C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (January 2021)
36 slides from C4 Therapeutics's investor presentation, Jan 12, 2021
Slide 1: Corporate Presentation January 2021
Corporate Presentation January 2021 Exhibit 99.1
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 runway to end of 2023* TORPEDO platform has potential to efficiently design highly potent degrader medicines 4 programs expected in the clinic by end of 2022 14 additional p
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 MonoDACs & BiDACS Focus on Catalytic Efficiency Ability to Design, Analyze & Predict Degrader Performance Investment in Cereblon as E3 Ligase Flexibility to address diff
Slide 10: TORPEDO Platform Offers Flexibility to Design MonoDACs and BiDACs
TORPEDO Platform Offers Flexibility to Design MonoDACs and BiDACs Flexibility to Address Different Targets with Tailored Approach 10
Slide 11: Enhanced Catalytic Activity Drives Efficacy
Enhanced Catalytic Activity Drives Efficacy Improved Catalytic Activity of Degrader A… …Drives Significant Improvement in Target Knockdown 11 Source: C4T data on file
Slide 12: 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 12 Analyze Cellular degradation data fitted using an enzymology framework Key parameters describe intrinsic degradatio
Slide 13: 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 13 Cereblon E3 Ligase Investment in rich toolkit of intellectual property with 14 structurally distinct Cereblon binders Cereblon is e
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 9 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 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 18 Source: C4T data on file QD Dosing NCI-H929 Tumor Volume (m
Slide 19: CFT7455 Demonstrates Tumor Regression in Multiple Myeloma Xenograft
CFT7455 Demonstrates Tumor Regression in Multiple Myeloma Xenograft Insensitive to Pomalidomide CFT7455 Active in RPMI-8226, Relative to Pomalidomide CFT7455 Active in RPMI-8226 After Tumor Progression on Pomalidomide Treatment 19 Source: C4T data on file D18
Slide 20: CFT7455 Phase 1/2 Trial Design Offers Potential for Accelerated Approval
CFT7455 Phase 1/2 Trial Design Offers Potential for Accelerated Approval Across Three Indications IND Submitted December 2020; Trial Expected to Initiate in 1H 2021 20 Phase 1 Dose Escalation R/R Multiple Myeloma Monotherapy N =~30 Cohort B1: R/R Multiple Myeloma Monotherapy N =~12 Cohort C: Non-Hod
Slide 21: BRD9 CFT8634
BRD9 CFT8634
Slide 22: BRD9: Drugging the Undruggable with a Degrader Approach
BRD9: Drugging the Undruggable with a Degrader Approach 22 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 23: BRD9 Dependency in Synovial Sarcoma
BRD9 Dependency in Synovial Sarcoma 23 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 24: 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 24 IND Submission for CFT8634 Expected in 2H 2021 Source: C4T data on file
Slide 25: BRAF
BRAF
Slide 26: BRAF: Utilizing a Degrader Approach to Overcome Resistance Mutations
BRAF: Utilizing a Degrader Approach to Overcome Resistance Mutations 26 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 27: 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 28: 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 28 IND Enabling Studies Planned for 2021 Tumor Volume (mm3) Days of Treatment BRAF program is partne
Slide 29: RET
RET
Slide 30: RET Degradation: Opportunity to Overcome Resistance Mutations
RET Degradation: Opportunity to Overcome Resistance Mutations 30 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 31: RET Degradation May Have Improved Activity Compared to RET Inhibitors
Mechanistic Rationale RET Degradation May Have Improved Activity Compared to Best-In-Class RET Inhibitors 31 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 32: 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 IND Enabling Studies Planned for 2021 32 KIF5B-RET Fusion Solvent Front Mutation Activating Mutation Drug Naïve, Driver Translocation/Mutation RET Inhibitor Acquired-Resistance Mutants Gatekee
Slide 33: Lead Programs Offer Compelling Opportunities to Address Unmet Need
Lead Programs Offer Compelling Opportunities to Address Unmet Need in Multiple Patient Populations 33 Sources: National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Database MM survival: https://seer.cancer.gov/archive/csr/1975_2015/browse_csr.php?sectionSEL=18&pageSEL=sect_
Slide 34: 2021 Milestones Support Progress Toward Four Clinical-Stage Programs
2021 Milestones Support Progress Toward Goal of Four Clinical-Stage Programs by Year-End 2022 34 IKZF1/3 (CFT7455) BRD9 (CFT8634) BRAF RET Phase 1/2 Initiation IND Submission Phase 1 Top-line Safety & Efficacy Proof of Mechanism Phase 1 Initiation Phase 1 Initiation Phase 1 Initiation IND Enabling S
Slide 35: C4T is Well Positioned to Develop Targeted Protein Degradation Medicines
C4T is Well Positioned to Develop Targeted Protein Degradation Medicines to Transform Patient Care 35 Strong balance sheet with runway to end of 2023* TORPEDO platform has potential to efficiently design highly potent degrader medicines 4 programs expected in clinic by end of 2022 14 additional prog
Slide 36: Thank You
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