Forma Therapeutics Holdings Inc
Forma Therapeutics — Investor Presentation (June 2021)
40 slides from Forma Therapeutics's investor presentation, Jun 11, 2021
Slide 1: European Hematology Association Investor Presentation
European Hematology Association INVESTOR PRESENTATION JUNE 11, 2021 Exhibit 99.2
Slide 2: Legal Disclaimer
Legal Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the company’s beliefs and expectations regarding its: business plans a
Slide 3: Meeting Agenda
Meeting Agenda FORMA THERAPEUTICS OVERVIEW Frank D. Lee, President, CEO and Director Etavopivat Results Presentation Patrick Kelly M.D., Chief Medical Officer David Cook, Ph.D. Chief Scientific Officer Question and Answer R. Clark Brown, M.D., Ph.D., Associate Professor Of Pediatrics, Emory Unive
Slide 4: Frank Lee, President, Chief Executive Officer, and Director
Frank Lee President, Chief Executive Officer, and Director
Slide 5: Transforming the lives of patients with rare hematologic diseases and cancers
Transforming the lives of patients with rare hematologic diseases and cancers
Slide 6: Forma Therapeutics' pipeline
Forma Therapeutics’ pipeline PROGRAM (TARGET) INDICATION DEVELOPMENT STAGE COMMERCIAL RIGHTS RECENT EVENTS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Etavopivat (PKR) Sickle Cell Disease Presented Phase 1 SCD data at EHA/ASH Ongoing Phase 1 SCD MAD/OLE Initiated Phase 2/3 pivotal trial (Hibiscus Study) Tha
Slide 7: Potential timelines and milestones
Potential timelines and milestones FPI, first patient in; IA, interim analysis; MAD, multiple ascending dose; NTD, non-transfusion dependent; OLE, open label extension; TD, transfusion-dependent PHASE 2: DOSE SELECTION PHASE 1 EHA Single dose SCD ASH MAD1 300mg EHA 12 week OLE Initial results ASCO P
Slide 8: Significant unmet needs remain in SCD
Significant unmet needs remain in SCD Prevalence ~100K SCD patients in the US ~1 in 365 Black Americans affected at birth 25-30yr Reduction in average life expectancy Symptoms May include anemia, inflammation, and painful vaso-occlusive crises ~55% Days with pain ↑Risk of Stroke Acute Chest Syndrome
Slide 9: Etavopivat is a potential foundational, disease-modifying therapy
Etavopivat is a potential foundational, disease-modifying therapy Granted FDA Fast Track and Rare Pediatric, Orphan Drug designations Multi-modal MoA ↓2,3-DPG and ↑ATP Potential to improve both hemoglobin levels and VOCs Improves RBC health and functions important to metabolic health, adhesion, and
Slide 10: Patrick Kelly, M.D., SVP, Chief Medical Officer
Patrick Kelly, M.D. SVP, Chief Medical Officer
Slide 11: Etavopivat Phase 1 Data Analysis as of May 2021
Etavopivat Phase 1 Data Analysis as of May 2021
Slide 12: Etavopivat-mediated PKR Activation: Sickle RBC Health and Function
Etavopivat-mediated PKR Activation: Sickle RBC Health and Function Multimodal MOA: Increase Hb and Decrease VOC GLUCOSE Hb Deoxy-Hb PYRUVATE ATP ADP PEP 2,3-DPG PKR Etavopivat HbS polymerization RBC membrane integrity Anticipated Clinical Outcomes: Increased Hb levels Decreased vaso-occlusion HYPOTH
Slide 13: Etavopivat Phase 1 Study: Design and Status
Etavopivat Phase 1 Study: Design and Status Randomized, Placebo-controlled, Multi-center (NCT03815695) Healthy volunteers3 (N=90] Patients with SCD Single Ascending Dose (Completed) Randomization vs placebo 700 mg 300 mg once daily Single Dose4 (Completed, N=7) Randomization vs placebo Multiple Asce
Slide 14: Etavopivat Phase 1 Study baseline characteristics
Parameter, Mean (range) or n (%) Etavopivat or Placebo once daily, 2 weeks Etavopivat once daily, 12 weeks 300 mg (N=10) 600 mg (N=10) 400 mg (N=10) Age, years 28.5 (19, 43) 24.0 (17, 64) 26.5 (17, 41) Male 3 (30%) 3 (30%) 3 (30%) Genotype HbSS 9 (90%) 8 (80%) 10 (100%) HbSβ+-thalassemia 1 (10%) 1 (
Slide 15: Etavopivat 300 mg and 600 mg Once Daily: Comparable Decrease in 2,3-DPG and Increase in ATP
Etavopivat 300 mg and 600 mg Once Daily for 2 Weeks: Comparable Decrease in 2,3-DPG and Increase in ATP Dose-proportional PK and comparable PD responses (↓ 2,3-DPG and ↑ ATP) with etavopivat 600 mg or 300 mg once daily for 2 weeks Confirms prior studies in healthy volunteers predicting doses ≥ 400 m
Slide 16: Etavopivat Once Daily for 2 Weeks was Well-tolerated
Parameters Placebo (N=4) Etavopivat 300 mg Once daily, 2 weeks (N=8) Etavopivat 600 mg Once daily, 2 weeks (N=8) AE, n (%) Any AE 1 (25.0) 7 (87.5) 6 (75.0) Related to study drug 0 2 (25.0) 0 Any SAE 0 0 1 (12.5) Related to study drug 0 0 0 AEs by severity Grade 1 Grade 2 Grade 3 Grade 4 3 2 1 1 6
Slide 17: Etavopivat Significantly Improves Hematologic and Hemolytic Parameters
Etavopivat 300 mg or 600 mg Once Daily for 2 Weeks Significantly Improves Hematologic and Hemolytic Parameters EOT=end of treatment; Hb=hemoglobin; LDH=lactate dehydrogenase Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Data as of May 10, 2021 In patients
Slide 18: Etavopivat Once Daily up to 12 Weeks was Well-tolerated
Etavopivat Once Daily up to 12 Weeks was Well-tolerated: Safety Profile Consistent with Underlying Disease AE, n (%) Etavopivat 400 mg once daily up to 12 weeks1 AE, n (%) All Grades (≥ 10%) N=8 Grade ≥ 3 N=8 Acute chest syndrome (ACS) 1 (12.5) 1 (12.5) Blood CPK abnormal 1 (12.5) 1 (12.5) Deep Vein
Slide 19: Etavopivat 400 mg: Improved and Sustained Hemoglobin Increase
Etavopivat 400 mg Once Daily up to 12 Weeks: Improved and Sustained Hemoglobin Increase Responder Parameter N=8 Maximal Hb increase, mean (SD), g/dL 1.5 (0.4) Hb increase > 1 g/dL, n (%) 7 (88) Maximal Hb increase in subjects with > 1 g/dL response, mean (SD), g/dL 1.6 (0.3) Hemoglobin Hb=hemoglobin
Slide 20: Etavopivat 400 mg: Decreased and Sustained RBC Turnover and Hemolysis
Etavopivat 400 mg Once Daily up to 12 Weeks: Decreased and Sustained RBC Turnover and Hemolysis LDH=lactate dehydrogenase; BL=baseline; wk=week Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Data as of May 24, 2021 Reticulocytes LDH Bilirubin Trend towards
Slide 21: Etavopivat 400 mg: Reduction in Systemic Markers of Sickle Cell Pathophysiology
Etavopivat 400 Mg Once Daily for 12 Weeks: Reduction in Systemic Markers of Sickle Cell Pathophysiology Lab Test Normal range Patients (n) Baseline Median % Maximum Change (range) P-value Tissue hypoxia Erythropoietin 2.6 – 18.5 mIU/mL 4 140.3 (106.7, 157.1) -42.3 (-66.6, -7.3) 0.1250 Hypercoagulabi
Slide 22: Etavopivat Improved the Functional Health of Sickle RBCs
EImax Pre EOT EOS P50 29.7 25.2 32 Pre EOT EOS POS EImax 40.6 30.7 40.8 0.32 0.52 0.49 Pre EOT EOS EImax 0.42 0.54 0.52 O2 Affinity Curve Osmoscan Healthy RBC: SCD RBC (Pre-dose): SCD RBC EOT (Day 15): SCD RBC EOS (Day 21): Oxygenscan POS EImax Patient with SCD before and after 2 wks of etavopivat a
Slide 23: Improvement in Sickle RBC Deformability May Persist after Treatment Discontinuation
Improvement in Sickle RBC Deformability May Persist after Etavopivat Treatment Discontinuation Oxygenscans performed at the indicated timepoints showed: Improved RBC deformability (EImax) after 2 weeks of etavopivat at both doses EImax returning to pre-treatment level during WO between etavopivat tr
Slide 24: Etavopivat Improved RBC Functions Important for Metabolic Health, Adhesion, and Survival
Etavopivat Improved RBC Functions Important for Metabolic Health, Adhesion, and Survival PS Expression n=11 n=13 n=13 n=8 A: B: C: D: GSH Reductase Activity SOD Activity PKR Activity RBCs from patients with SCD treated with etavopivat 300 mg or 600 mg QD for 2 wks showed: ↑ PKR activity over baselin
Slide 25: David Cook, Ph.D., SVP, Chief Scientific Officer
David Cook, Ph.D. SVP, Chief Scientific Officer
Slide 26: Etavopivat MOA and Novel Biology from Phase 1 Data
Etavopivat MOA and Novel Biology from Phase 1 Data
Slide 27: Etavopivat: Results Supporting Improved RBC Functional Health
Etavopivat: Results Supporting Improved RBC Functional Health 1 2 3 4 5 6 PKR= pyruvate kinase-R; 2,3-DPG=2,3-diphosphoglycerate; ATP=adenosine triphosphate; PS=phosphatidyl serine 7 Reduced potential for vascular activation and vaso-occlusion Reduced membrane damage Reduced protein, membrane & bloo
Slide 28: Sickle Cell Disease is Complex and Multifactorial
Sickle Cell Disease, although Driven by a Single Mutation, is Complex and Multifactorial Sickling Hemolysis Free Heme Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Activation of Innate Immune Pathways Vaso-occlusion Activation of Vascular Epithelium and Vaso-constriction I
Slide 29: Decreased 2,3-DPG: Reduced RBC Sickling
Decreased 2,3-DPG: Reduced RBC Sickling Etavopivat consistently decreases 2,3-DPG + DPG / −O2 − DPG / +O2 Decreased 2,3-DPG increases oxygen affinity and reduces polymerization and sickling Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusi
Slide 30: Increased ATP: Increased RBC Energy Charge
Increased ATP: Increased RBC Energy Charge Etavopivat consistently increases ATP and PKR activity ↑ ATP essential for membrane repair, ionic homeostasis, hydration and deformability Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascu
Slide 31: Decreased Hemolysis: Increased RBC Lifespan and Reduced Inflammation
Decreased Hemolysis: Increased RBC lifespan and Reduced Inflammation Etavopivat ↑ Hb and ↓ reticulocytes demonstrating increased RBC lifespan Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction Eta
Slide 32: Improved RBC Deformability and Hydration
Improved RBC Deformability and Hydration: Increased Ability to Transit Small Vessels Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction 4 4 Etavopivat results in higher baseline deformability as m
Slide 33: Decreased PS: Reduced Membrane Damage
Decreased PS: Reduced Membrane Damage Repeated sickling results in PS on the outer RBC membrane Etavopivat decreases PS expression on RBC outer membrane Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-const
Slide 34: Increased Anti-oxidant Enzyme Activity
Etavopivat increases activity of SOD and GSH Reductase Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction ↑ SOD and GSH reductase aid in elimination of toxic reactive oxygen species from sickle RB
Slide 35: Decreased Pro-inflammatory and Pro-coagulant Markers
Decreased Pro-inflammatory and Pro-coagulant Markers: Reduced Potential for Vascular Activation and Vaso-occlusion Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction 7 7 7 ATP=adenosine triphospha
Slide 36: Etavopivat-mediated PKR Activation Demonstrates Potential to Improve RBC Health
Etavopivat-mediated activation of glycolysis results in: Reduced RBC sickling – the key to all downstream pathology Decreased hemolysis – a driver of inflammation & vascular activation Improved RBC deformability & hydration – reducing vaso-occulsion Reduced membrane damage – reducing RBC adhesion an
Slide 37: Q&A
Q&A
Slide 38: Frank Lee, President, Chief Executive Officer, and Director
Frank Lee President, Chief Executive Officer, and Director
Slide 39: Summary – Etavopivat Phase 1 Results Support Hibiscus Study Design
Summary – Etavopivat Phase I Results Support Hibiscus Study Design And Potential as Foundational Therapy in SCD Rigorous Phase I study Etavopivat once daily A favorable tolerability profile in patients with SCD - supporting a safety margin for maximum dose selected for Hibiscus Study ( Phase 2/3 ) I
Slide 40: Thank you to our patients, caregivers, and investigators
Thank you to our patients, caregivers, and investigators
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