C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — AACR Annual Meeting 2021
13 slides from C4 Therapeutics's conference presentation, April 2021
Slide 1: CFT7455: A novel IKZF1/3 degrader in IMiD-resistant multiple myeloma xenograft models
CFT7455: A novel, IKZF1/3 degrader that demonstrates potent tumor regression in IMiD- resistant multiple myeloma (MM) xenograft models James A. Henderson, R. Jason Kirby, Samantha Perino, Roman V. Agafonov, Prasoon Chaturvedi, Bradley Class, David Cocozziello, Scott J. Eron, Andrew Good, Ashley A. H
Slide 2: Disclosure Information
Disclosure Information David Proia, PhD § I have the following financial relationships to disclose: • Stockholder in: C4 Therapeutics • Employee of: C4 Therapeutics § I will not discuss off label use and/or investigational use in my presentation.
Slide 3: Myeloma Therapies Have Improved OS But High Unmet Need Remains
Myeloma Therapies Have Improved OS But High Unmet Need Remains 2015 Daratumumab Improvement in OS From Median of 3 Years to 8-10 Years 2007 Doxorubicin 2015 Ixazomib 2018 Denosumab 1986 2015 Elotuzumab 2016 High-dose Dex 2003 CC-220 2019 Selinexor 1962 Bortezomib 2015 Panobinostat Prednisone 1960 19
Slide 4: Ikaros Transcription Factors are Central to Lymphoid Differentiation and Myeloma
Ikaros Transcription Factors are Central to Lymphoid Differentiation and Myeloma T-CELL LINEAGE T CELL PTCL DEPENDENT ON IKZF1 / IRF4 FOR GROWTH IKZF1 (Ikaros) and IKZF3 (Aiolos) control transcriptional programs central to the differentiation of lympho-myeloid multipotent progenitor cells through ma
Slide 5: CFT7455: Potent Small Molecule IKZF1/3 Degrader Optimized for Catalytic & Pharmacologic Properties
CFT7455: Potent Small Molecule IKZF1/3 Degrader Optimized for Catalytic & Pharmacologic Properties Goal: Develop an IKZF1/3 Monofunctional Ub Degradation Activating Compound Ub (MonoDAC) with these properties: Ub Ub Ub Ub IKZF3 IKZF3 Ub Ub Ub Ub § Class-leading catalytic activity to enable Ub Ub IKZ
Slide 6: High Catalytic Activity of CFT7455 Improves Anti-Cancer Activity in H929 MM Cells
High Catalytic Activity of CFT7455 Improves Anti-Cancer Activity in H929 MM Cells Binding Affinity (FP) Degradation Kinetics MM Cell Viability CFT7455; 1 hr Pomalidomide; 1 hr CFT7455 Pomalidomide CFT7455 Pomalidomide CFT7455; 2 hr Pomalidomide; 2 hr 1.0 Probe Fraction Bound % IKZF1 Remaining, H929
Slide 7: CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts
CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts CFT7455 Has Broad Antiproliferative Activity CFT7455 Promotes Durable Tumor Regression Vehicle (QDx21,PO) CFT7455 (10 μg/kg QDx21, PO) CFT7455 Pomalidomide Pomalidomide (3000 μg/kg QDx21, PO) CFT7455 (30 μg/kg QDx21, PO) CFT7455 (3 μg
Slide 8: CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts
CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts CFT7455 Has Broad Antiproliferative Activity CFT7455 Promotes Durable Tumor Regression Vehicle (QDx21, PO) CFT7455 Pomalidomide Pomalidomide (3000 μg/kg QDx21, PO) CFT7455 (100 μg/kg QDx21, PO) KMS-26 2500 QD Dosing Dosing Holiday RPM
Slide 9: Durable CFT7455 Single-Agent Activity in a Systemic MM Tumor Model
Durable CFT7455 Single-Agent Activity in a Systemic MM Tumor Model Lower Disease Burden in the MM.1S Model Early and Stable Regression of Disease QD Dosing Dosing Holiday 500 Vehicle (QDx21, PO) MM.1S-Luc Systemic BLI (photons/x106) 450 CFT7455 (300 μg/kg QDx21) Day 29 Day 33 Day 36 Day 40 Day 43 40
Slide 10: Depth and Duration of IKZF3 Degradation Associated with CFT7455 Efficacy
Depth and Duration of IKZF3 Degradation Associated with CFT7455 Efficacy Dose Dependent Efficacy Dose-Dependent IKZF3 Degradation Loss of IRF-4 via IKZF1/3 Degradation 100 CFT7455 (3 μg/kg, QD) 150 IKZF3 %Change RPMI-8226 Tumor Volume (Day21/Day0) % Analyte in Treated Tumor vs Vehicle 1400 % IKZF3 i
Slide 11: CFT7455 is Efficacious in MM Models Resistant or Insensitive to IMiDs
CFT7455 is Efficacious in MM Models Resistant or Insensitive to IMiDs Reduction in CRBN Expression CFT7455 Retains Activity in CFT7455 Promotes Regression in with Chronic IMiD Dosing Len- & Pom-Resistant MM Cells Tumors Insensitive to Pom m Po ta l à n 3000 Vehicle (QDx35, PO) C n n re LT Le Le Pa C
Slide 12: Expected Efficacy and Survival Outcomes When CFT7455 is Combined With Dexamethasone
Expected Efficacy and Survival Outcomes When CFT7455 is Combined With Dexamethasone CFT7455 Yields Robust Efficacy as Monotherapy Significant Improvement in Survival with CFT7455 + and in Combination with Dexamethasone Dexamethasone Combination Vehicle (QD, PO) Dex + CFT7455 (10µg/kg) 3000 Vehicle (
Slide 13: Summary
Summary § In vitro data with CFT7455 demonstrated: • High CRBN binding affinity (Kd = 0.9 nM) • Rapid, deep degradation of IKZF1/3 that is associated with apoptosis • Broad, potent antiproliferative activity in a panel of MM cell lines § In vivo MM models treated with CFT7455 demonstrated: • Regress