C4 Therapeutics, Inc. · NASDAQ:CCCC

C4 Therapeutics — Technical Presentation (December 2023)

39 slides from C4 Therapeutics's technical presentation, Dec 12, 2023

  1. Slide 1: CFT7455, IKZF1/3 Degrader, for Relapsed Refractory Multiple Myeloma: Phase 1 Dose Escalation Data

    CFT7455, IKZF1/3 Degrader, for the Potential Treatment of Relapsed Refractory Multiple Myeloma (R/R MM) December 12, 2023 Phase 1 Dose Escalation Data

  2. Slide 2: Forward-looking Statements and Intellectual Property

    Forward-looking Statements and Intellectual Property 2 Forward-looking 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

    Today’s Agenda 3 • © 2023 C4 Therapeutics, Inc. Topic Participants Introductions Courtney Solberg, Senior Manager of IR Opening Remarks Andrew Hirsch, President and CEO CFT7455 Preclinical Data Stew Fisher, Ph.D., CSO CFT7455 Phase 1 Data Len Reyno, M.D., CMO Q&A Session Andrew Hirsch, President and

  4. Slide 4: C4T is a Leader in Delivering on the Promise of Targeted Protein Degradation

    C4T is a Leader in Delivering on the Promise of Targeted Protein Degradation 4© 2023 C4 Therapeutics, Inc. WORLD-CLASS DEGRADER PLATFORM Robust patent portfolio of novel cereblon binders and demonstrated ability to design orally bioavailable, catalytically efficient degraders Our Mission To deliver

  5. Slide 5: Robust Pipeline of Degrader Medicines Pursuing Multiple Oncology Targets

    Robust Pipeline of Degrader Medicines Pursuing Multiple Oncology Targets 5© 2023 C4 Therapeutics, Inc. 1. Exclusive License and Collaboration Agreement with Betta Pharmaceuticals for the development and commercialization in Greater China Program Target Indications CFT7455 IKZF1/3 Multiple Myeloma &

  6. Slide 6: Execution Across Key 2023 Milestones

    Execution Across Key 2023 Milestones 6 • Cash runway into 2025 © 2023 C4 Therapeutics, Inc. CFT7455 IKZF1/3 CFT8634 BRD9 CFT1946 BRAF V600 CFT8919 EGFR L858R Discovery ✓ Present Phase 1 dose escalation data from the Phase 1/2 trial in R/R MM ✓ Present Phase 1 dose escalation data from the Phase 1/2

  7. Slide 7: Phase Update

    CFT7455 Phase 1 Update Andrew Hirsch

  8. Slide 8: Schedule Adjustment Yielding Expected Results for CFT7455 as a Potential MM Therapy

    Schedule Adjustment Yielding Expected Results for CFT7455 as a Potential MM Therapy 8© 2023 C4 Therapeutics, Inc. Established Safety Profile and Dosing Schedule • CFT7455 is well tolerated with no DLTs resulting in treatment discontinuations • The 14 days on/14 days off schedule is optimal Demonstra

  9. Slide 9: Background & Preclinical Rationale

    CFT7455 Background & Preclinical Rationale Stew Fisher

  10. Slide 10: IKZF1/3 Degradation Drives Three Distinct Areas of Hematopoietic Biology

    IKZF1/3 Degradation Drives Three Distinct Areas of Hematopoietic Biology; Degrading IKZF1/3 is a Validated Therapeutic Strategy in MM and NHL Ikaros Family Zinc Finger proteins 1 and 3 (IKZF1/3)); Multiple Myeloma (MM); Non-Hodgkin’s Lymphoma (NHL). © 2023 C4 Therapeutics, Inc IKZF1 / IKZF3 Transcri

  11. Slide 11: IKZF1/3 Degraders Are Effective Therapies that Require Drug Holidays

    IKZF1/3 Degrader Half Life (hours) Dosing Schedule Dosed + Dexamethasone Grade 3/4 Neutropenia Rate* 3-5 21 Days on / 7 Days off  33% 7.5 21 Days on / 7 Days off  41-48% Iberdomide 9-13 21 Days on / 7 Days off  45% Mezigdomide ~14 21 Days on / 7 Days off  76% IKZF1/3 Degraders are Effective Ther

  12. Slide 12: CFT7455 Designed to Overcome Shortcomings of Approved IKZF1/3 Degraders

    12 CFT7455 was Designed to Overcome Several Shortcomings of Approved MM and NHL IKZF1/3 Degraders Approved MM & NHL IKZF1/3 Degraders’ Shortcomings ❑ Modest on-target degradation and off-target liabilities ❑ Acquired resistance to approved IKZF1/3 degraders1 ❑ Many MM/NHL therapies require onerous d

  13. Slide 13: Differentiated PK and Class-leading Catalytic Activity of CFT7455

    Differentiated PK and Class-leading Catalytic Activity of CFT7455 Leads to Sustained Degradation Compared to Other Agents in this Class 13 mezigdomide (CC-92480); Ikaros family zinc finger protein (IKZF3); multiple myeloma (MM); pharmacodynamics (PD); pharmacokinetics (PK); once daily (QD) Source: A

  14. Slide 14: Preclinical Synergy of CFT7455 with Dexamethasone

    Preclinical Model Demonstrated Significant Synergy when CFT7455 is Combined with Dexamethasone 14 Twice a day (BID); Human Dose (HD), Daily Dosing (QD); Oral administration (PO) Source: C4T data on file 0 7 14 21 28 0 1000 2000 3000 4000 Day R P M I- 8 2 2 6 T u m o r V o lu m e (m m 3 ) CFT7455 (50

  15. Slide 15: Monotherapy Dose Escalation in R/R MM

    CFT7455 Monotherapy Dose Escalation in R/R MM Len Reyno

  16. Slide 16: Phase 1 Dose Escalation Trial Design in R/R MM and R/R NHL

    R/R MM Monotherapy Dosing: QD 21 Days on/7 Days off* N=5 Status: Complete CFT7455 Phase 1 Dose Escalation Trial’s Goal is to Define the Safety Profile and Identify Signs of Anti-Tumor Activity in R/R MM and R/R NHL 16 pharmacokinetic (PK); Monday, Wednesday, Friday dosing (M/W/F); once daily (QD); r

  17. Slide 17: Monotherapy Dose Escalation Complete in R/R MM

    CFT7455 Monotherapy Dose Escalation Complete in R/R MM; Sufficient Data Generated to Explore CFT7455 in Combination with Novel MM Agents 17 Multiple myeloma (MM); Eastern Cooperative Oncology Group Score (ECOG); Relapsed/Refractory (R/R); absolute neutrophil count (ANC), Hemoglobin (Hgb); Monday Wed

  18. Slide 18: Monotherapy Patient Population Heavily Pre-treated

    CFT7455 Monotherapy Patient Population was Heavily Pre-treated with a Median of 7 Prior Therapies 18 Extramedullary Disease (EMD); Eastern Cooperative Oncology Group (ECOG); Lenalidomide (Len); Pomalidomide (Pom); monoclonal antibody (mAB); International Staging System (ISS) Source: C4T data on file

  19. Slide 19: Monotherapy: Treatment Disposition of R/R MM Patients

    CFT7455 Monotherapy: Treatment Disposition of 22 R/R MM Patients Source: C4T data on file as of 11/28/2023 © 2023 C4 Therapeutics, Inc. Patient Disposition Safety Population (N = 22) Ongoing, n (%) 3 (14%) Discontinued, n (%) Progressive disease, n(%) Physician decision, n(%) Withdrawal by patient,

  20. Slide 20: Monotherapy is Well Tolerated with 14 Days On/14 Days Off Schedule

    CFT7455 Monotherapy is Well Tolerated with 14 Days on/14 Days off Schedule 20 Patients with AEs of Grade 3 or Higher, N (%) 25 µg MWF (N=3) 50 µg MWF (N=5) 75 µg MWF (N=5) 50 µg QD (N=5) 75 µg QD (N=4) Monotherapy R/R MM Total (N=22) Hematologic AEs Neutropenia 1 (33%) 1 (20%) 3 (60%) 3 (60%) 3 (75%

  21. Slide 21: Plasma Exposure of CFT7455 Monotherapy Increased Proportionally with Dose

    Plasma Exposure of CFT7455 Monotherapy Increased Proportionally with Cumulative Dose © 2023 C4 Therapeutics, Inc. Source: C4T data on file as of 11/28/23 21 Daily dosing(QD); Monday, Wednesday, Friday dosing (MWF) 0 6 12 18 24 30 36 42 48 0.00 0.05 0.10 0.15 0.30 0.60 Time (h) P la s m a C F T 7 4 5

  22. Slide 22: Pharmacodynamics Consistent with 14/14 Modeling Assumptions

    C1D1 PD C1D1 8hrs C1D2 C1D8 C1D14 C1D21 C2D1 -100 -50 0 50 100 150 IKZF1/3 expression measured by Mass Spec on PBMCs % e x p re s s io n r e la ti v e t o b a s e li n e Pharmacodynamics Consistent with 14 Days on/14 Days off Modeling Assumptions; Schedule is Sufficient for Neutrophil Recovery Daily

  23. Slide 23: International Myeloma Working Group Response Criteria

    International Myeloma Working Group (IMWG) Response Criteria sCR Stringent Complete Response CR Complete Response VGPR Very Good Partial Response PR Partial Response MR Minimal Response SD Stable Disease • CR as defined to The right, plus normal FLC ratio and absence of clonal cells in bone marrow b

  24. Slide 24: Evidence of Anti-Myeloma Monotherapy Activity

    Dosing Schedule Dose Level EMD Status Prior CAR-T or TCE Prior lines 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 14 days on/ 14 days off 25 µg M/W/F Yes Yes 8 PD Yes No 5 PD Yes No 6 PD 50 µg M/W/F No No 3 PD No Yes 4 MR Yes No 8 SD PD Yes No 10 NE No No 6 PD 75 µg M/W/F Yes Yes 7 PD No No 4 PD No Yes 5

  25. Slide 25: Clinical Evidence of Immune T-cell Activation with CFT7455 Monotherapy

    TEMRA TEM 0 20 40 60 80 100 % positive cells (C1D21 vs C1D1) % p o s it iv e c e ll s C1D1 C1D21 © 2023 C4 Therapeutics, Inc. Clinical Evidence of Immune T-cell Activation with CFT7455 Monotherapy ** **** TEMRA: Terminally differentiated T-cells TEM: Effector memory T-cells Peripheral Blood Mononucl

  26. Slide 26: Enhances Immune Cell Lysis of Daratumumab and Teclistamab

    CFT7455 Enhances Immune Cell Lysis of Daratumumab and Teclistamab in Non-clinical Translational Models 26 Bispecific T-Cell Engager (BiTE) Source: C4T data on file Darzalex is a registered trademark of Janssen; Tecvalyi is a registered trademark of J&J © 2023 C4 Therapeutics, Inc. Cmin and Cmax repr

  27. Slide 27: Monotherapy Well Tolerated with Anti-Myeloma and Immunomodulatory Effects

    CFT7455 Monotherapy is Well Tolerated and Demonstrates Anti- Myeloma Activity and Immunomodulatory Effects • Continuous target degradation is associated with CFT7455 dosing across all dose levels and shows anti- myeloma activity at the highest dose level • 14 days on/14 days off schedule provides th

  28. Slide 28: + Dexamethasone in R/R MM

    CFT7455 + Dexamethasone in R/R MM Len Reyno

  29. Slide 29: + Dexamethasone Dose Escalation in R/R MM

    CFT7455 + Dexamethasone Dose Escalation in R/R MM 29© 2023 C4 Therapeutics, Inc. Phase 1: Dose Escalation + Dexamethasone 14 Days On/14 Days Off CFT7455: 37.5 µg QD +Dex: 40 mg QW* N = <10 Phase 1 dose expansion currently enrolling CFT7455: 62.5 µg QD +Dex: 40 mg QW* N = <10 Phase 1 dose expansion c

  30. Slide 30: + Dexamethasone Patient Population Heavily Pre-treated

    CFT7455 + Dexamethasone Patient Population to Date was Heavily Pre-treated with a Median of 6 Prior Therapies © 2023 C4 Therapeutics, Inc. Characteristics Safety Population (N = 9) Prior therapies, median (range) 6 (4-12) Prior Len, n (%) 9 (100%) Prior Pom, n (%) 8 (89%) Anti-CD38 mAB refractory, n

  31. Slide 31: + Dexamethasone is Well Tolerated

    CFT7455 + Dexamethasone is Well Tolerated 31 Patients with AEs of Grade 3 or Higher, N (%) CFT7455: 50 µg MWF +Dex: 40 mg QW (N=5) CFT7455: 37.5 µg QD +Dex: 40 mg QW (N=4) CFT7455+Dex Total (N=9) Hematologic AEs Anemia 1 (20%) 2 (50%) 3 (33%) Neutropenia 1 (20%) 2 (50%) 3 (33%) Febrile neutropenia 1

  32. Slide 32: + Dexamethasone Resulted in Multiple Responses at Low Doses

    CFT7455 + Dexamethasone Resulted in Multiple Responses at Low Doses with Best Responses in Patients Refractory to BCMA Therapies © 2023 C4 Therapeutics, Inc. Dosing Schedule Dose Level EMD Status Prior CAR-T or TCE # of Prior Lines 1 2 3 4 5 6 7 8 9 10 11 14 days on/ 14 days off CFT7455: 50 µg MWF +

  33. Slide 33: Patient Vignette: sCR Achieved in a Pre-treated MM Patient

    Patient Vignette: sCR Achieved in a Pre-treated MM Patient When Treated with CFT7455 + Dexamethasone © 2023 C4 Therapeutics, Inc. • 65, female, enrolled 08/23/2023 into 37.5 µg QD 14/14 CFT7455 + dexamethasone cohort • Diagnosed with MM in 2018 • Received 5 lines of prior therapy; stage 2 R-ISS MM L

  34. Slide 34: + Dexamethasone Well Tolerated with Promising Efficacy Signals

    CFT7455 + Dexamethasone is Well Tolerated and Demonstrates Promising Efficacy Signals, Supporting Development in Multi-refractory MM Patients 34 • CFT7455 combined with dexamethasone is well tolerated in a heavily pre- treated population • Manageable neutropenia • Promising efficacy signals with mul

  35. Slide 35: Development Plan and Next Steps

    CFT7455 Development Plan and Next Steps Len Reyno

  36. Slide 36: Many MM Patients Progress Through Several Lines of Therapy

    Despite Numerous Treatment Options, Many MM Patients Progress through Several Lines of Therapy, Providing Opportunities for CFT7455 36© 2023 C4 Therapeutics, Inc. • 2/3-line triplet combinations with daratumumab or proteasome inhibitors • Combination partner for BCMA BiTEs, CAR-Ts and other 2/3-line

  37. Slide 37: CFT7455 Profile Supports Multiple Opportunities Across MM Landscape

    The CFT7455 Profile Supports Multiple Opportunities Across MM Landscape 37© 2023 C4 Therapeutics, Inc. CFT7455 + Dexamethasone Data Potential Enabled Opportunity Accelerated Approval in Multi-Refractory MM Potential Development Path Post-Transplant Maintenance Study + PI Studies + Anti-CD38 Studies

  38. Slide 38: Schedule Adjustment Yielding Expected Results for CFT7455 as a Potential MM Therapy

    Schedule Adjustment Yielding Expected Results for CFT7455 as a Potential MM Therapy 38© 2023 C4 Therapeutics, Inc. Established Safety Profile and Dosing Schedule • CFT7455 is well tolerated with no DLTs resulting in treatment discontinuations • The 14 days on/14 days off schedule is optimal Demonstr

  39. Slide 39: Q&A Session

    Q&A Session

C4 Therapeutics — Technical Presentation (December 2023) on 6ix