Proxy Statement (Form DEF 14A)

VIGIL NEUROSCIENCE, INC.

100 Forge Road, Suite 700

Watertown, MA 02472

NOTICE OF 2025 ANNUAL MEETING OF STOCKHOLDERS

To be held May 22, 2025

Notice is hereby given that the 2025 Annual Meeting of Stockholders of Vigil Neuroscience, Inc. (the "Annual Meeting") will be held online on May 22, 2025 at 8:00 a.m. EasteTime. The Annual Meeting will be held virtually, and you may attend the meeting via the Internet at www.virtualshareholdermeeting.com/VIGL2025, where you will be able to vote electronically and submit questions. You will need the 16-digitcontrol number included with the Notice of Internet Availability of Proxy Materials being mailed to you separately in order to attend the Annual Meeting.

Stockholders of record at the close of business on March 26, 2025, the record date for the Annual Meeting, are entitled to notice of, and to vote at, the Annual Meeting or any adjournment or postponement of the Annual Meeting. The purpose of the Annual Meeting is the following:

You can find more information on each of the matters to be voted on at the Annual Meeting, including information regarding the nominees for election to our board of directors, in the accompanying proxy statement. The board of directors recommends a vote "FOR" the election of each of the two nominees for class I directors and "FOR" the ratification of the appointment of our independent registered public accounting firm for the fiscal year ending December 31, 2025, as disclosed in the accompanying proxy statement.

This year, the Company is following the Securities and Exchange Commission's "Notice and Access" rule that allows companies to furnish their proxy materials by posting them on the Internet. As a result, we are mailing to our stockholders a Notice of Internet Availability of Proxy Materials (the "Notice") instead of a paper copy of the accompanying proxy statement and our Annual Report for the fiscal year ended December 31, 2024 (the "2024 Annual Report"). We are mailing the Notice on or about March 31, 2025, and it contains instructions on how to access both the 2024 Annual Report and accompanying proxy statement (the "Proxy Materials") over the Internet. This method provides our stockholders with expedited access to Proxy Materials and not only lowers the cost of printing and distribution but also reduces the environmental impact of the Annual Meeting. If you would like to receive a print version of the Proxy Materials, free of charge, please follow the instructions on the Notice.

To attend the Annual Meeting virtually via the Internet, please visit www.virtualshareholdermeeting.com/VIGL2025. This is a virtual meeting and you will not be able to attend the Annual Meeting in person.

Whether or not you expect to attend the Annual Meeting online, we encourage you to read the accompanying proxy statement and vote your shares as promptly as possible to ensure your representation and

the presence of a quorum at the Annual Meeting on the Internet as described in the instructions included in the Notice by voting online at www.proxyvote.com. If you requested and received a paper copy of the Proxy Materials, you can vote by signing, dating and returning the enclosed proxy card, calling 1-800-690-6903and following the recorded instructions, or online at www.proxyvote.com. If you vote your shares on the Internet or by telephone, you will need to enter the 16-digitcontrol number provided in the Notice.

Your vote is important regardless of the number of shares you own. If you attend the Annual Meeting online, you may vote your shares during the Annual Meeting virtually via the Internet even if you previously voted your proxy. Your proxy is revocable in accordance with the procedures set forth in the proxy statement.

If your shares are held in "street name," that is, held for your account by a broker or other nominee, you will receive instructions from the holder of record that you must follow for your shares to be voted.

Watertown, Massachusetts

March 31, 2025

Table of Contents

VIGIL NEUROSCIENCE, INC.

100 Forge Road, Suite 700

Watertown, MA 02472

PROXY STATEMENT

FOR THE 2025 ANNUAL MEETING OF STOCKHOLDERS

TO BE HELD MAY 22, 2025

This proxy statement contains information about the 2025 Annual Meeting of Stockholders, or the Annual Meeting, of Vigil Neuroscience, Inc., which will be held on May 22, 2025 at 8:00 a.m. EasteTime. The board of directors of Vigil Neuroscience, Inc. is using this proxy statement to solicit proxies for use at the Annual Meeting. In this proxy statement, the terms "Vigil Neuroscience," "we," "us," and "our" refer to Vigil Neuroscience, Inc. The mailing address of our principal executive office is Vigil Neuroscience, Inc., 100 Forge Road, Suite 700, Watertown, MA 02472.

All properly submitted proxies will be voted in accordance with the instructions contained in those proxies. If no instructions are specified, the proxies will be voted in accordance with the recommendation of our board of directors with respect to each of the matters set forth in the accompanying Notice of Meeting. You may revoke your proxy at any time before it is exercised at the meeting by giving our corporate secretary written notice to that effect.

We will make our proxy statement and our Annual Report to Stockholders for the fiscal year ended December 31, 2024 available to stockholders on or about March 31, 2025.

We are an "emerging growth company" under applicable federal securities laws and therefore permitted to conform with certain reduced public company reporting requirements. As an emerging growth company, we provide in this proxy statement the scaled disclosure permitted under the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, including the compensation disclosures required of a "smaller reporting company," as that term is defined in Rule 12b-2promulgated under the Securities Exchange Act of 1934, as amended, or the Exchange Act. In addition, as an emerging growth company, we are not required to conduct votes seeking approval, on an advisory basis, of the compensation of our named executive officers or the frequency with which such votes must be conducted, and we are not required to provide pay versus performance disclosure under Item 402(v) of Regulation S-K.We will remain an "emerging growth company" until the earliest of (i) the last day of the fiscal year following the fifth anniversary of our initial public offering in January 2022; (ii) the last day of the fiscal year in which our total annual gross revenue is equal to or more than $1.235 billion; (iii) the date on which we have issued more than $1 billion in nonconvertible debt during the previous three years; or (iv) the date on which we are deemed to be a large accelerated filer under the rules of the Securities and Exchange Commission, or the SEC. Even after we are no longer an "emerging growth company," we may remain a "smaller reporting company."

Important Notice Regarding the Availability of Proxy Materials for

the Annual Meeting of Stockholders to be Held on May 22, 2025:

This proxy statement and our 2024 Annual Report to Stockholders are

available for viewing, printing and downloading at https://materials.proxyvote.com/92673K

A copy of our Annual Report on Form 10-Kfor the fiscal year ended December 31, 2024, as filed with the SEC, except for exhibits, will be furnished without charge to any stockholder upon written request to Vigil Neuroscience, Inc., 100 Forge Road, Suite 700, Watertown, MA 02472, Attention: Corporate Secretary. This proxy statement and our Annual Report on Form 10-Kfor the fiscal year ended December 31, 2024 are also available on the SEC's website atwww.sec.gov.

VIGIL NEUROSCIENCE, INC

PROXY STATEMENT

FOR THE 2025 ANNUAL MEETING OF STOCKHOLDERS

GENERAL INFORMATION

When are this proxy statement and the accompanying materials scheduled to be sent to stockholders?

We have elected to provide access to our proxy materials to our stockholders via the Internet. Accordingly, on or about March 31, 2025, we will begin mailing a Notice of Internet Availability of Proxy Materials, or Notice. Our proxy materials, including the Notice of the 2025 Annual Meeting of Stockholders, this proxy statement and the accompanying proxy card or, for shares held in street name (i.e., held for your account by a broker or other nominee), a voting instruction form, and the 2024 Annual Report to Stockholders, or 2024 Annual Report, will be mailed or made available to stockholders on the Internet on or about the same date.

Why did I receive a Notice of Internet Availability of Proxy Materials instead of a full set of proxy materials?

Pursuant to rules adopted by the SEC, for most stockholders, we are providing access to our proxy materials over the Internet rather than printing and mailing our proxy materials. We believe following this process will expedite the receipt of such materials and will help lower our costs and reduce the environmental impact of our annual meeting materials. Therefore, the Notice will be mailed to holders of record and beneficial owners of our common stock starting on or about March 31, 2025. The Notice provides instructions as to how stockholders may access and review our proxy materials, including the Notice of the 2025 Annual Meeting of Stockholders, this proxy statement, the proxy card and our 2024 Annual Report, on the website referred to in the Notice or, alternatively, how to request that a copy of the proxy materials, including a proxy card, be sent to them by mail. The Notice also provides voting instructions. In addition, stockholders of record may request to receive the proxy materials in printed form by mail or electronically by e-mailon an ongoing basis for future stockholder meetings. Please note that, while our proxy materials are available at the website referenced in the Notice, and our Notice of the 2025 Annual Meeting of Stockholders, this proxy statement and our 2024 Annual Report are available on our website, no other information contained on either website is incorporated by reference in or considered to be a part of this proxy statement.

Who is soliciting my vote?

Our board of directors is soliciting your vote for the Annual Meeting, including at any adjournments or postponements of the Annual Meeting.

When is the record date for the Annual Meeting?

The record date for determination of stockholders entitled to vote at the Annual Meeting is the close of business on March 26, 2025.

How many votes can be cast by all stockholders?

There were 46,671,534 shares of our common stock, par value $0.0001 per share, outstanding on March 26, 2025, all of which are entitled to vote with respect to all matters to be acted upon at the Annual Meeting on May 22, 2025. Each stockholder of record is entitled to one vote for each share of our common stock held by such stockholder. None of our outstanding shares of Series A Non-VotingConvertible Preferred Stock are entitled to vote at the Annual Meeting on May 22, 2025.

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Who is entitled to vote?

Registered Stockholders. If shares of our common stock are registered directly in your name with our transfer agent, you are considered the stockholder of record with respect to those shares. As the stockholder of record, you have the right to grant your voting proxy directly to the individuals listed on the proxy card or vote on your own behalf at our virtual Annual Meeting. Throughout this proxy statement, we refer to these registered stockholders as "stockholders of record."

Street Name Stockholders. If shares of our common stock are held on your behalf in a brokerage account or by a bank or other nominee, you are considered to be the beneficial owner of shares that are held in "street name," and the proxy materials were forwarded to you by your broker or nominee, who is considered the stockholder of record with respect to those shares. As the beneficial owner, you have the right to direct your broker, bank or other nominee as to how to vote your shares. Beneficial owners are also invited to attend our virtual Annual Meeting. However, since a beneficial owner is not the stockholder of record, you may not vote your shares of our common stock on your own behalf at the Annual Meeting unless you follow your broker's procedures for obtaining a legal proxy. Note you should also be receiving a voting instruction form for you to use from your broker. Throughout this proxy statement, we refer to stockholders who hold their shares through a broker, bank or other nominee as "street name stockholders."

How do I vote?

If you are a stockholder of record, there are several ways for you to vote your shares.

If the Annual Meeting is adjourned or postponed, the deadlines above may be extended.

The voting deadlines and availability of telephone and Internet voting for beneficial owners of shares held in "street name" will depend on the voting processes of the organization that holds your shares. Therefore, we urge you to carefully review and follow the voting instruction card and any other materials that you receive from that organization. If you hold your shares of Vigil Neuroscience, Inc., common stock in multiple accounts, youshould vote your shares as described in each set of proxy materials you receive.

By Proxy

If you will not be attending the Annual Meeting, you may vote by proxy. You can vote by proxy over the Internet by following the instructions provided in the enclosed proxy card. Proxies submitted by mail must be received before the start of the Annual Meeting.

If you submit a proxy without giving voting instructions, your shares will be voted in the manner recommended by the board of directors on all matters presented in this proxy statement, and as the persons

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named as proxies in the proxy card may determine in their discretion with respect to any other matters properly presented at the Annual Meeting. You may also authorize another person or persons to act for you as proxy in a writing, signed by you or your authorized representative, specifying the details of those proxies' authority. The original writing must be given to each of the named proxies, although it may be sent to them by electronic transmission if, from that transmission, it can be determined that the transmission was authorized by you.

If any other matters are properly presented for consideration at the Annual Meeting, including, among other things, consideration of a motion to adjouthe Annual Meeting to another time or place (including, without limitation, for the purpose of soliciting additional proxies), the persons named in your proxy and acting thereunder will have discretion to vote on those matters in accordance with their best judgment. We do not currently anticipate that any other matters will be raised at the Annual Meeting.

How can I virtually attend the Annual Meeting?

To attend and participate in the Annual Meeting, stockholders will need to access the live webcast of the meeting. To do so, stockholders of record will need to visit www.virtualshareholdermeeting.com/VIGL2025, and beneficial owners of shares held in street name will need to follow the instructions provided in the voting instructions form by the broker, bank or other nominee that holds their shares.

The live webcast of the Annual Meeting will begin promptly at 8:00 a.m. EasteTime on May 22, 2025. We encourage stockholders to login to this website and access the webcast before the Annual Meeting's start time by following the instructions in the email received prior to the morning of the Annual Meeting. You should allow ample time in advance of the meeting.

Additionally, questions regarding how to attend and participate via the Internet can be answered by following the assistance instructions included on the virtual meeting website (www.virtualshareholdermeeting.com/VIGL2025) or by calling the phone number provided on the virtual meeting website on the day of the Annual Meeting.

If you wish to submit a question during the Annual Meeting, you may log into, and submit a question on, the virtual meeting platform using the unique link provided to you on your proxy card and following the instructions there. Our Annual Meeting will be governed by the Annual Meeting's Rules of Conduct, which will address the ability of stockholders to ask questions during the meeting and rules for how questions will be recognized and addressed. The Annual Meeting's Rules of Conduct will be available during the meeting on the virtual meeting website (www.virtualshareholdermeeting.com/VIGL2025).

How do I revoke my proxy?

You may revoke your proxy by (1) following the instructions on the Notice and entering a new vote by mail that we receive before the start of the Annual Meeting or over the Internet by the cutoff time of 11:59 p.m. EasteTime on May 21, 2025, (2) attending and voting at the Annual Meeting (although attendance at the Annual Meeting will not in and of itself revoke a proxy), or (3) by filing an instrument in writing revoking the proxy or another duly executed proxy bearing a later date with our corporate secretary. Any written notice of revocation or subsequent proxy card must be received by our corporate secretary prior to the taking of the vote at the Annual Meeting. Such written notice of revocation or subsequent proxy card should be hand delivered to our corporate secretary or sent to our principal executive offices at Vigil Neuroscience, Inc., 100 Forge Road, Suite 700, Watertown, MA 02472, Attention: Corporate Secretary.

If a broker, bank, or other nominee holds your shares, you must contact such broker, bank, or nominee in order to find out how to change your vote.

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How is a quorum reached?

Our Amended and Restated Bylaws, or bylaws, provide that the presence, in person, by remote communication, if applicable, or by proxy duly authorized, of the holders of a majority of the outstanding shares of stock entitled to vote, will constitute a quorum for the transaction of business at the Annual Meeting. Our outstanding Series A Non-VotingConvertible Preferred Stock is not entitled to vote at the Annual Meeting and is not counted for purposes of determining whether a quorum is present.

Under the General Corporation Law of the State of Delaware, shares that are voted "abstain" or "withheld" and broker "non-votes"are counted as present for purposes of determining whether a quorum is present at the Annual Meeting. If a quorum is not present, the meeting may be adjourned until a quorum is obtained. There were 46,671,534 shares of common stock outstanding and entitled to vote on March 26, 2025, our record date. Therefore, a quorum will be present if 23,335,768 shares of our common stock are present in person or represented by executed proxies timely received by us at the Annual Meeting. Shares present virtually during the Annual Meeting will be considered shares of common stock represented in person at the meeting.

How is the vote counted?

Under our bylaws, to be elected, each of the directors nominated in Proposal No. 1 must receive a plurality of the shares present in person, by remote communication, if applicable, or represented by proxy duly authorized at the meeting and entitled to vote generally on the election of directors, meaning that the director nominees receiving the highest number of affirmative votes will be elected as directors. You may vote for all the director nominees, withhold authority to vote your shares for all the director nominees or withhold authority to vote your shares with respect to any one or more of the director nominees. Withholding authority to vote your shares with respect to one or more director nominees will have no effect on the election of directors. Broker non-votesare not considered votes cast and will have no effect on the election of directors.

Under our bylaws, any proposal other than an election of directors is decided by the affirmative vote of a majority of shares present in person, by remote communication, if applicable, or represented by proxy duly authorized at the meeting and entitled to vote generally on the subject matter, except where a larger vote is required by law or by our Third Amended and Restated Certificate of Incorporation, or certificate of incorporation, or our bylaws. Abstentions are included in the tabulation of the voting results on any such proposal and, therefore, would count as a vote against any such proposal. Broker "non-votes"are not included in the tabulation of the voting results on any such proposal and, therefore, would not have an impact on any such proposal. A broker "non-vote"occurs when a nominee holding shares for a beneficial owner does not vote on a particular proposal because the nominee does not have discretionary voting power with respect to that item, and has not received instructions from the beneficial owner.

If your shares are held in "street name" by a brokerage firm, your brokerage firm is required to vote your shares according to your instructions. If you do not give instructions to your brokerage firm, the brokerage firm will still be able to vote your shares with respect to certain "discretionary" items, but will not be allowed to vote your shares with respect to "non-discretionary"items.

The election of directors (Proposal No. 1) is a "non-discretionary"item. If you do not instruct your broker how to vote your shares with respect to this proposal, your broker may not vote for these proposals, and those shares will be counted as broker "non-votes."Proposal No. 2 is considered to be a discretionary item, and your brokerage firm will be able to vote your shares on this proposal even if it does not receive instructions from you. Accordingly, we do not anticipate that there will be any broker non-voteson this proposal; however, any broker non-voteswill not be counted as "votes cast" and will therefore have no effect on this proposal.

Who pays the cost for soliciting proxies?

We are making this solicitation and will pay the entire cost of preparing and distributing the Notice and our proxy materials and soliciting votes. If you choose to access the proxy materials or vote over the Internet, you are

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responsible for any Internet access charges that you may incur. Our officers and employees may, without compensation other than their regular compensation, solicit proxies through further mailings, personal conversations, facsimile transmissions, e-mails,or otherwise. We have hired Broadridge Financial Solutions, Inc. to assist us in the distribution of proxy materials. Proxy solicitation expenses that we will pay include those for preparation, mailing, returning, and tabulating the proxies.

How may stockholders submit matters for consideration at next year's annual meeting?

The required notice must be in writing and received by our corporate secretary at our principal executive offices not later than the close of business on February 21, 2026, nor earlier than the close of business on January 22, 2026 (not less than 90 days nor more than 120 days prior to the first anniversary of the Annual Meeting). However, in the event that the date of next year's annual meeting is advanced by more than 30 days, or delayed by more than 60 days, from the first anniversary of the Annual Meeting, or if no annual meeting was held in the preceding year, a stockholder's notice must be so received no earlier than the 120th day prior to such annual meeting and not later than the close of business on the later of (A) the 90th day prior to such annual meeting and (B) the tenth day following the day on which notice of the date of such annual meeting was mailed or public disclosure of the date of such annual meeting was made, whichever first occurs. In addition, to comply with the SEC's universal proxy rules, stockholders who intend to solicit proxies in support of director nominees other than our nominees must provide notice by the same deadline noted herein to submit matters for consideration at the annual meeting. Such notice must comply with the additional requirements of Rule 14a-19(b).

In addition, any stockholder proposal intended to be included in the proxy statement for the next annual meeting of our stockholders in 2026 must also satisfy the requirements of SEC Rule 14a-8under the Exchange Act, and be received not later than December 1, 2025. If the date of the annual meeting is moved by more than 30 days from the date contemplated at the time of the previous year's proxy statement, then notice must be received within a reasonable time before we begin to print and send proxy materials. If that happens, we will publicly announce the deadline for submitting a proposal in a press release or in a document filed with the SEC.

How can I get help if I have trouble checking in or listening to the meeting online?

If you encounter any difficulties accessing the virtual meeting during the check-inor meeting time, please refer to the instructions on the virtual meeting website and the phone number made available the day of the meeting on the virtual meeting website.

How can I know the voting results?

We plan to announce preliminary voting results at the Annual Meeting. Final voting results will be published in a Current Report on Form 8-K,or Form 8-K,that we expect to file with the SEC within four business days after the Annual Meeting. If final voting results are not available to us in time to file a Form 8-Kwithin four business days after the Annual Meeting, we intend to file a Form 8-Kto publish preliminary results and, within four business days after the final results are known to us, file an additional Form 8-Kto publish the final results.

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PROPOSAL NO. 1 - ELECTION OF CLASS I DIRECTORS

Our board of directors currently consists of eight members. In accordance with the terms of our certificate of incorporation and bylaws, our board of directors is divided into three classes, class I, class II and class III, with members of each class serving staggered three-year terms. The members of the classes are divided as follows:

Upon the expiration of the term of a class of directors, directors in that class will be eligible to be elected for a new three-year term at the annual meeting of stockholders in the year in which their term expires.

Our certificate of incorporation and bylaws provide that the authorized number of directors may be changed only by resolution of our board of directors. Our certificate of incorporation also provides that our directors may be removed only for cause by the affirmative vote of the holders of at least two-thirds(2/3) of the outstanding shares then entitled to vote in an annual election of directors, and that any vacancy on our board of directors, including a vacancy resulting from an enlargement of our board of directors, may be filled only by vote of a majority of our directors then in office.

This year, the term of our class I directors, Gerhard Koenig, Ph.D. and Samantha Budd Haeberlein, Ph.D., is expiring. The nominees are presently directors, and have indicated a willingness to continue to serve as directors, if elected. If any nominee becomes unable or unwilling to serve, however, the proxies may be voted for a substitute nominee selected by our board of directors.

Our nominating and corporate governance committee's Policies and Procedures for Director Candidates, or the Director Guidelines, seeks to identify individuals who (i) possess relevant experience and expertise to enable him, her or their to offer germane advice and guidance to management; (ii) have proven achievement and competence in his, her or their field; (iii) have the ability to exercise sound business judgment; (iv) have an understanding of the fiduciary responsibilities required of a director; (v) are committed to devoting time and energy to the affairs of the Company; (vi) have a diverse personal background, perspective and experience; (vii) are committed to vigorously representing the long-term interests of the Company's stockholders; and (viii) have the highest personal integrity and ethics.

In addition to the information presented below regarding each of the nominees and continuing directors' specific experience, qualifications, attributes and skills that our board of directors and our nominating and corporate governance committee considered in determining that he or she should serve as a director, we also believe that each of our directors has demonstrated business acumen, integrity and an ability to exercise sound judgment, as well as a commitment of service to Vigil Neuroscience and our board of directors.

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Nominees for Election as Class I Directors

The following table and biographies identifies our director nominees, and sets forth their principal occupation and business experience during the last five years and their ages as of March 26, 2025.

Gerhard Koenig, Ph.D., has served as a member of our board of directors since July 2020. Since July 2024, Dr. Koenig has served as the Executive Chairman of Augustine Therapeutics, having previously served as its Non-executiveChairman from April 2023 to July 2024. From February 2018 through its sale to Janssen Pharmaceuticals, Inc. in December 2024, Dr. Koenig was the President and Chief Executive Officer of Arkuda Therapeutics, Inc., which he also co-founded.Since January 2022, Dr. Koenig has served as an Advisor to Atlas Venture having previously served as an Entrepreneur in Residence from November 2017 to January 2022. He also served as an advisor on the scientific advisory board at Disarm Therapeutics, Inc. from February 2017 to December 2020. From June 2016 to October 2017, Dr. Koenig was Chief Executive Officer of Quartet Medicine, Inc., a biotechnology company focused on non-opioidpain medications. Before that, he was Chief Scientific Officer and Senior Vice President of FORUM Pharmaceuticals Inc., a pharmaceutical company owned by Fidelity Investments, from February 2003 to May 2016. Dr. Koenig was Vice President, Scientific Programs and Evaluation of Fidelity Biosciences Group (now F-PrimeCapital) from September 2002 to December 2004. Dr. Koenig received his Ph.D. and MS in Molecular and Cellular Neurobiology with a minor in Biochemistry, graduating summa cum laude, from the University of Heidelberg, Germany. We believe Dr. Koenig is qualified to serve on our board of directors because of his extensive R&D leadership and drug discovery and development experience spanning early discovery through Phase 3 clinical trials as well as his experience working in the venture capital industry.

Samantha Budd Haeberlein, Ph.D., has served as a member of our board of directors since May 2023. Dr. Budd Haeberlein has more than 20 years of biopharmaceutical industry experience across research, translational medicine and clinical development with a focus on CNS indications. She is currently Chief Medical Officer at Enigma Biomedical USA responsible for clinical initiatives, with a focus on molecular imaging, a position she has held since March 2023. Since January 2025, Dr. Budd Haeberlein has also served as Venture Partner to the Life Sciences Team at Intermediate Capital Group (ICP: LN), where she was previously a Senior Advisor from July 2023 to January 2025. Prior to that, she held several executive positions, including as Senior Vice President and Head of Neurodegeneration Development, at Biogen (NASDAQ: BIIB) from March 2020 to March 2023, where she was responsible for the late-stage development of the company's Alzheimer's, dementia and movement disorder medications, including Aduhelm and LEQEMBI, and Vice President Clinical Development from February 2015 to March 2020. Previously, Dr. Budd Haeberlein was Vice President and Head of Translational Science & Global Programme Lead in Alzheimer's disease at AstraZeneca (NASDAQ: AZN) from April 2012 to January 2015. Dr. Budd Haeberlein currently serves on the Board of Trustees of The Boston Home, a nursing-care facility for adults with physical disabilities. Dr. Budd Haeberlein previously served on the boards of directors of Rodin Therapeutics from January 2016 to December 2016, and the Stockholm Brain Institute from 2007 to 2011. Prior to joining the biopharmaceutical industry, she was an instructor at Harvard Medical School and did research at The Burnham Institute. Dr. Budd Haeberlein holds a Ph.D. and B.Sc. in Biochemistry from the University of Dundee. Dr. Budd Haeberlein was also a member of the World Dementia Council. We believe Dr. Budd Haeberlein is qualified to serve on our board of directors because of her strong scientific background in CNS indications and her extensive experience in management, research and product development at multiple companies in the life science industry.

The proxies will be voted in favor of the above nominees unless a contrary specification is made in the proxy. The nominees have consented to serve as our directors if elected. However, if any nominee is unable to serve or for good cause will not serve as a director, the proxies will be voted for the election of such substitute nominee as our board of directors may designate.

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Vote Required

To be elected, each director nominee must receive a plurality of the shares present in person or represented by proxy duly authorized at the meeting and entitled to vote on the election of directors. Withheld votes and broker non-voteswill have no effect on the election of directors.

Board Recommendation

The board of directors recommends voting "FOR" the election of Gerhard Koenig, Ph.D. and Samantha Budd Haeberlein, Ph.D., as the class I directors, to serve for a three-year term ending at the annual meeting of stockholders to be held in 2028.

Directors Continuing in Office

The following table identifies our continuing directors, and sets forth their principal occupation and business experience during the last five years and their ages as of March 26, 2025.

Class II Directors (Term Expires at 2026 Annual Meeting)

Cheryl Renee Blanchard, Ph.D., has served as a member of our board of directors since November 2020. Dr. Blanchard has served as President and Chief Executive Officer of Anika Therapeutics, Inc. (NASDAQ: ANIK) since April 2020 after serving as interim Chief Executive Officer since February 2020 and has served on Anika's board since August of 2018. Prior to her work as an executive officer at Anika, she was President and Chief Executive Officer of Microchips Biotech, Inc. from July 2014 until its sale to Daré Bioscience, Inc. (NASDAQ: DARE) in November 2019. From July 2018 to July 2019, Dr. Blanchard served as President and Chief Executive Officer of Keratin Biosciences, Inc., a privately-held biotechnology company created by the business combination of Microchips Biotech, Inc. and KeraNetics, LLC. From September 2012 to April 2020, Dr. Blanchard was Principal at Blanchard Consulting, LLC, which provided consulting services to life science companies and private equity clients. Dr. Blanchard previously served on the board of directors of Dare Bioscience (NASDAQ: DARE) from November 2019 to June 2024, SeaSpine Holdings Corp (now Orthofix Medical Inc. NASDAQ: OFIX) from July 2015 to May 2019 and Neuronetics, Inc. (NASDAQ: STIM) from February 2019 to July 2020. Dr. Blanchard received her MS and Ph.D. in Materials Science and Engineering from the University of Texas at Austin and her BS in Ceramic Engineering from Alfred University. We believe Dr. Blanchard is qualified to serve on our board of directors because she is a biotech Chief Executive Officer and experienced as a public company board member, and due to her strong scientific background in biologics and regenerative medicine and her extensive experience in management, research and product development, business development, and regulatory affairs at multiple companies in the life science industry.

Mary Thistle, has served as a member of our board of directors since April 2022. Ms. Thistle served as Special Advisor to the Bill & Melinda Gates Medical Research Institute, a non-profitbiotech organization, from October 2020 until June 2022, and previously served as the organization's Chief of Staff from January 2018. Prior to that, she held senior leadership positions at Dimension Therapeutics, Inc., a gene therapy company, including Chief Operating Officer from 2016 to 2017 and Chief Business Officer from 2015 to 2016. Prior to

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joining Dimension Therapeutics, Inc., she held several executive positions, including Senior Vice President, Business Development, at Cubist Pharmaceuticals, Inc., a biopharmaceutical company, from 2014 to 2015, Vice President, Business Development from 2012 to 2013 and Senior Director, Business Development from 2009 to 2012. Ms. Thistle currently serves on the board of directors of Entrada Therapeutics, Inc. (NASDAQ: TRDA), a biotechnology company since May 2021, Q32 Bio Inc. (formerly Homology Medicines, Inc. (NASDAQ: QTTB)), a biotechnology company since March 2018, and Cullinan Therapeutics, Inc (NASDAQ: CGEM), a biotechnology company since August 2024. Ms. Thistle previously served on the board of Alaunos Therapeutics, Inc. (NASDAQ: TCRT) a biopharmaceutical company, from November 2020 to December 2023. Ms. Thistle holds a BS in Accounting from the University of Massachusetts, Boston. We believe that Ms. Thistle is qualified to serve on our board of directors due to her finance background and industry experience.

Stefan Vitorovic, MS, MBA, has served as a member of our board of directors since August 2021. From January 2017 to December 2024, Mr. Vitorovic was Co-Founderand Managing Director of Vida Ventures. Prior to founding Vida Ventures, Mr. Vitorovic was an investment professional at Third Rock Ventures, an early-stage life sciences venture capital firm, from July 2014 to January 2017. At Third Rock, he was part of the founding team of Decibel Therapeutics, Inc. (acquired by Regeneron Pharmaceuticals, Inc.), a hearing-focused drug discovery and development platform company. Before Third Rock, he was an investor at TPG Capital from August 2012 to June 2014, where he focused on majority, control stakes in healthcare companies. Mr. Vitorovic worked on a variety of equity and debt financings, including Aptalis Pharmaceutical Technologies (now Adare Pharma Solutions) and Biomet, Inc. (now Zimmer Biomet Holdings, Inc. (NYSE: ZBH)). Prior to TPG, Mr. Vitorovic was an investment banker at Credit Suisse's healthcare banking group from 2004 to 2008. Mr. Vitorovic currently serves on the board of directors of Tectonic Therapeutics, Inc. (NASDAQ: TECX) a biotechnology company since August 2021. Mr. Vitorovic previously served as a director or board observer of Kyverna Therapeutics, Inc. (NASDAQ: KYTX), Praxis Precision Medicines, Inc. (NASDAQ: PRAX) from March 2018 to August 2022, Volastra Therapeutics, Inc. and Souffle Therapeutics, Inc, Oyster Point Pharma, Inc. (formerly NASDAQ: OYST), Dyne Therapeutics (NASDAQ: DYN) and Sutro Biopharma, Inc. (NASDAQ: STRO). He received a BS with Honors in Biological Sciences and an MS in Biology from Stanford University, where he conducted biomedical research in the lab of Dr. Helen Blau at Stanford Medical School. Mr. Vitorovic received his MBA from Harvard Business School. We believe Mr. Vitorovic is qualified to serve on our board of directors because of his deep expertise in life sciences research and investing, as well as his extensive experience in new company formation and operations.

Class III Directors (Term Expires at 2027 Annual Meeting)

Bruce Booth, D.Phil, has served as Chairman of our board of directors since June 2020. Dr. Booth is currently a partner in Atlas Venture, which he joined in 2005. Dr. Booth also serves as Chairman of Kymera Therapeutics, Inc. (NASDAQ: KYMR) which he also co-founderedand was President and Chief Executive Officer of from September 2015 to August 2017. Dr. Booth is also a board member of several public and privately held companies, including Sionna Therapeutics, Inc. (NASDAQ: SION), a biopharmaceutical company since June 2020, Nimbus Therapeutics, LLC., and HotSpot Therapeutics, Inc. Dr. Booth previously served on the boards of directors of AvroBio, Inc. (now Tectonic Therapeutics, Inc. (NASDAQ: TECX)) from February 2016 to June 2024, Magenta Therapeutics, Inc. (now Dianthus Therapeutics, Inc. (NASDAQ: DNTH)) from February 2016 to September 2023, Unum Therapeutics, Inc. (now Cogent Biosciences, Inc. (NASDAQ: COGT)) from 2014 to July 2020, Miragen Therapeutics, Inc. (now Viridan Therapeutics, Inc. (NASDAQ: VRDN)) from 2007 to December 2018, and Zafgen, Inc. (now Larimar Therapeutics, Inc. (NASDAQ: LRMR)) from August 2006 to June 2018. Dr. Booth holds a Ph.D. in Molecular Immunology from Oxford University's Nuffield Department of Medicine and a BS in Biochemistry from Pennsylvania State University. We believe Dr. Booth's extensive leadership, executive, managerial and business experience with life sciences companies, including experience in the formation, development and business strategy of multiple start-upcompanies in the life sciences sector, qualifies him to serve on our board of directors.

Suzanne Bruhn, Ph.D., has served as a member of our board of directors since July 2022. Dr. Bruhn has more than 20 years of biopharmaceutical experience and a proven track record in developing and

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commercializing therapies for the treatment of serious diseases with significant unmet need. She is currently Chief Executive Officer of the Charcot-Marie-Tooth Association (CMTA) a patient advocacy group dedicated to finding a cure for CMT, a rare, debilitating peripheral neuropathy. Prior to that she was President and Chief Executive Officer of Tiaki Therapeutics from May 2019 to December 2023, dedicated to developing novel treatments for CNS diseases. Prior to that, she served as President and Chief Executive Officer at Proclara Biosciences from April 2017 to September 2018, where she led the clinical-stage company's evolution into orphan diseases, and served as President and Chief Executive Officer at Promedior from May 2012 to November 2015, where she negotiated an option deal with Bristol Myers Squibb to acquire the company. Previously, Dr. Bruhn held multiple leadership roles in global regulatory affairs, strategic planning, and program management at Shire Human Genetic Therapies (formerly Transkaryotic Therapies) from 1998 to 2012 and Cytotherapeutics from 1996 to 1998. Dr. Bruhn currently serves on the board of directors of Pliant Therapeutics (NASDAQ: PLRX), Travere Therapeutics (NASDAQ: TVTX), and MindMed (NASDAQ: MNMD). Dr. Bruhn previously served on the boards of Aeglea Biotherapeutics (now Spyre Therapeutics, Inc. (NASDAQ: SYRE)) from February 2017 to August 2020, Avalo Therapeutics (NASDAQ: AVTX) from April 2020 to November 2021, Novelion Therapeutics (formerly NASDAQ: NVLN) from October 2017 to January 2020, and Raptor Pharmaceuticals (now Horizon Pharmaceutical (NASDAQ: HZNP)) from April 2011 to October 2016. She holds a Bachelor of Science with distinction in chemistry from Iowa State University of Science and Technology, a Ph.D. in chemistry from Massachusetts Institute of Technology, and was a postdoctoral research fellow in the Department of Genetics at Harvard Medical School. We believe Dr. Bruhn's extensive leadership, executive, managerial and business experience with life sciences companies, including experience in developing and commercializing therapies for the treatment of serious diseases qualifies her to serve on our board of directors.

Ivana Magovčević-Liebisch, Ph.D., J.D., has served as our President and Chief Executive Officer and as a member of our board of directors since July 2020. Prior to Vigil, Dr. Magovčević-Liebisch was Executive Vice President, Chief Business Officer at Ipsen SA (XPAR: IPN), a pharmaceutical company, from March 2018 to April 2020, where she led the External Innovation, Business Development and Alliance Management functions. Prior to Ipsen, Dr. Magovčević-Liebisch was Executive Vice President, Chief Strategy and Corporate Development Officer at Axcella Health Inc. from May 2017 to March 2018, and Senior Vice President, Head of Global Business Development for the specialty drug business at Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) from March 2013 to May 2017. Dr. Magovčević-Liebisch previously worked at Dyax Corp. (acquired by Shire plc, now Takeda Pharmaceutical Co Ltd (NYSE: TAK)) from April 2001 to March 2013 in management roles of increasing scope and responsibility, including Executive Vice President and Chief Operating Officer, where she launched the company's first drug, Kalbitor^® for an orphan indication, Hereditary Angioedema. Dr. Magovčević-Liebisch began her biopharma career at Transkaryotic Therapies, Inc. (acquired by Shire plc, now Takeda Pharmaceutical Co Ltd), where she was Director of Intellectual Property and Patent Counsel from 1998 to 2001. Dr. Magovčević-Liebisch is currently a member of the board of directors of Acrivon Therapeutics, Inc. (NASDAQ: ACRV), a biotechnology company since February 2024 and Quanterix Corporation (NASDAQ: QTRX) a life sciences company since October 2024. Previously, she was the Chairperson of the board of directors of ABSCI Corporation (NASDAQ: ABSI) and was a member of the board of directors of Aeglea BioTherapeutics, Inc. (now Spyre Therapeutics, Inc. (NASDAQ: SYRE)) and Applied Genetic Technologies Corporation (acquired by Syncona Ltd, now Beacon Therapeutics Holdings Ltd). Dr. Magovčević-Liebisch is also a trustee of the Boston Museum of Science and of the Boston Ballet, and overseer of Beth Israel Deaconess Medical Center. She received a BA in Biology and Chemistry from Wheaton College, a Ph.D. in Genetics from Harvard University, and a J.D. in High Technology Law from Suffolk University Law School. We believe Dr. Magovčević-Liebisch's over 25 years of senior management experience in the biotechnology and pharmaceutical industry make her well qualified to serve on our board of directors.

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PROPOSAL NO. 2 - RATIFICATION OF THE APPOINTMENT OF PRICEWATERHOUSECOOPERS

LLP AS VIGIL NEUROSCIENCE'S INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

FOR THE FISCAL YEAR ENDING DECEMBER 31, 2025

Vigil Neuroscience's stockholders are being asked to ratify the appointment by the audit committee of the board of directors of PricewaterhouseCoopers LLP as the Company's independent registered public accounting firm for the fiscal year ending December 31, 2025. PricewaterhouseCoopers LLP has served as Vigil Neuroscience's independent registered public accounting firm since 2021.

The audit committee is solely responsible for selecting Vigil Neuroscience's independent registered public accounting firm for the fiscal year ending December 31, 2025. Stockholder approval is not required to appoint PricewaterhouseCoopers LLP as Vigil Neuroscience's independent registered public accounting firm. However, the board of directors believes that submitting the appointment of PricewaterhouseCoopers LLP to the stockholders for ratification is good corporate governance. If the stockholders do not ratify this appointment, the audit committee will reconsider whether to retain PricewaterhouseCoopers LLP. If the selection of PricewaterhouseCoopers LLP is ratified, the audit committee, at its discretion, may direct the appointment of a different independent registered public accounting firm at any time it decides that such a change would be in the best interest of Vigil Neuroscience and its stockholders.

A representative of PricewaterhouseCoopers LLP is expected to be present at the Annual Meeting and will have an opportunity to make a statement if he or she desires to do so and to respond to appropriate questions from our stockholders.

Principal Accountant Fees and Services

Vigil Neuroscience incurred the following fees from PricewaterhouseCoopers LLP for the audit of the consolidated financial statements and for other services related to the fiscal years ended December 31, 2024 and December 31, 2023.

Audit Committee Pre-approvalPolicy and Procedures

Our audit committee has adopted policies and procedures relating to the approval of all audit and non-auditservices that are to be performed by our independent registered public accounting firm. This policy provides that we will not engage our independent registered public accounting firm to render audit or non-auditservices unless the service is specifically approved in advance by our audit committee or the engagement is entered into pursuant to the pre-approvalprocedure described below.

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From time to time, our audit committee may pre-approvespecified types of services that are expected to be provided to us by our independent registered public accounting firm during the next 12 months. Any such pre-approvaldetails the particular service or type of services to be provided and is also generally subject to a maximum dollar amount.

During the fiscal years ended 2024 and 2023, no services were provided to us by PricewaterhouseCoopers LLP other than in accordance with the pre-approvalpolicies and procedures described above.

Vote Required

To ratify the appointment of PricewaterhouseCoopers LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2025, the affirmative vote of a majority of shares present in person or represented by proxy duly authorized at the meeting and entitled to vote on this Proposal No. 2 is required. Abstentions will count as a vote against this Proposal. This proposal is considered to be a discretionary item, and your broker will be able to vote on this proposal even if it does not receive instructions from you. Accordingly, we do not anticipate that there will be any broker non-voteson this proposal; however, any broker non-voteswill not be counted as "votes cast" and will therefore have no effect on this proposal.

Board Recommendation

The board of directors recommends voting "FOR" Proposal No. 2 to ratify the appointment of PricewaterhouseCoopers LLP as Vigil Neuroscience's independent registered public accounting firm for the fiscal year ending December 31, 2025.

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CORPORATE GOVERNANCE

Director Nomination Process

Our nominating and corporate governance committee is responsible for identifying individuals qualified to serve as directors, consistent with criteria approved by our board, and recommending such persons to be nominated for election as directors, except where we are legally required by contract, law or otherwise to provide third parties with the right to nominate.

The process followed by our nominating and corporate governance committee to identify and evaluate director candidates includes requests to board members and others for recommendations, meetings from time to time to evaluate biographical information and background material relating to potential candidates, and interviews of selected candidates by management, recruiters, members of the committee and our board. The qualifications, qualities and skills that our nominating and corporate governance committee believes must be met by a committee recommended nominee for a position on our board of directors are as follows:

Stockholders may recommend individuals to the nominating and corporate governance committee for consideration as potential director candidates. Any such proposals should be submitted to our corporate secretary at our principal executive offices no later than the close of business on the 90th day nor earlier than the close of business on the 120th day prior to the one-yearanniversary of the date of the preceding year's annual meeting and should include appropriate biographical and background material to allow the nominating and corporate governance committee to properly evaluate the potential director candidate and the number of shares of our stock beneficially owned by the stockholder proposing the candidate. Stockholder proposals should be addressed to Vigil Neuroscience, Inc., 100 Forge Road, Suite 700, Watertown, MA 02472, Attention: Michael Cohen, Corporate Secretary. Assuming that biographical and background material has been provided on a timely basis in accordance with our bylaws, any recommendations received from stockholders will be evaluated in the same manner as potential nominees proposed by the nominating and corporate governance committee. If our board of directors determines to nominate a stockholder recommended candidate and recommends his, her or their election, then his, her or their name will be included on our proxy card for the next annual meeting of stockholders. See "Stockholder Proposals" for a discussion of submitting stockholder proposals.

Director Independence

Applicable Nasdaq Stock Market LLC, or Nasdaq, rules require a majority of a listed company's board of directors to be comprised of independent directors within one year of listing. In addition, the Nasdaq rules require that, subject to specified exceptions, each member of a listed company's audit, compensation and nominating and corporate governance committees be independent and that audit committee members also satisfy independence criteria set forth in Rule 10A-3under the Exchange Act and that compensation committee members satisfy independence criteria set forth in Rule 10C-1under the Exchange Act. Under applicable Nasdaq

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rules, a director will only qualify as an "independent director" if, in the opinion of the listed company's board of directors, that person does not have a relationship that would interfere with the exercise of independent judgment in carrying out the responsibilities of a director. In order to be considered independent for purposes of Rule 10A-3,a member of an audit committee of a listed company may not, other than in his, her or their capacity as a member of the audit committee, the board of directors, or any other board committee, accept, directly or indirectly, any consulting, advisory, or other compensatory fee from the listed company or any of its subsidiaries or otherwise be an affiliated person of the listed company or any of its subsidiaries. In addition, in affirmatively determining the independence of any director who will serve on a company's compensation committee, Rule 10C-1under the Exchange Act requires that a company's board of directors must consider all factors specifically relevant to determining whether a director has a relationship to such company which is material to that director's ability to be independent from management in connection with the duties of a compensation committee member, including: the source of compensation to the director, including any consulting, advisory or other compensatory fee paid by such company to the director, and whether the director is affiliated with the company or any of its subsidiaries or affiliates.

Our board of directors has determined that all members of the board of directors, except Ivana Magovčević-Liebisch, Ph.D., J.D. are independent directors, including for purposes of the rules of Nasdaq and the SEC. In making such independence determination, our board of directors considered the relationships that each non-employeedirector has with us and all other facts and circumstances that our board of directors deemed relevant in determining their independence, including the beneficial ownership of our capital stock by each non-employeedirector. In considering the independence of the directors listed above, our board of directors considered the association of our directors with the holders of more than 5% of our common stock. There are no family relationships among any of our directors or executive officers. Dr. Magovčević-Liebisch is not an independent director under these rules because she is an executive officer of the Company.

Board Committees

Our board of directors has established an audit committee, a compensation committee and a nominating and corporate governance committee. Each of the audit committee, compensation committee and nominating and corporate governance committee operates under a charter that satisfies the applicable standards of the SEC and Nasdaq. Each such committee reviews its respective charter at least annually. A current copy of the charter for each of the audit committee, compensation committee and nominating and corporate governance committee is posted on the corporate governance section of our website https://investors.vigilneuro.com/corporate-governance/documents-charters.

Audit Committee

Mary Thistle, Suzanne Bruhn, Ph.D. and Samantha Budd Haeberlein, Ph.D. serve on the audit committee, which is chaired by Ms. Thistle. Our board of directors has determined that each member of the audit committee is "independent" for audit committee purposes as that term is defined by the rules of the SEC and Nasdaq, and that each has sufficient knowledge in financial and auditing matters to serve on the audit committee. Our board of directors has designated Ms. Thistle as an "audit committee financial expert," as defined under the applicable rules of the SEC. During the fiscal year ended December 31, 2024, the audit committee met four times. The audit committee's responsibilities include:

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All audit and non-auditservices, other than de minimis non-auditservices, to be provided to us by our independent registered public accounting firm must be approved in advance by our audit committee.

Compensation Committee

Cheryl Blanchard, Ph.D., Bruce Booth, D.Phil and Suzanne Bruhn, Ph.D. serve on the compensation committee, which is chaired by Dr. Blanchard. Our board of directors has determined that each member of the compensation committee is "independent" as defined in the applicable Nasdaq rules. During the fiscal year ended December 31, 2024, the compensation committee met four times. The compensation committee's responsibilities include:

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The compensation committee may establish and delegate authority to one or more subcommittees consisting of one or more of its members to carry out its responsibilities. For example, to the extent permitted by applicable law and the provisions of a given equity-based plan, the compensation committee may delegate to a committee consisting of one or more of our executive officers, including the Chief Executive Officer, all or part of the authority and duties, with respect to granting stock awards, to any individuals who are (i) not subject to the reporting and other provisions of Section 16 of the Exchange and (ii) are at or below the level of Senior Vice President, such power to be subject to the parameters and limitations set forth in the applicable resolutions adopted by the compensation committee.

Nominating and Corporate Governance Committee

Stefan Vitorovic, MS, MBA, Cheryl Blanchard, Ph.D. and Samantha Budd Haeberlein, Ph.D. serve on the nominating and corporate governance committee, which is chaired by Mr. Vitorovic. Our board of directors has determined that each member of the nominating and corporate governance committee is "independent" as defined in the applicable Nasdaq rules. During the fiscal year ended December 31, 2024, the nominating and corporate governance committee met four times. The nominating and corporate governance committee's responsibilities include:

The nominating and corporate governance committee considers candidates for board of directors membership suggested by its members and the Chief Executive Officer. Additionally, in selecting nominees for directors, the nominating and corporate governance committee will review candidates recommended by stockholders in the same manner and using the same general criteria as candidates recruited by the committee and/or recommended by our board of directors. Any stockholder who wishes to recommend a candidate for consideration by the committee as a nominee for director should follow the procedures described later in this proxy statement under the heading "Stockholder Proposals." The nominating and corporate governance committee will also consider whether to nominate any person proposed by a stockholder in accordance with the provisions of our bylaws relating to stockholder nominations as described later in this proxy statement under the heading "Stockholder Proposals."

Identifying and Evaluating Director Nominees. Our board of directors is responsible for filling vacancies on our board of directors and for nominating candidates for election by our stockholders each year in the class of directors whose term expires at the relevant annual meeting. The board of directors delegates the selection and nomination process to the nominating and corporate governance committee, with the expectation that other members of the board of directors, and of management, will be requested to take part in the process as appropriate.

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Generally, the nominating and corporate governance committee identifies candidates for director nominees in consultation with management, through the use of search firms or other advisors, through the recommendations submitted by stockholders or through such other methods as the nominating and corporate governance committee deems to be helpful to identify candidates. Once candidates have been identified, the nominating and corporate governance committee confirms that the candidates meet all of the minimum qualifications for director nominees established by the nominating and corporate governance committee. The nominating and corporate governance committee may gather information about the candidates through interviews, detailed questionnaires, comprehensive background checks or any other means that the nominating and corporate governance committee deems to be appropriate in the evaluation process. The nominating and corporate governance committee then meets as a group to discuss and evaluate the qualities and skills of each candidate, both on an individual basis and taking into account the overall composition and needs of our board of directors. Based on the results of the evaluation process, the nominating and corporate governance committee recommends candidates for the board of directors' approval to fill a vacancy or as director nominees for election to the board of directors by our stockholders each year in the class of directors whose term expires at the relevant annual meeting.

Board Diversity Policies

Our Director Guidelines provide that the value of diversity should be considered in determining director candidates as well as other factors such as a candidate's character, judgment, skills, education, expertise and absence of conflicts of interest. Our priority in selection of board members is identification of members who will further the interests of our stockholders through their established records of professional accomplishment, their ability to contribute positively to the collaborative culture among board members, and their knowledge of our business and understanding of the competitive landscape in which we operate and adherence to high ethical standards. The nominating and corporate governance committee and the full board of directors are committed to creating a board of directors with diversity, including diversity of expertise, experience, ethnicity, race, background and gender, and are committed to identifying, recruiting and advancing candidates offering such diversity in future searches.

Board and Committee Meetings Attendance

The full board of directors met eight times during 2024. During 2024, each member of the board of directors attended in person or participated in 75% or more of the aggregate of (i) the total number of meetings of the board of directors (held during the period for which such person has been a director), and (ii) the total number of meetings held by all committees of the board of directors on which such person served (during the periods that such person served).

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The role of the board of directors in overseeing the management of our risks is conducted primarily through committees of the board of directors, as disclosed in the descriptions of each of the committees above and in the charters of each of the committees. The full board of directors (or the appropriate board committee in the case of risks that are under the purview of a particular committee) discusses with management our major risk exposures, their potential impact on us, and the steps we take to manage them. When a board committee is responsible for evaluating and overseeing the management of a particular risk or risks, the chairman of the relevant committee reports on the discussion to the full board of directors during the committee reports portion of the next board meeting. This enables the board of directors and its committees to coordinate the risk oversight role, particularly with respect to risk interrelationships.

Communication with the Directors of Vigil Neuroscience

Any interested party with concerns about our company may report such concerns to the board of directors or the Chairman of our board of directors and nominating and corporate governance committee, by submitting a written communication to the attention of such director at the following address:

c/o Vigil Neuroscience, Inc.

100 Forge Rd, Suite 700

Watertown, MA 02472

United States

You may submit your conceanonymously or confidentially by postal mail. You may also indicate whether you are a stockholder, customer, supplier or other interested party.

A copy of any such written communication may also be forwarded to our legal counsel and a copy of such communication may be retained for a reasonable period of time. The director may discuss the matter with our legal counsel, with independent advisors, with non-managementdirectors, or our management, or may take other action or no action as the director determines in good faith, using reasonable judgment and applying his, her or their own discretion.

Communications may be forwarded to other directors if they relate to important substantive matters and include suggestions or comments that may be important for other directors to know. In general, communications relating to corporate governance and long-term corporate strategy are more likely to be forwarded than communications relating to ordinary business affairs, personal grievances and matters as to which we tend to receive repetitive or duplicative communications.

The audit committee oversees the procedures for the receipt, retention, and treatment of complaints received by Vigil Neuroscience regarding accounting, internal accounting controls, or audit matters, and the confidential, anonymous submission by employees of concerns regarding questionable accounting, internal accounting controls or auditing matters. We have also established a toll-free telephone number for the reporting of such activity, which is 1-833-869-0464,which permits submissions on a confidential and anonymous basis.

Executive Officers Who Are Not Directors

The following table identifies our executive officers who are not directors, and sets forth their current positions at Vigil Neuroscience and their ages as of March 26, 2025.

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David Gray, Ph.D., has served as our Chief Science Officer since February 2023. Prior to joining Vigil Neuroscience, Dr. Gray served as Chief Scientific Officer at Inscopix, Inc. and led the development of its first therapeutic research programs. Prior to Inscopix, he was Vice President of Chemistry at Cerevel Therapeutics Holdings, Inc., where he led the development of late-stage clinical programs for Parkinson's disease, or PD, and Alzheimer's disease, or AD, and was responsible for advancing early-stage programs. Before that, Dr. Gray held several roles during his 16 years at Pfizer Inc., including Senior Director, Neuroscience Biology, leading preclinical research teams and progressing programs from discovery to clinical studies in multiple neuroscience-related diseases, including PD, AD and schizophrenia. He holds a Ph.D. in Organic Chemistry from The Scripps Research Institute and a BS in Chemistry from the University of Minnesota.

Petra Kaufmann, M.D., F.A.A.N., has served as our Chief Medical Officer since March 2024. Prior to joining Vigil Neuroscience, Dr. Kaufmann most recently served as Chief Medical Officer of Affinia Therapeutics, Inc., an AAV gene therapy company, from February 2021 to March 2024. Prior to joining Affinia, Dr. Kaufmann served as senior vice president and head of clinical development, analytics and translational medicine at Novartis Gene Therapies, Inc., or Novartis, from May 2020 to January 2021 and vice president, R&D translational medicine at AveXis, Inc. from February 2018 to May 2020, prior to its acquisition by Novartis. Prior to moving to AveXis, she served as director of the Office of Rare Diseases Research at the National Institutes of Health from September 2015 to February 2018. Dr. Kaufmann earned an M.Sc. in biostatistics at Columbia University, where she also trained in neurology and served as a tenured faculty member. She received her M.D. and a doctorate for experimental work from the University of Bonn, Germany.

Jennifer Ziolkowski, CPA, has served as our Chief Financial Officer since March 2021. Prior to joining Vigil Neuroscience, Ms. Ziolkowski was Chief Financial Officer of Solid Biosciences Inc. (NASDAQ: SLDB), or Solid, from May 2017 to January 2021, where she played a key role in transforming Solid from a private, preclinical company to a publicly-held, clinical-stage biotech company. Previously, Ms. Ziolkowski held various leadership positions at Philips Healthcare, TransMedics, Inc. and Cytyc Corporation (acquired by Hologic, Inc. (NASDAQ: HOLX)). Ms. Ziolkowski began her career at PricewaterhouseCoopers LLP. Ms. Ziolkowski holds a BS in Accounting from Boston College and is a Certified Public Accountant.

The principal occupation and employment during the past five years of each of our executive officers was carried on, in each case except as specifically identified in this proxy statement, with a corporation or organization that is not a parent, subsidiary or other affiliate of us. There is no arrangement or understanding between any of our executive officers and any other person or persons pursuant to which he or she was or is to be selected as an executive officer.

There are no material legal proceedings to which any of our directors, executive officers, or affiliates is a party adverse to us or our subsidiary or in which any such person has a material interest adverse to us or our subsidiary.

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Director Compensation

The table below shows all compensation earned by or paid to our non-employeedirectors during 2024. Other than as set forth below, we did not pay any compensation, make any equity awards or non-equityawards to, or pay any other compensation to any of the non-employeemembers of our board of directors in 2024. Ivana Magovčević-Liebisch, Ph.D., J.D., our Chief Executive Officer, does not receive any compensation for her services as director and, consequently, is not included in this table. The compensation received by Dr. Magovčević-Liebisch during 2024 is set forth in the section of this proxy statement captioned "Executive Compensation - Summary Compensation Table."

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Our board of directors has adopted the non-employeedirector compensation policy that is designed to enable us to attract and retain, on a long-term basis, highly qualified non-employeedirectors. In June 2024, following a review of peer group practices with the compensation committee's independent compensation consultant, the board of directors adopted an amended and restated non-employeedirector compensation policy that (i) decreased the value of the Initial Award (as defined below) from $182,000 to $80,000 and (ii) decreased the size of the Annual Award (as defined below) from $91,000 to $40,000. Under the policy, we pay our non-employeedirectors a cash retainer for service on the board of directors and for service on each committee on which the director is a member. The chairman of each committee receives a higher retainer for such service. The fees paid to non-employeedirectors for service on the board of directors and for service on each committee of the board of directors on which the director is a member pursuant to the amended and restated non-employeedirector compensation policy are as follows:

Each non-employeedirector may elect to receive the entirety (but not a portion) of the cash retainer in the form of a stock option award to purchase common stock of the Company with an aggregate value equal to the amount of the cash retainer to be received by such non-employeedirector, referred to as the "Retainer Grant". Such Retainer Grant vests in four equal quarterly installments commencing on the date of grant, subject to the director's continued service with the Company through each applicable vesting date.

In addition, the amended and restated non-employeedirector compensation policy provides that, upon initial election to our board of directors, each non-employeedirector will be granted a stock option award to purchase a number of shares having a grant date fair value of $80,000, or the Initial Award, subject to the maximum annual compensation limits set forth in the policy and such other limits as may be set forth in the Vigil Neuroscience, Inc. 2021 Stock Option and Incentive Plan, or the 2021 Plan. Initial Awards vest in equal monthly installments over three years from the date of grant, subject to continued service through the applicable vesting date. Furthermore, on the date of each annual meeting of stockholders, each non-employeedirector (other than a director who received an Initial Award on or after January 1 in the calendar year of such annual meeting) who continues as a non-employeedirector following such meeting will be granted a stock option to purchase a number of shares having a grant date fair value of $40,000, or the Annual Award, subject to the maximum annual compensation limits set forth in the policy and such other limits as may be set forth in the 2021 Plan. Annual Awards vest in full upon the earlier of (i) the first anniversary of the date of grant or the date of the next Annual Meeting, subject to continued service through the applicable vesting date. All outstanding Retainer Grants, Initial Awards and Annual Awards will become fully vested and exercisable upon the effective time of a Sale Event (as such term is defined in the 2021 Plan).

On May 3, 2024, the board of directors approved a stock option repricing in accordance with the terms of the 2021 Plan. Pursuant to the repricing, the exercise price of certain outstanding options to purchase shares of our common stock granted under the 2021 Plan prior to January 1, 2024 held by employees and non-employeedirectors with exercise prices in excess of $3.03 per share were reduced to $3.03 per share, the closing trading

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price of the Company's common stock on the Nasdaq Global Select Market on May 3, 2024. The stock option repricing is described in more detail under the heading "Executive Compensation - Narrative to Summary Compensation Table - Stock Option Repricing" below.

We also reimburse our non-employeedirectors for reasonable travel and out-of-pocketexpenses incurred by our non-employeedirectors in connection with attending our meetings of the board of directors and committees thereof.

Executive Compensation

This section describes the material elements of compensation awarded to, earned by or paid to our named executive officers in 2024, who were Ivana Magovčević-Liebisch, Ph.D., J.D., our President and Chief Executive Officer, Petra Kaufmann, M.D., F.A.A.N., our Chief Medical Officer, and Jennifer Ziolkowski, CPA, our Chief Financial Officer. These individuals represent our principal executive officer and our next two most highly compensated executive officers in the year ended December 31, 2024. We are an "emerging growth company," within the meaning of the JOBS Act, and have elected to comply with the reduced compensation disclosure requirements available to emerging growth companies under the JOBS Act. This section also provides qualitative information regarding the manner and context in which compensation is awarded to and earned by our named executive officers and is intended to place in perspective the data presented in the tables and narrative that follow.

2024 Summary Compensation Table

The following table presents the compensation awarded to, earned by or paid to each of our named executive officers for the years indicated.

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Narrative to Summary Compensation Table

Our board of directors and compensation committee review compensation annually for our executives. In setting executive base salaries and bonuses and granting equity incentive awards, we consider compensation for comparable positions in the market, the historical compensation at Vigil Neuroscience of our executives, individual performance as compared to our expectations and objectives, our desire to motivate our employees to achieve short- and long-term results that are in the best interests of our stockholders, and a long-term commitment to our Company. We target a general competitive position, based on independent third-party benchmark analytics to inform the mix of compensation of base salary, bonus and long-term incentives.

Our compensation committee is primarily responsible for determining the compensation for our executive officers. Our compensation committee typically reviews and discusses management's proposed compensation with our Chief Executive Officer for all executives other than the Chief Executive Officer. Based on those discussions and its discretion, taking into account the factors noted above, the compensation committee then sets the compensation for each executive officer other than the Chief Executive Officer and recommends the compensation for the Chief Executive Officer to our board of directors for approval. Our board of directors discusses the compensation committee's recommendation and ultimately approves the compensation of our Chief Executive Officer without members of management present.

In 2024, the compensation committee retained the services of Aon's Human Capital Solutions practice, a division of Aon plc, or Aon, as its external independent compensation consultant. During 2024, Aon did not provide material services to us other than the services to our compensation committee described herein. Our compensation committee requires that its compensation consultants be independent of Company management and performs an annual assessment of the compensation consultants' independence to determine whether the consultants are independent. Aon advises our compensation committee on best practices in executive compensation and provides our compensation committee with market data in an effort to ensure our compensation program is competitive and designed to attract, retain, and incentivize our NEOs. Based on its evaluation, our compensation committee has determined that Aon is independent and that its work has not raised any conflict of interests.

Base Salaries

Our named executive officers each receive a base salary to compensate them for services rendered to our Company. The base salary payable to each named executive officer is intended to provide a fixed component of compensation reflecting the executive's skill set, experience, role and responsibilities. Base salaries are reviewed annually, typically in connection with our annual performance review process, approved by our board of directors or the compensation committee of the board of directors, and may be adjusted from time to time to realign salaries with market levels after taking into account individual responsibilities, performance and experience.

The annual base salaries for each of our named executive officers for the fiscal year ended December 31, 2024 are set forth in the table below:

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Cash Bonuses

For the fiscal year ended December 31, 2024, each of the named executive officers was eligible to eaan annual cash bonus based on the achievement of certain corporate performance milestones and individual performance. The target annual bonus for each of our named executive officers for the fiscal year ended December 31, 2024 was equal to the percentage of the executive's respective annual base salary specified below:

Each named executive officer's annual cash bonus is determined by reference to the achievement of pre-determinedcorporate, research and development, clinical and regulatory, as well as chemistry manufacturing and controls goals, which are weighted, with respect to Dr. Magovčević-Liebisch, at 100%, and in the case of each of our other named executive officers, at 80%, and individual performance goals, which are weighted at 20%. Following review and determination of corporate performance for 2024, the board of directors determined that the corporate performance goals were achieved at 90% of target and that the individual performance goals were met at 100% of target for Dr. Kaufmann and 110% of target for Ms. Ziolkowski. Dr. Kauffmann's annual cash bonus for 2024 was pro-ratedbased on her date of hire. The annual cash bonus paid to each of our named executive officers for the fiscal year ended December 31, 2024 is set forth in the "Non-EquityIncentive Plan Compensation" column of the "Summary Compensation Table" above.

Equity-Based Compensation

We believe that equity grants provide our executives with a strong link to our long-term performance, create an ownership culture and help to align the interests of our executives and our stockholders. In addition, we believe that equity grants promote executive retention because they incentivize our executive officers to remain in our employment during the vesting period. Accordingly, our board of directors or our compensation committee periodically reviews the equity incentive compensation of our named executive officers and may grant equity incentive awards to them from time to time. In furtherance of these goals, in 2024 each of our named executive officers was granted stock option awards. For additional information regarding outstanding equity awards held by our named executive officers as of December 31, 2024, see the "Outstanding Equity Awards at 2024 Fiscal Year End" table below.

Stock Option Repricing

As previously disclosed, on May 3, 2024, our board of directors approved a repricing of certain outstanding stock options, including certain options held by our named executive officers. The option repricing was undertaken in accordance with the terms of the 2021 Plan and applies to all outstanding options to purchase shares of the Company's common stock granted under the 2021 Plan prior to January 1, 2024 held by employees, including executive officers, and non-employeedirectors as of May 3, 2024, to the extent such options have an exercise price in excess of $3.03 per share, the closing trading price of our common stock on the Nasdaq Global Select Market on May 3, 2024.

Under the terms of the option repricing, a repriced option will revert to its original exercise price if it is exercised during the period that commenced on May 3, 2024 and ends upon the earliest of (i) May 3, 2025, (ii) a Sale Event (as defined in the 2021 Plan), (iii) the termination of the optionholder's Service Relationship (as defined in the 2021 Plan) by us other than for Cause (as defined in the 2021 Plan) or due to the optionholder's death or disability, and (iv) for optionholders who are eligible for severance benefits upon a termination of employment by the optionholder for Good Reason (as defined in the applicable optionholder's employment agreement or offer letter with the Company), the termination of the optionholder's Service Relationship for Good Reason. We refer to this period as the Retention Period.

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The repricing does not change the number of shares, the vesting schedule, or the expiration date of the repriced options. Stock options covering an aggregate of 652,000 and 245,000 shares of common stock held by Dr. Magovčević-Liebisch and Ms. Ziolkowski, respectively, were repriced on May 3, 2024.

401(k) Plan

We maintain a retirement savings plan, or 401(k) plan, that is intended to qualify for favorable tax treatment. U.S. employees are generally eligible to participate in the 401(k) plan, subject to certain criteria. Participants may make pre-taxand certain after-tax(Roth) salary deferral contributions to the plan from their eligible earnings up to the statutorily prescribed annual limit under the Internal Revenue Code of 1986, as amended, or the Code. We provide matching contributions to the 401(k) Plan in an amount equal to 100% of each participant's contribution up to a maximum of 4% of the participant's annual eligible cash compensation, subject to certain other limits.

Other Benefits and Perquisites

Our executive officers participate in the Company's benefits programs available to employees generally. It is generally our policy not to extend perquisites to our executives that are not available to our employees generally.

Outstanding Equity Awards at 2024 Fiscal Year End

The following table lists all outstanding equity awards held by our named executive officers as of December 31, 2024.

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Ivana Magovčević-Liebisch

Pursuant to the employment agreement with Dr. Magovčević-Liebisch, or the CEO Agreement, Dr. Magovčević-Liebisch's current annual base salary is $638,600, which is subject to periodic review and adjustment, and she is eligible to eaan annual bonus with a target amount equal to 55% of her base salary. Dr. Magovčević-Liebisch is also eligible to participate in the employee benefit plans available to our employees, subject to the terms of those plans.

Pursuant to the CEO Agreement, if Dr. Magovčević-Liebisch's employment is terminated by us without Cause or by Dr. Magovčević-Liebisch for Good Reason outside of the Change in Control Period (as such terms are defined in the CEO Agreement), subject to her execution and the effectiveness of a separation agreement, including a general release of claims in our favor, then Dr. Magovčević-Liebisch will be entitled to (i) 12 months of continuation of her then-current base salary; (ii) 50% acceleration of any unvested Founders Shares (as defined in the CEO Agreement) and accelerated vesting of all stock options and other stock-based awards subject solely to time-based vesting held by Dr. Magovčević-Liebisch that would have vested during the 12 month period following such termination; and (iii) subject to Dr. Magovčević-Liebisch's copayment of premium amounts at the applicable active employees' rate and proper election to continue COBRA health coverage, payment of the portion of the premiums equal to the amount that we would have paid to provide health insurance to Dr. Magovčević-Liebisch had she remained employed with us until the earliest of (A) 12 months following termination, (B) Dr. Magovčević-Liebisch's eligibility for group medical plan benefits under any other employer's group medical plan or (C) the end of Dr. Magovčević-Liebisch's COBRA health continuation period.

If Dr. Magovčević-Liebisch's employment is terminated by us without Cause or by Dr. Magovčević-Liebisch for Good Reason within the Change in Control Period then, subject to her execution and the effectiveness of a separation agreement, including a general release of claims in our favor, Dr. Magovčević-Liebisch will be entitled to (i) a lump sum cash payment equal to 1.5 times the sum of her then-current base salary (or her base salary in effect immediately prior to the Change in Control (as defined in the CEO Agreement), if higher) and her target bonus for the then-current year (or her target bonus in effect immediately prior to the Change in Control, if higher), (ii) full acceleration of all stock options and other stock-based awards subject solely to time-based vesting held by Dr. Magovčević-Liebisch, and (iii) subject to Dr. Magovčević-Liebisch's copayment of premium amounts at the applicable active employees' rate and proper election to continue COBRA health coverage, payment of the portion of the premiums equal to the amount that we would have paid to provide health insurance to Dr. Magovčević-Liebisch had she remained employed with us until the earliest of (A) 18 months following termination, (B) Dr. Magovčević-Liebisch's eligibility for group medical plan benefits under any other employer's group medical plan or (C) the end of Dr. Magovčević-Liebisch's COBRA health continuation period. In addition, the CEO Agreement provides for full acceleration upon a Change in Control of all stock options and other stock-based awards held by Dr. Magovčević-Liebisch as of the effective date of the CEO Agreement that are subject solely to time-based vesting. If the payments or benefits payable to Dr. Magovčević-Liebisch in connection with a change in control would be subject to the excise tax on golden parachutes imposed under Section 4999 of the Code, then those payments or benefits will be reduced if such reduction would result in a higher net after-taxbenefit to Dr. Magovčević-Liebisch.

Dr. Magovčević-Liebisch's post-employment restrictive covenants obligations pursuant to the Restrictive Covenants Agreement (as defined in the CEO Agreement) have been preserved.

Petra Kaufmann

Pursuant to the employment agreement with Dr. Kaufmann, or CMO Agreement, Dr. Kaufmann's current annual base salary is $494,400, which is subject to periodic review and adjustment, and she is eligible to eaan annual bonus with a target amount equal to 40% of her base salary. Dr. Kaufmann is also eligible to participate in the employee benefit plans available to our employees, subject to the terms of those plans.

Pursuant to the CMO Agreement, if Dr. Kaufmann's employment is terminated by us without Cause or by Dr. Kaufmann for Good Reason outside of the Change in Control Period (as such terms are defined in the CMO

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Agreement), subject to her execution and the effectiveness of a separation agreement, including a general release of claims in our favor, then Dr. Kaufmann will be entitled to (i) nine months of continuation of her then-current base salary and (ii) subject to Dr. Kaufmann's copayment of premium amounts at the applicable active employees' rate and proper election to continue COBRA health coverage, payment of the portion of the premiums equal to the amount that we would have paid to provide health insurance to Dr. Kaufmann had she remained employed with us until the earliest of (A) nine months following termination, (B) Dr. Kaufmann's eligibility for group medical plan benefits under any other employer's group medical plan or (C) the end of Dr. Kaufmann's COBRA health continuation period.

If Dr. Kaufmann's employment is terminated by us without Cause or by Dr. Kaufmann for Good Reason within the Change in Control Period then, subject to her execution and the effectiveness of a separation agreement, including a general release of claims in our favor, Dr. Kaufmann will be entitled to (i) a lump sum cash payment equal to 1.0 times the sum of her then-current base salary (or her base salary in effect immediately prior to the Change in Control (as defined in the CMO Agreement), if higher) and her target bonus for the then-current year (or her target bonus in effect immediately prior to the Change in Control, if higher), (ii) full acceleration of all time-based stock options and other time-based stock awards held by Dr. Kaufmann, and (iii) subject to Dr. Kaufmann's copayment of premium amounts at the applicable active employees' rate and proper election to continue COBRA health coverage, payment of the portion of the premiums equal to the amount that we would have paid to provide health insurance to Dr. Kaufmann had she remained employed with us until the earliest of (A) 12 months following termination, (B) Dr. Kaufmann's eligibility for group medical plan benefits under any other employer's group medical plan or (C) the end of Dr. Kaufmann's COBRA health continuation period. If the payments or benefits payable to Dr. Kaufmann in connection with a change in control would be subject to the excise tax on golden parachutes imposed under Section 4999 of the Code, then those payments or benefits will be reduced if such reduction would result in a higher net after-taxbenefit to Dr. Kaufmann.

Dr. Kaufmann's post-employment restrictive covenants obligations pursuant to the Restrictive Covenants Agreement (as defined in the CMO Agreement) have been preserved.

Jennifer Ziolkowski

Pursuant to the employment agreement with Ms. Ziolkowski, or CFO Agreement, Ms. Ziolkowski's current annual base salary is $476,900, which is subject to periodic review and adjustment, and she is eligible to eaan annual bonus with a target amount equal to 40% of her base salary. Ms. Ziolkowski is also eligible to participate in the employee benefit plans available to our employees, subject to the terms of those plans.

Pursuant to the CFO Agreement, if Ms. Ziolkowski's employment is terminated by us without Cause or by Ms. Ziolkowski for Good Reason outside of the Change in Control Period (as such terms are defined in the CFO Agreement), subject to her execution and the effectiveness of a separation agreement, including a general release of claims in our favor, then Ms. Ziolkowski will be entitled to (i) nine months of continuation of her then-current base salary and a pro-ratedportion of her target bonus for the calendar year in which the termination occurs and (ii) subject to Ms. Ziolkowski's copayment of premium amounts at the applicable active employees' rate and proper election to continue COBRA health coverage, payment of the portion of the premiums equal to the amount that we would have paid to provide health insurance to Ms. Ziolkowski had she remained employed with us until the earliest of (A) nine months following termination, (B) Ms. Ziolkowski's eligibility for group medical plan benefits under any other employer's group medical plan or (C) the end of Ms. Ziolkowski's COBRA health continuation period.

If Ms. Ziolkowski's employment is terminated by us without Cause or by Ms. Ziolkowski for Good Reason within the Change in Control Period then, subject to her execution and the effectiveness of a separation agreement, including a general release of claims in our favor, Ms. Ziolkowski will be entitled to (i) a lump sum cash payment equal to 1.0 times the sum of her then-current base salary (or her base salary in effect immediately

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prior to the Change in Control (as defined in the CFO Agreement), if higher) and her target bonus for the then-current year (or her target bonus in effect immediately prior to the Change in Control, if higher), (ii) full acceleration of all time-based stock options and other time-based stock awards held by Ms. Ziolkowski, and (iii) subject to Ms. Ziolkowski's copayment of premium amounts at the applicable active employees' rate and proper election to continue COBRA health coverage, payment of the portion of the premiums equal to the amount that we would have paid to provide health insurance to Ms. Ziolkowski had she remained employed with us until the earliest of (A) 12 months following termination, (B) Ms. Ziolkowski's eligibility for group medical plan benefits under any other employer's group medical plan or (C) the end of Ms. Ziolkowski's COBRA health continuation period. If the payments or benefits payable to Ms. Ziolkowski in connection with a change in control would be subject to the excise tax on golden parachutes imposed under Section 4999 of the Code, then those payments or benefits will be reduced if such reduction would result in a higher net after-taxbenefit to Ms. Ziolkowski.

Ms. Ziolkowski's post-employment restrictive covenants obligations pursuant to the Restrictive Covenants Agreement (as defined in the CFO Agreement) have been preserved.

Compensation Risk Assessment

We believe that although a portion of the compensation provided to our executive officers and other employees is performance-based, our executive compensation program does not encourage excessive or unnecessary risk taking. Our compensation programs are designed to encourage our executive officers and other employees to remain focused on both short-term and long-term strategic goals, in particular in connection with our pay-for-performancecompensation philosophy. As a result, we do not believe that our compensation programs are reasonably likely to have a material adverse effect on us.

Equity Compensation Plan Information

The following table provides information as of December 31, 2024 with respect to the shares of our common stock that may be issued under our existing equity compensation plans.

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CERTAIN RELATIONSHIPS AND RELATED PARTY TRANSACTIONS

Certain Relationships and Transactions

Other than the compensation agreements and other arrangements described under "Executive Compensation" and "Director Compensation" in this proxy statement and the transactions described below, since January 1, 2023, there has not been and there is not currently proposed, any transaction or series of similar transactions to which we were, or will be, a party in which the amount involved exceeded, or will exceed, $120,000 (or, if less, 1% of the average of our total assets amounts at December 31, 2023 and 2024) and in which any director, executive officer, holder of five percent or more of any class of our capital stock or any member of the immediate family of, or entities affiliated with, any of the foregoing persons, had, or will have, a direct or indirect material interest.

Agreements with Our Stockholders

In connection with our preferred stock financings prior to our initial public offering in January 2022, or IPO, we entered into an investors' rights agreement, voting agreement, and right of first refusal and co-saleagreement, in each case, with the purchasers of our preferred stock and certain holders of our common stock. All of the material provisions of these agreements terminated immediately prior to the completion of our IPO, other than the provisions relating to registration rights, which continued in effect following the completion of our IPO and entitle the holders of such rights to demand that we file a registration statement, subject to certain limitations, and to request that their shares be covered by a registration statement that we are otherwise filing.

Indemnification Agreements

We have entered into agreements to indemnify our directors and executive officers. These agreements, among other things, require us to indemnify these individuals for certain expenses (including attorneys' fees), judgments, fines and settlement amounts reasonably incurred by such person in any action or proceeding, including any action by or in our right, on account of any services undertaken by such person on behalf of our Company or that person's status as a member of our board of directors to the maximum extent allowed under Delaware law.

Related Person Transaction Policy

Our board of directors reviews and approves transactions with directors, officers and holders of five percent or more of our voting securities and their affiliates, each a related party. The material facts as to the related party's relationship or interest in the transaction are disclosed to our board of directors prior to their consideration of such transaction, and the transaction is not considered approved by our board of directors unless a majority of the directors who are not interested in the transaction approve the transaction. Further, when stockholders are entitled to vote on a transaction with a related party, the material facts of the related party's relationship or interest in the transaction are disclosed to the stockholders, who must approve the transaction in good faith.

We have adopted a written related party transactions policy that such transactions must be approved by our audit committee.

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PRINCIPAL STOCKHOLDERS

The following table sets forth information, to the extent known by us or ascertainable from public filings, with respect to the beneficial ownership of our common stock as of March 26, 2025 by:

The column entitled "Shares Beneficially Owned" is based on a total of 46,671,534 shares of our common stock outstanding as of March 26, 2025.

Beneficial ownership is determined in accordance with the rules and regulations of the SEC and includes voting or investment power with respect to our common stock. Shares of our common stock subject to options that are currently exercisable or exercisable within 60 days of March 26, 2025 are considered outstanding and beneficially owned by the person holding the options for the purpose of calculating the percentage ownership of that person but not for the purpose of calculating the percentage ownership of any other person. Except as otherwise noted, the persons and entities in this table have sole voting and investing power with respect to all of the shares of our common stock beneficially owned by them, subject to community property laws, where applicable. Except as otherwise indicated in the table below, addresses of named beneficial owners are in care of Vigil Neuroscience, Inc., 100 Forge Rd, Suite 700, Watertown, MA 02472.

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Dr. Booth is a member of Atlas Venture Associates XII, LLC and is obligated to transfer the economic benefit, if any, received upon the sale of the shares issuable upon exercise of these options to Atlas Venture Life Science Advisors, LLC. Also consists of: (i) 4,808,896 shares of common stock held by Atlas Venture Fund XII, L.P., or Atlas Fund XII, and (ii) 1,027,978 shares of common stock held by Atlas Venture Opportunity Fund I, L.P., or AVAO I.

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REPORT OF THE AUDIT COMMITTEE

The audit committee is appointed by the board of directors to assist the board of directors in fulfilling its oversight responsibilities with respect to (1) the integrity of Vigil Neuroscience's financial statements and financial reporting process and systems of internal controls regarding finance, accounting, and compliance with legal and regulatory requirements, (2) the qualifications, independence, and performance of Vigil Neuroscience's independent registered public accounting firm, (3) the performance of Vigil Neuroscience's internal audit function, if any, and (4) other matters as set forth in the charter of the audit committee approved by the board of directors.

Management is responsible for the preparation of Vigil Neuroscience's financial statements and the financial reporting process, including its system of internal control over financial reporting and its disclosure controls and procedures. The independent registered public accounting firm is responsible for performing an audit of Vigil Neuroscience's financial statements in accordance with the standards of the Public Company Accounting Oversight Board (PCAOB) and issuing a report thereon. The audit committee's responsibility is to monitor and oversee these processes.

In connection with these responsibilities, the audit committee reviewed and discussed with management and the independent registered public accounting firm the audited consolidated financial statements of Vigil Neuroscience's for the fiscal year ended December 31, 2024. The audit committee also discussed with the independent registered public accounting firm the matters required to be discussed by the PCAOB's Auditing Standard No. 1301, Communication with Audit Committees. In addition, the audit committee received written communications from the independent registered public accounting firm confirming their independence as required by the applicable requirements of the PCAOB and has discussed with the independent registered public accounting firm their independence.

Based on the reviews and discussions referred to above, the audit committee recommended to the board of directors that the audited consolidated financial statements of Vigil Neuroscience be included in Vigil Neuroscience's Annual Report on Form 10-Kfor the fiscal year ended December 31, 2024, that was filed with the SEC. The information contained in this report shall not be deemed to be (1) "soliciting material," (2) "filed" with the SEC, (3) subject to Regulations 14A or 14C of the Exchange Act, or (4) subject to the liabilities of Section 18 of the Exchange Act. This report shall not be deemed incorporated by reference into any of our other filings under the Exchange Act or the Securities Act, except to the extent that we specifically incorporate it by reference into such filing.

March 31, 2025

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HOUSEHOLDING

Some banks, brokers and other nominee record holders may be participating in the practice of "householding" proxy statements and annual reports. This means that only one copy of our documents, including the annual report to stockholders and proxy statement, may have been sent to multiple stockholders in your household. We will promptly deliver a separate copy of either document to you upon written or oral request to Vigil Neuroscience, Inc., 100 Forge Road, Suite 700, Watertown, Massachusetts 02472, Attention: Corporate Secretary, telephone: 857-254-4445.If you want to receive separate copies of the proxy statement or annual report to stockholders in the future, or if you are receiving multiple copies and would like to receive only one copy per household, you should contact your bank, broker or other nominee record holder, or you may contact us at the above address and phone number.

STOCKHOLDER PROPOSALS

A stockholder who would like to have a proposal considered for inclusion in our 2026 proxy statement must submit the proposal in accordance with the procedures outlined in Rule 14a-8of the Exchange Act so that it is received by us no later than December 1, 2025. However, if the date of the 2026 annual meeting of stockholders is changed by more than 30 days from the date of the previous year's meeting, then the deadline is a reasonable time before we begin to print and send our proxy statement for the 2026 annual meeting of stockholders. SEC rules set standards for eligibility and specify the types of stockholder proposals that may be excluded from a proxy statement. Stockholder proposals should be addressed to Vigil Neuroscience, Inc., 100 Forge Road, Suite 700, Watertown, Massachusetts 02472, Attention: Corporate Secretary. We also encourage you to submit any such proposals via email to investors@vigilneuro.com.

If a stockholder wishes to propose a nomination of persons for election to our board of directors or present a proposal at an annual meeting but does not wish to have the proposal considered for inclusion in our proxy statement and proxy card, our bylaws establish an advance notice procedure for such nominations and proposals. Stockholders at an annual meeting may only consider proposals or nominations specified in the notice of meeting or brought before the meeting by or at the direction of the board of directors or by a stockholder of record on the record date for the meeting, who is entitled to vote at the meeting and who has delivered timely notice in proper form to our corporate secretary of the stockholder's intention to bring such business before the meeting.

The required notice must be in writing and received by our corporate secretary at our principal executive offices not less than 90 days nor more than 120 days prior to the first anniversary of the preceding year's annual meeting. However, in the event that the date of the annual meeting is advanced by more than 30 days, or delayed by more than 60 days, from the first anniversary of the preceding year's annual meeting, a stockholder's notice must be so received no earlier than the 120th day prior to such annual meeting and not later than the close of business on the later of (A) the 90th day prior to such annual meeting and (B) the tenth day following the day on which notice of the date of such annual meeting was mailed or public disclosure of the date of such annual meeting was made, whichever first occurs. For stockholder proposals to be brought before the 2026 annual meeting of stockholders, the required notice must be received by our corporate secretary at our principal executive offices no earlier than January 21, 2026 and no later than February 22, 2026. Stockholder proposals and the required notice should be addressed to Vigil Neuroscience, Inc., 100 Forge Road, Suite 700, Watertown, Massachusetts 02472, Attention: Corporate Secretary.

To comply with the SEC's universal proxy rules, stockholders who intend to solicit proxies in support of director nominees other than the Company's nominees must provide notice by the same deadline noted herein to submit a notice of nomination for the 2026 annual meeting of stockholders. Such notice must comply with the additional requirements of Rule 14a-19(b).

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OTHER MATTERS

Our board of directors does not know of any other matters to be brought before the Annual Meeting. If any other matters not mentioned in this proxy statement are properly brought before the meeting, the individuals named in the enclosed proxy intend to use their discretionary voting authority under the proxy to vote the proxy in accordance with their best judgment on those matters.

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Important Notice Regarding the Availability of Proxy Materials for the Annual Meeting of

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