C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Technical Presentation (December 2023)
39 slides from C4 Therapeutics's technical presentation, Dec 12, 2023
Slide 1: CFT7455 Phase 1 Dose Escalation Data in R/R MM
CFT7455, IKZF1/3 Degrader, for the Potential Treatment of Relapsed Refractory Multiple Myeloma (R/R MM) Phase 1 Dose Escalation Data December 12, 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: Today's Agenda
Today’s Agenda Topic Participants • Introductions Courtney Solberg, Senior Manager of IR Opening Remarks Andrew Hirsch, President and CEO CFT7455 Preclinical Data Stew Fisher, Ph.D., CSO CFT7455 Phase 1 Data Len Reyno, M.D., CMO Q&A Session Andrew Hirsch, President and CEO Stew Fisher, Ph.D., CSO Le
Slide 4: 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 Robust patent portfolio of novel cereblon binders and demonstrated ability to design orally bioavailable, catalytically efficient degraders Our Mission RIGOROUS TARGET SELECTION To deliver on t
Slide 5: Robust Pipeline of Degrader Medicines Pursuing Multiple Oncology Targets
Robust Pipeline of Degrader Medicines Pursuing Multiple Oncology Targets Early phase Late phase Program Target Indications Discovery Pre-clinical Rights development development Multiple Myeloma & CFT7455 IKZF1/3 Non-Hodgkin’s Lymphoma CFT1946 BRAF-V600 V600 Mutant Cancers Non-Small Cell Lung CFT8919
Slide 6: Execution Across Key 2023 Milestones
Execution Across Key 2023 Milestones CFT7455 • Cash runway into 2025 ✓ Present Phase 1 dose escalation data from the Phase 1/2 trial in IKZF1/3 R/R MM CFT8634 ✓ Present Phase 1 dose escalation data from the Phase 1/2 trial in BRD9 Synovial Sarcoma and SMARCB1-null tumors CFT1946 ✓ First patient dose
Slide 7: CFT7455 Phase 1 Update
CFT7455 Phase 1 Update Andrew Hirsch
Slide 8: 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 9: CFT7455 Background & Preclinical Rationale
CFT7455 Background & Preclinical Rationale Stew Fisher
Slide 10: 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 11: IKZF1/3 Degraders Require Drug Holidays Based on PK Properties
IKZF1/3 Degraders are Effective Therapies that Require Drug Holidays Based on PK Properties to Overcome On-Target Neutropenia IKZF1/3 Half Life Dosing Dosed + Grade 3/4 Degrader (hours) Schedule Dexamethasone Neutropenia Rate* 21 Days on / Anti-MM 3-5 7 Days off 33% and NHL Neutropenia Activity 21
Slide 12: CFT7455 Designed to Overcome Shortcomings of Approved IKZF1/3 Degraders
CFT7455 was Designed to Overcome Several Shortcomings of Approved MM and NHL IKZF1/3 Degraders Approved MM & NHL IKZF1/3 Degraders’ Shortcomings CFT7455 Preclinical Solutions ❑ Modest on-target degradation and off-target liabilities ✓ Reduce off-target toxicity and provide versatile combo potential
Slide 13: Differentiated PK and Class-leading Catalytic Activity of CFT7455
Normalized to GAPDH in NCI-H929 Tumors Differentiated PK and Class-leading Catalytic Activity of CFT7455 Leads to Percent of IKZF3 Remaining/ Normalized to GAPDH in NCI-H929 Tumors Sustained Degradation Compared to Other Agents in this Class 100 Percent of IKZF3 Remaining/ 100 50 Extended Plasma and
Slide 14: Preclinical Synergy of CFT7455 with Dexamethasone
Preclinical Model Demonstrated Significant Synergy when CFT7455 is Combined with Dexamethasone CFT7455 + Dexamethasone Shows Robust Tumor Regressions Compared to Monotherapy Regimens CFT7455 50 µg QD Human Dose Equivalent +/- Dexamethasone RPMI-8226 Multiple Myeloma Xenograft 4000 Vehicle (QD, PO) D
Slide 15: CFT7455 Monotherapy Dose Escalation in R/R MM
CFT7455 Monotherapy Dose Escalation in R/R MM Len Reyno
Slide 16: Phase 1 Dose Escalation Trial Goal and Design
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 the maximum Sta
Slide 17: Monotherapy Dose Escalation Complete in R/R MM
CFT7455 Monotherapy Dose Escalation Complete in R/R MM; Sufficient Data Generated to Explore CFT7455 in Combination with Novel MM Agents Phase 1: Dose Escalation Monotherapy 14 Days On/14 Days Off KEY INCLUSION CRITERIA • Adults with MM, R/R at 75 µg least 3 prior lines that have QD 2 DLTs3 included
Slide 18: Monotherapy Patient Population Heavily Pre-treated with Median of 7 Prior Therapies
CFT7455 Monotherapy Patient Population was Heavily Pre-treated with a Median of 7 Prior Therapies Baseline Characteristics: Prior Therapies: Safety Population Safety Population Characteristics Characteristics (N = 22) (N = 22) Age, median (range) 64 (47-79 years old) Male, n (%) 14 (64%) Prior thera
Slide 19: Monotherapy: Treatment Disposition of R/R MM Patients
CFT7455 Monotherapy: Treatment Disposition of 22 R/R MM Patients Patient Disposition Safety Population (N = 22) Ongoing, n (%) 3 (14%) Discontinued, n (%) 19 (86%) Progressive disease, n(%) 12 (55%) Physician decision, n(%) 3 (14%) Withdrawal by patient, n(%) 2 (9%) Death, n (%) 1 (5%) Adverse event
Slide 20: Monotherapy is Well Tolerated with 14 Days on/14 Days off Schedule
CFT7455 Monotherapy is Well Tolerated with 14 Days on/14 Days off Schedule Monotherapy Patients with AEs of Grade 3 or 25 µg MWF 50 µg MWF 75 µg MWF 50 µg QD 75 µg QD R/R MM Higher, N (%) (N=3) (N=5) (N=5) (N=5) (N=4) Total (N=22) Hematologic AEs Neutropenia 1 (33%) 1 (20%) 3 (60%) 3 (60%) 3 (75%) 1
Slide 21: Plasma Exposure Increased Proportionally with Cumulative Dose
Plasma Exposure of CFT7455 Monotherapy Increased Proportionally with Cumulative Dose Pharmacokinetics (PK) 0.60 Plasma CFT7455 Conc (ng/mL) 0.30 75 μg QD (Patient 2) 0.15 75 μg QD (Patient 3) 75 μg QD (Patient 4) 50 μg QD 0.10 Target Concentration from H929 Monotherapy 37.5 μg QD 75 μg MWF 0.05 50 μ
Slide 22: Pharmacodynamics Consistent with 14/14 Modeling Assumptions
Pharmacodynamics Consistent with 14 Days on/14 Days off Modeling Assumptions; 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 IKZF1/3 expression measured by Mass Spec on PBMCs 10 0 100 % expression % exp
Slide 23: International Myeloma Working Group (IMWG) Response Criteria
International Myeloma Working Group (IMWG) Response Criteria sCR CR VGPR PR MR SD Stringent Complete Complete Very Good Partial Partial Response Minimal Response Stable Disease Response Response Response • > 50% reduction of serum M-protein • CR as defined to • Negative • Serum and • ≥25% but ≤49% •
Slide 24: Evidence of Anti-Myeloma Monotherapy Activity at Maximum Administered Dose
Evidence of Anti-Myeloma Monotherapy Activity: All 4 Patients at the Maximum Administered Dose Level had Stable Disease or Better Prior Cycles Dosing Dose EMD Prior CAR-T 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Schedule Level Status lines or TCE Yes Yes 8 PD 25 µg Yes No 5 PD M/W/F Yes No 6 PD No No
Slide 25: Clinical Evidence of Immune T-cell Activation with CFT7455
Clinical Evidence of Immune T-cell Activation with CFT7455 Monotherapy Supports potential of CFT7455 as a % positive cells (C1D21 vs C1D1) maintenance therapy option and 100 C1D1 **** C1D21 in combination with novel MM agents to improve efficacy: 80 ** ✓ CFT7455 induces CD8+ T-cell % positive cells
Slide 26: Enhances Immune Cell Lysis of Daratumumab and Teclistamab
CFT7455 Enhances Immune Cell Lysis of Daratumumab and Teclistamab in Non-clinical Translational Models Daratumumab (Anti-CD38) Combo Teclistamab (BCMA BiTE) Combo Antibody-Dependent Cell-Mediated Cytotoxicity Assay (ADCC) T-cell Dependent Cellular Cytotoxicity Assay (TDCC) Daratumumab (2ng/mL) + CFT
Slide 27: Monotherapy is Well Tolerated with Anti-Myeloma Activity and Immunomodulatory Effects
CFT7455 Monotherapy is Well Tolerated and Demonstrates Anti- Myeloma Activity and Immunomodulatory Effects • Continuous target degradation is associated with CFT7455 dosing across all dose levels and shows anti- myeloma activity at the highest dose level • 14 days on/14 days off schedule provides th
Slide 28: CFT7455 + Dexamethasone in R/R MM
CFT7455 + Dexamethasone in R/R MM Len Reyno
Slide 29: CFT7455 + Dexamethasone Dose Escalation in R/R MM
CFT7455 + Dexamethasone Dose Escalation in R/R MM 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 escalation have included lenalidomide, pomalidomide, a proteasome inhibitor, a CFT7455
Slide 30: CFT7455 + Dexamethasone Patient Population Median of 6 Prior Therapies
CFT7455 + Dexamethasone Patient Population to Date was Heavily Pre-treated with a Median of 6 Prior Therapies Baseline Characteristics: Prior Therapies: Safety Population Safety Population Characteristics Characteristics (N = 9) (N = 9) Age, median (range) 68 (59-82 years) Prior therapies, median (r
Slide 31: CFT7455 + Dexamethasone is Well Tolerated
CFT7455 + Dexamethasone is Well Tolerated CFT7455: 50 µg MWF CFT7455: 37.5 µg QD CFT7455+Dex Patients with AEs of Grade 3 or +Dex: 40 mg QW +Dex: 40 mg QW Total Higher, N (%) (N=5) (N=4) (N=9) Hematologic AEs Anemia 1 (20%) 2 (50%) 3 (33%) Neutropenia 1 (20%) 2 (50%) 3 (33%) Febrile neutropenia 1 (2
Slide 32: Multiple Responses at Low Doses with Dexamethasone
CFT7455 + Dexamethasone Resulted in Multiple Responses at Low Doses with Best Responses in Patients Refractory to BCMA Therapies Cycles Prior Dosing EMD # of Prior Dose Level CAR-T 1 2 3 4 5 6 7 8 9 10 11 Schedule Status Lines or TCE No No 6 PD CFT7455: 50 µg No Yes 4 SD PD MWF No No 5 SD MR PR +Dex
Slide 33: Patient Vignette: sCR Achieved in a Pre-treated MM Patient
Patient Vignette: sCR Achieved in a Pre-treated MM Patient When Treated with CFT7455 + Dexamethasone • 65, female, enrolled 08/23/2023 into 37.5 µg QD 14/14 CFT7455 + % change in dFLC relative to baseline IKZF1 expression measured by Mass Spec on PBMCs dFLC measurement (37.5ug QD 14/14 +dex) dexamet
Slide 34: CFT7455 + Dexamethasone Well Tolerated with Promising Efficacy Signals
CFT7455 + Dexamethasone is Well Tolerated and Demonstrates Promising Efficacy Signals, Supporting Development in Multi-refractory MM Patients • CFT7455 combined with dexamethasone is well tolerated in a heavily pre- treated population • Manageable neutropenia • Promising efficacy signals with multip
Slide 35: CFT7455 Development Plan and Next Steps
CFT7455 Development Plan and Next Steps Len Reyno
Slide 36: Many MM Patients Progress through Several Lines of Therapy, Providing Opportunities for CFT7455
Despite Numerous Treatment Options, Many MM Patients Progress through Several Lines of Therapy, Providing Opportunities for CFT7455 Annual Addressable MM Treatment Potential Opportunity for CFT7455: Patients (US, 2023) ~22,000 ~11,000 • Front-line triplet combinations with daratumumab or 1st Line tr
Slide 37: The CFT7455 Profile Supports Multiple Opportunities Across MM Landscape
The CFT7455 Profile Supports Multiple Opportunities Across MM Landscape Potential Potential Data Enabled Opportunity Development Path CFT7455 + CFT7455 + Dexamethasone Accelerated Approval in Dexamethasone Registrational Study Multi-Refractory MM + PI Studies Approvals in Early Line MM + Anti-CD38 S
Slide 38: Schedule Adjustment Yielding Expected Results; Next Milestones
Schedule Adjustment Yielding Expected Results for CFT7455 as a Potential MM Therapy + Next Milestones: • Present complete CFT7455 dose escalation data + dexamethasone for R/R MM in 2024 Established Safety Profile Demonstrated Promising Responses + and Dosing Schedule Monotherapy Activity Dexamethaso
Slide 39: Q&A Session
Q&A Session
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