Slide 1: Preliminary Results from a Phase 1 Study of CFT1946, a Novel BiDAC Degrader in Mutant BRAF V600 Solid Tumors
Preliminary Results from a Phase 1 Study of CFT1946, a Novel BiDACTM Degrader in Mutant BRAF V600 Solid Tumors Maria Vieito, MD1, Meredith McKean, MD2, Alexander I. Spira, MD, PhD3, Ezra Rosen, MD, PhD4, Jordi Rodon Ahnert, MD, PhD5, Victor Moreno, MD6, Valentina Gambardella, MD7, Omar Saavedra, MD8
Slide 2: Declaration of Interests
DECLARATION OF INTERESTS Maria Vieito Villar Consulting or Advisory Role: BMS; Speaker’s Bureau: Novocure; Research Funding: C4 Therapeutics, Roche, Novartis, Thermo Fisher Scientific, Astrazeneca, BeiGene, Taiho Oncology; Other relationship: Roche, BMS, Debiopharm Group, Incyte, Novartis, PharmaMar
Slide 3: CFT1946 Targeted Degradation of BRAF V600X
CFT1946 Targeted Degradation of BRAF V600X Potential advantages of CFT1946, a novel, oral, BRAF V600X BiDAC degrader: Degradation of BRAF V600X with CFT1946 ✓ Prevents BRAF V600 mutant mono/heterodimer formation1 ✓ Avoids paradoxical activation seen with approved inhibitors1 ✓ Addresses MAPK pathway
Slide 4: CFT1946 Shows Activity Alone and in Combination in Pre-Clinical Models
CFT1946 Shows Activity Alone and in Combination in Pre- Clinical Models Describing Tumor Types Driven by BRAF V600X MELANOMA CRC NSCLC A375, BRAF V600E (CDX) HT-29, BRAF V600E (CDX) BRAF V600E (PDX) A375, BRAF V600E (CDX) HT-29, BRAF V600E (CDX) BRAF V600E (PDX) End of Treatment 2000 1250 2000 Tumor
Slide 5: CFT1946-1101: Study Design and Study Status
CFT1946-1101: Study Design and Study Status Phase 1 trial in BRAF V600 Mutant Solid Tumors Monotherapy Dose Escalation PD Backfill Exploratory Expansion KEY INCLUSION CRITERIA1 • BRAF V600 mutant measurable solid tumors Melanoma with ≥1 prior line of SoC therapy for unresectable locally advanced or
Slide 6: CFT1946-1101: Baseline Characteristics and Disease History
CFT1946-1101: Baseline Characteristics and Disease History BRAFi-Pretreated Population with Advanced or Metastatic BRAF V600 Mutant Solid Tumors Baseline Characteristics Patients Dosed Disease History Patients Dosed (N = 36) (N = 36) Age, years Solid Tumor Type, n (%) Mean 54 Melanoma 14 (39%) Media
Slide 7: CFT1946 Phase 1 Monotherapy Safety
CFT1946 Phase 1 Monotherapy Safety CFT1946 Monotherapy is Well Tolerated with No DLTs Observed 20 mg BID 80 mg BID 160 mg BID 320 mg BID 640 mg BID Total (N = 5) (N = 5) (N = 9) (N = 12) (N = 5) (N = 36) Subjects with Any TEAEs, n (%) 4 (80) 4 (80) 7 (78) 11 (92) 5 (100) 31 (86) Grade ≥ 3 TEAEs, n (
Slide 8: CFT1946 Phase 1 Monotherapy Safety: Majority of TEAEs Mild to Moderate
CFT1946 Phase 1 Monotherapy Safety Majority of TEAEs Observed were Mild to Moderate Summary of TEAEs ≥ 10% of 36 subjects treated with CFT1946 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Total Preferred Term n (%) n (%) n (%) n (%) n (%) (N=36) • No DLTs Subjects with any TEAEs 3 (8) 14 (39) 11 (31) 2 (
Slide 9: Initial CFT1946 PK/PD Data Supports Proof of Mechanism
Initial CFT1946 PK/PD Data Supports Proof of Mechanism CFT1946 C1D15 Pharmacokinetics BRAF V600E Degradation at 320 mg (Paired Biopsy) CFT1946 BRAF V600E Degradation by IHC Screening C1D15 BRAF V600E expression 20 mg BID (N=3) 10000 80 mg BID (N=5) 300 160 mg BID (N=9) Plasma PK (ng/mL) 320 mg BID (
Slide 10: Early Evidence of Anti-Tumor Activity by RECIST 1.1
CFT1946 Phase 1 Monotherapy Anti-Tumor Activity Early Evidence of Anti-Tumor Activity by RECIST 1.1 V600R V600K V600K SD SD SD PR SD PD 5 SD PR 4 SD PR # 3 2 PD 1 PR *Other tumor types include cholangiocarcinoma, non-small cell lung cancer, pancreatic carcinoma, and small intestine cancer; BRAF V600
Slide 11: CFT1946 Phase 1 Monotherapy Anti-Tumor Activity
CFT1946 Phase 1 Monotherapy Anti-Tumor Activity Early Evidence of Anti-Tumor Activity # Ongoing SD at 16.6 months N/A N/A * N/A *Subject had confirmed PR after data cut off, Other tumor types include cholangiocarcinoma, non-small cell lung cancer, pancreatic carcinoma, and small intestine cancer; #A
Slide 12: Case Study: Patient with BRAF V600K Melanoma
Case Study: Patient with BRAF V600K Melanoma Early Evidence of Anti-Tumor Activity Baseline Cycle 5 (67% ) • 72-year-old male with BRAF V600K Stage IV Melanoma • Initial diagnosis Stage II in 2019 • Prior surgery and four lines of anti-neoplastic therapy: - Surgery: Wide local excision right posteri
Slide 13: Case Study: Patient with BRAF V600E Pancreatic Cancer
Case Study: Patient with BRAF V600E Pancreatic Cancer Early Evidence of Anti-Tumor Activity • 63-year-old male BRAF V600E Pancreatic carcinoma (w/ two liver metastases) Decrease in BRAF V600E allele fraction • Initial diagnosis Stage IV in 2021 measured in ctDNA using WES • Four lines of prior anti-
Slide 14: Conclusions
Conclusions Encouraging Results from Ongoing CFT1946 Phase 1 Monotherapy Study • Single agent CFT1946 has a well-tolerated safety profile • Only one Grade ≥3 treatment-related adverse event • No drug interruptions, reductions, or discontinuations due to treatment-related adverse events • No Grade ≥3
Slide 15: Acknowledgments
Acknowledgments • We thank the patients and their families for participating in this study • We thank all the investigators and support staff • The study (CFT1946-1101) was sponsored by C4 Therapeutics, Inc. • All authors contributed to and approved the presentation • For questions, please reach out