C4 Therapeutics, Inc. · NASDAQ:CCCC

C4 Therapeutics — International Myeloma Society (IMS) Annual Meeting 2025

39 slides from C4 Therapeutics's conference presentation, Sep 22, 2025

  1. Slide 1: Updated Data From Phase 1 Trial of Cemsidomide in Multiple Myeloma & Next Steps

    Updated Data From Phase 1 Trial of Cemsidomide in Multiple Myeloma & Next Steps International Myeloma Society (IMS) Annual Meeting September 2025

  2. Slide 2: Legal Disclaimer Statements and Intellectual Property

    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,

  3. Slide 3: Today's Agenda

    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 Tod

  4. Slide 4: Opening Remarks

    Opening Remarks Andrew Hirsch President and Chief Executive Officer

  5. Slide 5: C4T Is Positioned to Unlock Value Across the Portfolio

    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

  6. Slide 6: Cemsidomide Has the Potential to Be Best-in-Class IKZF1/3 Degrader

    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-myel

  7. Slide 7: Cemsidomide First-in-Human Clinical Program Relapsed Refractory Multiple Myeloma

    Cemsidomide First-in-Human Clinical Program Relapsed Refractory Multiple Myeloma

  8. Slide 8: Degrading IKZF1/3 Leads to Myeloma Cell Death and T-Cell Activation

    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/Ab

  9. Slide 9: Phase 1 Dose Escalation Trial Enabled Advancement to Next Phase of Development

    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

  10. Slide 10: Cemsidomide + Dexamethasone Phase 1 MM Dose Escalation Is Complete

    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 a

  11. Slide 11: Enrolled a Heavily Pre-Treated MM Patient Population

    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 thera

  12. Slide 12: Safety & Tolerability Profile Cemsidomide + Dexamethasone

    Safety & Tolerability Profile Cemsidomide + Dexamethasone

  13. Slide 13: Cemsidomide's Differentiated Safety & Tolerability Profile Is Ideal for Combinations

    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 relate

  14. Slide 14: Differentiated Tolerability Profile With Minimal Dose Reductions and Discontinuations

    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 t

  15. Slide 15: Neutropenia Was Manageable and Consistent Across All Dose Levels

    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) Neu

  16. Slide 16: Majority of Neutropenic Events Occurred in Earlier Cycles

    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

  17. Slide 17: Anti-myeloma Activity Profile Cemsidomide + Dexamethasone

    Anti-myeloma Activity Profile Cemsidomide + Dexamethasone

  18. Slide 18: Cemsidomide Phase 1 Data Has Demonstrated Class-leading Anti-myeloma Activity

    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 o

  19. Slide 19: Pharmacokinetics Were Dose Proportional and Demonstrated Optimal Degradation of IKZF1/3

    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

  20. Slide 20: T-cell Activation Is Observed Across All Dose Levels

    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

  21. Slide 21: 100 µg Dose Level Drives Sufficient Exposure and Light Chain Reductions

    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 + de

  22. Slide 22: 50% of Patients With Elevated Light Chains Achieved at Least 50% dFLC Decrease

    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 treate

  23. Slide 23: Class-leading Anti-myeloma Activity With 40% and 50% ORR at Two Highest Doses

    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 pati

  24. Slide 24: Duration of Response and Swimmer Plot

    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 (

  25. Slide 25: Patient Population Was More Heavily Pre-treated Than Other IKZF1/3 Degraders

    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

  26. Slide 26: Minimal Treatment Disruptive Adverse Events, Differentiated From Other Degraders

    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

  27. Slide 27: Compelling Anti-Myeloma Activity and Median Duration of Response

    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

  28. Slide 28: Patient Vignette: Penta-class Refractory Patient With EMD

    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

  29. Slide 29: Patient Vignette: 90-Year-Old Patient Achieved Very Good Partial Response

    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 Un

  30. Slide 30: Potential Best-in-Class Profile Supports Opportunity to Be IKZF1/3 Degrader of Choice

    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 evalu

  31. Slide 31: Market Opportunity & Path Forward for Cemsidomide

    Market Opportunity & Path Forward for Cemsidomide

  32. Slide 32: Addressable Patients by Treatment Line and Initial Development Opportunity

    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 +

  33. Slide 33: Multiple Myeloma Is a Growing Patient Population With Persistent Unmet Need

    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

  34. Slide 34: Opportunity: Cemsidomide Could Increase BCMA BiTE Efficacy

    © 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

  35. Slide 35: Development Plan Provides Efficient Path to Registration

    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 en

  36. Slide 36: Phase 2 Initial ORR Data of Cemsidomide + Dex in 4L+ Expected in 2H 2027

    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

  37. Slide 37: Phase 1b Trial Will Evaluate Optimal Dose in Combination With a BCMA BiTE

    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

  38. Slide 38: Cemsidomide Has the Potential to Be Best-in-Class Across Multiple Lines of Therapy

    • 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), ClearV

  39. Slide 39: Q&A

    Q&A

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