as a vote against the Metacrine merger proposal. Shares of Metacrine common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon. If a Metacrine stockholder returns a signed proxy card without indicating voting preferences on such proxy card, the shares of Metacrine common stock represented by that proxy will be counted as present for purposes of determining the presence of a quorum for the Metacrine virtual special meeting and all of such shares will be voted as recommended by the Metacrine Board.

Pursuant to an action by unanimous written consent of the Metacrine Board dated September 5, 2022, which was reaffirmed by the Metacrine Board on October 19, 2022, the Metacrine Board determined that the Merger Agreement and the transactions contemplated thereby were in the best interests of Metacrine 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 recommended that Metacrine’s stockholders adopt the Merger Agreement.

This proposal would permit the Metacrine Board to adjourn from time to time the Metacrine virtual special meeting, if necessary, to solicit additional proxies if there are not sufficient votes to approve the Metacrine merger proposal.

Pursuant to the Metacrine bylaws, notice need not be given of any such adjourned meeting if the time and place thereof are announced at the meeting at which adjournment is taken. If the adjournment is for more than 30 days or if after the adjournment a new record date is fixed for the adjourned meeting, a notice of the adjourned meeting shall be given to each stockholder of record entitled to vote at the Metacrine virtual special meeting. At any adjourned meeting, any business may be transacted which might have been transacted at the original meeting.

Approval of the Metacrine adjournment proposal requires the holders of Metacrine common stock representing a majority of the votes cast on such matter at the Metacrine virtual special meeting (whether or not a quorum exists). For the Metacrine adjournment proposal, abstentions and broker “non-votes” will have no effect on the outcome of the proposal. Shares of Metacrine common stock represented by properly executed, timely received and unrevoked proxies will be voted in accordance with the instructions indicated thereon. If a Metacrine stockholder returns a signed proxy card without indicating voting preferences on such proxy card, the shares of Metacrine common stock represented by that proxy will be counted as present for purposes of determining the presence of a quorum for the Metacrine virtual special meeting and all of such shares will be voted as recommended by the Metacrine Board.

The following section summarizes the material provisions of the Merger Agreement, which is included in this joint proxy statement/prospectus as Annex A and is incorporated herein by reference in its entirety. The rights and obligations of Equillium and Metacrine are governed by the express terms and conditions of the Merger Agreement and not by this summary or any other information contained in this joint proxy statement/prospectus. Equillium and Metacrine stockholders are urged to read the Merger Agreement carefully and in its entirety as well as this joint proxy statement/prospectus before making any decisions regarding the Merger, including the adoption by the Metacrine stockholders of the Merger Agreement or the approval by the Equillium stockholders of the issuance of shares of Equillium common stock in connection with the Merger. This summary is qualified in its entirety by reference to the Merger Agreement.

The Merger Agreement, as amended on October 26, 2022 to join Acquisition Sub II as a party, is described in this joint proxy statement/prospectus to provide you with information regarding its terms. The Merger Agreement is not intended to provide any other factual information about Equillium or Metacrine, their respective businesses, or the actual conduct of their respective businesses during the period prior to the consummation of the Merger or the other transactions contemplated therein. The Merger Agreement contains representations and warranties that are the product of negotiations among the parties thereto which were made only for purposes of such agreement and as of specified dates. The assertions embodied in those representations and warranties are subject to qualifications and limitations agreed to by the respective parties and are also qualified in important part by confidential disclosure letters delivered by and to each of Equillium and Metacrine in connection with the Merger Agreement. The representations and warranties may be subject to standards of materiality applicable to the contracting parties that differ from those applicable to stockholders or investors. Information concerning the subject matter of the representations and warranties may change after the date of the Merger Agreement, which subsequent information may or may not be fully reflected in Equillium’s or Metacrine’s public disclosures.

Accordingly, the representations and warranties and other provisions of the Merger Agreement should not be read alone, but instead should be read together with the information provided elsewhere in this joint proxy statement/prospectus and in the documents incorporated by reference into this joint proxy statement/prospectus. See “Where You Can Find More Information” beginning on page 141 of this joint proxy statement/prospectus.

Pursuant to the Merger Agreement, and in accordance with Delaware law, at the effective time of the Merger, Merger Sub will be merged with and into Metacrine, with Metacrine continuing as a direct wholly owned subsidiary of Equillium.

At the effective time of the Merger, each share of Metacrine common stock issued and outstanding (other than shares held in treasury, if any), will be automatically converted into the right to receive a number of validly issued, fully paid and non-assessable shares of Equillium common stock as determined by applying the Exchange Ratio, which we refer to as the merger consideration.

As used in this joint proxy statement/prospectus, the Exchange Ratio means (x) (a) 125% of Metacrine’s net cash as defined below, or Metacrine Net Cash, as of the closing of the Merger, or the Upfront Merger Consideration, divided by (b) the price per share of Equillium common stock determined based on the 10 day trading volume weighted average price per share of Equillium common stock calculated 10 trading days prior to the closing date of the Merger, provided that in no event will such value of the price per share of Equillium common stock be less than $2.70 per share or greater than $4.50 per share, or the Equillium Stock Price, divided by (y) the aggregate fully diluted shares of Metacrine, or Metacrine’s as defined below, or Aggregate Fully Diluted Shares, subject to adjustment for as a result of any reclassification, stock split (including a reverse stock split), stock dividend or distribution, recapitalization, merger, reorganization, subdivision, or other similar transaction. In the event of any reclassification, stock split, reverse stock split, stock dividend, stock distribution, recapitalization, subdivision or other similar transaction with respect to the shares of Metacrine common stock or shares of Equillium common stock prior to the effective time of the Merger, the merger consideration will be equitably adjusted to eliminate the effects of such event on the merger consideration as contemplated by the Merger Agreement.

Metacrine Net Cash means (a) the sum of (i) Metacrine’s and its subsidiaries’ cash and cash equivalents, and (ii) to the extent not already reflected in the immediately foregoing prong (i), the aggregate amount of all

deposits, prepaid expenses, and including short term investments held by Metacrine or its subsidiaries (in each including any interest, earnings or other income earned thereon), in each case as of the anticipated Closing Date, minus (b) the sum of the Metacrine’s short and long term liabilities, including accounts payable and accrued expenses (without duplication of any expenses accounted for below), in each case as of such date and determined in a manner consistent with the manner in which such items were historically determined and in accordance with Metacrine’s audited financial statements and unaudited balance sheet as of June 30, 2022 to the extent consistent with GAAP, minus (c) the amount of all fees and expenses incurred by Metacrine and its subsidiaries in connection with the transactions contemplated by the Merger Agreement, including for the avoidance of doubt transaction expenses incurred by Metacrine and its subsidiaries, to the extent unpaid as of the Closing, minus (d) the cash cost of any unpaid change of control payments or severance, termination or similar payments pursuant to a contract, plan or applicable Law that are or become due to any current or former employee, director or independent contractor of Metacrine and its subsidiaries, or any other third party arising out of, relating to, or in connection with the occurrence of the Closing, minus (e) the cash cost of any paid time off, accrued and unpaid retention payments or other bonuses due to any current or former employee, director or independent contractor of Metacrine and its subsidiaries as of the Closing Date, minus (f) all payroll, employment or other withholding Taxes incurred by Metacrine and its subsidiaries and any affiliate of Metacrine (to the extent paid or to be paid by Metacrine on the behalf of such affiliate) in connection with any payment amounts set forth in clauses (d) or (e) and the exercise of any Metacrine Option on or prior to the Effective Time, minus (g) the cash cost of any unpaid retention payment amounts due under any insurance policy with respect to any legal proceeding against Metacrine or any of its subsidiaries, minus (h) the expected cost and expenses of the aggregate liability of Metacrine or any of its subsidiaries for liabilities arising from legal proceedings, minus (i) notice payments, fines or other payments to be made by Metacrine or any of its subsidiaries in order to terminate any existing agreement to which Metacrine is a party, minus (j) payments up to the unpaid deductible amount under Metacrine’s director and officer insurance reasonably expected to be payable in connection with legal proceedings in effect as of the date of the Merger Agreement or initiated following the date of the Merger Agreement and before the Closing assumed by the insurer or expected to be assumed by the insurer, minus (k) the expected cost, and/or any premium related to the director and officer insurance tail policy, minus (l) the amount of any accounts payable of Metacrine or any of its subsidiaries that are past the original vendor due date as of the anticipated Closing Date, minus (m) the amount of any indebtedness, plus (n) any interest expenses required to be paid by Metacrine under its existing loan and security agreement on or after October 1, 2022 and prior to the Closing Date.

Aggregate Fully Diluted Shares means the aggregate number of shares of Metacrine common stock, but excluding shares of Metacrine common stock held in treasury, that are (a) issued and outstanding immediately prior to the Effective Time; or (b) issuable upon, or subject to, the exercise or settlement of any Metacrine warrants, convertible securities, stock options or other equity awards or other similar securities, in each case as of immediately prior to the Effective Time.

Equillium will not issue fractional shares of Equillium common stock pursuant to the Merger Agreement. Instead, each Metacrine stockholder who otherwise would have been entitled to receive a fraction of a share of Equillium common stock will receive cash in lieu thereof, as provided in the Merger Agreement.

At least five days prior to the anticipated closing date of the Merger, which date shall be agreed upon by Equillium and Metacrine 10 days prior to the later of (i) the Equillium virtual special meeting and (ii) the Metacrine virtual special meeting, in each case subject to adjournment or postponement, Metacrine shall deliver to Equillium a schedule setting forth a good faith estimated calculation of the Metacrine Net Cash as of the anticipated closing date of the Merger, or the Net Cash Schedule. Within three days after delivery of the Net Cash Schedule, Equillium has the right to dispute any part of the Net Cash Schedule by delivering a written notice identifying in reasonable detail the nature of any proposed revisions to the Net Cash Schedule. If Equillium does not respond within three days after the delivery of the Net Cash Schedule or notifies Metacrine that it has no objections, the Net Cash Schedule shall be final and represent the Metacrine Net Cash.

If Equillium timely disputes the Net Cash Schedule, Equillium and Metacrine shall promptly meet and attempt in good faith to resolve the disputed item(s) and negotiate an agreed upon determination of Metacrine Net Cash. If Equillium and Metacrine are unable to negotiate an agreed upon determination of Metacrine Net Cash, within three days of Equillium delivering a dispute notice to the Net Cash Schedule, Equillium and

Metacrine shall select an independent auditor to resolve any remaining disagreements to the calculation of Metacrine Net Cash. Equillium and Metacrine shall use commercially reasonable efforts to cause the auditor to make its determination within 10 days of after accepting its selection. The determination of the Metacrine Net Cash made by the auditor shall be deemed final for purposes of the Merger Agreement. The fees of the auditor shall be borne by the parties in the same proportion that the disputed amount of Metacrine Net Cash was unsuccessfully disputed by such party based on the total disputed amount of Metacrine Net Cash. The parties shall not be required to determine Metacrine Net Cash again after it is finally determined even if the closing of the Merger occurs after the anticipated closing date of the Merger, except either party may request a re-determination of Metacrine Net Cash if the closing of the Merger is more than five business days after the anticipated closing date of the Merger.

Prior to the effective time of the Merger, the parties will designate American Stock Transfer & Trust Company, LLC, or AST, or if AST is unwilling or unable to serve then such other mutually agreeable bank or trust company to act as the exchange agent in connection with the Merger, or the Exchange Agent. At the Closing, Equillium will issue and cause to be deposited with the Exchange Agent (i) non-certificated shares of Equillium common stock issuable pursuant to the Merger Agreement in book-entry form equal to the aggregate merger consideration (excluding any cash in lieu of fractional shares payable pursuant to the Merger Agreement) and (ii) cash in immediately available funds in an amount sufficient to pay in lieu of fractional shares payable pursuant to the Merger Agreement, in each case, for the sole benefit of the holders of shares of Metacrine common stock.

Upon surrender of stock certificates, if such shares of Metacrine common stock are represented by a stock certificate, accompanied by an executed letter of transmittal and other documents described in the instructions or, in the case of uncertificated shares, an “agent’s message” in customary form, of Metacrine common stock for cancellation, a Metacrine stockholder will receive the following: (i) the share consideration to which such Metacrine stockholder is entitled and (ii) cash in lieu of fractional shares of Equillium common stock, if any. Metacrine stockholders will not receive any fractional shares of Equillium common stock pursuant to the Merger. After the effective time of the Merger, Metacrine will not register any transfers of the shares of Metacrine common stock. Shares of Equillium common stock issued in connection with the Merger will be issued in uncertificated, book-entry form.

After the effective time of the Merger, shares of Metacrine common stock will no longer be issued and outstanding, will be canceled and will cease to exist, and (A) each certificate, if any, that previously represented Metacrine common stock and (B) each book-entry account formerly representing any uncertificated shares of Metacrine common stock will represent only the right to receive the merger consideration as described above. With respect to such shares of Equillium common stock deliverable upon the surrender of Metacrine share certificates, until holders of such Metacrine share certificates have surrendered such stock certificates to the exchange agent for exchange, those holders will not receive dividends or distributions with respect to such shares of Equillium common stock with a record date after the effective time of the Merger.

Equillium stockholders need not take any action with respect to their stock certificates.

The closing of the Merger will take place (a) via electronic exchange of required closing documentation, as soon as reasonably practicable, and in no event later than three business days after the satisfaction or waiver of the conditions to the closing of the Merger have been satisfied or waived (other than conditions that by their nature cannot be satisfied until the closing of the Merger, which shall be required to be so satisfied or waived in accordance with the Merger Agreement upon the closing date of the Merger) or (b) at such other time, date or place as Equillium and Metacrine may agree in writing. The Merger will become effective upon the filing of the certificate of Merger with the Secretary of State of the State of Delaware, in accordance with the laws of Delaware.

The Merger Agreement contains representations and warranties made by each of Equillium, Acquisition Sub I, Acquisition Sub II, Merger Sub and Metacrine related to, among other things: