CCCC 8-K
C4 Therapeutics, Inc. (CCCC)
8-K
2025-09-22
For: 2025-09-22
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April 10, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): September 22, 2025 (September 20, 2025)
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(Exact name of Registrant as Specified in Its Charter)
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Registrant’s Telephone Number, Including Area Code: (617 ) 231-0700
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(Former Name or Former Address, if Changed Since Last Report)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o
Item 7.01 Regulation FD Disclosure.
On September 20, 2025, C4 Therapeutics, Inc. (the “Company”) issued a press release announcing data from its Phase 1 clinical trial of cemsidomide, an orally bioavailable IKZF1/3 degrader, in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma (“RRMM”), as presented in an oral presentation at the International Myeloma Society Annual Meeting (the "IMS Meeting"). A copy of the press release is being furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information contained in Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such a filing. The furnishing of this information hereby shall not be deemed an admission as to the materiality of any such information.
Item 8.01 Other Events.
On September 20, 2025, the Company presented data from its Phase 1 clinical trial of cemsidomide in combination with dexamethasone for the treatment of RRMM in an oral presentation at the IMS Meeting. A copy of the slides from this presentation, which has been published to the “Events & Presentations” page of the investor relations section of the Company’s website, is filed as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits. The exhibits shall be deemed to be filed or furnished, depending on the relevant item requiring such exhibit, in accordance with the provisions of Item 601 of Regulation S-K (17 CFR 229.601) and Instruction B.2 to this form.
Exhibit Number | Description | |||||||
| 99.1 | ||||||||
| 99.2 | ||||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| C4 Therapeutics, Inc. | ||||||||
Date: | By: | /s/ Jolie M. Siegel | ||||||
| Jolie M. Siegel | ||||||||
| Chief Legal Officer and Secretary | ||||||||
Exhibit 99.1
C4 Therapeutics Presents Cemsidomide Phase 1 Multiple Myeloma Data Supporting Potential Best-in-Class Profile at the International Myeloma Society Annual Meeting
Cemsidomide in Combination With Dexamethasone Achieved a 50% Overall Response Rate (ORR) at the Highest Dose Level (100 µg) and a 40% ORR at the 75 µg Dose Level in a Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma Patient Population
Responses Across Dose Levels With Median Duration of Response of 9.3 Months as of the Data Cut-off Date; Median Duration of Response Not Yet Reached at Two Highest Doses
No Discontinuations Related to Cemsidomide and Few Dose Reductions Support a Safety Profile That May Be Ideal for Combination Regimens
C4T to Pursue Differentiated Development Strategy With Two Distinct Opportunities for Accelerated Approval in Second Line and Later
C4T to Host Webcast Today at 3 pm ET; Webcast Link Available Here
WATERTOWN, Mass., Sept. 20, 2025 (GLOBE NEWSWIRE) -- C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, today presented data from the Phase 1 clinical trial of cemsidomide, an orally bioavailable IKZF1/3 degrader, in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM) in an oral presentation at the International Myeloma Society (IMS) Annual Meeting. With enrollment in the Phase 1 trial complete, data continue to show cemsidomide’s differentiated safety and tolerability profile and potentially class-leading anti-myeloma activity, supporting clear development paths for second line and later patient populations.
“Cemsidomide’s clinical trial results to date have shown compelling anti-myeloma activity, a differentiated safety and tolerability profile and immunomodulatory effects across all dose levels, which have allowed us to create a derisked development plan that we are prepared to rapidly execute to potentially bring cemsidomide to patients, caregivers and hematologist-oncologists,” said Len Reyno, M.D., chief medical officer of C4 Therapeutics. “As we prepare to initiate the Phase 2 study in Q1 2026 to evaluate cemsidomide in combination with dexamethasone and the Phase 1b study in Q2 2026 to evaluate cemsidomide and dexamethasone in combination with a BCMA BiTE—both development pathways that have the potential for accelerated approval—we are excited to further differentiate cemsidomide as the IKZF1/3 degrader of choice among approved medicines in this class, which are used across lines of therapy and in various combination regimens. We look forward to generating data in the future that further demonstrates cemsidomide’s potential to become a class-leading IKZF1/3 degrader across the growing populations of relapsed/refractory multiple myeloma patients.”
Approved IKZF1/3 degraders remain backbone therapy across lines of multiple myeloma treatment, even as novel therapeutic approaches enter the treatment landscape. Recent advances in treatment, including immune-directed therapies, are not cures and the majority of patients ultimately relapse, creating a need for new medicines targeted at these heavily pretreated patients. This need for therapeutic options in later lines of therapy, which continue to incorporate IKZF1/3 degradation into the treatment regimen to promote myeloma cell death and T-cell activation, is expected to grow as patients live longer on newer treatments but still ultimately progress.
“The clinical data presented today for this potent Cereblon-based IKZF1/3 degrader shows a potentially class-leading safety profile and impressive evidence of anti-myeloma activity in a population of patients with extensive prior therapies—including 75% of patients who have progressed despite having received prior immune-based therapies, including BiTEs or CAR-Ts,” said Binod Dhakal, M.D., M.S., associate professor of medicine, Medical College of Wisconsin, Division of Hematology. “Cemsidomide in combination with dexamethasone is well positioned both as a potential therapeutic option for patients with multi-refractory disease, and as the potential combination regimen of choice with immune-directed therapies due to its ability to enhance the immune response and add additional direct anti-myeloma effects via IKZF1/3 degradation.”
Phase 1 Results
At the IMS Annual Meeting, C4T presented data from the Phase 1 dose escalation trial, for which enrollment is now complete. These data demonstrate cemsidomide’s potential to have a class-leading profile based on both its anti-myeloma activity and safety and tolerability profile, which positions the investigational medicine to become the IKZF1/3 degrader of choice across lines of therapy.
As of the July 23, 2025 data cutoff, a total of 72 patients received cemsidomide in combination with dexamethasone across five dose levels (50 µg dosed Monday, Wednesday, Friday [MWF]; 37.5 µg dosed once daily [QD]; 62.5 µg QD; 75 µg QD; 100 µg QD). The trial enrolled a heavily pretreated relapsed/refractory patient population that had received a median of seven prior therapies. Fifty-four patients (75%) received prior BCMA-targeted therapy, and 54 patients (75%) received prior CAR-T or T-cell engager therapy.
Safety: Cemsidomide in combination with dexamethasone was generally well tolerated over the range of doses tested.
•As of the data cutoff date, 72 patients were evaluable for safety.
•Cemsidomide was generally well tolerated with manageable incidents of on-target neutropenia across all dose levels; there were low rates of febrile neutropenia across all dose levels: three patients (4%) at Grade 3, one patient (1%) at Grade 4 and no patients at Grade 5.
•There were low rates of thrombocytopenia across all dose levels: five patients (7%) at Grade 3, three patients (4%) at Grade 4 and no patients at Grade 5.
•All treatment emergent adverse events were manageable; there were minimal dose reductions (four patients; 6%) and no discontinuations related to cemsidomide treatment.
•The maximum administered dose is 100 µg QD.
Pharmacodynamics: Cemsidomide in combination with dexamethasone leads to robust IKZF1/3 degradation and T-cell activation, reinforcing its potential to be administered with dexamethasone, and with dexamethasone in combination with a B-cell maturation antigen bispecific T-cell engager (BCMA BiTE).
•Cemsidomide achieved >50% degradation of IKZF1 and > 80% degradation of IKZF3, as assessed by mass spectrometry in human peripheral blood mononuclear cells (PBMCs).
•Across all dose levels, cemsidomide in combination with dexamethasone led to significant T-cell activation associated with an enhancement of cytokine production, including IL-2.
Anti-myeloma activity: Cemsidomide in combination with dexamethasone demonstrates the potential for class-leading anti-myeloma activity.
•As of the data cutoff, 67 patients were evaluable for anti-myeloma activity.
•Across all dose levels, 23 patients (34%) achieved a partial response (PR) or better, with a median duration of response of 9.3 months.
•At the 100 μg dose level, seven patients (50%) achieved a PR or better.
◦One patient achieved a minimal residual disease (MRD) negative complete response.
◦After the data cutoff and as of September 5, 2025, one patient who had achieved a very good partial response (VGPR) converted to a complete response (CR).
◦After the data cutoff and as of September 5, 2025, one patient who became efficacy evaluable achieved a PR; this PR is not included in the ORR reported above.
•At the 75 μg dose level, eight patients (40%) achieved a PR or better.
•Ten of the 15 efficacy evaluable patients (67%) who achieved a PR or better at the 75 µg and 100 µg dose levels remain on treatment; median duration of response has not yet been reached at 100 μg and 75 μg.
Cemsidomide’s Regulatory Path
Based on the Phase 1 trial results supporting cemsidomide’s differentiated safety and anti-myeloma activity, as well as insights gathered in the June 2025 Type C Meeting with the U.S. Food & Drug Administration (FDA), C4T plans to advance cemsidomide through two clinical trials that will position the investigational medicine for two distinct potential accelerated approvals.
•Fourth line of therapy or later: C4T expects to initiate a Phase 2 single-arm registrational trial in the first quarter of 2026 to evaluate cemsidomide in combination with dexamethasone; initial ORR data is expected in the second half of 2027. If the data are supportive, C4T will pursue accelerated approval. In this setting, cemsidomide has the potential to provide a safe, tolerable and efficacious treatment option for highly refractory patients, including those who have received anti-BCMA therapies.
•Second line of therapy or later: C4T plans to initiate a Phase 1b trial in the second quarter of 2026 to evaluate the safety and tolerability of cemsidomide and dexamethasone in combination with a BCMA BiTE; data are expected by mid-2027. If the data are supportive, C4T will advance this combination regimen directly into a single, randomized controlled Phase 3 study. This Phase 3 study will be designed to support the full approval for both the cemsidomide and dexamethasone pathway, as described above, and the cemsidomide and dexamethasone in combination with a BCMA BiTE pathway. In preclinical studies, the combination of cemsidomide with a BCMA BiTE exhibits a strong immunomodulatory effect and enhances T-cell dependent cellular cytotoxicity of multiple myeloma cells while continuing to demonstrate anti-myeloma activity.
Expected Upcoming Milestones:
•Formally align with FDA on the recommended Phase 2 dose of cemsidomide for the Phase 2 trial by the end of 2025.
•Initiate a Phase 2 single-arm registrational trial in the first quarter of 2026 to evaluate cemsidomide in combination with dexamethasone.
•Initiate a Phase 1b trial in the second quarter of 2026 to evaluate the safety and tolerability of cemsidomide and dexamethasone in combination with a BCMA BiTE.
C4T Webcast for Analysts and Investors
C4T will host an investor webcast today, September 20, 2025, at 3 pm ET. To join the webcast, please visit this link or the “Events & Presentations” page of the Investors section on the company’s website at www.c4therapeutics.com. A replay of the webcast will be archived and available following the event.
About Cemsidomide
Cemsidomide is an investigational, orally bioavailable small-molecule degrader in clinical development for the treatment of relapsed/refractory multiple myeloma. Data from the Phase 1 trial, which has completed enrollment, show cemsidomide’s differentiated safety and tolerability profile and potentially class-leading anti-myeloma activity that support the potential for durable outcomes. Two clinical trials are planned to further evaluate cemsidomide in relapsed/refractory multiple myeloma: a Phase 2 single-arm registrational trial to evaluate cemsidomide in combination with dexamethasone, which is expected to initiate in Q1 2026; and a Phase 1b trial to evaluate the safety and tolerability of cemsidomide and dexamethasone in combination with a BCMA BiTE, which is expected to initiate in Q2 2026.
About Multiple Myeloma
Multiple myeloma (MM) is a rare blood cancer affecting plasma cells. Approximately 36,000 people in the United States are diagnosed with MM each year. Despite advances in treatment, MM remains incurable. Treatment combinations include IKZF1/3 degraders, which are established backbone therapies, across lines of therapy.
About C4 Therapeutics
C4 Therapeutics (C4T) (Nasdaq: CCCC) is a clinical-stage biopharmaceutical company dedicated to delivering on the promise of targeted protein degradation science to create a new generation of medicines that transforms patients’ lives. C4T is progressing targeted oncology programs through clinical studies and leveraging its TORPEDO® platform to efficiently design and optimize small-molecule medicines to address difficult-to-treat diseases. C4T’s degrader medicines are designed to harness the body’s natural protein recycling system to rapidly degrade disease-causing proteins, offering the potential to overcome drug resistance, drug undruggable targets and improve patient outcomes. For more information, please visit www.c4therapeutics.com.
Forward Looking Statements
This press release contains “forward-looking statements” of C4 Therapeutics, Inc., within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements may include, but may not be limited to, express or implied statements regarding our ability to develop potential therapies for patients; the safety, tolerability, design and potential efficacy of our therapeutic approaches and product candidates; the predictive capability of our TORPEDO® platform in the development of novel, selective, orally bioavailable BiDAC™ and MonoDAC™ degraders; the potential initiation, timing, design, results and advancement of our preclinical studies and clinical trials, including the potential timing for and receipt of regulatory authorization and guidance related to clinical trials and other clinical development activities including clinical trial commencement or cohort initiation; the potential for accelerated approval of our product candidates; our ability and the potential to successfully manufacture and supply our product candidates for clinical trials; our ability to replicate results achieved in our preclinical studies or clinical trials in any future studies or trials; and our ability to fund our future
operations. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties related to the initiation, timing, advancement and conduct of preclinical and clinical studies and other development requirements for our product candidates; the risk that any one or more of our product candidates will cost more to develop or may not be successfully developed and commercialized; the risk that our product candidates will not receive accelerated approval or that we will need to redesign our regulatory strategy; and the risk that the results of preclinical studies and/or clinical trials will or will not be predictive of results in connection with future studies or trials. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in C4 Therapeutics’ most recent Annual Report on Form 10-K and/or Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission. All information in this press release is as of the date of the release and C4 Therapeutics undertakes no duty to update this information unless required by law.
Updated Data From Phase 1 Trial of Cemsidomide in Multiple Myeloma & Next Steps International Myeloma Society (IMS) Annual Meeting September 2025
Legal Disclaimer Statements and Intellectual Property LEGAL DISCLAIMER STATEMENTS The following presentation contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions. These forward-looking statements include, but are not limited to, statements regarding the therapeutic potential of C4 Therapeutics, Inc.’s technology and products; expectations for timing, progress and results from ongoing and planned preclinical and clinical development activities; our ability to successfully manufacture and supply our product candidates for clinical trials; our ability to replicate results achieved in our preclinical studies or clinical trials in any future studies or trials; expectations for future regulatory submissions and potential approvals; the anticipated timing and content of presentations of data from our clinical trials; and our ability to fund our future operations.. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, as well as the fact that the product candidates that we are developing or may develop may not demonstrate success in clinical trials. Prospective investors are cautioned not to place undue reliance on these forward- looking statements, which speak only as of the date hereof. The forward-looking statements included in this presentation are subject to a variety of risks and uncertainties, including those set forth in our most recent and future filings with the Securities and Exchange Commission. Our actual results could vary significantly from those anticipated in this presentation, and our financial condition and results of operations could be materially adversely affected. C4 Therapeutics, Inc. undertakes no obligation to update or revise the information contained in this presentation, whether as a result of new information, future events or circumstances or otherwise. This presentation also contains estimates, projections and other information concerning the markets for C4 Therapeutics, Inc.’s product candidates, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions and patient use of medicines. Information that is based on estimates, forecasts, projections, market research, or similar methodologies is inherently subject to uncertainties and actual events, and circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, the Company obtained this industry, business, market and other data from reports, research surveys, clinical trials studies and similar data prepared by market research firms and other third parties, from industry, medical and general publications, from other publicly available information, and from government data and similar sources. INTELLECTUAL PROPERTY C4 Therapeutics, Inc. owns various registered and unregistered trademarks and service marks in the U.S. and internationally, including, without limitation, C4 THERAPEUTICS, our housemark logo, the name of our TORPEDO platform, and the names of our BIDAC and MONODAC degrader products. All trademarks, service marks, or trade names referred to in this presentation that we do not own are the property of their respective owners. Solely for convenience, the trademarks, service marks, and trade names in this presentation are referred to without the symbols ®, SM and , but those references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights to. 2 © 2025 C4 Therapeutics, Inc.
Cemsidomide Phase 1 MM Data & Next Steps Len Reyno, M.D., CMO Concluding Remarks & Q&A Session Andrew Hirsch, President and CEO Len Reyno, M.D., CMO Kendra Adams, CFO Binod Dhakal, M.D., M.S Introductions Courtney Solberg, Associate Director of IR Opening Remarks Andrew Hirsch, President and CEO Today’s Agenda 3© 2025 C4 Therapeutics, Inc.
Opening Remarks Andrew Hirsch President and Chief Executive Officer
C4T Is Positioned to Unlock Value Across the Portfolio © 2025 C4 Therapeutics, Inc. Source: 1 Health Advances (2022), ClearView (2023), and C4T analysis, opportunity across two market segments – 2L+ with BCMA BiTE and 4L+ with dexamethasone Unlocking the clinical potential of a class-leading IKZF1/3 degrader and quickly delivering on an optimized portfolio of degraders against novel targets to address sizeable indications of unmet need Deliver value from high-potential clinical programs Build upon ~10 years of experience developing degraders against multiple target classes • Advance a new portfolio of novel targets in non-oncology and oncology indications with the potential for multiple development candidates Continue to advance our established collaborations in oncology and non-oncology • Expand application of targeted protein degradation through high-value collaborations • Advance cemsidomide to realize its potential as an IKZF1/3 degrader with class-leading efficacy and a differentiated safety & tolerability profile with potential $2.5B-$4B1 peak revenue for label opportunities • Utilize CFT8919 Phase 1 data to determine next steps 5
Cemsidomide Has the Potential to Be Best-in-Class IKZF1/3 Degrader in a Large and Growing Relapsed/Refractory Multiple Myeloma Market © 2025 C4 Therapeutics, Inc. Large Market Opportunity Potential to be clear leader in 2L+ or 4L+ in combo w/ a BCMA BiTE and dex, respectively Class-leading anti-myeloma activity with 50% ORR achieved at highest dose level Median DOR of 9.3 months across all dose levels and not yet reached at two highest dose levels Differentiated safety & tolerability profile Phase 1 data de-risks upcoming clinical trials Differentiated label-enabling strategy Two distinct opportunities for accelerated approval Phase 3 trial has potential to unlock full approval MM market projected to be $46B by 20301 Potential $2.5B-$4B2 peak revenue opportunity across two market segments: 2L+ with a BCMA BiTE and 4L+ with dex Captures 2L+ treatment landscape, where IKZF1/3 degraders are widely used Efficient Path Forward Clear and distinct paths to market Highly Competitive Profile Potential to be best-in-class; MOA is relevant across multiple lines of MM treatment Source: C4T data on file as of 7/23/2025 Sources: 1Evaluate Pharma (8/14/2025) 2 Health Advances (2022), ClearView (2023), and C4T analysis Overall Response Rate (ORR); Duration of Response (DOR); Mechanism of Action (MOA); Dexamethasone (dex); Second line or later (2L+); Fourth line or later (4L+); Multiple myeloma (MM) 6
Cemsidomide First-in-Human Clinical Program Relapsed Refractory Multiple Myeloma
Degrading IKZF1/3 Leads to Myeloma Cell Death and T-Cell Activation, Supporting This Target’s Important Role in Treating MM © 2025 C4 Therapeutics, Inc. Multiple myeloma (MM) Common Myeloid Progenitor Cell Common Lymphoid Progenitor Cell Neutrophil Platelets B-Cell Plasma Cell Oncogenic Mutations/Aberrations IKZF1/3 and IRF4 Multiple Myeloma IRF4 Physiological Functions: • IKZF1/3 directly regulate the activity of IRF4, another transcription factor that regulates downstream immune cell differentiation Oncogenic Functions: • Multiple myeloma cells rely on IKZF1/3 and IRF4 for survival IKZF1/3 Degradation Leads to: • Downregulation of IRF4 promoting the death of myeloma cells • T-cell activation • On-target neutropenia Key Roles of IKZF1/3 IKZF1/3 Hematopoietic Stem Cell Multiple myeloma (MM) is a cancer of plasma cells, which are part of the immune system T-cell Activation Adapted from Chen and Gooding, 2022 IKZF1/3 Degrader 8
Phase 1 Dose Escalation Trial Enabled Advancement to Next Phase of Development with Two Opportunities for Accelerated Approvals in RRMM © 2025 C4 Therapeutics, Inc. NOW: ENTERING NEXT PHASE OF DEVELOPMENT TO SUPPORT REGISTRATION Monday, Wednesday, Friday dosing (MWF); Once daily (QD); Dexamethasone (dex); Relapsed refractory multiple myeloma (RRMM); Bispecific T-cell engager (BCMA BiTE); Cemsidomide (cemsi) Phase 1 data reinforces potential best-in-class profile with compelling anti-myeloma activity, enhanced immunomodulatory effects, and a differentiated safety & tolerability profile, de-risking next clinical trials Potential accelerated approval PHASE 1 DOSE ESCALATION TRIAL Status: Complete R/R MM Dex Combo Potential accelerated and full approval (2L+) Potential full approval (4L+) Status: Complete RRMM Monotherapy Status: Complete RM Dex Combo PHASE 2 PHASE 1B 4L+ RRMM Dex Combo 2L+ RRMM BCMA BiTE Combo Status: On Track to Initiate in Q1 2026 Status: On Track to Initiate in Q2 2026 2L+ RRMM BCMA BiTE Combo PHASE 3 9
Cemsidomide + Dexamethasone Phase 1 MM Dose Escalation Is Complete; 100 µg Is the Maximum Administered Dose © 2025 C4 Therapeutics, Inc. *Cemsidomide administered as 14 days on/14 days off in a 28-day cycle; Dex was dosed on days 1, 8, 15, and 22 at doses of 40 mg orally for patients ≤75 years old and 20 mg orally for patients >75 years old; #1 patient at 100 µg QD expansion did not complete C1 as of data cut-off and is not included in the safety analysis set 1DLT at 62.5 µg QD was due to Grade 4 neutropenia lasting >7 days; 2 Three patients at 100 µg QD had 5 DLT events (G4 neutropenia, G3 pneumonia in 2 patients, G3 ALT increase, G3 febrile neutropenia) Eastern Cooperative Oncology Group (ECOG); Maximum tolerated dose (MTD); Monday Wednesday Friday (MWF); Multiple myeloma (MM); Once daily (QD); Pharmacodynamics (PD); Pharmacokinetic (PK); Recommended Phase 2 dose (RP2D); relapsed refractory (R/R); Dexamethasone (dex); Dose limiting toxicity (DLT) DOSE ESCALATION CEMSIDOMIDE 14/14 + DEX* Utilizing a Bayesian logistic regression model until determination of the MTD and/or RP2D 50 µg MWF Expansion; N=1 37.5 µg QD Expansion; N=8 62.5 µg QD Expansion; N=10 75 µg QD Expansion; N=16 50 µg MWF N=5 37.5 µg QD N=4 75 µg QD N=4 62.5 µg QD N=6 | 1 DLT1 KEY INCLUSION CRITERIA • Adults with MM, R/R to at least 3 prior lines of therapy that have included lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody • Nonresponsive to or progressed within 60 days of prior therapy • Creatinine clearance ≥40 mL/min • ECOG ≤2 Phase 1 Study Endpoints • Primary: assess safety, tolerability and define the RP2D/MTD • Secondary: assess PK, PD, and preliminary anti-tumor activity EXPANSION COHORTS 100 µg QD N=10 |3 DLTs2 100 µg QD Expansion; N=9# Maximum administered dose Source: C4T data on file as of 7/23/2025 10
Characteristics Safety Population (N=72) Prior therapies, median (range) 3L, n (%) 4L, n (%) ≥ 5L, n (%) 7 (3-22) 3 (4) 11 (15) 58 (81) Prior stem cell transplant, n (%) 43 (60) Prior lenalidomide, n (%) 72 (100) Prior pomalidomide, n (%) 71 (99) Prior anti-CD38 mAb, n (%) 72 (100) Prior CAR-T therapy, n (%) 36 (50) Prior T-cell engager therapy, n (%) 39 (54) Prior CAR-T or T-cell engager therapy, n (%) 54 (75) Prior CAR-T and T-cell engager therapy, n (%) 21 (29) Prior BCMA therapy, n (%) 54 (75) Prior GPRC5D therapy, n (%) 34 (47) Triple-class exposed*, n (%) 72 (100) Penta-class exposed†, n (%) 57 (79) Baseline Characteristics Prior Therapies Enrolled a Heavily Pre-Treated MM Patient Population, 75% of Whom Received Prior BCMA Therapy © 2025 C4 Therapeutics, Inc. Characteristics Safety Population (N=72) Age, median (range) 67 (39-90 years) Male, n (%) 43 (60) Time since initial diagnosis, median (range) 7 (2-22 years) ECOG performance status, n (%) 0 1 2 17 (24) 52 (72) 3 (4) Asian Black or African American, n (%) White, n (%) Other, n (%) 1 (1) 14 (19) 50 (69) 7 (10) Revised ISS at screening, n (%) Stage 1 Stage 2 Stage 3 Missing 24 (33) 29 (40) 9 (13) 10 (14) Presence of EMD, n (%) 23 (32) B-cell maturation antigen (BCMA); extramedullary disease (EMD); International Staging System (ISS); Monoclonal antibody (mAb); Chimeric Antigen Receptor T-cell Therapy (CAR-T); Eastern Cooperative Oncology Group (ECOG); Multiple myeloma (MM) *Defined as exposed to ≥1 immunomodulatory agent, ≥ 1 proteasome inhibitor, and 1 anti-CD38 monoclonal antibody; † Defined as exposed to ≥2 immunomodulatory agents, ≥ 2 proteasome inhibitors, and 1 anti-CD38 monoclonal antibody. Source: C4T data on file as of 7/23/2025 11
Safety & Tolerability Profile Cemsidomide + Dexamethasone
Cemsidomide’s Differentiated Safety & Tolerability Profile Is Ideal for Combinations © 2025 C4 Therapeutics, Inc. Source: C4T data on file as of 7/23/2025 Treatment emergent adverse events (TEAEs); Granulocyte colony-stimulating factor (G-CSF) Favorable safety profile with no discontinuations related to safety of ✓No unexpected safety signals ✓Well-tolerated profile, including at the two highest dose levels evaluated ✓Low incidence of neutropenic complications Favorable safety profile with no discontinuations related to safety of ✓No unexpected safety signals ✓Well-tolerated profile, including at the two highest dose levels evaluated ✓Low incidence of neutropenic complications Risk of neutropenia does not increase over time; limited G-CSF use highlights minimal impact of neutropenia on patient experience Few neutrop nic events occurred in later cycles coupled with low rates of G-CSF observed No discontinuations related to cemsidomide and minimal dose reductions TEAEs leading to dose reductions: 4/72 (6%) 1 TEAE leading to discontinuation, unrelated to cemsidomide Favorable safety profile with no discontinuations related to safety of ✓No unexpected safety signals ✓Well-tolerated profile, including at the two highest dose levels evaluated ✓Low incidence of neutropenic complications Differentiated safety profile with manageable neutropenia Across all dose levels, Grade 3 neutropenia was 24% and Grade 4 neutropenia was 33% Low rates of febrile neutropenia across all dose levels, with only 4% at Grade 3 and 1% at Grade 4 13
Cemsidomide Demonstrated a Differentiated Tolerability Profile With Minimal Dose Reductions and Discontinuations © 2025 C4 Therapeutics, Inc. Minimal Dose Reductions • TEAEs leading to dose reductions: 4/72 (6%)1 No Discontinuations Related to Cemsidomide • 1 TEAE led to discontinuation, unrelated to cemsidomide2 1 Dose Reductions: 1 patient at 75 µg had grade 4 thrombocytopenia possibly related to cemsidomide resulting in dose reduction; A patient at 100 µg had grade 3 pneumonia and another patient at 100 µg had grade 3 neutropenia, both possibly related to cemsidomide and resulting in dose reduction; a patient at 100 µg had two dose reductions after two events of pseudomonal bacteremia, deemed unrelated to cemsidomide 2 Patient at 75 µg discontinued due to grade 5 AE of septic shock, deemed unrelated to cemsidomide * 2 patients experienced grade 5 AEs (septic shock and subdural hematoma), both deemed unrelated to cemsidomide Treatment emergent adverse events (TEAEs) Common (>20% All Grades) TEAEs and Events of Interest, n (%) All Grades (N=72) Grade 3 (N=72) Grade 4 (N=72) Grade 5* (N=72) Neutropenia 44 (61) 17 (24) 24 (33) 0 Infections Pneumonia Upper Respiratory Tract Infection Septic Shock Sepsis 42 (58) 10 (14) 10 (14) 1 (1) 2 (3) 17 (24) 9 (13) 2 (3) 0 2 (3) 0 0 0 0 0 1 (1) 0 0 1 (1) 0 Anemia 27 (38) 16 (22) 1 (1) 0 Fatigue 26 (36) 0 0 0 Diarrhea 26 (36) 1 (1) 0 0 Leukopenia 21 (29) 9 (13) 8 (11) 0 Thrombocytopenia 14 (19) 5 (7) 3 (4) 0 Lymphopenia 13 (18) 6 (8) 2 (3) 0 Febrile Neutropenia 4 (6) 3 (4) 1 (1) 0 Source: C4T data on file as of 7/23/2025 14
Neutropenia Was Manageable and Relatively Consistent Across All Dose Levels With Low Rates of Febrile Neutropenia © 2025 C4 Therapeutics, Inc. Common Hematologic and Infections Grade ≥3 TEAEs, n (%) 50 µg MWF (N=6) 37.5 µg QD (N=12) 62.5 µg QD (N=16) 75 µg QD (N=20) 100 µg QD (N=18) Total (N=72) Neutropenia1 3 (50) 7 (58) 7 (44) 14 (70) 10 (56) 41 (57) Anemia 1 (17) 3 (25) 3 (19) 5 (25) 5 (28) 17 (24) Infections Upper respiratory tract infection Pneumonia Septic shock Sepsis 0 0 0 0 0 4 (33) 0 3 (25) 0 1 (8) 4 (25) 1 (6) 2 (13) 0 1 (6) 5 (25) 1 (5) 1 (5) 1 (5) 0 5 (28) 0 3 (17) 0 0 18 (25) 2 (3) 9 (13) 1 (1) 2 (3) Thrombocytopenia 2 (33) 1 (8) 1 (6) 2 (10) 2 (11) 8 (11) Lymphopenia 0 3 (25) 2 (13) 0 3 (17) 8 (11) Febrile neutropenia 1 (17) 1 (8) 0 1 (5) 1 (6) 4 (6) Treatment Emergent Adverse Events (TEAEs); Once daily (QD); Monday, Wednesday, Friday dosing (MWF) Source: C4T data on file as of 7/23/2025 • 195% of patients at the 75 µg dose level received prior stem cell transplants, the highest percentage of patients at any of the dose levels studied. Across other dose levels, the rate of prior stem cell transplant ranged from 33% - 56% • Patients who have received prior stem cell transplant are highly susceptible to neutropenia 15
Majority of Neutropenic Events Occurred in Earlier Cycles and Resulted in Low Rates of G-CSF Usage and Limited Clinical Consequences © 2025 C4 Therapeutics, Inc. 42% 23% 14% 5% 16% 9% 8% 9% 13% 7% 3% 5% 3% 3% 8% 0% 19% 23% 9% 7% 14% 13% 8% 9% 0% 25% 50% 75% 100% Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Cycle 7 Cycle 8 P ts w it h G ra d e ≥ 3 A E s o r G -C S F U se Rate of Grade ≥3 Neutropenia Rate of Grade ≥3 Infection % of Pts Receiving G-CSF Rates of Neutropenia, Infections, and G-CSF Use by Cycle (All doses) Total Pts 72 71 58 44 37 32 25 23 Risk of neutropenia does not increase over time: • 29/72 (40%) of patients received G-CSF across the study • Only 4/72 (6%) of patients experienced Grade ≥3 neutropenia for the first time after completing cycle 2 Source: C4T data on file as of 7/23/2025 Granulocyte – Colony Stimulating Factor (G-CSF); Patients (Pts) 16
Anti-myeloma Activity Profile Cemsidomide + Dexamethasone
Cemsidomide Phase 1 Data Has Demonstrated Class-leading Anti-myeloma Activity © 2025 C4 Therapeutics, Inc. Favorable safety profile with no discontinuations related to safety of ✓No unexpected safety signals ✓Well-tolerated profile, including at the two highest dose levels evaluated ✓Low incidence of neutropenic complications Favorable safety profile with no discontinuations related to safety of ✓No unexpected safety signals ✓Well-tolerated profile, including at the two highest dose levels evaluated ✓Low incidence of neutropenic complications Favorable safety profile with no discontinuations related to safety of ✓No unexpected safety signals ✓Well-tolerated profile, including at the two highest dose levels evaluated Patients who responded experienced durable benefit, supporting cemsidomide’s differentiated profile in a eavily pre-treated patient popul tion As f data cu off, m dian duration of response was 9.3 months across all doses and median duration f r sponse ot yet r ached at two high st dose levels 67% of effica y evaluable patients who chieved a PR or better at the 75 µg and 100 µg dose levels remain on treatment C mpelling anti-myeloma activity achieved at the two high st dose levels Achiev d 40% ORR a the 75 µg dose level and 50% ORR at the 100 µg dose level MRD negativity achieved in 1 patient with a CR at the 100 µg dose level Higher exposure with cemsidomide is correlated with greater reductions in dFLC Across all doses, 50% of multiple myeloma patients with elevated light chains achieved at least a 50% decrease in dFLC Difference in involved and uninvolved free light chain (dFLC); Complete response (CR); Overall response rate (ORR) Source: C4T data on file as of 7/23/2025 18
Pharmacokinetics Were Dose Proportional and Demonstrated Optimal Degradation of IKZF1/3 at 100 µg Dose Level 19 *1 patient censored due to abnormal mass spectrometry values Note: PD data were not available for all patients at all time points Ikaros zinc finger protein 1/3 (IKZF1/3); Monday Wednesday Friday (MWF); Peripheral blood mononuclear cell (PBMC); Once daily (QD); Difference in involved and uninvolved free light chain (dFLC); Dexamethasone (dex); Once daily (QD); Monday, Wednesday, Friday dosing (MWF) • Cemsidomide 14/14 exposure was dose- proportional when combined with dex • The overall geometric mean half-life estimate is approximately 2 days Dose Proportional Exposure 0 6 12 18 24 30 36 42 48 0.0 0.1 0.2 0.3 0.4 0.5 Time (h) M e a n P la s m a P K ( n g /m L ) 62.5 μg QD (N=9) 37.5 μg QD (N=11) 50 μg MWF (N=6) 75 μg QD (N=14) 100 μg QD (N=10) Source: C4T data on file as of 7/23/2025 • Cemsidomide 14/14 + dex achieves >50% degradation of IKZF1 and >80% degradation of IKZF3, as assessed by mass spectrometry in human PBMCs • Sustained IKZF3 degradation up to day 20 observed at the two highest doses of cemsidomide (75 µg and 100 µg) Pharmacodynamics 0 7 14 21 28 35 42 49 56 -100 0 100 200 Aiolos (IKZF3) Expression in PBMCs Days % c h a n g e f ro m b a s e li n e 100ug QD (N=8) 75ug QD (N=16) 62.5ug QD (N=14*) 37.5ug QD (N=7) 50ug MWF (N=4) 0 7 14 21 28 35 42 49 56 -100 0 100 200 Ikaros (IKZF1) Expression in PBMCs Days % c h a n g e f ro m b a s e li n e 37.5ug QD (N=11) 50ug MWF (N=6) 100ug QD (N=14) 75ug QD (N=18) 62.5ug QD (N=15*) Red bar indicates the 14-day periods of cemsidomide dosing © 2025 C4 Therapeutics, Inc.
T-cell Activation Is Observed Across All Dose Levels With Cemsidomide + Dex © 2025 C4 Therapeutics, Inc. C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 0 20 40 60 80 100 CD8+ T-cells % H L A D R c e ll s 37.5ug cemsid + dex (n=8, QD) 62.5ug cemsid + dex (n=15, QD) 75ug cemsid + dex (n=20, QD) 100ug cemsid + dex (n=11, QD) C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 0 20 40 60 80 100 CD8+ T-cells % C D 3 8 c e ll s 37.5ug cemsid + dex (n=8, QD) 62.5ug cemsid + dex (n=15, QD) 75ug cemsid + dex (n=20, QD) 100ug cemsid + dex (n=11, QD) C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 C 1D 1 C 1D 7 C 1D 14 C 1D 21 C 2D 1 0 1000 2000 3000 4000 IL-2 Cytokine Expression (serum) C o n c e n tr a ti o n ( fg /m L ) 37.5ug cemsid + dex (n=12, QD) 62.5ug cemsid + dex (n=15, QD) 75ug cemsid + dex (n=17, QD) 100ug cemsid + dex (n=5, QD) Cemsidomide + Dexamethasone: • Significant elevation of CD8+ T-cells harboring HLA-DR and CD38 markers after 7 and 14 days of dosing • Activated T-cells continued to be observed until Cycle 1 Day 21 • CD8+ T-cell activation translates to increased serum IL-2 cytokine expression compared to baseline Source: C4T data on file as of 7/23/2025 baseline Cemsidomide Monotherapy: • Data shared previously demonstrated clinical evidence of T-cell activation with monotherapy1 Source: 1C4T data on file as of 11/28/2023 presented in December 2023 (https://ir.c4therapeutics.com/static-files/ec59b02e-3074-484d-ad88-e81831bf37ed) Dexamethasone (dex); Human leukocyte antigen-DR isotype (HLA-DR); Interleukin 2 (IL2); Once daily (QD) 20
Exposure (AUC) Quartiles <Q1 (N=14) Q1-Q2 (N=14) Q2-Q3 (N=14) >Q3 (N=14) Mean AUC0-28d (ng*h/mL) 16.8 34.9 51.9 103.3 Mean Change in dFLC from Baseline +10% -11% -31% -52% Cemsidomide 100 µg Dose Level Drives Sufficient Exposure, Resulting in Meaningful Reductions in Light Chains 21 Cemsidomide + dex PK Exposure vs. dFLC Change *Includes 56 patients with abnormal baseline sFLC defined as (A) kappa FLC >19.4 mg/L or lambda FLC >26.3 mg/L and (B) kappa-to-lambda FLC ratio >4 or <0.5. Area under the curve (AUC); Dexamethasone (dex); Difference in involved and uninvolved free light chain (dFLC,); Maximum response (Emax); Monday Wednesday Friday dosing (MWF); Once daily (QD); Population pharmacokinetics (popPK); Pharmacokinetic (PK) 0 40 80 120 160 200 -100% -50% 0% 50% 100% 150% 350% PopPK-derived AUC0-28d (ngh/mL) % d F L C C h n a g e f ro m B a s e li n e 50 μg MWF (N=6) 37.5 μg QD (N=11) 62.5 μg QD (N=12) 75 μg QD (N=19) 100 μg QD (N=8) Emax Model Fit * Source: C4T data on file as of 7/23/2025 © 2025 C4 Therapeutics, Inc.
Across All Doses, 50% of Multiple Myeloma Patients With Elevated Light Chains Achieved at Least a 50% Decrease in dFLC © 2025 C4 Therapeutics, Inc. Dexamethasone (dex); Difference in involved and uninvolved free light chain (dFLC); Monday Wednesday Friday (MWF); Once daily (QD) *Only includes treated subjects who meet both criterion (A) and (B): (A) baseline kappa free light chain value >19.4 mg/L or baseline lambda free light chain value >26.3 mg/L; (B) ratio of baseline free light chain kappa over baseline free light chain value lambda >4:1 or <1:2. Best Change in dFLC from Baseline (Cemsidomide 14/14 + Dex) Multiple Myeloma Patients w/ Elevated Light Chain Disease (N=64)* • Cemsidomide 14/14 + dex induced dFLC decrease in 73% (47/64) of patients, with 50% of patients having a reduction of ≥ 50% • Cemsidomide 14/14 + dex demonstrated anti-myeloma activity across a broad range of doses Source: C4T data on file as of 7/23/2025 22
Class-leading Anti-myeloma Activity With a 40% and 50% ORR at the Two Highest Dose Levels 23 *Investigator assessed response a1 patient in the 37.5 µg cohort achieved a PR based on light chains, no follow up M protein available; §1patient at 62.5 µg did not have a post-baseline assessment and 4 patients in 100 µg did not have a post-baseline assessment performed at the time of data cutoff; #1 patient in 100 µg had a PR confirmed after data cut off date, which is reflected in the graph above Clinical benefit rate (CBR); Dexamethasone (dex); Minimal response (MR); Monday Wednesday Friday (MWF); Objective response rate (ORR); Progressive disease (PD); Partial response (PR); Once daily (QD); Relapsed/refractory multiple myeloma (RRMM); Stringent complete response (sCR); Stable disease (SD); Very good partial response (VGPR); Minimal residual disease MRD); Complete response (CR) Best Response: Multiple Myeloma – Cemsidomide 14/14 + Dex* 33% (2) 8% (1) 7% (1) 20% (4) 21% (3) 16% (11) 50% (3) 50% (6) 47% (7) 25% (5) 14% (2) 34% (23) 17% (2) 20% (3) 15% (3) 14% (2) 15% (10) 17% (1) 8% (1) 20% (3) 40% (8) 29% (4#) 25% (17) 8% (1) 7% (1) 14% (2) 6% (4) 7% (1) 1% (1)8% (1) 1% (1) 0% 25% 50% 75% 100% 50 µg MWF (N=6) 37.5 µg QD (N=12) 62.5 µg QD (N=15) 75 µg QD (N=20) 100 µg QD (N=14) TOTAL (N=67) B e s t R e s p o n s e % ( N ) sCR CR VGPR PR MR SD PD CBR 17% CBR 42% CBR 47% ORR 17% ORR 25% ORR 27% ORR 40% ORR 34% CBR 49% a CBR 55% ORR 50% CBR 64% §§ • ORR (≥ PR) of 34% (23/67) was achieved across all dose levels with a clinical benefit rate (≥ MR) of 49% • ORR at the highest dose level of cemsidomide (100 µg) was 50% with a clinical benefit rate of 64% • MRD negativity achieved in 1 patient with a CR at the highest dose level of cemsidomide (100 µg) Source: C4T data on file as of 7/23/2025 § 1 1As of September 5, 2025 at the 100 µg dose level: • One patient (not reflected in the graph) became efficacy evaluable and achieved a PR • One patient who was included in the table as a VGPR converted to a CR © 2025 C4 Therapeutics, Inc.
b Adverse event (AE); Duration of response (DOR); End of treatment (EOT); Extramedullary disease (EMD); Minimal response (MR); Progression-free survival (PFS); Progressive disease (PD); Partial response (PR); Once daily (QD); Relapsed/refractory multiple myeloma (RRMM); Stringent complete response (sCR); Stable disease (SD); Very good partial response (VGPR); Complete response (CR); stable disease (SD); Best overall response (BOR); Progression free survival (PFS); Confidence interval (CI); Not estimable (NE) *Investigator assessed response and swimmer plot only includes patients that achieved and MR or better (33/72) patients a Patient at 75 µg had EOT reason updated from discontinued due to AE to disease progression after data cut off, b Patient at 75 µg discontinued due to grade 5 AE of septic shock, deemed unrelated to cemsidomide. C After the data cut off date, patient at 100 µg cohort depicted as VGPR in the figure converted to a CR, d Patient at 100 µg had PR confirmed after data cut off date b a c In a Heavily Pre-treated Population, Patients Who Responded Remained on Therapy for Clinically Meaningful Duration © 2025 C4 Therapeutics, Inc. 67% (10/15) of efficacy evaluable patients who achieved a PR or better remain on treatment at two highest dose levels evaluated (75 μg and 100 μg) Source: C4T data on file as of 7/23/2025 All doses (N=72) Months (95% CI) Median PFS 3.7 (2.9-5.6) Median DOR 9.3 (2.8-NE) C li n ic a l R e sp o n se s (M R o r B e tt e r) *: d 24
Cemsidomide Phase 1 Patient Population Was More Heavily Pre-treated Than Other IKZF1/3 Degraders in Development, Representative of Current Multi-Refractory Patients © 2025 C4 Therapeutics, Inc. Cemsidomide Dose Escalation N=72 Mezigdomide Dose Escalation1 N=77 Iberdomide Dose Escalation2 N=90 Prior lines of therapy, median (range) 7 (3-22) 6 (2-13) 5 (4-8) Prior BCMA therapy 75% 12% N/A3 Prior anti-CD38 mAb4 100% 78% 76% Triple-class exposed5 100% 56% 59% Source: C4T data on file as of 7/23/2025 Sources: 1Richardson 2023 NEJM. 2 Phase I dose escalation (Lonial 2022 Lancet Haematology); 3 Dose escalation trial was conducted from 2016 – 2020 and BCMA therapies were not approved until 2021 4 Anti-CD38 mAB is also known as Anti-CD38 antibody 5 Triple-class exposed is defined as refractory to at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one CD38 monoclonal antibody. Monoclonal antibody (mAb) Prior Therapies 25
Cemsidomide Demonstrated Minimal Treatment Disruptive Adverse Events, Differentiated From Other IKZF1/3 Degraders in Development 24% 33% 25% 6% 6% 23% 48% 40% 9% 25% 21% 21% 25% 3% 24% 0% 10% 20% 30% 40% 50% 60% Cemsi Dose Escalation Mezi Dose Escalation Iber Dose Escalation Mezi Grade 3 neutropenia Grade 4 neutropenia Grade > 3 infections Febrile neutropenia Dose reductions due to TEAEs3 Cemsi Mezi Iber Cemsi Iber Cemsi Mezi IberCemsi Mezi Iber Cemsi Mezi Iber Sources:1Richardson 2023 NEJM. 2 Phase I dose escalation (Lonial 2022 Lancet Haematology) 3 Cemsidomide and Iber reported reductions due to TEAEs, while Mezi reported reductions due to AEs Cemsidomide (Cemsi); Mezigdomide (Mezi); Iberdomide (Iber); Treatment Emergent Adverse Events (TEAEs); Adverse events (AEs); B-cell maturation antigen (BCMA) 1 2 Cross-trial comparisons should be used with caution and only as benchmarks for relative comparison; no head-to-head studies have been conducted Source: C4T data on file as of 7/23/2025 N=90N=77N=72 © 2025 C4 Therapeutics, Inc. 26
Cemsidomide Demonstrates Compelling Anti-Myeloma Activity and Median Duration of Response 34% 50% 25% 55% 32% 31% 0% 10% 20% 30% 40% 50% 60% ORR Across all Doses ORR at Highest Dose Level Cemsi Dose Escalation Mezi Dose Escalation Iber Dose Escalation Cemsi N=67 Mezi N=77 Cemsi N=14 Mezi N=11 Iber N=90 Iber N=13 Cross-trial comparisons should be used with caution and only as benchmarks for relative comparison; no head-to-head studies have been conducted Sources: 1Richardson 2023 NEJM. 2 Phase I dose escalation (Lonial 2022 Lancet Haematology); 3 As of the July 23, 2025 data cutoff, the upper duration of response has not been achieved as patients continue on the study; 4 Dose escalation trial was conducted from 2016 – 2020 and BCMA therapies were not approved until 2021 Cemsidomide (Cemsi); Mezigdomide (Mezi); Iberdomide (Iber); Overall response rates (ORR); Not estimable (NE) 1 2 Source: C4T data on file as of 7/23/2025 Cemsi and Mezi Have Similar Response Rate In Respective Phase 1 Dose Escalation Trials Cemsi-treated Patients Have Compelling Duration of Response Median Duration of Response Months (95% CI) Cemsi Dose Escalation 9.3 (2.8-NE)3 Mezi1 Dose Escalation 6.0 (1.9-11.1) Iber2 Dose Escalation 10.4 (4.6-15.7) Patients treated with cemsi are in a more contemporaneous and relevant late-line setting and 75% were pre-treated with BCMA therapies © 2025 C4 Therapeutics, Inc. 75% received prior BCMA 12% received prior BCMA N/A received prior BCMA4 27
Patient Vignette: Penta-class Refractory Patient With EMD Who Progressed on Prior T-Cell Engager Therapy Achieved MRD Negative CR, With Treatment Ongoing © 2025 C4 Therapeutics, Inc. • 42-year-old male, enrolled at the 100 µg dose level of cemsidomide in December 2024 • Stage 2 MM diagnosed in June 2020 • Patient with EMD received 17 prior therapies; last treatment prior to study start was talquetamab (GPRC5D – T-cell engager) where the best overall response was progressive disease • As of data cutoff, patient remained on cemsidomide treatment at cycle 8 Per IMWG response criteria, patient achieved MRD negative complete response Source: C4T data on file as of 7/23/2025 Per IMWG response criteria, patient achiev RD negative complete response Baseline C3D1C2D1 C5D1 SPD: 9290 mm2 SPD: 1372 mm2 (-85%) SPD: None SPD: None 28 Multiple myeloma (MM); International Myeloma Working Group (IMWG); Extramedullary disease (EMD); Sum of products of the maximal perpendicular diameters of measured lesions (SPD); Minimal Residual Disease (MRD)
Time IgG Levels (mg/dL) Serum M Protein (g/dL) Urine M Protein mg/24 hr Kappa (mg/L) Lambda (mg/L) BOR: Cemsi + dex Baseline 758 Undetectable 124 426 1.3 C2D1 811 Undetectable Not done 35 (-93.5%) 1.3 VGPR C2D14 546 Undetectable Not done 13.2 (-97.7%) 1.3 C2D22 Undetectable (IFE + Kappa) C3D1 685 Undetectable Not done 33.4 (-94%) 1.3 VGPR Multiple myeloma (MM); Chimeric antigen receptor t-cell therapy (CAR-T); Pomalidomide (pom); Very good partial response (VGPR) Patient Vignette: 90-Year-Old Patient Who Progressed on Prior IKZF1/3 Degraders Achieved a Very Good Partial Response With Cemsidomide © 2025 C4 Therapeutics, Inc. Source: C4T data on file as of 7/23/2025 • 90-year-old female enrolled at the 100 µg dose level of cemsidomide in May 2025 • Stage 3 MM diagnosed in August 2020 • Patient received 5 prior therapies; last treatment prior to study start was teclistamab –Did not receive prior CAR-T therapy • As of data cutoff, patient remained on cemsidomide treatment at cycle 4 29
Cemsidomide’s Potential Best-in-Class Profile Supports Opportunity to be the IKZF1/3 Degrader of Choice Across the MM Landscape Favorable safety profile with no discontinuations related to safety of ✓No unexpected safety signals ✓Well-tolerated profile, including at the two highest dose levels evaluated Differentiated safety & tolerability profile with no discontinuations related to cemsidomide safety and minimal dose reductions Well-tolerated profile, including at the two highest dose levels evaluated Manageable neutropenia supported by low G-CSF use and patients remaining on treatment Mechanism of Action (MOA); Overall response rate (ORR); Granulocyte colony stimulatory factor (G-CSF); Bispecific T-cell engager (BCMA BiTE); Minimal response (MR); Minimal residual disease (MRD); Chimeric antigen receptor t-cell therapy (CAR-T) Source: C4T data on file as of 7/23/2025 30 complications Class-leading anti-myeloma activity in heavily pre-treated patient population, a majority of whom received a prior BCMA BiTE or T-cell engager, highlighting that IKZF1/3 degradation is a critical MOA regardless of prior treatment 75% of patients received prior BCMA therapy 40% ORR at the 75 µg dose level and 50% ORR at 100 µg dose level 1 patient at 100 µg dose level achieved MRD negativity Patients who responded experienced durable benefit, supporting cemsidomide’s differentiated profile Median duration of response is 9.3 months across all doses; median duration of response not yet reached at two highest dose levels 67% of efficacy evaluable patients who achieved a PR or better at the 75 µg and 100 µg dose levels remain on treatment ✓Low incidence of neutropenic complications Cemsidomide, as a monotherapy and in combination with dex, activates T-cells, providing a strong rationale for a BCMA BiTE combination © 2025 C4 Therapeutics, Inc. 30
Market Opportunity & Path Forward for Cemsidomide
2L ~56,000 1L ~65,000 3L ~49,000 4L ~42,000 5L+ ≥23,000 U.S. + EU4 + UK Addressable Patients (2024)4 Treatment Line Selinexor based regimen bortez/carfilz + pom + dex BCMA CAR-T ide-cel / cilta- cel Dara + len/pom + dex PI + IKZF1/3 Degrader doublets for frail patients (D)KRd (Dara) + carfilzomib + len + dex DKd dara + carfilzomib + dex elotuzumab based regimen isatuximab + len/pom + dex ixazomib + len/pom + dex Dara regimen rechallenge BCMA bispecific teclistamab / elranatamab GPRC5D bispecific talquetamab PI + IKZF1/3 Degrader doublets for frail patients Initial Cemsidomide Development Opportunity: Anti-CD38 mAb-based regimen Proteasome inhibitor-based regimen CAR-T Bispecific T-cell engager Dex+ cemsidomide Treatment Regimens for 2/3 Line2: Treatment Regimens for 4/5 Line2: BCMA BiTE + cemsidomide TOTAL GLOBAL PROJECTED MM MARKET IS $46B BY 20303 Sources: 1Health Advances (2022), ClearView (2023), and C4T analysis 2 NCCN guidelines 3 Evaluate Pharma (8/14/2025) 4 EvaluatePharma (accessed 8/28/25) 5 Linovesltamab is only approved in 5L Relapsed refractory multiple myeloma (RRMM); Dexamethasone (dex); Bispecifc T-cell engager (BCMA BiTE) $2.5 to $4B1 peak revenue potential, if labels are achieved in combinations with a BCMA BiTE and dex Other IKZF1/3 degrader regimen BCMA bispecific linvoseltamab5 Cemsidomide Is Well-Positioned to Compete in the RRMM Treatment Paradigm and Be Incorporated as a 2L+ Treatment Option © 2025 C4 Therapeutics, Inc. 32
Multiple Myeloma Is a Growing Patient Population With Persistent Unmet Need as Patients Continue to Progress © 2025 C4 Therapeutics, Inc. In the US, UK, and EU4, the addressable patient population in 2024 for: Majority of Patients Continue to Progress Despite Novel Treatment Options: MM Represents a Large and Growing Population With Tremendous Unmet Need • Many patients experience relapse after receiving a BCMA therapy - Despite high initial response rates, 2/3 of CARVYKTI- treated patients relapse before 5 years3 • Later lines are expected to grow as patients live longer on newer treatments but ultimately progress - Range of median OS for patients treated with BiTEs: 22 – 34 months4 Survival outcomes with current options are low1: 4L = ~42,0002 2L = ~56,0002 Sources: 1 Mammoth Study (275 patients evaluated across the study) Podar, K., & Leleu, X. (2021). Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond. Cancers, 13(20), 5154 https://pmc.ncbi.nlm.nih.gov/articles/PMC6820050/ 2 EvaluatePharma (accessed 8/28/25) 3 Legend Biotech Press Release June 3, 2025 (https://investors.legendbiotech.com/news-releases/news-release-details/legend-biotech-unveils-groundbreaking-5-year-survival-data) 4 https://www.jnjmedicalconnect.com/media/attestation/congresses/oncology/2024/ims/longterm-followup-from-the-phase-12-majestec1-trial-of-teclistamab-in-patients-with-relapsedrefracto.pdf; https://www.pfizer.com/news/press-release/press-release- detail/elrexfiotm-shows-median-overall-survival-more-two-years ; https://www.jnjmedicalconnect.com/products/talvey/medical-content/talvey-monumental1-mmy1001-study Overall Survival (OS); Germany, Italy, France, and Spain (EU4) Median OS in RRMM (penta-refractory) ~5.6 months Median OS (triple/quad refractory) ~9.2 months 33
© 2025 C4 Therapeutics, Inc. Opportunity: By activating T-cells with a potential best-in-class profile, cemsidomide could increase BCMA BiTE efficacy to be in line with CAR-Ts while offering a more attractive overall profile, thereby potentially taking market share from CAR-Ts 0.0 5.0 10.0 15.0 20.0 Revenue ($B) 2024 1.9 18.0 2030 10.3 6.4 1.3 BCMA CAR-T BCMA BiTE GPRC5D BiTE Sources: 1 Packaging Insert for each product (carvykti, tecvayli; elrexflo; lynozyfic) accessed 8/26/25 – the data is not a head-to-head trial . 2 Evaluate Pharma; C4T Analysis (accessed 8/15/2025) Compound Annual Growth Rate (CAGR) ORR Range CAR-T ~85% VS BCMA BiTEs ~58% - 70% Challenge: CAR-T Has Better ORR Than BiTEs1 Validated Biology Mechanism of resistance against t-cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies “Long-term exposure to bispecific antibodies with chronic T-cell stimulation further aggravates T-cell dysfunction, which could contribute to failure of disease control” CAR-T and BCMA-BiTE Market Predicted to Grow at ~50% CAGR2 Combination With BCMA-BiTE Has Potential to Capture Growing Market by Being a More Convenient Regimen Option With Potentially Similar Efficacy to CAR-Ts 34
Cemsidomide Development Plan Provides Efficient Path to Registration and Addresses a Growing Patient Population © 2025 C4 Therapeutics, Inc. A single, randomized controlled Phase 3 study would be used to support accelerated approval in 2L+ and full approval in 2L+ and 4L+ based on a time-to-event endpoint Accelerated Approval Full Approval 4L or later Phase 2 (Single Arm) Cemsi + dex ORR endpoint N= ~100 Time-to-event endpoint 2L or later Phase 1b Cemsi + BCMA BiTE Characterize safety and tolerability N = 30 - 50 ORR endpoint Phase 2 trial de-risked based on Phase 1 dose escalation data Phase 3 Cemsi + BCMA BiTE Q1 2026 Initiation: Q2 2026 Initiation: 2 trials pave way for 2 distinct potential accelerated approvals based on ORR endpoint = next trial initiations 35Overall response rate (ORR); Dexamethasone (dex)
Phase 2 Initial ORR Data of Cemsidomide + Dex in 4L+ Expected in 2H 2027 © 2025 C4 Therapeutics, Inc. PHASE 2 TRIAL DESIGN: • Endpoints: ORR per IMWG response criteria assessed by independent review committee – 100 patients will provide ~94% power to detect a 20% absolute improvement with a 1-sided alpha of 0.025 • Objective: ORR in RRMM • RP2D: Expect to formally align with FDA by year- end on an RP2D • Schedule: QD 14/14 Dexamethasone (dex); Overall response rate (ORR); Bispecific t cell engager (BCMA BiTE); Second line (2L); Fourth line (4L); Recommended Phase 2 dose (RP2D); Overall response (ORR); International Myeloma Working Group (IMWG); Once daily (QD) Phase 2 initial ORR data expected in 2H 2027 Potential for accelerated approval Phase 2 Trial Cemsidomide + dex (single arm) 4L+ N = ~100 Formally select RP2D by year-end Q1 2026 EXPECTED TRIAL INITIATION 36
Phase 1b Trial Will Evaluate Optimal Dose for Safety and T-Cell Activation in Combination With a BCMA BiTE, With Data Expected by Mid-2027 © 2025 C4 Therapeutics, Inc. PHASE 1b TRIAL DESIGN: Primary Objectives: • Characterize the safety and tolerability of cemsidomide in combination with a BCMA BiTE Dosing Regimen: • Cemsidomide: QD 14/14 • Dexamethasone: QW through cycle 4 • BCMA BiTE: Per label Dexamethasone (dex); Bispecific t cell engager (BCMA BiTE); Once daily (QD); Once weekly (QW); Cemsidomide (cemsi) Phase 1b data expected by mid-2027 Phase 1b Cemsi + BCMA BiTE 2L+ N = 30 - 50 Evaluation of three cemsidomide doses: • 50 µg QD • 75 µg QD • 100 µg QD Potential to expand at each dose level Q2 2026 EXPECTED TRIAL INITIATION 37
• De-risked development plan with two distinct opportunities for accelerated approval Clear and distinct regulatory path Cemsidomide Has the Potential to Be Best-in-Class For Use Across Multiple Lines of Therapy in Multiple Myeloma © 2025 C4 Therapeutics, Inc. Source: 1Health Advances (2022), ClearView (2023), and C4T analysis Bispecific T cell engagers (BCMA BiTE); Dexamethasone (dex); Multiple myeloma (MM) • Differentiated safety & tolerability profile with class-leading anti- myeloma activity Potential best-in-class profile • Potential $2.5 - $4B1 peak revenue in combination with a BCMA BiTE in the 2L+ and with dexamethasone in 4L+ Large addressable market opportunity • Formally align with the FDA on a recommended Phase 2 dose by year-end • Initiate Phase 2 trial of cemsidomide + dex in Q1 2026 • Initiate Phase 1b of cemsidomide + BCMA BiTE in Q2 2026 Next steps 38
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