C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Undruggable Leaders Forum Europe 2021
23 slides from C4 Therapeutics's conference presentation, Apr 13, 2021
Slide 1: Undruggable Leaders Forum Europe
Undruggable Leaders Forum Europe Stewart Fisher April 13, 2021
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,” “believ e,”
Slide 3: Targeted Protein Degradation Has the Potential to Transform Treatment of Disease
Targeted Protein Degradation Has the Potential to Transform Treatment of Disease POST TREATMENT <15% $63B Of Human Proteome 2018 Global z Addressable by Small Before z 15 weeks 23 weeks z Revenue Molecule Inhibitors Adapt ed from W agle et al, J Clin Oncol, 2011 Substantial opportunity to dev elop C
Slide 4: The Human Body Has A Natural Process to Destroy Unwanted Proteins
The Human Body Has A Natural Process to Destroy Unwanted Proteins 1 2 3 4 © 2021 C4 Therapeutics, I nc. 4
Slide 5: Targeted Protein Degradation Leverages the Body's Natural Process to Destroy Disease-Causing Proteins
Targeted Protein Degradation Leverages the Body’s Natural Process to Destroy Disease-Causing Proteins Focus on Overall Catalytic Degradation © 2021 C4 Therapeutics, I nc. 5
Slide 6: Targeted Protein Degradation Offers Fundamental Advantages Over Protein Inhibition
Targeted Protein Degradation Offers Fundamental Advantages Over Protein Inhibition 1 Improved Potency 2 Fast Response 3 High Selectivity 4 Expansive Target Landscape © 2021 C4 Therapeutics, I nc. 6
Slide 7: TORPEDO Platform Offers Flexibility to Design MonoDAC and BiDAC Degraders
TORPEDO Platform Offers Flexibility to Design MonoDAC and BiDAC Degraders Flexibility to Address Different Targets with Tailored Approach © 2021 C4 Therapeutics, I nc. 7
Slide 8: TORPEDO Platform Has Delivered a Robust Degrader Pipeline
TORPEDO Platform Has Delivered a Robust Degrader Pipeline; Four Clinical Programs Expected by End of 2022 Target Indication(s) Discov ery Preclinical Clinical Ownership IKZF1/3 (CFT7455) Multiple Myeloma & Lymphoma Synov ial Sarcoma & SMARCB1 Deleted BRD9 (CFT8634) Tumors Drug-Resistant BRAF mutant
Slide 9: Three Strategic Target Platform Collaborations Expand Platform Potential
Three Strategic Target Platform Collaborations Expand Platform Potential Signed March 2016 5-year term 4.5-year term beginning and continues until beginning March 2017 January 2019 completion of six programs Focus is on treating Focus is on neurological diseases of aging, conditions with up to Focus
Slide 10: TORPEDO Platform: Robust Drug Discovery Process Enabling Higher Confidence in In Vivo Efficacy
TORPEDO Platform: Robust Drug Discovery Process Enabling Higher Confidence in In Vivo Efficacy Design Analyze Predict Computational method Cellular degradation data Universal modeling framework incorporates experimental fitted using an enzymology merges degradation activity data to identify top mode
Slide 11: Degraders Are Essential Catalytic Activators
Degraders Are Essential Catalytic Activators Fisher and Phillips, Curr Opin Chem Biol. 2018, 44, 47 © 2021 C4 Therapeutics, I nc. 11
Slide 12: Applying an Enzymology Framework Provides Quantitative Assessments of Degrader Activity
Applying an Enzymology Framework Provides Quantitative Assessments of Degrader Activity Vmax 120 % Protein Remaining 100 80 60 Kpc 40 KI 20 0 Emax ∝ Vmax: (kact)*[Ligase] – ksyn 1000 nM 3162.278 nM 100 nM 0.001 nM 0.003 nM 0.032 nM 0.316 nM 3.162 nM 316.228 nM 10 nM 1 nM 31.623 nM 0.01 nM 10000 nM 0
Slide 13: Proprietary PK/PD Models Founded on Degradation Enzymology Framework
Proprietary PK/PD Models Founded on Degradation Enzymology Framework Enzymology Framework 120 Prediction % Protein Remaining 100 80 60 40 20 Time DMPK Properties 0 0.001… 1000… 1000… 0.01… 100 nM 0.1 nM 10 nM 1 nM C4T Proprietary PK/PD Exposure Time Dependence Models 120 100 Remaining % Protein 80 6
Slide 14: PK/PD Models Provide Robust Predictions Across Diverse Targets and Degrader Classes
PK/PD Models Provide Robust Predictions Across Diverse Targets and Degrader Classes 100 1.5 100 5000 Plasma PK (ng/ml) Plasma PK (ng/ml) 4000 75 75 [BRD9] (%) [IKZFZ1] % 1.0 3000 50 50 2000 0.5 25 25 1000 0 0.0 0 0 0 6 12 18 24 0 6 12 18 24 30 36 Time (hr) Time (hr) CFT7455, 1 mg/kg dose po, KI-KJ A
Slide 15: PK/PD Models Provide Robust Predictions Across Diverse Targets and Degrader Classes
PK/PD Models Provide Robust Predictions Across Diverse Targets and Degrader Classes 100 1.5 100 5000 Predicted PD Predicted PD Plasma PK (ng/ml) Plasma PK (ng/ml) 4000 75 75 Plasma PK Plasma PK [BRD9] (%) [IKZFZ1] % 1.0 3000 50 50 2000 0.5 25 25 1000 0 0.0 0 0 0 6 12 18 24 0 6 12 18 24 30 36 Time (h
Slide 16: PK/PD Models Provide Robust Predictions Across Diverse Targets and Degrader Classes
PK/PD Models Provide Robust Predictions Across Diverse Targets and Degrader Classes 100 1.5 100 5000 Predicted PD Predicted PD Plasma PK (ng/ml) Plasma PK (ng/ml) Observed PD Observed PD 4000 75 75 Plasma PK Plasma PK [BRD9] (%) [IKZFZ1] % 1.0 3000 50 50 2000 0.5 25 25 1000 0 0.0 0 0 0 6 12 18 24 0
Slide 17: 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 18: CFT7455: Potent Small Molecule IKZF1/3 Degrader Optimized for Catalytic and Pharmacologic Properties
CFT7455: Potent Small Molecule IKZF1/3 Degrader Optimized for Catalytic and Pharmacologic Properties Goal: Develop an IKZF1/3 Monofunctional Ub Degradation Activating Compound Ub Ub (MonoDAC) with these properties: Ub Ub Ub IKZF3 IKZF3 Ub Ub Ub • Class-leading catalytic activity to enable Ub Ub Ub p
Slide 19: 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; 2 hr Pomalidomide; 2 hr CFT7455 Pomalidomide 1.0 Probe Fraction Bound % IKZF1 Remaining, H929
Slide 20: CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts
CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts CFT7455 Has Broad Anti-proliferative 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 μ
Slide 21: CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts
CFT7455 Demonstrates High Potency in MM Cell Lines and Xenografts CFT7455 Has Broad Anti-proliferative 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 *
Slide 22: 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 CFT7455; IMiD resistant Pom; IMiD resistant 3000 Vehicle (QDx
Slide 23: Thank You
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