Cogent Biosciences, Inc. · NASDAQ:COGT
Cogent Biosciences — Investor Presentation (November 2020)
31 slides from Cogent Biosciences's investor presentation, Nov 30, 2020
Slide 1: Developing Precision Therapies for Genetically Defined Diseases
Exhibit 99.1 Developing Precision therapies for genetically defined diseases Corporate Presentation Q4 2020Exhibit 99.1 Developing Precision therapies for genetically defined diseases Corporate Presentation Q4 2020
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: Cogent Biosciences: Emerging Leader in Precision Medicines for Genetically Defined Diseases
Cogent Biosciences: Emerging Leader in Precision Medicines for Genetically Defined Diseases PLX9486, a potential best-in-class KIT exon 17 inhibitor, has demonstrated promising clinical efficacy and safety results in a Phase 1/2 clinical trial in patients with gastrointestinal stromal tumors (GIST),
Slide 4: PLX9486: Next-Generation KIT exon 17 Inhibitor
PLX9486: Next‐Generation KIT exon 17 InhibitorPLX9486: Next‐Generation KIT exon 17 Inhibitor
Slide 5: PLX9486 is a Highly Selective and Potent KIT Mutant Inhibitor
PLX9486 is a Highly Selective and Potent KIT Mutant Inhibitor with Potential to Demonstrate Best-in-Class Clinical Profile PLX9486 Encouraging Clinical Activity 12 months mPFS demonstrated with combination of • Specifically targets KIT exon 17 D816V PLX9486 + sunitinib in heavily pre-treated GIST pa
Slide 6: PLX9486 Designed as Potent and Selective KIT exon 17 D816V Inhibitor
PLX9486 Designed as Potent and Selective KIT exon 17 D816V Inhibitor PLX9486 is a Type I Inhibitor designed to selectively bind the active conformation of mutant KIT • Comparable potency observed relative to avapritinib with potential selectivity advantages • Limited blood-brain-barrier penetration
Slide 7: Dual-conformation KIT Inhibition Drives Tumor Regression in Heterogeneous GIST Mouse Models
Dual-conformation KIT Inhibition Drives Tumor Regression in Heterogeneous GIST mouse models Ex11 (W557_K558del), Ex17 (N822K) Ex13 (K642E), Ex17 (D823Y) 7Dual-conformation KIT Inhibition Drives Tumor Regression in Heterogeneous GIST mouse models Ex11 (W557_K558del), Ex17 (N822K) Ex13 (K642E), Ex17 (
Slide 8: Systemic Mastocytosis & KIT exon 17 D816V mutations
Systemic Mastocytosis& KIT exon 17 D816V mutationsSystemic Mastocytosis& KIT exon 17 D816V mutations
Slide 9: Significant Unmet Need Remains for Systemic Mastocytosis Patients
Significant Unmet Need Remains for Neurological Headache, brain fog, Systemic Mastocytosis Patients cognitive dysfunction, anxiety, depression Systemic Mastocytosis Systemic • Disease driven by over-accumulation of mast Anaphylaxis cells across various internal organs in the body Cutaneous (skin) Ad
Slide 10: Systemic Mastocytosis: Primarily Driven by KIT exon 17 D816V Mutations
Systemic Mastocytosis (SM): Primarily Driven by KIT exon 17 D816V Mutations KIT exon 17 D816V mutation is 1 detected in >90% of SM patients o Occurs within the activation loop domain and causes a conformational change in the enzymatic pocket of the receptor o This conformational change results in li
Slide 11: Large, Yet Not Well Understood Population of SM Patients
Large, Yet Not Well Understood Population of SM Patients Systemic Mastocytosis: Estimated prevalence in the U.S. is 20,000–30,000 patients ISM Significant unmet medical need Comprises upwards of for clinically active, well tolerated 1 90% of all cases of SM treatment options for this patient populat
Slide 12: PLX9486 Positioned to Move Rapidly Into ASM and ISM Clinical Studies
PLX9486 Positioned to Move Rapidly Into ASM and ISM Clinical Studies Pre-clinical KIT selectivity and potency along with clinical experience – safety + target engagement Phase 2 start as single agent in Phase 2 start as single agent in Advanced Indolent Systemic Mastocytosis (ASM) Systemic Mastocyto
Slide 13: GIST & KIT exon 13/17 mutations
GIST & KIT exon 13/17 mutationsGIST & KIT exon 13/17 mutations
Slide 14: Significant Unmet Need Remains for GIST Patients
Significant Unmet Need Remains for GIST Patients Gastrointestinal Stromal Tumor (GIST) • Between 4,000 to 6,000 GIST cases diagnosed each year 1 in the United States • Tumors can start anywhere in the GI tract, but they occur most often in the stomach (about 60%) or the small 4 Symptoms 2 intestine
Slide 15: Mutations in KIT exon 13 and KIT exon 17 are Key Drivers of Resistance
Mutations in KIT exon 13 and KIT exon 17 are Key Drivers of Resistance ORR ORR ORR ORR ~60% ~7% PFS ~5% PFS ~9% 1L 2L 3L 4L PFS ~19 ~6 ~4.8 PFS ~6.3 months months months months Imatinib Sunitinib Regorafenib Ripretinib 60% of GIST patients Resistance mutations 2,000-3,500 imatinib- develop resistanc
Slide 16: GIST: Imatinib-resistance linked to KIT exon 13 and KIT exon 17 mutations
Gastrointestinal Stromal Tumor (GIST): Imatinib-resistance linked to KIT exon 13 and KIT exon 17 mutations Imatinib-resistant patients most commonly exhibited secondary KIT 1 exon 13 and/or KIT exon 17 mutations • 15-26 different mutations were found in KIT exons 17/18 in both tumor and liquid biops
Slide 17: Phase 1/2 Study of PLX9486 + sunitinib in Heavily Pre-Treated GIST Patients
Phase 1/2 Study of PLX9486 + sunitinib in Heavily Pre‐Treated GIST PatientsPhase 1/2 Study of PLX9486 + sunitinib in Heavily Pre‐Treated GIST Patients
Slide 18: Study PLX121-01: Phase 1/2 Study of PLX9486 + Sunitinib
Study PLX121-01: Phase 1/2 Study of PLX9486 + Sunitinib Part 2e: PLX9486 + Sunitinib Eligibility Dose Level 3 • Relapsed/Refractory GIST Dose Level 1 (N=3) Dose Level 2 (N=5) (N=10) • Previous imatinib treatment PLX9486: 500mg PLX9486: 1000mg PLX9486: 1000mg Sunitinib: 25 mg Sunitinib: 25 mg Sunitin
Slide 19: Demographics and Prior Therapy: Heavily Pretreated GIST Patients
Demographics and Prior Therapy: Heavily Pretreated GIST Patients Total Dose Level 1 Dose Level 2 Dose Level 3 (N=18) (n=3) (n=5) (n=10) Age, Median (range) 62 (44 – 78) 57 (46 – 68) 55 (44 – 78) 62 (53 – 65) Sex, male, n (%) 9 (50) 0 3 (60) 6 (60) Prior Regimens, Median (range) 3 (1 – 6) 2 (1 – 2) 3
Slide 20: Combination Safety Results Generally Similar to Single-Agent Sunitinib
Combination Safety Results Generally Similar to Single-Agent sunitinib observed in a separate, third-party clinical study Total Dose Level 1 Dose Level 2 Dose Level 3 (n=18) (n=3) (n=5) (n=10) Preferred term, n Any Gr Gr ≥ 3 Any Gr Gr ≥ 3Any Gr Gr ≥ 3 Any Gr Gr ≥ 3 Any AE 18 16 3 2 5 5 10 9 Diarrhea
Slide 21: PLX9486 + Sunitinib: 12-Month mPFS in Heavily Pretreated GIST Patients
PLX9486 + Sunitinib: 12-Month mPFS in Heavily Pretreated GIST Patients • Estimated 12-month mPFS in PLX9486- naïve patients receiving combination • mPFS improvement observed for patients receiving higher dose of single-agent PLX9486 • In subset of patients with ≥ 2 prior therapies (n=11), estimated
Slide 22: PLX9486 + Sunitinib: Clinical Benefit Observed in Majority of Patients
PLX9486 + Sunitinib: Clinical Benefit Observed in Majority of Patients ORR = 20% (1 CR, 2PR) Best Overall Response: CBR = 80% • Excludes combination therapy patients who had previously received PLX9486 ORR: Overall Response Rate (CR+PR) db snapshot: 10July2020 CBR: Clinical benefit rate (CR+PR+SD at
Slide 23: Durable Responses in Patients Treated with PLX9486 + Sunitinib
Durable Responses in Patients Treated with PLX9486 + Sunitinib • The median duration of PLX9486 + sunitinib treatment was 10 months (range: 1 to 27 months) • Four patients remain on therapy, including 1 CR and 2 PR • Durable response >18 months in patients achieving confirmed response 23 * Patient p
Slide 24: Patient Achieved Complete Response Following Three Prior Therapies
Patient Achieved Complete Response Following Three Prior Therapies When Treated at RP2D of PLX9486 + Sunitinib • 65 yr old female previously refractory to imatinib (PD) and sunitinib (PD); intolerant to regorafenib • Metabolically active right abdominal and subcutaneous masses • Mutation status (ctD
Slide 25: PLX9486 Monotherapy Exploratory Analysis: Changes in ctDNA
PLX9486 Monotherapy Exploratory Analysis: Changes in ctDNA Support Specificity of Kinase Inhibition Patient 1 Patient 2 Months on Treatment Black line: represents average of Sum of Product Diameters 25 Individual lesions represented in colorPLX9486 Monotherapy Exploratory Analysis: Changes in ctDNA
Slide 26: Cogent Biosciences: Emerging Leader in Field of Precision Medicines
Cogent Biosciences: Emerging Leader in Field of Precision Medicines for Genetically Defined DiseasesCogent Biosciences: Emerging Leader in Field of Precision Medicines for Genetically Defined Diseases
Slide 27: Experienced Leadership Team
Experienced Leadership Team Cogent’s leadership possesses biotech and large pharma drug development experience and deep scientific expertise in developing precision medicines for genetically defined diseases. ERIN SCHELLHAMMER JESSICA SACHS, M.D. ANDREW ROBBINS BRAD BARNETT JOHN GREEN Chief People O
Slide 28: Financial Overview
Financial Overview As of September 30, 2020, Cogent’s current cash balance was $129.4 million. We expect that our current cash will be sufficient to fund our operating expenses and capital expenditure requirements into 2023. Company Capitalization Structure 1 Converted Common Shares As of November 9
Slide 29: Current Shareholders
Current Shareholders Common Shares (1) Preferred Shares (2) (3) Total (Fully Converted) Fairmount Funds Management LLC 1,558,976 16,853,500 18,412,476 Venrock Healthcare Capital Partners 1,088,818 3,409,000 4,497,818 Perceptive Advisors LLC 1,988,750 3,977,500 840,384 2,841,000 3,681,384 Atlas Ventu
Slide 30: Current Analyst Coverage
Current Analyst Coverage Institution Analyst Jefferies Biren Amin Wedbush David Nierengarten Ladenburg Matt Kaplan 30Current Analyst Coverage Institution Analyst Jefferies Biren Amin Wedbush David Nierengarten Ladenburg Matt Kaplan 30
Slide 31: Thank You
Thank You CogentBio.com Cogent Biosciences, Inc. | 200 Cambridge Park Drive Suite 2500 | Cambridge, MA 02140 USAThank You CogentBio.com Cogent Biosciences, Inc. | 200 Cambridge Park Drive Suite 2500 | Cambridge, MA 02140 USA
Cogent Biosciences — Investor Presentation (November 2020) on 6ix