C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (May 2024)
30 slides from C4 Therapeutics's investor presentation, May 2024
Slide 1: Protein degraded. Disease targeted. Lives transformed.
Protein degraded. Disease targeted. Lives transformed. May 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: Prioritized Pipeline to Deliver Near-Term Value
Prioritized 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 (CFT7455) Lymphoma BRAF V600X Mutant CFT1946 V600X Cancers EGFR Non-Small Cell Lung CFT89191 L85
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 • 2H 2024: Present updated data from Phase 1 dose escalation +dex trial in R/R MM (CFT7455) • 2H 2024: Present data from Pha
Slide 7: Cemsidomide (CFT7455)
Cemsidomide (CFT7455) 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 (CFT7455) Leads to Sustained Degradation Compared to Other 100 Agents in Percent of IKZF3 Remaining/ Normalized to GAPDH in NCI-H929 Tumors this Class Percent of IKZF3 Remaining/ 100 50 Exten
Slide 10: Cemsidomide Phase 1 Dose Escalation Trial's Goal is to Define the Safety Profile
Cemsidomide (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 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 th
Slide 11: Schedule Adjustment Yielding Expected Results for Cemsidomide as a Potential MM Therapy
Schedule Adjustment Yielding Expected Results for Cemsidomide (CFT7455) as a Potential MM Therapy + Cemsidomide (CFT7455) is a potential treatment for multi- refractory MM patients Established Safety Profile Demonstrated Promising Responses with with the ability to move and Dosing Schedule Monothera
Slide 12: Cemsidomide Monotherapy Pharmacodynamics Consistent with 14 Days On/14 Days Off Modeling
Cemsidomide (CFT7455) Monotherapy Pharmacodynamics Consistent with 14 Days On/14 Days Off Modeling; Schedule is Sufficient for Neutrophil Recovery Modeled PK/PD of 14 Days On/ Clinical PD of 14 Days On/ 14 Days Off Schedule 14 Days Off Schedule 10 100 IKZF1/IKZF3 expression measured by Mass Spec on
Slide 13: Cemsidomide Monotherapy Data Support Opportunity for Combination with Novel MM Agents
Cemsidomide (CFT7455) Monotherapy Data Support Opportunity for Combination with Novel MM Agents Grade 3 or greater drug related effects were, as expected, neutropenia and Well Tolerated other hematologic effects in Heavily Pre- Treated Patients No DLTs resulting in discontinuation across the entire
Slide 14: Clinical Evidence of Immune T-cell Activation with Cemsidomide Monotherapy
Clinical Evidence of Immune T-cell Activation with Cemsidomide (CFT7455) Monotherapy Supports potential of cemsidomide % positive cells (C1D21 vs C1D1) (CFT7455) as a maintenance 100 C1D1 **** C1D21 therapy option and in combination with novel MM agents to improve 80 ** efficacy: % positive cells 60
Slide 15: Cemsidomide Combined with Novel MM Agents Demonstrated Enhanced Immune Cell Lysis
Cemsidomide (CFT7455) 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)
Slide 16: Cemsidomide + Dexamethasone Dose Escalation in R/R MM Continues to Progress
Cemsidomide (CFT7455) + Dexamethasone Dose Escalation in R/R MM Continues to Progress Phase 1: Dose Escalation + Dexamethasone Phase 2 14 Days On/14 Days Off KEY INCLUSION CRITERIA • Adults with R/R MM, at Potential for further dose least 3 prior lines that escalation have included lenalidomide, Cem
Slide 17: Cemsidomide + Dexamethasone is Well Tolerated and Best Responses in BCMA-Refractory Patients
Cemsidomide (CFT7455) + 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 T
Slide 18: Cemsidomide Profile Supports Multiple Opportunities across MM Landscape
Cemsidomide (CFT7455) Profile Supports Multiple Opportunities across MM Landscape Potential Data Development Path Potential Opportunity Cemsidomide Cemsidomide (CFT7455) + Accelerated Approval in (CFT7455) Dexamethasone Multi-Refractory MM + Dexamethasone Registrational Study + PI Studies Approvals
Slide 19: CFT1946
CFT1946 Targeting BRAF V600X Melanoma, Colorectal (CRC) & Non-Small Cell Lung Cancer (NSCLC)
Slide 20: CFT1946 has the Potential to Overcome Resistance Mechanisms Seen with Inhibition in BRAF V600X Cancers
CFT1946 has the Potential to Overcome Resistance Mechanisms Seen with Inhibition in BRAF V600X Cancers BRAF V600X CONDITION Potential Advantages of Active BRAF V600X causes uncontrolled MAPK BRAF V600X Degradation signaling, leading to tumorigenesis, tumor growth, and tumor maintenance • Specificall
Slide 21: BRAF V600X Degrader Advantages Vary by Indication and May Require Combination
BRAF V600X Degrader Advantages Vary by Indication and May Require Combination Melanoma & NSCLC CRC Intrinsic Resistance Acquired Resistance Potential for ERK Pathway Rebound from Inhibition EGFR RAS RAS BRAF wtRAF V600X CFT1946 in CFT1946 in combination with BRAF wtRAF combination with trametinib/ME
Slide 22: CFT1946 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 23: CFT1946 is More Efficacious than SOC in CRC & NSCLC BRAF V600X 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 24: 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 25: CFT1946 Phase 1/2 Dose Escalation Trial Continues to Progress
CFT1946 Phase 1/2 Dose Escalation Trial Continues to Progress KEY INCLUSION CRITERIA 1 Phase 1: Dose Escalation Monotherapy Arm for V600X Solid Tumors Safety • ≥18 years of age including CRC, Melanoma and NSCLC (Post BRAF Inhibitor) Combination • Evidence of a BRAF V600X Cohorts mutation obtained fr
Slide 26: CFT1946 Degrades BRAF V600E in Melanoma Tissue and Rapidly 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 in Melanoma Tissue and Results in Reduced ERK Signaling 15 Days of CFT1946 Treatment at
Slide 27: CFT8919
CFT8919 Targeting EGFR L858R Non-Small Cell Lung Cancer (NSCLC)
Slide 28: 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 29: 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 30: 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 • 2H 2024: Present updated data from Phase 1 dose escalation +dex trial in R/R MM (CFT7455) • 2H 2024: Present data from Pha