C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (September 2024)
29 slides from C4 Therapeutics's investor presentation, September 2024
Slide 1: Protein degraded. Disease targeted. Lives transformed.
Protein degraded. Disease targeted. Lives transformed. September 2024
Slide 2: Forward-looking Statements and Intellectual Property
Forward-looking Statements and Intellectual Property 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: C4T is a Recognized Leader in Delivering on the Promise of Targeted Protein Degradation
C4T is a Recognized Leader in Delivering on the Promise of Targeted Protein Degradation WORLD-CLASS DEGRADER PLATFORM Robust patent portfolio of novel cereblon binders; Demonstrated ability to design orally bioavailable, catalytically efficient degraders Our Mission RIGOROUS TARGET SELECTION To deli
Slide 4: We Have Designed and Advanced Degraders into the Clinic Across a Range of Target Classes
We Have Designed and Advanced Degraders into the Clinic Across a Range of Target Classes, Resulting in Robust Target Degradation Interrogated Diverse Attained Achieved Desirable Degraded Target as Target Classes IND Clearance Drug-like Properties Predicted Discovered degraders and advanced To date,
Slide 5: Advancing Pipeline to Deliver Near-Term Value
Advancing Pipeline to Deliver Near-Term Value Early phase Late phase Program Target Indications Discovery Preclinical Rights development development Multiple Myeloma & Cemsidomide IKZF1/3 Non-Hodgkin’s Lymphoma BRAF V600X Mutant CFT1946 V600X Cancers EGFR Non-Small Cell Lung CFT89191 L858R Cancers D
Slide 6: 2024 Milestones: Advancing High-potential Programs
2024 Milestones: Advancing High-potential Programs Multiple Value Inflection Points over Next 12 Months with Sufficient Runway (into 20271) Beyond These Milestones Cemsidomide • 4Q 2024: Present updated data from Phase 1 dose escalation +dex trial in R/R MM • 4Q 2024: Present data from Phase 1 dose
Slide 7: Cemsidomide
Cemsidomide Targeting IKZF1/3 Multiple Myeloma (MM) & Non-Hodgkin’s Lymphoma (NHL)
Slide 8: 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 IKZF1 / IKZF3 Transcription Factors Drive MM and NHL Cell Activate Fully Regulate Hematopoietic Growth and Survival Differentiated T-cells Stem Cell Different
Slide 9: Differentiated PK and Class-leading Catalytic Activity of Cemsidomide
Normalized to GAPDH in NCI-H929 Tumors Differentiated PK and Class-leading Catalytic Activity of Cemsidomide Percent of IKZF3 Remaining/ Normalized to GAPDH in NCI-H929 Tumors Leads to Sustained Degradation Compared to Other Agents in this Class 100 Percent of IKZF3 Remaining/ 100 50 Extended Plasma
Slide 10: Cemsidomide Phase 1 Dose Escalation Trial's Goal is to Define the Safety Profile
Cemsidomide 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 Phase 1 Dose Escalation Trial Endpoints R/R MM Monotherapy Primary: Dosing: QD 21 days on/7 days off • Safety and tolerability N=5 • Determine the maximum
Slide 11: Schedule Adjustment Yielding Expected Results for Cemsidomide as a Potential MM Therapy
Schedule Adjustment Yielding Expected Results for Cemsidomide as a Potential MM Therapy + Cemsidomide is a potential treatment for multi-refractory MM patients with the Established Safety Profile Demonstrated Promising Responses with ability to move into and Dosing Schedule Monotherapy Activity Cems
Slide 12: Clinical Evidence of Immune T-cell Activation with Cemsidomide Monotherapy
Clinical Evidence of Immune T-cell Activation with Cemsidomide Monotherapy Supports potential of cemsidomide % positive cells (C1D21 vs C1D1) as a maintenance therapy option 100 C1D1 **** C1D21 and in combination with novel MM agents to improve efficacy: 80 ** ✓ Cemsidomide induces CD8+ T- % positiv
Slide 13: Cemsidomide Combined with Novel MM Agents Demonstrated Enhanced Immune Cell Lysis
Cemsidomide Combined with Novel MM Agents Demonstrated Enhanced Immune Cell Lysis in Non-clinical Translational Models Daratumumab (Anti-CD38) Combo Teclistamab (BCMA BiTE) Combo Antibody-Dependent Cell-Mediated Cytotoxicity Assay T-cell Dependent Cellular Cytotoxicity Assay (ADCC) (TDCC) Daratumuma
Slide 14: Cemsidomide + Dexamethasone Dose Escalation in R/R MM Continues to Progress
Cemsidomide + Dexamethasone Dose Escalation in R/R MM Continues to Progress KEY INCLUSION CRITERIA • Adults with R/R MM, at Phase 1: Dose Escalation + Dexamethasone Phase 2 least 3 prior lines that 14 Days On/14 Days Off have included lenalidomide, Cemsidomide: DL5 QD pomalidomide, a +dex: 40 mg QW*
Slide 15: Cemsidomide + Dexamethasone is Well Tolerated and Best Responses in BCMA-Refractory Patients
Cemsidomide + Dexamethasone is Well Tolerated and Best Responses in Patients Refractory to BCMA Therapies Anti-myeloma Activity: Prior Dosing EMD # of Prior Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Cycle Dose Level CAR-T 1 2 3 4 5 6 7 8 9 10 11 Schedule Status Lines or TCE No No 6
Slide 16: Cemsidomide Profile Supports Multiple Opportunities across MM Landscape
Cemsidomide Profile Supports Multiple Opportunities across MM Landscape Potential Data Development Path Potential Opportunity Cemsidomide + Cemsidomide Accelerated Approval in Dexamethasone + Dexamethasone Multi-Refractory MM Registrational Study + PI Studies Approvals in Early Line MM + Anti-CD38 S
Slide 17: CFT1946
CFT1946 Targeting BRAF V600X Melanoma, Colorectal (CRC) & Non-Small Cell Lung Cancer (NSCLC)
Slide 18: Strong Rationale for Advancing CFT1946, a Selective BRAF V600X Degrader
Strong Rationale for Advancing CFT1946, a Selective BRAF V600X Degrader • BRAF V600X is a clinically validated target, but resistance mechanisms limit benefit of inhibition • Strong degrader rationale for overcoming limitations and resistance mechanisms of inhibitors • ~100K annual incidence of BRAF
Slide 19: CFT1946 has the Potential to Overcome Several Shortcomings Seen with Inhibitors
CFT1946 has the Potential to Overcome Several Shortcomings Seen with Inhibitors for BRAF V600X Cancers Key Liabilities of BRAF V600X Potential Advantages of BRAF V600X Inhibitors Degradation ✓ Degrader prevents dimer formation and avoids paradoxical ❑ Promote dimer resistance and paradoxical activat
Slide 20: BRAF V600X Degrader Advantages Vary by Indication and Treatment Paradigms
BRAF V600X Degrader Advantages Vary by Indication and Treatment Paradigms May Require Combination The Degrader Benefit in BRAF V600X Monomer and Dimer-Dependent Diseases 20
Slide 21: CFT1946 has the Potential to Address Multiple Tumor Types with BRAF V600X Mutations
CFT1946 has the Potential to Address Multiple Tumor Types with BRAF V600X Mutations Where BRAF Inhibitors are Insufficient BRAF V600X 2023 U.S. Incidence of Approved BRAF Inhibitor Mutation Rate BRAF V600X Patients4 BRAF Inhibitors Regimen mPFS5 • Dabrafenib 1 • Encorafenib 11.4 months ~35% ~35,000
Slide 22: CFT1946 is More Efficacious than SOC in CRC & NSCLC Xenograft Models
CFT1946 is More Efficacious than SOC in CRC & NSCLC BRAF V600X Xenograft Models and in a Melanoma PDX BRAF Inhibitor Resistance Model CRC NSCLC MELANOMA CFT1946 as a monotherapy and CFT1946 as a monotherapy shows CFT1946 + trametinib shows deep tumor + cetuximab shows enhanced responses Vehicle, PO/
Slide 23: CFT1946 is Active in Preclinical Metastatic Melanoma CNS Models
CFT1946 is Active in Preclinical Metastatic Melanoma CNS Models CFT1946 Prolongs Survival Compared to CFT1946 Reduces CNS Tumor Burden in Metastatic Encorafenib (BRAF inhibitor) in CDX Model Melanoma CNS Model BRAF Intracranial Model, Survival 1.5 Vehicle 1.5 Vehicle 100 Encorafenib, 35 mg/kg Encora
Slide 24: CFT1946 Phase 1/2 Dose Escalation Trial Continues to Progress
CFT1946 Phase 1/2 Dose Escalation Trial Continues to Progress Phase 1: Dose Escalation for V600X Solid Tumors including CRC, Melanoma and NSCLC KEY INCLUSION 1 (Post BRAF Inhibitor) CRITERIA • ≥18 years of age • Evidence of a BRAF V600X Potential for further dose mutation obtained from escalation an
Slide 25: CFT1946 Degrades BRAF V600E in Melanoma Tissue and Decreases VAF in ctDNA
At 80 mg, CFT1946 Degrades BRAF V600E in Melanoma Tissue and Demonstrates Rapid Decrease of BRAF V600E VAF in ctDNA Patient 1: At 80 mg, CFT1946 Degrades BRAF V600E in Patient 2: Rapid Decrease of BRAF V600E VAF at Melanoma Tissue and Results in Reduced ERK Signaling 15 Days of CFT1946 Treatment at
Slide 26: CFT8919
CFT8919 Targeting EGFR L858R Non-Small Cell Lung Cancer (NSCLC)
Slide 27: Potential for CFT8919 to Improve Outcomes for NSCLC Patients with EGFR L858R Mutations
Potential for CFT8919 to Improve Outcomes for NSCLC Patients with EGFR L858R Mutations Strong Rationale for an EGFR L858R Degrader CFT8919 Key Properties • Orally bioavailable • Potent and selective against L858R, EGFRL858R regardless of secondary mutations 1L • Allosteric binding osimertinib 1st-ge
Slide 28: CFT8919 is a Potent, Oral, Allosteric, Mutant-selective Degrader of EGFR L858R
CFT8919 is a Potent, Oral, Allosteric, Mutant-selective Degrader of EGFR L858R • CFT8919 exploits allosteric binding site, close CFT8919 to L858R activating mutation • Allosteric binding site avoids known Orthosteric resistance-causing mutations in orthosteric Inhibitor binding site • Allosteric bin
Slide 29: 2024 Milestones: Advancing High-potential Programs
2024 Milestones: Advancing High-potential Programs Multiple Value Inflection Points over Next 12 Months with Sufficient Runway (into 20271) Beyond These Milestones Cemsidomide • 4Q 2024: Present updated data from Phase 1 dose escalation +dex trial in R/R MM • 4Q 2024: Present data from Phase 1 dose
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