Slide 1: CFT7455 Phase 1/2 Cohort A Data Investor Call
CFT7455 Phase 1/2 Cohort A Data Investor Call American Association for Cancer Research Annual Meeting 2022 Abstract CT186 April 8, 2022 Exhibit 99.2
Slide 2: 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,” “could,” “estimate,” “expect,” “goal,” “intend,” “loo
Slide 3: Today's Agenda
Today’s Agenda © 2022 C4 Therapeutics, Inc. 3
Slide 4: Robust Pipeline of Degrader Medicines Pursuing Meaningful Targets
Robust Pipeline of Degrader Medicines Pursuing Meaningful Targets Enrolling Recommended Phase 2 Dose Initiate Phase 1 trial Submit IND application and initiate Phase 1 trial Complete IND-enabling activities 4 targets 5 targets 1 target through March 2023 © 2022 C4 Therapeutics, Inc. 4 Number of targ
Slide 5: C4T Presentations at AACR Annual Meeting 2022
C4T Presentations at AACR Annual Meeting 2022 Jim Henderson, Ph.D., Vice President of Chemistry, C4 Therapeutics Abstract Number: 7922, Oral Time: Monday, 4/11/22, 10:15 AM –11:45 AM CT Location: La Nouvelle Orleans A-B Session: New Drugs on the Horizon: Part 3 New Orleans Convention Center, La Nouv
Slide 6: Advancing Multiple Oncology Programs to Patients
Advancing Multiple Oncology Programs to Patients © 2022 C4 Therapeutics, Inc. 6
Slide 7: CFT7455: Potent Small Molecule IKZF1/3 Degrader with Enhanced Catalytic & Pharmacologic Properties
IKZF1/3 are transcription factors required for cancer cell growth and survival in multiple myeloma (MM) Approved IMiDs (lenalidomide, pomalidomide) are widely used in MM treatment and are IKZF1/3 degraders Relapsed/refractory MM remains a high unmet medical need Class-leading catalytic activity to e
Slide 8: High Catalytic Activity of CFT7455 Improves Activity in H929 MM Cells Compared to Pomalidomide
High Catalytic Activity of CFT7455 Improves Activity in H929 MM Cells Compared to Pomalidomide* © 2022 C4 Therapeutics, Inc. 8 *Pomalidomide is an approved IKZF1/3 degrader while CC-220, CC-92480 and CFT7455 are all investigational compounds. C4 Therapeutics data on file. Binding Affinity (FP) Degra
Slide 9: CFT7455 Demonstrates Superior Efficacy in NCI-H929 MM Xenograft Model
In comparison to CC-92480, CFT7455 achieves equivalent efficacy at 1/100th of the dose In the NCI-H929 xenograft model, 100 μg/kg/day of CFT7455 resulted in durable tumor regressions CFT7455 Demonstrates Superior Efficacy in NCI-H929 MM Xenograft Model QD Dosing No Drug Administered CFT7455 vs. Comp
Slide 10: CFT7455 is Highly Efficacious in a Model of Systemic Multiple Myeloma
CFT7455 is Highly Efficacious in a Model of Systemic Multiple Myeloma CFT7455 vs Comparators in a Model of Systemic MM © 2022 C4 Therapeutics, Inc. 10 Day 14 *Mouse missing in CFT7455 100 µg/kg group due to changes unrelated to treatment or disease
Slide 11: Single Dose PK/PD in H929 Xenografts Differentiates CFT7455 from CC-92480
CFT7455 and CC-92480* Tumor and Plasma Concentrations Degradation Kinetics for CFT7455, CC-92480 and Pomalidomide *CC-92480 was created in-house based on compound described in: Hansen JD, et al. J Med Chem. 2020;63(13):6648-6676. Single Dose PK/PD in H929 Xenografts Differentiates CFT7455 from CC-92
Slide 12: PK Profile of a Novel IKZF1/3 Degrader, CFT7455, and Initial Treatment Cohort Results
Pharmacokinetic (PK) Profile of a Novel IKZF1/3 Degrader, CFT7455, Enables Significant Potency Advantage over Other IKZF1/3 Degraders in Models of Multiple Myeloma (MM) and the Results of the Initial Treatment Cohort from a First-in-Human (FIH) Phase 1/2 Study of CFT7455 in MM Sagar Lonial, MD, FACP
Slide 13: CFT7455 Phase 1/2 Trial Design
CFT7455 Phase 1/2 Trial Design Phase 1 Dose Escalation R/R Multiple Myeloma Monotherapy N =~30 Cohort B1: R/R Multiple Myeloma Monotherapy N =~15 Status: Enrolling Cohort C: Non-Hodgkin’s Lymphoma Monotherapy N =~15 Status: Enrolling Mantle Cell Lymphoma N=~20 Peripheral T-Cell Lymphoma N=~20 Cohort
Slide 14: Cohort A Enrolled Heavily Pre-Treated and Highly Refractory MM Patients
Cohort A Enrolled Heavily Pre-Treated and Highly Refractory MM Patients © 2022 C4 Therapeutics, Inc. 14
Slide 15: Observed Steady State Exposures Suggest CFT7455 QD Achieves Efficacious Exposures
Observed Steady State Exposures Suggest CFT7455 50 µg QD Achieves Efficacious Exposures Patient 4 received 50 µg for 8 days followed by 25 µg for 13 days followed by the regular 7-day rest period in Cycle 1; subsequent cycles continued at 25 µg 21 days on and 7 days off in a 28-day cycle. Data not a
Slide 16: Deep and Sustained Degradation of IKZF1/3 Observed in Cycle 1
Deep and Sustained Degradation of IKZF1/3 Observed in Cycle 1 of Single Agent CFT7455 Data not available for Patient 1 and Patient 3 due to compromised sample integrity PBMC, peripheral blood mononuclear cells Key Takeaways: IKZF3 degradation was deeper in human PBMCs at 50 and 25 μg/day than was pr
Slide 17: Meaningful Decreases in dFLC Achieved with Single Agent CFT7455
Meaningful Decreases in dFLC Achieved with Single Agent CFT7455 at Lower Exposure and Dose Than Seen with Another Investigational IKZF1/3 Degrader Patient 4 had an increase in dFLC of 56%, however it is not plotted as exposure data is not available; Patient 5 sample was not obtained dFLC, difference
Slide 18: Responses to Single Agent CFT7455
Responses to Single Agent CFT7455 * Patients were dose reduced from 50 μg to 25 μg Each bar represents one patient in the study. Right arrow cap indicates continued on study. dFLC, difference between iFLC and uninvolved FLC; SCR, Stringent Complete Response; CR, Complete Response; VGPR, Very Good Pa
Slide 19: Patient Vignette: Encouraging CFT7455 Single Agent Activity in Heavily Pre-treated MM Patient
Patient 2 Vignette: Encouraging CFT7455 Singe Agent Activity in Heavily Pre-treated, High-risk MM Patient 60-year-old female enrolled 2 June 2021 into Cohort A Diagnosed with MM (IgG κ) Jan 2017 Heavily pretreated Per IMWG response criteria, patient achieved Stable Disease: Best response of 78.1% de
Slide 20: Summary of Adverse Events
Summary of Adverse Events No Serious Adverse Events © 2022 C4 Therapeutics, Inc. 20 *Thrombocytopenia includes the preferred term thrombocytopenia and platelet decreased
Slide 21: On-target Neutropenia Seen Across Patients; Most Severe at Day 21
Patient 4 received 50 µg for 8 days, followed by 25 µg Patient 5 received 25 µg dose On-target Neutropenia Seen Across Patients; Most Severe at Day 21 Key Takeaways: Neutropenia tended to worsen following day 15 and recovery was incomplete during the 7-day drug holiday The mechanism is considered du
Slide 22: Alternative CFT7455 Dosing Schedule Expected to Increase Therapeutic Index
Alternative CFT7455 Dosing Schedule Expected to Increase Therapeutic Index 22 There is insufficient time for neutrophil recovery during the 21 day on, 7 day off schedule. A 14 day on, 14 day off schedule may limit neutropenia by permitting neutrophil maturation and recovery while effecting tumor apo
Slide 23: Summary of Preclinical and Clinical CFT7455 Findings
Pre-clinically, single agent CFT7455 demonstrates increased activity in vivo in comparison to CC-92480 CFT7455 has longer exposure compared to CC-92480, resulting in sustained IKZF1/3 degradation in pre-clinical models After 21 days of once-daily dosing, CFT7455 100 μg/kg/day resulted in durable tum
Slide 24: Cohorts B and C Enrolling With Alternative Dosing Schedule
Cohorts B and C Enrolling At Starting Dose of 25 μg With Alternative Dosing Schedule Phase 1 Dose Escalation Phase 2 Expansion 28-day cycle / dose limiting toxicity (DLT) window Combination therapy cohorts will open once the selected CFT7455 dose level has been cleared for safety Note: 6–12 patient
Slide 25: Q&A Session
Q&A Session