Cogent Biosciences, Inc. · NASDAQ:COGT
Cogent Biosciences — Unum Therapeutics — Investor Presentation (October 2020)
22 slides from Cogent Biosciences's investor presentation, Oct 5, 2020
Slide 1: Precision therapies for genetically defined diseases: Corporate Presentation October 2020
Precision therapies for genetically defined diseases Corporate Presentation October 2020 Exhibit 99.2
Slide 2: Forward-Looking Statements and Risk Factors
Forward-Looking Statements and Risk Factors This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materiall
Slide 3: Building a Rational Precision Therapy Company
Building a Rational Precision Therapy Company PLX9486, a potential best-in-class KIT D816V inhibitor, is a foundational program with promising clinical efficacy and safety in gastrointestinal stromal tumors (GIST) Accelerated timeline to proof-of-concept serum tryptase data in advanced systemic mast
Slide 4: Lead Program PLX9486 is a Highly Selective and Potent KIT Mutant Inhibitor
Lead Program PLX9486 is a Highly Selective and Potent KIT Mutant Inhibitor with a Potentially Best-in-Class Clinical Profile 11 months PFS shown in 18 heavily treatment-experienced GIST patients treated with PLX9486 in combination with sunitinib Single agent & combination activity and safety data in
Slide 5: By Design, PLX9486 has Potency and Selectivity to KIT D816V
By Design, PLX9486 has Potency and Selectivity to KIT D816V PLX9486 is a Type I Inhibitor designed to selectively bind the active conformation of mutant KIT Comparable potency relative to avapritinib with potential selectivity advantages Limited blood-brain-barrier penetration and no CNS toxicities
Slide 6: PLX9486 Can Rapidly Move Into 3 Mid-to-Late Stage Clinical Trials
Cogent’s Lead Program PLX9486 Has Phase 2 Data and Can Rapidly Move Into 3 Mid-to-Late Stage Clinical Trials Phase 3 start in GIST in combination with sunitinib (2H’2021) Phase 2 start as single agent in Indolent Systemic Mastocytosis (2H’2021) Phase 2 start as single agent in Advanced Systemic Mast
Slide 7: PLX9486 Future Clinical Programs: ASM and ISM
PLX9486 FUTURE CLINICAL PROGRAMS Advanced Systemic Mastocytosis (ASM) Indolent Systemic Mastocytosis (ISM)
Slide 8: Both Advanced SM and Indolent SM Are Primarily Driven by D816V Mutations
Both Advanced SM and Indolent SM Are Primarily Driven by D816V Mutations The most common KIT mutation in patients with systemic mastocytosis, aspartate to valine at residue 816 (D816V), lies within the activation loop domain and causes a conformational change in the enzymatic pocket of the receptor
Slide 9: Unmet Need in ASM and ISM
Advanced Systemic Mastocytosis Median survival of approximately ≤ 3.5 years FDA approved drug, Rydapt (Midostaurin), broad spectrum TKI, challenging tolerability Indolent and Smoldering Mastocytosis Poor quality of life No approved therapies: current treatments include H1 and H2 anti-histamines, mas
Slide 10: Encouraging Tolerability Profile as Single Agent
Preferred Term Total (n=24) Any Grade CTCAE >3 Subjects reporting ≥1 AE 24 (100) 14 (58.3) Fatigue 12 (50.0) 2 (8.3) AST Increased 11 (45.8) 0 Diarrhea 10 (41.7) 0 Nausea 10 (41.7) 2 (8.3) ALT increased 8 (33.3) 0 Vomiting 8 (33.3) 3 (12.5) Anemia 7 (29.2) 3 (12.5) Blood ALP increased 7 (29.2) 0 Blo
Slide 11: Preliminary Plans: ASM and ISM Registration Clinical Program Design
Preliminary Plans: ASM and ISM Registration Clinical Program Design Global Advanced Systemic Mastocytosis (ASM) Program [Subject to Regulatory Feedback] Global Indolent Systemic Mastocytosis (ISM) Program [Subject to Regulatory Feedback] PLX9486 Dose Finding Arms Single Arm Pivotal Study Phase 2a Do
Slide 12: PLX9486 Program: GIST
PLX9486 Program: GIST
Slide 13: PLX9486 and Sunitinib Combination Tackle GIST Heterogeneity
PLX9486 and Sunitinib Combination Tackle GIST Heterogeneity by Targeting Exon 13 and Exon 17 Simultaneously KIT Primary Mutations KIT Secondary Mutations Exon 8 Exon 9 Exon 11 Exon 13 Exon 14 Exon 17 Exon 18 Imatinib 1st Line Sunitinib 2nd Line Regorafenib 3rd Line PLX9486 PLX9486 + Sunitinib EX8 EX
Slide 14: Mutations in Exon 13 and Exon 17 are Key Drivers of Resistance
Mutations in Exon 13 and Exon 17 are Key Drivers of Resistance Imatinib Primary mutations: Exon 9 / Exon 11 Sunitinib Regorafenib Ripretinib ORR ~60% PFS ~19 months ORR ~7% PFS ~6 months ORR ~5% PFS ~4.8 months ORR ~9% PFS ~6.3 months 1L 2L 3L 4L Avapritinib approved for PDGFRα Exon 18 mutations (~
Slide 15: Dual-conformation KIT Inhibition Drives Tumor Regression in GIST mouse models
Dual-conformation KIT Inhibition Drives Tumor Regression in Heterogeneous GIST mouse models Ex11 (W557_K558del), Ex17 (N822K) Ex13 (K642E), Ex17 (D823Y)
Slide 16: PLX9486 Has Completed a Phase 1b/2a Trial in GIST with Encouraging Results
PLX9486 Has Completed a Phase 1b/2a Trial in GIST with Encouraging Results Phase 1b: Advanced Solid Tumors, Including GIST PLX9486 Single Agent Dose Escalation (n=24) Study Objectives Safety and PK Single agent MTD/RP2D Efficacy including ORR (RECIST 1.1), DOR and PFS Phase 2a: Treatment Refractory
Slide 17: PLX9486 Has Completed a P1b/2a Trial in GIST with Encouraging Results
PLX9486 Has Completed a P1b/2a Trial in GIST with Encouraging Results 0.00 0.25 0.50 0.75 1.00 0 4 8 12 16 20 24 28 Progression Free Survival (months) PFS probability (GIST Patients) Strata PLX9486 +Sunitinib 18 13 11 7 6 3 1 0 PLX9486 +Sunitinib Number at risk PLX9486 + Sunitinib Has Shown Median P
Slide 18: Encouraging Tolerability of PLX9486 in Combination With Sunitinib
Encouraging Tolerability of PLX9486 in Combination With Sunitinib Gives Us Confidence to Move Forward Into a Pivotal Study Select sunitinib single agent AEs (GIST) Diarrhea — 40% Anorexia — 33% Skin discoloration — 30% Mucositis/stomatitis — 29% Preferred Term Total (n=17) Any Grade CTCAE ≥ 3 Subjec
Slide 19: Preliminary Plans: Sunitinib +/- PLX9486 Registrational Programs
Preliminary Plans: Sunitinib +/- PLX9486 Registrational Programs Phase 1b/2a data accepted for oral presentation at CTOS 2020 PLX9486 + sunitinib Phase III Refractory GIST (under consideration – seeking FDA feedback) Patient Population: Late line GIST Primary Endpoint: PFS Secondary Endpoints: ORR,
Slide 20: Anticipated Near-term Milestones
July 2020 Present detailed PLX9486 + sunitinib data at CTOS 2020 1H’21 start dose finding study in ASM December 2021 2H’21 start pivotal study in GIST Anticipated Near-term Milestones 2H’21 start dose finding study in ISM Serum tryptase data will provide rapid proof of concept for ASM & ISM programs
Slide 21: Financial Overview
Financial Overview Cogent’s current cash balance includes gross proceeds of a $104.4 million private placement in July 2020 and $8.1 million from the sale of the BOXR technology in August 2020. Based on current projections, current cash will fund Cogent's operations into 2023. Company Capitalization
Slide 22: Thank You
Thank You CogentBio.com Cogent Biosciences Inc. | 200 Cambridge Park Drive Suite 2500 | Cambridge, MA 02140 USA
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