C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (May 2021)
42 slides from C4 Therapeutics's investor presentation, May 26, 2021
Slide 1: Corporate Presentation May 2021
Corporate Presentation May 2021 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: Targeted Protein Degradation Has the Potential to Transform Treatment of Disease
z Oncology small molecule therapies generate significant revenue despite known limitations z Targeted Protein Degradation Has the Potential to Transform Treatment of Disease 3 Targeted Protein Degradation Has Potential to Drug the Remaining ~85% of the Human Proteome and Overcome Resistance to Exist
Slide 4: C4T is Well Positioned to Develop Targeted Protein Degradation Medicines
C4T is Well Positioned to Develop Targeted Protein Degradation Medicines to Transform Patient Care 4 Strong balance sheet with $346M in cash as of 3/31/21 TORPEDO platform has potential to efficiently design highly potent degrader medicines 4 programs expected in the clinic by end of 2022 14 additio
Slide 5: The Human Body Has A Natural Process to Destroy Unwanted Proteins
The Human Body Has A Natural Process to Destroy Unwanted Proteins 5 1 2 3 4
Slide 6: Focus on Overall Catalytic Degradation
Focus on Overall Catalytic Degradation Targeted Protein Degradation Leverages the Body’s Natural Process to Destroy Disease-Causing Proteins 6
Slide 7: Targeted Protein Degradation Offers Fundamental Advantages Over Protein Inhibition
Targeted Protein Degradation Offers Fundamental Advantages Over Protein Inhibition 7 Improved Potency Fast Response High Selectivity Expansive Target Landscape 1 2 3 4
Slide 8: TORPEDO Platform
TORPEDO (Target ORiented ProtEin Degrader Optimizer) Platform
Slide 9: Our TORPEDO Platform Has Potential to Efficiently Design Highly Potent Degrader Medicines
Our TORPEDO Platform Has Potential to Efficiently Design Highly Potent Targeted Protein Degrader Medicines Ability to Develop Both MonoDAC & BiDAC Degraders Focus on Catalytic Efficiency Ability to Design, Analyze & Predict Degrader Performance Investment in Cereblon as E3 Ligase Flexibility to addr
Slide 10: Enhanced Catalytic Activity Drives Efficacy
Enhanced Catalytic Activity Drives Efficacy Improved Catalytic Activity of Degrader A… …Drives Significant Improvement in Target Knockdown 10 Source: C4T data on file
Slide 11: TORPEDO Platform: Robust Drug Discovery Process
TORPEDO Platform: Robust Drug Discovery Process Enabling Higher Confidence in In Vivo Efficacy Rapid Delivery of Potent Drug Candidates Through Informed and Efficient Drug Discovery 11 Analyze Cellular degradation data fitted using an enzymology framework Key parameters describe intrinsic degradatio
Slide 12: TORPEDO is Based on a Deep Focus on Cereblon
TORPEDO is Based on a Deep Focus on Cereblon, Providing the Largest Target Selection Opportunity Programs Benefit from Desirable Properties of C4T’s Cereblon Binders 12 Cereblon E3 Ligase Investment in rich toolkit of intellectual property with more than 15 structurally distinct Cereblon binders Cer
Slide 13: 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 13
Slide 14: TORPEDO Platform Has Delivered a Robust Degrader Pipeline
TORPEDO Platform Has Delivered a Robust Degrader Pipeline; Four Clinical Programs Expected by End of 2022 Nine Additional Undisclosed Collaborator Programs in Discovery 14
Slide 15: Three Strategic Target Platform Collaborations Expand Platform Potential
Three Strategic Target Platform Collaborations Expand Platform Potential 15 4.5-year term beginning January 2019 Focus is on neurological conditions with up to 5 targets total 5-year term beginning March 2017 Focus is on treating diseases of aging, including cancer Signed March 2016 and continues un
Slide 16: IKZF1/3 CFT7455
IKZF1/3 CFT7455
Slide 17: IKZF1/3: Maximal Catalytic Activity Leads to Improved Efficacy
IKZF1/3: Maximal Catalytic Activity Leads to Improved Efficacy 17 Source: NIH SEER Database, Primary Literature Consensus Patient figures represent estimated U.S. annual incidence PTCL = peripheral T-cell lymphoma; MCL = mantle cell lymphoma Compelling Development Opportunity Potential for accelerat
Slide 18: CFT7455: Potent Small Molecule IKZF1/3 Degrader
CFT7455: Potent Small Molecule IKZF1/3 Degrader Optimized for Catalytic & Pharmacologic Properties 18 CFT7455 DDB1 E3 Ubiquitin Ligase Complex CRBN RBX1 E2 IKZF1, IKZF3 degradation Death of myeloma and lymphoma cells IKZF1 IKZF1 IKZF3 IKZF3 Ub CUL4 Goal: Develop an IKZF1/3 Monofunctional Degradation
Slide 19: CFT7455 Demonstrates Improved Efficacy Compared to Other IKZF1/3 Degraders
CFT7455 Demonstrates Improved Efficacy Compared to Both Approved and Most Advanced Development-stage IKZF1/3 Degraders CFT7455 In Vivo Efficacy – Complete Regression in MM Model CFT7455 In Vivo Efficacy Durable After End of Dosing Period 19 Source: C4T data on file QD Dosing NCI-H929 Tumor Volume (m
Slide 20: 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 20 Source: C4T data on file
Slide 21: CFT7455 Demonstrates Tumor Regression in Multiple Myeloma Xenograft
CFT7455 Demonstrates Tumor Regression in Multiple Myeloma Xenograft Insensitive to Pomalidomide Reduction in CRBN Expression with Chronic IMiD Dosing CFT7455 Retains Activity in Len- & Pom-Resistant MM Cells CFT7455 Promotes Regression in Tumors Insensitive to Pomalidomide 21 crossover Len, lenalido
Slide 22: CFT7455 Phase 1/2 Trial Design
CFT7455 Phase 1/2 Trial Design Offers Potential for Accelerated Approval Across Three Indications Trial Open for Enrollment, First Clinical Data Expected in 2022 22 Phase 1 Dose Escalation R/R Multiple Myeloma Monotherapy N =~30 Cohort B1: R/R Multiple Myeloma Monotherapy N =~15 Cohort C: Non-Hodgki
Slide 23: BRD9 CFT8634
BRD9 CFT8634
Slide 24: BRD9: Drugging the Undruggable with a Degrader Approach
BRD9: Drugging the Undruggable with a Degrader Approach 24 Source: NIH SEER Database, Primary Literature Consensus Compelling Development Opportunity Well defined path to registration in SS and metastatic population already under management at academic centers Precedent for approval with a single-ar
Slide 25: BRD9 Dependency in Synovial Sarcoma
BRD9 Dependency in Synovial Sarcoma 25 Specifically degrades BRD9 and spares BRD4 and BRD7, avoiding potential off-target toxicities Oncogenicity of BRD9 depends on sub-domains not addressed by traditional inhibitors Advantages of BRD9 degradation Mechanistic Rationale Leveraging a protein degrader
Slide 26: Robust Responses of CFT8634 Seen in Preclinical Synovial Sarcoma Models
Robust Responses of CFT8634 Seen in Preclinical Synovial Sarcoma Models Dose Response Activity Yamato Xenograft Model Dose Response Activity Patient Derived Xenograft Model 26 Source: C4T data on file
Slide 27: CFT8634 First-in-Human Protocol Concept Schema
CFT8634 First-in-Human Protocol Concept Schema IND Submission for CFT8634 Expected in 2H 2021 27 MTD = Maximum Tolerated Dose; RP2D = Recommended Phase 2 Dose
Slide 28: EGFR CFT8919
EGFR CFT8919
Slide 29: EGFR: Utilizing a Degrader Approach to Overcome Resistance
EGFR: Utilizing a Degrader Approach to Overcome Resistance to Approved EGFR Inhibitors and Address a Wider Range of Mutations 29 Source: https://www.nejm.org/doi/10.1056/NEJMoa1713137, NIH SEER Database, Primary Literature Consensus Compelling Development Opportunity Target Population: patients who
Slide 30: EGFR Activating Mutations Drive NSCLC Cancer Growth
EGFR Activating Mutations Drive NSCLC Cancer Growth 30 Normal Physiology Mutant EGFR Tumor Cells No signaling Downstream signaling Downstream signaling in absence of extracellular signal Cell Proliferation Cell Survival Growth Factors Signaling is activated in response to extracellular growth factor
Slide 31: CFT8919 May Overcome Resistance to Approved EGFR Inhibitors
CFT8919 May Overcome Resistance to Approved EGFR Inhibitors and Address a Wide Range of Acquired EGFR Resistance Mutations 31 IND Submission Expected mid-2022 with Potential Phase 1/2 Trial Initiation by YE 2022 CFT8919 Compelling Profile Orally bioavailable, selective, allosteric degrader of EGFR L
Slide 32: BRAF
BRAF
Slide 33: BRAF: Utilizing a Degrader Approach to Overcome Resistance Mutations
BRAF: Utilizing a Degrader Approach to Overcome Resistance Mutations 33 Source: NIH SEER Database, Primary Literature Consensus Compelling Development Opportunity Large patient population defined by failure of available BRAF inhibitors Target Population: V600E melanoma and/or NSCLC after failure of
Slide 34: Advantages of BRAF V600E Degradation
Advantages of BRAF V600E Degradation Specifically target mutant BRAF over wildtype BRAF Prevent mutant BRAF incorporation into RAF dimers Avoid paradoxical activation and associated failure of therapy due to resistance mechanisms dependent on BRAF inhibitor mediated paradoxical activation BRAF Degra
Slide 35: BRAF Degraders Show Superior Efficacy Compared to Approved BRAF Inhibitors
BRAF Degraders Show Superior Efficacy Compared to Approved BRAF Inhibitors C4T BRAF Degrader Shows More Durable Efficacy Than Encorafenib C4T BRAF Degrader Shows More Durable Efficacy Than Dabrafenib 35 IND Enabling Studies Planned for 2021 Tumor Volume (mm3) Days of Treatment BRAF program is partne
Slide 36: RET
RET
Slide 37: RET Degradation: Opportunity to Overcome Resistance Mutations
RET Degradation: Opportunity to Overcome Resistance Mutations 37 Sources: NIH SEER Database, https://pubmed.ncbi.nlm.nih.gov/29284153/, Primary Literature Consensus Compelling Development Opportunity Well defined registration path in existing, genetically defined patient population with no effective
Slide 38: Mechanistic Rationale: RET Degradation
Mechanistic Rationale RET Degradation May Have Improved Activity Compared to Best-In-Class RET Inhibitors 38 Advantages of RET Degradation RET degrader is active against key secondary mutations that cause resistance, including both the gatekeeper and solvent front mutations Against RET without secon
Slide 39: RET Degrader Has an Excellent Cell Growth Inhibition Profile
RET Degrader Has an Excellent Cell Growth Inhibition Profile In RET Fusions and Common Resistance Mutations Continue Lead Optimization Activities in 2021 39 KIF5B-RET Fusion Solvent Front Mutation Activating Mutation Drug Naïve, Driver Translocation/Mutation RET Inhibitor Acquired-Resistance Mutants
Slide 40: 2021 Milestones Support Progress Toward Four Clinical-Stage Programs
2021 Milestones Support Progress Toward Goal of Four Clinical-Stage Programs by Year-End 2022 40 Phase 1/2 Initiation IND Submission Lead Optimization IND Enabling Studies IND Enabling Studies Phase 1 Top-line Safety & Efficacy Proof of Mechanism Phase 1 Initiation IND Submission Phase 1 Initiation
Slide 41: C4T is Well Positioned to Develop Targeted Protein Degradation Medicines
C4T is Well Positioned to Develop Targeted Protein Degradation Medicines to Transform Patient Care 41 Strong balance sheet with $346M in cash as of 3/31/21 TORPEDO platform has potential to efficiently design highly potent degrader medicines 4 programs expected in the clinic by end of 2022 14 additi
Slide 42: Thank You
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