C4 Therapeutics, Inc. · NASDAQ:CCCC
C4 Therapeutics — Investor Presentation (November 2020)
23 slides from C4 Therapeutics's investor presentation, Nov 19, 2020
Slide 1: Corporate Presentation November 2020
Corporate Presentation November 2020 © 2020 C4 Therapeutics, Inc.
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,” “believe,”
Slide 3: C4 Therapeutics' Vision
C4 Therapeutics’ Vision © 2020 C4 THERAPEUTICS, INC. Harnessing the body’s natural cellular quality control mechanisms to target and destroy disease-causing proteins Perfecting a novel discovery and validation platform to rapidly and cost-effectively bring transformative medicines to patients Pionee
Slide 4: Lead product candidate CFT7455 exhibited complete regression in preclinical myeloma model
Lead product candidate (CFT7455) exhibited complete regression of tumor in preclinical multiple myeloma mouse model Potency and speed of lead molecule results in cell death at very low doses IND filing for lead program expected by end of 2020 Enables quick and efficient advancement of programs from
Slide 5: Degradation Leverages Natural Cellular Machinery to Target Diseases
Degradation Leverages Natural Cellular Machinery to Target Diseases Protein degraders harness the body's natural protein degradation machinery to target and destroy selected disease-causing proteins 3. “The Destroyer” – The Proteasome Labelled proteins are destroyed by the cell’s “recycling plant,”
Slide 6: Targeted Protein Degradation: An Integrated Approach for a Novel Modality
Targeted Protein Degradation: An Integrated Approach for a Novel Modality C4 Therapeutics maintains a broad focus on overall catalytic degradation rather than a specific part of the degradation cycle, providing opportunities to drug the undruggable Degraders control protein levels by leveraging the
Slide 7: Protein Degradation is Fundamentally Different than Protein Inhibition
Protein Degradation is Fundamentally Different than Protein Inhibition Protein degraders allow for a more potent and durable pharmacological response at lower overall exposure levels than inhibitors Improved Potency Degraders are recycled and can engage multiple target proteins, resulting in improve
Slide 8: TORPEDO Platform: Robust Drug Discovery and Higher Confidence in Clinical Outcomes
TORPEDO Platform: Robust Drug Discovery and Higher Confidence in Clinical Outcomes Design Analyze Predict Computational method incorporates experimental data to identify top models Atomic-level degrader design utilized to improve selectivity and potency Cellular degradation data fitted using an enzy
Slide 9: PK/PD Models Provide Robust Predictions Across the Lead Programs
PK/PD Models Provide Robust Predictions Across the Lead Programs CFT-12521, 30 mg/kg dose iv, KIF-5B:RET Fusion model CFT7455, 1 mg/kg dose po, KI-KJ ALCL model CFT7503, 10 mg/kg dose po, Yamato Synovial Sarcoma model CFT-17977, 30 mg/kg dose po, A375 model © 2020 C4 THERAPEUTICS, INC. PK = pharmaco
Slide 10: Cereblon E3 Ligase: Deep Focus on Cereblon
Cereblon E3 Ligase TORPEDO is Based on a Deep Focus on Cereblon, Rather than the Entire Set of Available Ligases Our TORPEDO platform has a diverse and rich toolkit of novel, structurally distinct Cereblon binders – small molecules that are suitable for clinical targeted protein degradation Invested
Slide 11: Robust Pipeline With Four Clinical Programs Anticipated By End of 2022
Robust Pipeline With Four Clinical Programs Anticipated By End of 2022 Target selection emphasizes target validated, mitigated tolerability risks and opportunity for accelerated approval © 2020 C4 THERAPEUTICS, INC.
Slide 12: CFT7455: Clear Unmet Need Combined with Compelling Development Opportunity
CFT7455: Clear Unmet Need Combined with Compelling Development Opportunity IKZF1/3 Mutations Strong Mechanistic Rationale Multiple myeloma (MM) and Non-Hodgkin lymphomas (NHLs) are dependent on IKZF1/3 Clear Unmet Need IKZF1/3 degraders are the backbone of MM treatment Relapsed / refractory MM remai
Slide 13: CFT7455 Is a Potent IKZF1/3 MonoDAC, as Demonstrated in Preclinical Studies
CFT7455 Is a Potent IKZF1/3 MonoDAC, as Demonstrated in Preclinical Studies CFT7455 Viability Profile CFT7455 Degradation Potency Catalytic activity results in potent degradation and activity © 2020 C4 THERAPEUTICS, INC.
Slide 14: CFT7455: Potent Efficacy, In Vivo, with Complete Regressions as Single Agent in MM
CFT7455: Potent Efficacy, In Vivo, with Complete Regressions as Single Agent in MM Potency and speed of CFT7455 translates into better cell killing with lower doses achieving the same endpoint Improvement in oral bioavailability (i.e., half dose provides same exposure) Pharmacologic properties trans
Slide 15: Multiple Myeloma Xenograft Insensitive to Pomalidomide Responds to CFT7455
Multiple Myeloma Xenograft Insensitive to Pomalidomide Responds to CFT7455 CFT7455 is active in RPMI-8226, relative to pomalidomide CFT7455 is active in RPMI-8226 after the tumor has progressed on pomalidomide treatment RPMI-8226 Tumor Volume (mm3) Days of Treatment Pomalidomide, 3,000 µg/kg Vehicle
Slide 16: CFT7455 Phase 1 Trial Design
(1) 28-day cycle / dose limiting toxicity (DLT) window (2) Combination therapy cohorts will open once each CFT7455 dose level has been cleared for safety Phase 1 Dose Escalation R/R Multiple Myeloma Monotherapy N =~30 Cohort B1: Monotherapy R/R Multiple Myeloma N =~12 Cohort C: Monotherapy Non-Hodgk
Slide 17: BRD9 Degradation: Clear Clinical Opportunity
BAF subunit mutations are present in >20% of cancers BRD9 Degradation: Clear Clinical Opportunity BRD9/BAF Complex Alterations Summary Strong Mechanistic Rationale Bromodomain containing protein 9 (BRD9) is a BAF complex component and is non-essential in normal cells Synovial sarcoma is dependent on
Slide 18: Robust, Dose-Dependent Response in Yamato Xenograft Model with CFT8634
Robust, Dose-Dependent Response in Yamato Xenograft Model Achieved with CFT8634* at Tolerable Dose Levels * CFT8634 is the purified enantiomer of CFT7503 (a racemic mixture) and is the drug candidate moving into clinical development Tolerated at all doses Dose responsive activity © 2020 C4 THERAPEUT
Slide 19: CFT8634 First-in-Human Protocol Concept Schema
Phase 1 Dose Escalation Phase 2 Expansion CFT8634 MTD/RP2D Cohort B: CFT8634 Monotherapy Synovial Sarcoma N = 20 Cohort A: CFT8634 Monotherapy Synovial Sarcoma and SMARCB1 deleted solid tumors N =~18 Cohort C: CFT8634 Monotherapy SMARCB1 deleted tumors N = TBD CFT8634 First-in-Human Protocol Concept
Slide 20: BRAF Degrader to Overcome Liability of Approved BRAF Inhibitors
BRAF Degrader to Overcome Liability of Approved BRAF Inhibitors Specifically target mutant BRAF over wildtype Prevents mutant BRAF incorporation into RAF dimers, avoiding paradoxical RAF activation and activation-associated toxicity Overcome resistance to current standard of care Effect deeper and m
Slide 21: RET Degradation May Significantly Improve Activity of Best-In-Class RET Inhibitors
RET Degradation May Significantly Improve Activity of Best-In-Class RET Inhibitors Overcome resistance to standard of care RET inhibitors Potential to effect deeper and more durable response due to advantages of degraders Potential advantages of RET Degradation Mechanistic Rationale C4T RET degrader
Slide 22: Potential for Multiple Near-term Milestones Across Lead Programs
Potential for Multiple Near-term Milestones Across Lead Programs Pro-Forma cash balance of $390M as of 9/30/20 provides runway into H2 2023 Note: Other undisclosed targets have potential milestones during this time frame; cash runway guidance as of 11/12/2020 IKZF1/3 (CFT7455) BRD9 (CFT8634) BRAF RE
Slide 23: C4 Therapeutics
@@@ C4 Therapeutics ses m J I 7 $i camerapeutics
C4 Therapeutics — Investor Presentation (November 2020) on 6ix