C4 Therapeutics, Inc.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 14A INFORMATION

PROXY STATEMENT PURSUANT TO SECTION 14(a)

OF THE SECURITIES EXCHANGE ACT OF 1934

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Dear Fellow Shareholders,

C4 Therapeutics has made meaningful progress in advancing our mission to discover and develop targeted protein degradation medicines to transform patients’ lives. Over the past year, we have taken three critical actions to position the company for success:

1. Advanced our clinical pipeline through data-driven decisions that enabled us to prioritize capital allocation to programs that we believe have the greatest potential to benefit patients and create meaningful shareholder value;

2. Developed a new discovery strategy focused on learnings from 10 years of experience as a leading targeted protein degradation company; and

3. Strengthened our balance sheet by completing a financing in October 2025, which extended our cash runway to the end of 2028, through key value inflection points.

These efforts position us to deliver on ambitious 2026 milestones and support our vision of becoming a fully integrated biopharmaceutical company.

Prioritization of Cemsidomide Development in Multiple Myeloma

In 2025, we advanced cemsidomide and CFT1946 to data-driven decision points, enabling us to prioritize cemsidomide given its clinical profile and market opportunity. Cemsidomide is a potential best-in-class IKZF1/3 degrader for multiple myeloma and the Phase 1 data evaluating cemsidomide in combination with dexamethasone demonstrated compelling anti-myeloma activity in a heavily pre-treated patient population. In addition, these data presented a clinically meaningful differentiated safety and tolerability profile compared to other IKZF1/3 degraders for multiple myeloma. Together, these results have supported our decision to advance cemsidomide into the recently initiated Phase 2 and Phase 1b clinical trials that position cemsidomide as a potential new treatment option for multiple myeloma patients.

Our Phase 2 MOMENTUM trial is evaluating cemsidomide plus dexamethasone in multiple myeloma patients who have received four or more prior lines of therapy, a similar patient population we studied in our Phase 1 trial. We are also conducting a Phase 1b trial evaluating cemsidomide in combination with elranatamab, a B-cell maturation antigen CD3 targeted bispecific antibody, under a clinical trial collaboration and supply agreement with Pfizer. We believe this combination has the potential to leverage cemsidomide’s potent anti-myeloma activity across multiple dose levels and its ability to enhance T-cell activation to deliver deep and durable responses compared to a bispecific t-cell engager therapy alone. Additionally, we are planning a separate Phase 1b combination trial evaluating cemsidomide with approved multiple myeloma therapies to further establish cemsidomide’s profile across multiple lines of multiple myeloma treatment.

We are excited about the potential value creation opportunity of cemsidomide. As a wholly owned post proof-of-concept asset, cemsidomide has the potential to become a best-in-class therapy in a foundational pathway highly relevant to the large and growing multiple myeloma market.

Introduction of a New Discovery Strategy

During the year, we implemented a new discovery strategy focused on inflammation, neuroinflammation, and neurodegeneration (INN). This strategy prioritizes novel targets in clinically validated pathways where targeted protein degradation may offer advantages over other standard –of-care modalities. Leveraging our decade of expertise in designing degraders with finely tuned degradation kinetics that can cross the blood brain barrier, we believe we are well positioned to develop first-in-class therapies in these areas of significant unmet need. As we make progress with these targets, we will share more details at the appropriate time.

Advanced Discovery Programs with Collaboration Partners

Our strategic collaborations continue to expand and support the potential reach of our TORPEDO® platform. In partnership with Biogen, we designed and delivered two development candidates that Biogen has now advanced into Phase 1 clinical development, which highlights the value of our platform. We also entered into a new collaboration agreement with Roche to advance research in the emerging degrader-antibody conjugate modality.

Anticipated Milestones through 2028

Looking ahead, the next few years represent an important period of execution and value creation for the company. Our planned activities and expected highlights include:

•2026: Enrollment of patients in two clinical trials for cemsidomide across multiple lines of therapy for multiple myeloma. We are also planning an additional combination trial as part of the cemsidomide development plan. In parallel, we continue to make progress advancing our discovery programs in INN.

•2027: We are focused on positioning the company for future success, while continuing to build our pipeline. We expect to reach several important clinical milestones, including completing enrollment for the Phase 2 MOMENTUM trial and sharing initial overall response rate data from the study in the second half of the year. We also plan to present the Phase 1b data evaluating cemsidomide in combination with elranatamab and initiate preparations for a Phase 3 program.

•2028: We will aim to unlock the full value of our portfolio through key development milestones. This includes initiating a Phase 3 cemsidomide trial in multiple myeloma, presenting efficacy and safety data from the Phase 2 MOMENTUM trial, and potentially submitting our first NDA for cemsidomide. We also have the potential to deliver up to three development candidates from our internal discovery pipeline as we continue to build a diversified portfolio of degrader medicines in INN.

Together, we believe these efforts will highlight the potential of targeted protein degradation across oncology and INN while positioning C4 Therapeutics for long-term growth and building value for all our stakeholders. We are entering the next phase of execution with confidence, clarity, and a strengthened foundation, and we thank you for your continued support.

Ronald Harold Wilfred Cooper

Chair

C4 Therapeutics, Inc.

Watertown, Massachusetts 02472

NOTICE OF 2026 ANNUAL MEETING OF STOCKHOLDERS

To be held June 24, 2026

Notice is hereby given that the 2026 Annual Meeting of Stockholders, or Annual Meeting, of C4 Therapeutics, Inc., will be held online on Wednesday, June 24, 2026, at 8:30 a.m. Eastern Time. You will be able to attend, vote and submit your questions atwww.virtualshareholdermeeting.com/CCCC2026. The Annual Meeting will be held via live webcast over the Internet only. There will be no physical meeting location. You will need the 16-digit control number included with these proxy materials to attend the Annual Meeting. The purpose of the Annual Meeting is the following:

1. To elect three Class III directors to our Board of Directors, each to serve until the 2029 annual meeting of stockholders and until his or her successor has been duly elected and qualified, or until his or her earlier resignation or removal;

2. To cast a non-binding, advisory vote to approve the compensation of our named executive officers;

3. To ratify the appointment of KPMG LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2026;

4. To approve an amendment to our 2020 Stock Option and Incentive Plan, or the 2020 Plan, to amend the evergreen provision to include any outstanding pre-funded warrants in the total number of shares of common stock that are issued and outstanding as of each December 31 for purposes of calculating the evergreen increase; and

5. To transact any other business properly brought before the Annual Meeting or any adjournment or postponement of the Annual Meeting.

The proposal for the election of directors relates solely to the election of Class III directors nominated by the Board of Directors. Only C4 Therapeutics, Inc., stockholders of record at the close of business on April 27, 2026 will be entitled to vote at the Annual Meeting and any adjournment or postponement thereof.

We are pleased to take advantage of Securities and Exchange Commission rules that allow companies to furnish their proxy materials over the Internet. We believe that this e-proxy process will not only expedite stockholders’ receipt of proxy materials, but also lower the costs of printing and distributing our proxy materials, as well as reduce the environmental impact of our Annual Meeting. We will mail the Notice of Availability of Proxy Materials, or Notice, instead of a paper copy of our proxy materials and our 2025 Annual Report to Stockholders, or 2025 Annual Report, on or about April 29, 2026. The Notice contains instructions on how to access those documents and to cast your vote via the Internet. The Notice also contains instructions on how to request a paper copy of our proxy materials and our 2025 Annual Report.

Your vote is important. Whether or not you are able to attend the meeting in person, it is important that your shares be represented. To ensure that your vote is recorded promptly, please vote as soon as possible, even if you plan to attend the meeting, by submitting your proxy via the Internet at the address listed on the proxy card or by signing, dating and returning the proxy card.

By order of the Board of Directors,

Andrew J. Hirsch

President and Chief Executive Officer

Watertown, Massachusetts

April 29, 2026