C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (February 2024)
30 slides from C4 Therapeutics's investor presentation, February 2024
Slide 1: Protein degraded. Disease targeted. Lives transformed.
Protein degraded. Disease targeted. Lives transformed. February 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- lookingstatements, whichareoftenindicatedbytermssuchas“anticipate,”“believe,” “could,”“
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 & CFT7455 IKZF1/3 Non-Hodgkin’s Lymphoma BRAF V600X Mutant CFT1946 V600X Cancers EGFR Non-Small Cell Lung CFT89191 L858R Cancers Und
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 CFT7455 • 2H 2024: Present updated data from Phase 1 dose escalation +dex trial in R/R MM • 2H 2024: Present data from Phase 1 dose esca
Slide 7: CFT7455
CFT7455 Targeting IKZF1/3 Multiple Myeloma (MM) & Non-Hodgkin’s LymphomaNHL) (
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: CFT7455 Phase 1 Dose Escalation Trial Design and Endpoints
CFT7Phase 45 1DoseEscalationTrial’sGoalistoDefinetheSafety 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 Status: Comple
Slide 10: Schedule Adjustment Yielding Expected Results for CFT7455 as a Potential MM Therapy
Schedule Adjustment Yielding Expected Results for CFT7455 as a Potential MM Therapy + CFT7455 is a potential treatment for multi- refractory MM patients with the ability to move Established Safety Profile Demonstrated Promising Responses with into earlier lines with and Dosing Schedule Monotherapy A
Slide 11: CFT7455 Monotherapy Pharmacodynamics Consistent with Days On/14 Days Off Modeling
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 PBMCs % expres
Slide 12: CFT7455 Monotherapy Data Support Opportunity for Combination with Novel MM Agents
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 monotherapy ar
Slide 13: Clinical Evidence of Immune T-cell Activation with CFT7455 Monotherapy
Clinical Evidence of Immune T-cell Activation with CFT7455 Monotherapy Supports potential of CFT7455 as a % positive cells (C1D21 vs C1D1) 100 maintenance therapy option and C1D1 **** C1D21 in combination with novel MM agents to improve efficacy: 80 ** ✓ CFT7455 induces CD8+ T-cell % positive cells
Slide 14: CFT7455 Combined with Novel MM Agents Demonstrates Enhanced Immune Cell Lysis
CFT7455 Combined with Novel MM Agents Demonstrates 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) Daratumumab (2
Slide 15: CFT7455 + Dexamethasone Dose Escalation in R/R MM Continues to Progress
CFT7455 + Dexamethasone Dose Escalation in R/R MM Continues to Progress Phase 1: Dose Escalation + Dexamethasone 14 Days On/14 Days Off KEY INCLUSION CRITERIA • Adults with R/R MM, at least 3 prior lines that Potential for further dose have included escalation lenalidomide, pomalidomide, a proteasom
Slide 16: CFT7455 + Dexamethasone is Well Tolerated and Best Responses in Patients Refractory to BCMA
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 TCE No No 6 PD
Slide 17: CFT7455 Profile Supports Multiple Opportunities across MM Landscape
CFT7455 Profile Supports Multiple Opportunities across MM Landscape Potential Data Development Path Potential Opportunity CFT7455 CFT7455 + Dexamethasone Accelerated Approval in + Dexamethasone Registrational Study Multi-Refractory MM + PI Studies Approvals in Early Line MM + Anti-CD38 Studies + BCM
Slide 18: CFT1946
CFT1946 Targeting BRAF V600X Melanoma, Colorectal (CRC) & Non-Small Cell Lung Cancer (NSCLC)
Slide 19: 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 20: 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 21: 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 22: 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 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 1 Dose Escalation: Monotherapy Arm for V600X Solid Tumors KEY INCLUSION CRITERIA including CRC, Melanoma and NSCLC (Post BRAF Inhibitor)2 • 8≥1yearsofage • Evidence of a BRAF V600X mutation obtained from Further Dose Escalation tumor tiss
Slide 25: Plasma Exposure of CFT1946 Increased Roughly Proportionally with Dose
Plasma Exposure of CFT1946 Increased Roughly Proportionally with Dose Cycle 1 Day 1 Cycle 1 Day 15 1000 1000 Plasma PK (ng/mL) Plasma PK (ng/mL) 100 100 10 10 0 4 8 12 0 4 8 12 Time (h) Time (h) Pharmacokinetic (PK) Source: C4T data on file as of 11/9/2023 © 2024 C4 Therapeutics, Inc. 25
Slide 26: 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 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 CFT7455 • 2H 2024: Present updated data from Phase 1 dose escalation +dex trial in R/R MM • 2H 2024: Present data from Phase 1 dose esca
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