C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — American Society of Hematology (ASH) Annual Meeting 2024
35 slides from C4 Therapeutics's conference presentation, Dec 9, 2024
Slide 1: Updated Data in Multiple Myeloma and First Data in Non-Hodgkin's Lymphoma
Updated Data in Multiple Myeloma and First Data in Non-Hodgkin’s Lymphoma from the Ongoing Cemsidomide Phase 1/2 Trial American Hematology Annual Meeting (ASH) December 8, 2024
Slide 2: Forward-looking Statements and Intellectual Property
Forward-looking Statements and Intellectual Property 2 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
Cemsidomide Phase 1 MM & NHL Data & Next Steps Len Reyno, M.D., CMO Concluding Remarks & Q&A Session Andrew Hirsch, President and CEO Len Reyno, M.D., CMO Kendra Adams, CFO Introductions Courtney Solberg, Senior Manager of IR Opening Remarks Andrew Hirsch, President and CEO Today’s Agenda 3© 2024 C4
Slide 4: Opening Remarks
Opening Remarks Andrew Hirsch President and Chief Executive Officer
Slide 5: C4T Has Delivered a Steady Flow of Clinical Updates and Innovative Collaborations
C4T Has Delivered a Steady Flow of Clinical Updates and Innovative Collaborations Over the Past 12 Months… Cemsidomide Collaborations Have Further Validated TORPEDO Platform CFT1946 CFT8919 Significant Progress Across Clinical Programs © 2024 C4 Therapeutics, Inc. 5 ✓ Compelling activity in both mul
Slide 6: …Which Set the Stage to Unlock Value
…Which Set the Stage to Unlock Value © 2024 C4 Therapeutics, Inc. C4T is positioned to become a fully integrated biotechnology company focused on orally bioavailable degraders KEY CATALYSTSVALUE DRIVERS Cemsidomide IKZF1/3 Further development in multiple myeloma and non- Hodgkin’s lymphoma positions
Slide 7: Cemsidomide First-in-Human Clinical Program
Cemsidomide First-in-Human Clinical Program Relapsed Refractory Multiple Myeloma and Non-Hodgkin's Lymphoma
Slide 8: IKZF1/3 Are Key Promoters of Myeloma and Lymphoma Cell Survival
IKZF1/3 Are Key Promoters of Myeloma and Lymphoma Cell Survival and Will Remain Important Therapeutic Targets in MM and NHL © 2024 C4 Therapeutics, Inc. Key Roles of IKZF1/3 Physiological Functions: • IKZF1/3 are key transcriptional regulators of hematopoietic stem cell differentiation • IKZF1/3 dir
Slide 9: Cemsidomide First-in-Human Phase 1 Trial Continues to Progress
R/R NHL Monotherapy Dosing: MWF & QD 14 days on/ 14 days off N=~25 Status: Enrolling R/R MM Dex Combo Dosing: MWF & QD 14 days on/ 14 days off N=~40 Status: Enrolling R/R MM Monotherapy Dosing: MWF & QD 14 days on/ 14 days off N=22 Status: Complete Cemsidomide First-in-Human Phase 1 Trial Continues
Slide 10: Multiple Myeloma: Cemsidomide + Dexamethasone
Multiple Myeloma Cemsidomide + Dexamethasone
Slide 11: Cemsidomide Positioned to Be an IKZF1/3 Degrader of Choice Across Combinations
With a Potentially Best-in-Class Profile, Cemsidomide Is Positioned to Be an IKZF1/3 Degrader of Choice Across Various Combinations Post-Transplant Maintenance1 Anti-CD38 Combos Proteasome Inhibitor Combos CAR-Ts (+/- Maintenance Therapy) Other MOAs2 1Approximately 30% of multiple myeloma patients u
Slide 12: Cemsidomide + Dexamethasone Dose Escalation Trial in MM Continues to Progress
Cemsidomide + Dexamethasone Dose Escalation Trial in MM Continues to Progress; Have Not Exceeded the Maximum Tolerated Dose 12© 2024 C4 Therapeutics, Inc. DOSE ESCALATION CEMSIDOMIDE 14/14 + DEX* Utilizing a Bayesian logistic regression model until determination of the MTD and/or RP2D 50 µg MWF Back
Slide 13: Baseline Characteristics and Prior Therapies
© 2024 C4 Therapeutics, Inc. Characteristics Safety Population (N=47) Age, median (range) 67 (39-82 years) Male, n (%) 25 (53) Years since initial diagnosis, median (range) 7 (2-18) ECOG performance status, n (%) 0 1 2 10 (21) 34 (72) 3 (7) Black or African American, n (%) White, n (%) Other, n (%)
Slide 14: Cemsidomide Was Well-Tolerated With Manageable Neutropenia
Cemsidomide Was Well-Tolerated With Manageable Neutropenia and No Treatment Emergent Adverse Events Lead to Dose Reductions © 2024 C4 Therapeutics, Inc. 14 Common (>20% All Grades) TEAEs and Events of Interest, n (%) All Grades (N=47) Grade 3 (N=47) Grade 4 (N= 47) Grade 5 (N=47) Neutropenia 22 (47)
Slide 15: Grade ≥3 Neutropenia, Febrile Neutropenia and Infections Were Infrequent
Grade ≥3 Neutropenia, Febrile Neutropenia and Infections Were Infrequent and Rates Did Not Increase With Higher Cemsidomide Doses © 2024 C4 Therapeutics, Inc. 15 Common Hematologic and Infection Grade ≥3 TEAEs, n (%) 50 µg MWF (N=6) 37.5 µg QD (N=12) 62.5 µg QD (N=15) 75 µg QD (N=14) Total (N=47) Ne
Slide 16: Compelling Cemsidomide Safety Profile With Low Rates of Neutropenia and Infections
Compelling Cemsidomide Safety Profile With Low Rates of Neutropenia and Infections With Limited G-CSF Use 28% 26% 6% 5% 13% 0% 14% 0% 8% 7% 3% 5% 0% 0% 0% 0% 11% 19% 6% 0% 13% 0% 14% 0% 0% 25% 50% 75% 100% Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Cycle 7 Cycle 8 P ts w it h G ra d e ≥ 3 A E s
Slide 17: 40% of MM Patients With Elevated Light Chains Had at Least 50% Decrease in dFLC
Across Doses, 40% (14/35) of Multiple Myeloma Patients With Elevated Light Chains Demonstrated at Least a 50% Decrease in dFLC 17© 2024 C4 Therapeutics, Inc Best Change in dFLC from Baseline (Cemsidomide + Dex) Multiple Myeloma Patients w/ Elevated Light Chain Disease (N=35)* Data cutoff: 10/11/24 0
Slide 18: 75 µg Dose Level or Greater Drives Sufficient Exposure
Exposure (AUC) Quartiles <Q1 (N=9) Q1-Q2 (N=8) Q2-Q3 (N=8) >Q3 (N=9) Mean AUC0-28d (ng*h/mL) 14.6 28.8 37.9 65.2 Mean Change in dFLC from Baseline +10% -12% -20% -53% Cemsidomide + Dex Dose ~17 μg QD ~35 μg QD ~45 μg QD ~78 μg QD 18© 2024 C4 Therapeutics, Inc. Data cutoff: 10/11/24 Cemsidomide 75 µg
Slide 19: Cemsidomide Demonstrated Anti-Myeloma Activity Across Dose Levels
a Cemsidomide Demonstrated Anti-Myeloma Activity Across Dose Levels 19© 2024 C4 Therapeutics, Inc. Data cutoff: 10/11/24 As of the data cutoff: • 26% ORR and 40% clinical benefit rate across all dose levels evaluated • At the two highest dose levels evaluated to date (62.5 μg and 75 μg), 62% of all
Slide 20: 75 µg Dose Level Resulted in 36% ORR and 45% CBR
75 µg Cemsidomide Dose Level Resulted in Compelling Anti-Myeloma Activity With a 36% ORR and 45% CBR 20 33% (2) 8% (1) 18% (2) 12% (5) 50% (3) 58% (7) 46% (6) 36% (4) 48% (20) 17% (2) 23% (3) 9% (1) 14% (6) 17% (1) 8% (1) 15% (2) 36% (4) 19% (8) 8% (1) 8% (1) 5% (2)8% (1) 2% (1) 0% 25% 50% 75% 100%
Slide 21: Cemsidomide's Differentiated Safety Profile Well Suited for Combination Studies
Cemsidomide’s Differentiated Safety Profile Is Well Suited for Combination Studies, Potentially Resulting in Fewer Disruptive Adverse Events © 2024 C4 Therapeutics, Inc. 21 Cemsidomide + Dex Key Grade ≥3 Adverse Events 23% 22% 48% 54% 9% 15% 40% 35% 0% 25% 50% 75% 100% Dose Escalation - All Doses (N
Slide 22: Cemsidomide Has the Potential to Be a Backbone Therapy of Choice
Cemsidomide + dex was well-tolerated with a compelling safety profile – 38% of patients experienced Grade 3/4 neutropenia, which was manageable, and no cases resulted in cemsidomide discontinuation Cemsidomide Has the Potential to Be a Backbone Therapy of Choice Where IKZF1/3 Degradation Is Warrante
Slide 23: Next Steps: Complete Phase 1 Dose Escalation, Initiate Combination Trials
NEXT STEPS: Complete Phase 1 dose escalation trial in multiple myeloma to establish go forward doses Initiate initial combination trials Engage regulatory authorities on registrational path © 2024 C4 Therapeutics, Inc. INITIAL COMBINATION TRIALS: Trial DesignPrior Lines of Therapy Cemsidomide + BCMA
Slide 24: Non-Hodgkin's Lymphoma (NHL) Monotherapy Cemsidomide
Non-Hodgkin’s Lymphoma (NHL) Monotherapy Cemsidomide
Slide 25: U.S. Annual Incidence of NHL Subtypes and Cemsidomide Opportunity
U.S. Annual Incidence (2023)1 ~26,000 ~15,000 ~5,000 ~4,000 ~5,000 Lenalidomide FDA Approved2 Lenalidomide in NCCN Guidelines 25 DLBCL Diffuse Large B-Cell Lymphoma FL Follicular Lymphoma MZL Marginal Zone Lymphoma MCL Mantle Cell Lymphoma PTCL Subtypes Peripheral T-Cell Lymphoma B
Slide 26: Dose Exploration Continues for Cemsidomide Monotherapy Trial in R/R NHL
Dose Exploration Continues for the Cemsidomide Monotherapy Dose Escalation Trial in R/R NHL KEY INCLUSION CRITERIA • Adults with NHL, R/R to prior therapy • PTCL patients must have received at least 1 prior alkylator-based chemotherapy • ALCL patients must have also received a CD-30 mAb • Nonrespons
Slide 27: Heavily Pre-Treated Population Majority Diagnosed With PTCL
Heavily Pre-Treated Population Where Majority of Patients Were Diagnosed With PTCL, Reflecting High Unmet Need 27 Data cutoff: 10/11/24 © 2024 C4 Therapeutics, Inc. Characteristics Safety Population (N=23) Age, median (range) 68 (28-85 years) Male, n (%) 14 (61) Years since initial diagnosis, median
Slide 28: Cemsidomide Well-tolerated With Manageable On-target Neutropenia
Cemsidomide Was Well-tolerated With Manageable Incidents of On- target Neutropenia Common (>20% All Grades) TEAEs and Events of Interest*, n (%) All Grade (N=23) Grade 3 (N=23) Grade 4 (N=23) Infections Upper respiratory tract infection Sepsis Bacteremia Pneumonia 15 (65) 4 (17) 1(4) 1(4) 2 (9) 4 (1
Slide 29: Cemsidomide Monotherapy Adverse Events by Dose Level
Cemsidomide Monotherapy Adverse Events by Dose Level Common Grade ≥3 TEAEs, n (%) 25 µg MWF (N=3) 50 µg MWF (N=3) 37.5 µg QD (N=9) 62.5 µg QD (N=4) 100 µg QD (N=4) Total (N=23) Neutropenia 0 0 5 (56) 4 (100) 2 (50) 11 (48) Infections Pneumonia Sepsis Urinary tract infection Bacteremia Skin infection
Slide 30: Clinical Responses Were Observed Across a Broad Range of Doses
Clinical Responses Were Observed Across a Broad Range of Doses a a b b a Both patients were not evaluable based on PET-CT but were considered progressive disease due to CT scan. b Both patients dose reduced to 62.5 ug following DLTs. Anaplastic large cell lymphoma (ALCL); adult T-cell leukemia/lymph
Slide 31: Compelling and Deep Responses Achieved Across PTCL Subtypes
Compelling and Deep Responses Achieved Across PTCL Subtypes 19% (1) 25% (1) 20% (1) 20% (1) 25% (3) 75% (3) 50% (1) 0% 25% 50% 75% 100% All PTCL (N=16) AITL (N=4) ALCL (N=2) ATLL (N=5) PTCL-NOS (N=5) B e st R e sp o n se % ( N ) CMR PMR PET-CT–based Assessment of PMR or Better by PTCL Subtype* (N=16
Slide 32: Cemsidomide Well-suited for Further Development in Earlier Lines and Combination
32© 2024 C4 Therapeutics, Inc. Data cutoff: 10/11/24 Bayesian logistic regression model (BLRM); complete metabolic response (CMR); dose limiting toxicities (DLTs); overall response rate (ORR); peripheral t-cell lymphoma (PTCL) Cemsidomide was well-tolerated with additional dose finding ongoing – 2 D
Slide 33: Cemsidomide Supports Development Across Multiple Lines in NHL, ~$30B Opportunity
Cemsidomide Profile Supports Development Across Multiple Lines of Treatment in NHL, Estimated to Be ~$30B Market Opportunity by 20301 33© 2024 C4 Therapeutics, Inc. NEXT STEPS: Complete Phase 1 dose escalation trial in NHL and identify go forward dose Initiate expansion cohort for PTCL Engage regula
Slide 34: Cemsidomide Positioned to Potentially Be Best-in-Class in Two Indications
Cemsidomide Is Positioned to Potentially Be a Best-in-Class Therapy in Two Distinct Indications with Opportunities Across Multiple Lines of Therapy © 2024 C4 Therapeutics, Inc. IKZF1/3 is a fundamental target for MM and NHL and data supports cemsidomide as a potential backbone therapy within the evo
Slide 35: Q&A
Q&A
C4 Therapeutics — American Society of Hematology (ASH) Annual Meeting 2024 on 6ix