C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (January 2025)
37 slides from C4 Therapeutics's investor presentation, Jan 14, 2025
Slide 1: Protein degraded. Disease targeted. Lives transformed.
Protein degraded. Disease targeted. Lives transformed. January 2025
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,
Slide 3: Our Mission
Our Mission To deliver on the promise of targeted protein degradation science to create a new generation of medicines that transform patients’ lives. Our portfolio of degrader medicines pursues targets that may benefit from a degrader approach: Cemsidomide targeting IKZF1/3 for multiple myeloma and
Slide 4: C4T at the Forefront of TPD Science, Path to Fully Integrated Biotech
C4T Has Been at the Forefront of TPD Science and Is On the Path to Becoming a Fully Integrated Biotechnology Company © 2025 C4 Therapeutics, Inc. Built TORPEDO platform to design highly catalytic, orally bioavailable degraders Established collaborations with leading global pharmaceutical companies,
Slide 5: C4T Is Advancing a Portfolio of Rationally Designed Degraders
C4T Is Advancing a Portfolio of Rationally Designed Degraders Against Targets of High Unmet Need in Oncology TORPEDO platform has produced highly catalytic, brain penetrant, oral degraders across a broad range of target classes Degrader Rationale CFT8919 Targeting EGFR L858R Receptor Tyrosine Kinase
Slide 6: Multiple 2025 Data Based Inflection Points to Unlock Value
Multiple 2025 Data Based Inflection Points to Unlock Value Across Entire Portfolio © 2025 C4 Therapeutics, Inc. 6 Cemsidomide IKZF1/3 2025: Enable initiation of the next phase of clinical development for MM and PTCL. These new studies are expected to initiate in early 2026 2H 2025: Complete Phase 1
Slide 7: Advancing a Portfolio of Degrader Medicines Targeting High Unmet Need
PROGRAM TARGET INDICATIONS DISCOVERY PRECLINICAL EARLY DEVELOPMENT LATE DEVELOPMENT RIGHTS Cemsidomide IKZF1/3 Multiple Myeloma & Non-Hodgkin’s Lymphoma CFT1946 BRAF V600 Mutant V600 Mutant Cancers CFT89191 EGFR L858R Non-Small Cell Lung Cancer Discovery Stage Programs Various Cancers 1License and c
Slide 8: Advancing Oncology and Non-oncology Discovery Programs with Collaboration Partners
Advancing Multiple Oncology and Non-oncology Discovery Programs with Collaboration Partners © 2025 C4 Therapeutics, Inc. • Evaluating two targets in autoimmune diseases & cancer • Discovering targeted protein degraders against critical oncogenic proteins • Discovering and developing degrader antibod
Slide 9: Cemsidomide IKZF1/3 Degrader
Cemsidomide IKZF1/3 Degrader Multiple Myeloma & Non-Hodgkin’s Lymphoma
Slide 10: IKZF1/3 Are Key Promoters of Myeloma and Lymphoma Cell Survival
IKZF1/3 Are Key Promoters of Myeloma and Lymphoma Cell Survival and Will Remain Important Therapeutic Targets for These Indications © 2025 C4 Therapeutics, Inc. Multiple myeloma (MM); non-Hodgkin’s lymphoma (NHL) 10 Hematopoietic Stem Cell Common Myeloid Progenitor Cell Common Lymphoid Progenitor Ce
Slide 11: Cemsidomide Phase 1 Dose Escalation Trial in MM Continues to Progress
Cemsidomide Phase 1 Dose Escalation Trial in MM Continues to Progress; Have Not Exceeded the Maximum Tolerated Dose DL 4 (75 µg QD) DL 3 (62.5 µg QD) DL 2 (37.5 µg QD) DL 1 (50 µg MWF) Potential for further dose escalation and/or exploration DL 5 (100 µg QD) Back-fill cohorts DOSE ESCALATION CEMSIDO
Slide 12: Cemsidomide Positioned as IKZF1/3 Degrader of Choice Across Combinations
With a Potentially Best-in-Class Profile, Cemsidomide Is Positioned to Be an IKZF1/3 Degrader of Choice Across Various Combinations Post-Transplant Maintenance1 Anti-CD38 Combos Proteasome Inhibitor Combos CAR-Ts (+/- Maintenance Therapy) Other MOAs2 1Approximately 30% of multiple myeloma patients u
Slide 13: Clinical Evidence of Immune T-cell Activation With Cemsidomide 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 © 2025 C4 Therapeutics, Inc. Clinical Evidence of Immune T-cell Activation With Cemsidomide Monotherapy ** **** TEMRA: Terminally differentiated T-cells TEM: Effector memory T-cells Peripheral blood mono
Slide 14: Cemsidomide Well-Tolerated With Manageable Neutropenia
Cemsidomide Is Well-Tolerated With Manageable Neutropenia and No Treatment Emergent Adverse Events Lead to Dose Reductions Common (>20% All Grades) TEAEs and Events of Interest, n (%) All Grades (N=47) Grade 3 (N=47) Grade 4 (N= 47) Grade 5 (N=47) Neutropenia 22 (47) 6 (13) 12 (26) 0 Infections Pneu
Slide 15: Cemsidomide Dose Level Resulted in Anti-Myeloma Activity
75 µg Cemsidomide Dose Level Resulted in Compelling Anti-Myeloma Activity With a 36% ORR and 45% CBR 15 33% (2) 8% (1) 18% (2) 12% (5) 50% (3) 58% (7) 46% (6) 36% (4) 48% (20) 17% (2) 23% (3) 9% (1) 14% (6) 17% (1) 8% (1) 15% (2) 36% (4) 19% (8) 8% (1) 8% (1) 5% (2)8% (1) 2% (1) 0% 25% 50% 75% 100%
Slide 16: Cemsidomide Differentiated Safety Profile Suited for Combination Studies
Cemsidomide’s Differentiated Safety Profile Is Well Suited for Combination Studies, Potentially Resulting in Fewer Disruptive Adverse Events © 2025 C4 Therapeutics, Inc. 16 Cemsidomide + Dex Key Grade ≥3 Adverse Events 23% 22% 48% 54% 9% 15% 40% 35% 0% 25% 50% 75% 100% Dose Escalation - All Doses (N
Slide 17: Cemsidomide Potential Across Lines of Therapy in MM
Cemsidomide Has the Potential to Become a Treatment Option Across Lines of Therapy and Address a Growing Patient Population 2L ~56,000 1L ~65,000 3L ~49,000 4L ~42,000 5L+ ≥23,000 U.S. + EU4 + UK Addressable Patients (2024)1 Treatment Line Phase 1/2 (Escalation/Expansion) Cemsidomide/Dex + Anti-CD38
Slide 18: Annual Incidence of NHL Subtypes and Cemsidomide Opportunity
U.S. + EU4 + UK Annual Incidence (2024)1 ~54,000 ~33,000 ~12,000 ~8,000 ~16,000 Lenalidomide FDA Approved2 Lenalidomide in NCCN Guidelines DLBCL Diffuse Large B-Cell Lymphoma FL Follicular Lymphoma MZL Marginal Zone Lymphoma MCL Mantle Cell Lymphoma PTCL Subtypes Peripheral T-Cell
Slide 19: Cemsidomide Phase 1 Dose Escalation Trial in NHL Continues to Progress
Cemsidomide Phase 1 Dose Escalation Trial in NHL Continues to Progress 19 DOSE ESCALATION CEMSIDOMIDE 14/14 Utilizing a Bayesian logistic regression model until determination of the MTD and/or RP2D DL 4 (62.5 µg QD) DL 3 (37.5 µg QD) DL 2 (50 µg QD) DL 1 (25 µg MWF) Potential to resume enrollment at
Slide 20: Cemsidomide Well-tolerated With Manageable On-target Neutropenia in NHL
Cemsidomide Was Well-tolerated With Manageable Incidents of On- target Neutropenia Common (>20% All Grades) TEAEs and Events of Interest*, n (%) All Grade (N=23) Grade 3 (N=23) Grade 4 (N=23) Infections Upper respiratory tract infection Sepsis Bacteremia Pneumonia 15 (65) 4 (17) 1(4) 1(4) 2 (9) 4 (1
Slide 21: Deep Responses Achieved Across PTCL Subtypes
Compelling and Deep Responses Achieved Across PTCL Subtypes 19% (1) 25% (1) 20% (1) 20% (1) 25% (3) 75% (3) 50% (1) 0% 25% 50% 75% 100% All PTCL (N=16) AITL (N=4) ALCL (N=2) ATLL (N=5) PTCL-NOS (N=5) B e st R e sp o n se % ( N ) CMR PMR PET-CT–based Assessment of PMR or Better by PTCL Subtype* (N=16
Slide 22: Cemsidomide NHL Data Supports Development in PTCL
Cemsidomide NHL Data Supports Further Development in PTCL, Which Provides the Fastest Path to Market Phase 2 (Single Arm) Cemsidomide Monotherapy (2L+ R/R PTCL) Randomized Phase 3 Cemsidomide + SOC2 (treatment naïve) Study Currently Being Enabled Study for Registrational Intent Potential Accelerated
Slide 23: Strategic Path to Backbone Therapy for MM and NHL
2 Cemsidomide Has a Strategic Path to Become a Potential Backbone Therapy for MM and NHL Across Various Lines of Treatment Dex combination in late-line MM In combination with MM agents in 2/3L Establish as backbone treatment across MM (1L+) • Highest unmet patient need opportunities • Fastest path t
Slide 24: CFT1946 BRAF Mutant V600 Degrader
CFT1946 BRAF Mutant V600 Degrader Colorectal Cancer, Melanoma & Other BRAF Mutant Solid Tumors
Slide 25: CFT1946 Is an Oral, Potent Degrader of BRAF V600 Mutants
CFT1946 Is an Oral, Potent Degrader of BRAF V600 Mutants With Potential to Improve Outcomes for Patients 1Kreger B et al. Abstract 1658, AACR 2024 Adverse event (AE);); colorectal cancer (CRC); central nervous system (CNS); mitogen- activated protein kinase (MAPK);progression free survival (PFS); BR
Slide 26: CFT1946 Phase 1/2 Trial Continues to Progress
CFT1946 Phase 1/2 Trial Continues to Progress Across BRAF V600 Mutant Driven Solid Tumors MONOTHERAPY DOSE ESCALATION 160 mg BID PK, PD, ANTI-TUMOR ACTIVITY EVALUATION 1 640 mg BID 1Evaluating additional patients for pharmacodynamic assessment via pre- and post-drug exposure biopsies Colorectal canc
Slide 27: Initial CFT1946 PK and PD Data Support Proof of Mechanism
Initial CFT1946 Pharmacokinetic and Pharmacodynamic Data Support Proof of Mechanism 27© 2025 C4 Therapeutics, Inc. Mean plasma concentration shown for n > 2 Exhibited dose-dependent bioavailability measured by IHC in paired different dose levels α -B R A F -V 6 0 0 E 100um BRAF V600E degradation det
Slide 28: Well-Tolerated Monotherapy Safety Profile of CFT1946
Preferred Term Grade 1 n (%) Grade 2 n (%) Grade 3 n (%) Grade 4 n (%) Grade 5 n (%) Total (n=36) n (%) Patients with any TEAEs^ 3 (8) 14 (39) 11 (31) 2 (6) 1 (3)# 31 (86) Anemia 1 (3) 4 (11) 2 (6) 0 0 7 (19) Abdominal pain 4 (11) 1 (3) 2 (6) 0 0 7 (19) Peripheral edema 5 (14) 1 (3) 0 0 0 6 (17) Pyr
Slide 29: Early Signs of CFT1946 Anti-tumor Activity
PR PD PRSD SD SDV 60 0K V 60 0K V 60 0R PR PD PRSD SD SD # 29 Source: ESMO Congress 2024; C4T data on file as of 7/19/2024 (https://ir.c4therapeutics.com/static-files/b648e3ae-c2db-4f5e-9d47-324b0c8a2b2b) Early Signs of CFT1946 Anti-tumor Activity: 59% of Patients Demonstrated Target Lesion Tumor Re
Slide 30: Multiple Paths to a Label for CFT1946
Potential for Multiple Paths to a Label for CFT1946 to Address High Unmet Needs in BRAF V600 Mutant Melanoma and CRC Data-Driven Decisions to Inform Next Steps + cetuximab CRC data will inform fastest path to label: Melanoma (BRAF V600 Mutation Rate: ~35%1) Development Rationale: • Limited efficacio
Slide 31: CFT8919 EGFR L858R Degrader
CFT8919 EGFR L858R Degrader Non-Small Cell Lung Cancer
Slide 32: CFT8919 Is a Potent, Oral, Allosteric Mutant-selective EGFR L858R Degrader
CFT8919 Is a Potent, Oral, Allosteric, Mutant-selective Degrader of EGFR L858R With Potential to Improve Outcomes for NSCLC Patients CFT8919 Orthosteric Inhibitor Potential Degrader Advantages of CFT8919: CFT8919 exploits an allosteric binding site created by the L858R mutation, thereby avoiding res
Slide 33: CFT8919 Binds to Allosteric Site, Avoiding Impact of Co-mutations
CFT8919 Binds to Allosteric Site, Avoiding Impact of L858R Non-classical Co-mutations in the Orthosteric Binding Pocket Sources: 1. From Black Diamond’s analyses of 94,939 sequencing reports from treatment naive NSCLC (Guardant Health) presented at AACR 2024 (https://blackdiamondtherapeutics.com/ass
Slide 34: CFT8919 Selective for EGFR L858R and Active in Osimertinib Resistance
CFT8919 Is Selective for EGFR L858R and Active in a Setting of Osimertinib Resistance in Preclinical Models © 2025 C4 Therapeutics, Inc. Source: C4T data on file; Presented at Keystone Symposium 2021 (https://c4therapeutics.com/wp-content/uploads/Preclinical-Evaluation-of-CFT8919-as-a-Mutant-Selecti
Slide 35: CFT8919 Demonstrates Activity in Brain Metastasis Model
CFT8919 Demonstrates Activity in Brain Metastasis Model Source: C4T data on file; presented at TPD Summit 2021 (https://c4therapeutics.com/wp-content/uploads/C4_CFT8919_TPD_Summit_Presentation.pdf) By mouth (PO); twice daily (BID) © 2025 C4 Therapeutics, Inc. Mean Plasma & Tumor Concentration In viv
Slide 36: CFT8919 Potential to Address Multiple Opportunities With High Unmet Needs
CFT8919 Has the Potential to Address Multiple Opportunities with High Unmet Needs CFT8919’s Fastest Path to Market Is in 2L+ With Potential to Expand Into Front-Line Development Rationale: • Fast path to market • Lack of therapies after patients relapse with secondary mutation (i.e., C797S) 2L+ Deve
Slide 37: Multiple 2025 Inflection Points to Unlock Value Across Entire Portfolio
Multiple 2025 Inflection Points to Unlock Value Across Entire Portfolio © 2025 C4 Therapeutics, Inc. C4T is on a path to become a fully integrated biotechnology company focused on orally bioavailable degraders KEY CATALYSTSVALUE DRIVERS Cemsidomide IKZF1/3 Further development in multiple myeloma and
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