C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (July 2023)
29 slides from C4 Therapeutics's investor presentation, July 2023
Slide 1: Protein degraded. Disease targeted. Lives transformed.
Protein degraded. Disease targeted. Lives transformed. July 2023
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 Leader in Delivering on the Promise of Targeted Protein Degradation
C4T is a Leader in Delivering on the Promise of Targeted Protein Degradation WORLD-CLASS DEGRADER PLATFORM Demonstrated ability to design orally bioavailable, catalytically efficient degraders that maximize the benefits of degradation Our Mission RIGOROUS TARGET SELECTION To deliver on the promise F
Slide 4: TORPEDO Platform Delivers MonoDAC and BiDAC Degraders against a Diverse Array of Target Types
TORPEDO Platform Delivers MonoDAC and BiDAC Degraders against a Diverse Array of Target Types Projects successfully MonoDAC and BiDAC transitioned to hit Late lead optimization1 Projects Initiated1 4 identifcation1 Clinical programs expected by early 2024 50 30 11 Targets Cereblon- Programs Differen
Slide 5: Robust Pipeline of Degrader Medicines Pursuing Multiple Targets in Oncology
Robust Pipeline of Degrader Medicines Pursuing Multiple Targets in Oncology Early phase Late phase Program Target Indications Discovery Pre-clinical Rights development development Multiple Myeloma & Non- CFT7455 IKZF1/3 Hodgkin’s Lymphoma Synovial Sarcoma & CFT8634 BRD9 SMARCB1-null Cancers CFT1946
Slide 6: CFT7455
CFT7455 Targeting IKZF1/3 Multiple Myeloma (MM) & Non-Hodgkin’s Lymphoma (NHL)
Slide 7: Establish CFT7455 as a Standard of Care IKZF1/3 Degrader
Establish CFT7455 as a Standard of Care IKZF1/3 Degrader Currently approved IKZF1/3 CFT7455 has the degraders (lenalidomide, pomalidomide) potential to become a backbone are suboptimal for multiple myeloma: therapy for multiple myeloma: Class-leading catalytic activity to enable potent, rapid, Not o
Slide 8: Single Agent CFT7455 Arm A Data Demonstrated Potent On Target Degradation; Dosing Schedule Modified
Single Agent CFT7455 Arm A Data Demonstrated Potent On Target Degradation; Dosing Schedule Modified to Improve Therapeutic Index Deep Degradation of IKZF1/3 Meaningful Reductions in dFLC Grade 4 Neutropenia Modified Dosing Schedule with 14 Days Off Source: C4T data on file; AACR 2022 © 2023 C4 Thera
Slide 9: Phase 1/2 Trial Progressing through Dose Escalation; Dexamethasone Combination Arm Opened
Phase 1/2 Trial Progressing through Dose Escalation; Safety Data and Enrollment Strategy Supported Opening of Dexamethasone Combination Arm Phase 1 Dose Escalation Phase 2 Expansion R/R Multiple Myeloma Arm B1: Monotherapy R/R Multiple Myeloma Arm B2: N = ~30 Monotherapy R/R Multiple Myeloma N = ~15
Slide 10: Multiple Paths to Success for CFT7455 across Evolving Multiple Myeloma Landscape
Multiple Paths to Success for CFT7455 across Evolving Multiple Myeloma Landscape Potential for CFT7455 to replace other IKFZ1/3 Potential to combine CFT7455 with next- degraders and become a backbone therapy generation therapies IKZF1/3 degrader competitive landscape 1L 2L 3L 4L CAR T-Cell Bi-specif
Slide 11: CFT8634
CFT8634 Targeting BRD9 Synovial Sarcoma & SMARCB1-Null Solid Tumors
Slide 12: Oncogenic SS18-SSX Fusion Leads to BRD9 Dependency in Synovial Sarcoma
Oncogenic SS18-SSX Fusion Leads to BRD9 Dependency in Synovial Sarcoma cBAF ncBAF 1 Incorporation of SS18-SSX fusion results in eviction of SMARCB1 BCL7 BCL7 ▪ cBAF complex compromised Actin A/B/C Actin ACTL6A A/B/C ▪ Oncogenic state ARID1A/B BRM/ SS18 ACTL6A SS18 BRG1 BRM/ SSX SMARCB1 BRD9 SMARC BR
Slide 13: BRD9 is Currently Considered an Undruggable Target, Where Inhibitors are Ineffective
BRD9 was BRD9 is Currently Considered Previously Undruggable Considered Target,Target an Undruggable Wherewhere Inhibitors Inhibitors are Ineffective are Ineffective for Synovial Sarcoma Unmet Need Degrader Rationale Oncogenicity of BRD9 depends on protein function not addressed by traditional inhib
Slide 14: CFT8634 Demonstrated Deep Degradation and Robust Responses in Preclinical Synovial Sarcoma Models
CFT8634 Demonstrated Deep Degradation and Robust Responses in Preclinical Synovial Sarcoma Models PDX 310 PDX SA13412 Near Complete BRD9 Degradation Durable Tumor Regression Source: C4T data on file; AACR 2022 By mouth (PO); Once daily (QD); Pharmacodynamics (PD); Twice daily (BID); Three times dail
Slide 15: CFT8634 Phase 1/2 Trial Progressing through Dose Escalation
CFT8634 Phase 1/2 Trial Progressing through Dose Escalation Phase 2 Expansion Phase 1 Dose Escalation CFT8634 Monotherapy Synovial Sarcoma N = ~30 CFT8634 Monotherapy Synovial Sarcoma and SMARCB1-null Solid RP2D Tumors N = ~20 CFT8634 Monotherapy Status: Enrolling SMARCB1-null Solid Tumors N = ~20 P
Slide 16: CFT8634 Pharmacokinetic and Pharmacodynamic Data Supportive of Proof of Mechanism
CFT8634 Pharmacokinetic and Pharmacodynamic Data Supportive of Proof of Mechanism Dose-proportional Exposure with Strong Oral Robust BRD9 Degradation in Tumor Samples Bioavailability Screening Cycle 1 Day 15 2 mg 8 mg a-BRD9 immunohistochemistry Effective Degradation of a Previously Undruggable Targ
Slide 17: Recent Publications Support Potential Additional Indications for BRD9
Recent Publications Support Potential Additional Indications for BRD9 Interferonopathies Clear Cell Renal Cell Carcinoma BRD9 is a druggable component of Aberrant activation of m6A demethylase FTO interferon-stimulated gene expression renders HIF2αlow/− clear cell renal cell and antiviral activity c
Slide 18: CFT1946
CFT1946 Targeting BRAF V600 Melanoma, Colorectal (CRC) & Non-Small Cell Lung Cancer (NSCLC)
Slide 19: Current Standard of Care BRAF Inhibitors Lead to Resistance
Current Standard of Care BRAF Inhibitors Lead to Resistance Unmet Need Degrader Rationale Resistance to approved BRAF Inhibitor causes paradoxical ~$2B inhibitors results in a median PFS approved activation of wild-type RAF of less than 15 months2 BRAF inhibitor Toxicity associated with market1 inhi
Slide 20: CFT1946 Shows Superior Efficacy Compared to Approved BRAF Inhibitor in Preclinical Models
CFT1946 Shows Superior Efficacy Compared to Approved BRAF Inhibitor in Preclinical Models Combination Treatment of BRAFi Resistant Xenograft CFT1946 Shows More Durable Efficacy than Encorafenib Model with CFT1946 and MEKi Shows Tumor Growth Inhibition/Regression A375 Xenograft A375 + NRAS-Q61K Xenog
Slide 21: CFT1946 is the First Clinical BRAF V600 Degrader
CFT1946 is the First Clinical BRAF V600 Degrader Phase 2 Expansion Phase 1 Dose Escalation Monotherapy Arm A: V600 Melanoma and Monotherapy1 NSCLC RP2D V600 solid tumors Post BRAF inhibitor including CRC, N =~30 Melanoma and NSCLC CFT1946 + trametinib Post BRAF inhibitor Arm B: V600 Melanoma and N=~
Slide 22: CFT1946 Has the Potential to Address Multiple Tumor Types with BRAF V600 Mutations
CFT1946 Has the Potential to Address Multiple Tumor Types with BRAF V600 Mutations ~70-90% 1.9M Cancer Diagnoses Each Year in V600 of BRAF mutations the United States1 are V600 BRAF Mutations Occur in ~5% of All 35% 1-2% Cancers2 Late-stage Non-Small Melanoma2 Cell Lung Cancer3 ~100K annual incidenc
Slide 23: CFT8919
CFT8919 Targeting EGFR L858R EGFR L858R + Non-Small Cell Lung Cancer (NSCLC)
Slide 24: Potential for CFT8919 to Improve Outcomes for NSCLC Patients with L858R Mutations
Potential for CFT8919 Single Agent CFT8919to Improve Provides Outcomes to Opportunity forImprove NSCLC Patients Outcomeswithfor EGFR L858R NSCLCMutations Patients with L858R Mutations Degrader Rationale Osimertinib and other inhibitors ~$6B provide suboptimal response for approved NSCLC patients wit
Slide 25: Strategic Partnership with Betta Pharmaceuticals in Greater China
Strategic Partnership with Betta Pharmaceuticals in Greater China Expert Partner in Expedite Greater China Development • High prevalence of • Betta has a proven EGFR L858R driven NSCLC track record in Greater China allows for of developing NSCLC faster clinical Deal Terms: medicines including develo
Slide 26: EGFR L858R Driven NSCLC has Higher Prevalence in Asia
EGFR L858R Driven NSCLC has Higher Prevalence in Asia Non-Small Cell Lung Cancer (NSCLC) ~200K ~693K Patients in the US Patients in Asia diagnosed in diagnosed in 2022 2020 ~10 – 15% ~40% of NSCLC patients have mutant EGFR (mEGFR) in the of NSCLC patients have mEGFR in the U.S. population Asian popu
Slide 27: CFT8919 is Selective for EGFR L858R and Active in a Setting of Osimertinib Resistance
CFT8919 is Selective for EGFR L858R and Active in a Setting of Osimertinib Resistance in Preclinical Models Specific for EGFR Exon 21 Mutants Active in setting of EGFR C797S Vehicle PO BID BaF3 EGFRL858R/T790M/C797S 2000 Osimertinib 25 mpk PO QD Tumor volume (mm3) CFT8919 10 mpk PO BID EGFR-L861Q CF
Slide 28: 2023 Expected to be a Transformative Year for C4T with Two Clinical Readouts
2023 Expected to be a Transformative Year for C4T with Two Clinical Readouts CFT7455 • Cash runway into 2025 • Present Phase 1 dose escalation data from the Phase 1/2 trial 2H IKZF1/3 CFT8634 • Present Phase 1 dose escalation data from the Phase 1/2 trial 2H BRD9 CFT1946 ✓ First patient dosed in the
Slide 29: Thank You!
Thank You! © 2023 C4 Therapeutics, Inc. 29