Forma Therapeutics Holdings Inc
Forma Therapeutics — ASH Investor Briefing 2021
44 slides from Forma Therapeutics's conference presentation, Dec 13, 2021
Slide 1: ASH Investor Briefing
ASH Investor Briefing December 13, 2021 Exhibit 99.2
Slide 2: Legal Disclaimer
Legal Disclaimer This Presentation contains forward-looking statements and information of Forma Therapeutics Holdings, Inc. (“we,” “us,” “our,” “Forma” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our current and future prospects and our op
Slide 3: Frank Lee, President, Chief Executive Officer, and Director
Frank Lee President, Chief Executive Officer, and Director
Slide 4: Meeting Agenda
Highlights of etavopivat Phase 1 results Patrick Kelly M.D., Chief Medical Officer Introduction of RBC Health and Implications in SCD David Cook, Ph.D., Chief Scientific Officer Mark T. Gladwin, M.D., Professor and Chair of the University of Pittsburgh Department of Medicine Questions and Answers
Slide 5: Ifeyinwa (Ify) Osunkwo, M.D., M.P.H.
Ifeyinwa (Ify) Osunkwo, M.D., M.P.H. Director, Sickle Cell Disease Enterprise and Professor of Medicine Levine Cancer Institute Professor of Medicine and Pediatrics, Atrium Health
Slide 6: Transforming the lives of patients with rare hematologic diseases and cancers
Transforming the lives of patients with rare hematologic diseases and cancers
Slide 7: Forma Therapeutics Pipeline
Forma Therapeutics Pipeline PROGRAM (TARGET) INDICATION DEVELOPMENT STAGE COMMERCIAL RIGHTS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Etavopivat (PKR) Sickle Cell Disease TD SCD TD/NTD Thalassemia Pediatric SCD FT-7051 (CBP/p300) mCRPC Olutasidenib (IDH1m) R/R AML Glioma B1-1701963 (KRAS) Solid Tumors IDH
Slide 8: Forma - Key Takeaways
Forma - Key Takeaways Increased Hb levels and reduced hemolysis; encouraging trend in VOCs First comprehensive data set demonstrating global improvements in SCD RBC health Favorable tolerability and safety profile consistent with underlying disease FT-7051 Phase 1 mCRPC Olutasidenib, NDA ready SCD p
Slide 9: Patrick Kelly, M.D. SVP, Chief Medical Officer
Patrick Kelly, M.D. SVP, Chief Medical Officer
Slide 10: Etavopivat-Mediated PKR Activation: Multimodal MoA
Etavopivat-Mediated PKR Activation: Multimodal MoA Hb=hemoglobin, HbS=sickle hemoglobin; MoA=mechanism of action; PEP=phosphoenolpyruvate Potential to Increase Hb and Decrease VOC by Improving RBC Health Etavopivat (FT-4202) is an investigational, once-daily, selective erythrocyte pyruvate kinase (P
Slide 11: Etavopivat Phase 1 Study Design and Status
Etavopivat Phase 1 Study Design and Status BID=twice daily; QD=every day; wk=week 1. Kalfa TA, et al. Blood. 2019;134(suppl 1):616. 2. Estepp JH, et al. Hemasphere. 2020;4:709-10. Randomized, Placebo-Controlled, Multicenter (NCT03815695) Study ongoing; data as of Nov 1, 2021 700 mg2 MAD1 300 mg QD S
Slide 12: Significant and Sustained Hb Increase with Etavopivat Once Daily for up to 12 Weeks
Significant and Sustained Hb Increase with Etavopivat Once Daily for up to 12 Weeks Least square mean (LSM) values presented are estimated from a mixed model repeated measures analysis BL=baseline; SE=standard error Study ongoing; data as of Nov 23, 2021 Responder parameter 12-wk cohort N=15 Maximal
Slide 13: Increased RBC Lifespan and Decreased Hemolysis Sustained Over 12 Weeks
Significant decreases in reticulocytes, indirect bilirubin, and LDH sustained over 12 weeks Increased RBC Lifespan and Decreased Hemolysis are Sustained Over 12 Weeks of Etavopivat Treatment Study ongoing; data as of Nov 23, 2021 Least square mean (LSM) values presented are estimated from a mixed mo
Slide 14: Etavopivat Once Daily for 12 Weeks Improved Sickle RBC Deformability
Analysis of sickle RBCs exposed to an oxygen gradient from a patient before (pre-dose), and after 12 weeks of etavopivat once daily (EOT) (A) Significant shift in PoS to lower O2 pressures (B) with improved deformability (C) of sickle RBCs observed by 2 weeks of etavopivat treatment and sustained du
Slide 15: Etavopivat Improved Sickle RBC Hydration Across an Osmotic Gradient
Analysis of sickle RBCs exposed to an osmotic gradient from a patient before (pre-dose) and after 12 weeks of etavopivat once daily (EOT) (A) Significant improvement in deformability of sickle RBCs across an osmotic gradient was observed over the course of 12 weeks of etavopivat (B) Analysis of sick
Slide 16: Decreased Systemic Markers of SCD Pathophysiology
Significant reduction in markers of inflammation, hypercoagulability, and hypoxia observed on etavopivat treatment Etavopivat Once Daily for up to 12 Weeks Decreased Systemic Markers of SCD Pathophysiology *p<0.05,**p<0.01, ***p<0.001 for maximum decrease observed during treatment compared with base
Slide 17: Etavopivat Once Daily for up to 12 Weeks was Well Tolerated
Etavopivat 400 mg Once Daily for up to 12 Weeks was Well Tolerated ACS=acute chest syndrome; CPK=creatine phosphokinase On-treatment: 3 SAEs reported in 2 patients: 1 pt with Gr 3 VOC precipitated by Gr 3 COVID infection, both unrelated 1 pt with Gr 3 left femoral vein DVT, possibly related Off-trea
Slide 18: Decreasing Trend in VOCs Observed with Etavopivat Once Daily
Decreasing Trend in VOCs Observed with Etavopivat Once Daily for up to 12 Weeks Cohort N Prior History Once Daily Etavopivat On-Treatment N Annualized VOCa Rate (no. events) Annualized VOCb Rate (no. events) Exposure Duration (Patient Years) Etavopivat 2-wk cohorts 16 0.88 (13) 0.00 (0) 0.61 Etavopi
Slide 19: Summary of etavopivat Phase 1 results
Etavopivat improved sickle RBC health resulting in a significantly increased RBC lifespan with decreased intravascular hemolysis Hb levels increased in all patients receiving etavopivat with 11 of 15 patients demonstrating a > 1 g/dL increase A significant reduction in absolute reticulocytes, indire
Slide 20: David Cook, Ph.D. SVP, Chief Scientific Officer
David Cook, Ph.D. SVP, Chief Scientific Officer
Slide 21: The Health of Red Blood Cells is Greatly Improved in Patients with Sickle Cell Disease
The Health of Red Blood Cells is Greatly Improved in Patients with Sickle Cell Disease Click to add text Improving RBC health may lead to a reduction in VOCs, anemia, hemolysis and organ damage and as a result, transform patient quality of life Cellular Energy Hb-oxygen Binding Capacity Deformabilit
Slide 22: PKR Activation Holds Broad Promise Beyond SCD
PKR Activation Holds Broad Promise Beyond SCD Sickle Cell Disease Thalassemia Sickle Cell Disease Thalassemia Myelodysplastic Syndrome w/refractory anemia Idiopathic Pulmonary Fibrosis PKR Activation 2,3-DPG ATP Hb O2 Binding Oxidative Stress Improved Diseased RBC Health & Lifespan Improved Transfus
Slide 23: Mark T. Gladwin, M.D.
Mark T. Gladwin, M.D. Jack D. Myers Distinguished Professor and Chairman of the Department of Medicine Associate Dean for Physician-Scientist Mentoring Associate Vice Chancellor for Science Strategy, Health Sciences UPMC and the University of Pittsburgh School of Medicine
Slide 24: Sunnd, Gladwin, Novelli. Annual Reviews of Pathology. 2019
Sunnd, Gladwin, Novelli. Annual Reviews of Pathology. 2019
Slide 25: Effects of PKR activation on RBC health and hemolysis
Sunnd, Gladwin, Novelli. Annual Reviews of Pathology. 2019 Decreased DPG, P50, intracellular polymerization and decreased HbS concentration (activation of Gardos) Increased ATP Reduction in hemolytic anemia Increasing Hb levels Increased ATP Improved RBC deformability Reduced PS exposure Reduced inf
Slide 26: Complications of Hemolytic Anemia
Complications of Hemolytic Anemia ↓ Hemoglobin ↑ Reticulocyte count ↑ Lactate dehydrogenase (LDH) ↑ Aspartate amino transferase ↑ Indirect and direct bilirubin Kato Gladwin, Novelli. Chapter 4. Hemolysis and Endothelial Dysfunction. Sickle cell disease. McGraw-Hill Education / Medical; 1st edition (
Slide 27: Does the severity of hemolytic anemia determine disease severity?
Does the severity of hemolytic anemia determine disease severity?
Slide 28: Hemolysis Rate and Vascular Complications
Hemolysis Rate and Vascular Complications 100 200 300 400 500 600 700 800 900 1000 1100 1200 0.0 0.1 0.2 0.3 n=214 LDH (IU/L) Fraction of Patients 121 - 189 190 - 511 512 - 1171 0.0 0.1 0.2 0.3 0.4 p<0.001 LDH Range (IU/L) History of Leg Ulcer (Fraction) Leg Ulcers 121 - 189 190 - 511 512 - 1171 0.0
Slide 29: Impact of Etavopivat on measures of hemolysis
Impact of Etavopivat on measures of hemolysis LDH Indirect Bilirubin *P<0.05, **P<0.001, or ***P<0.0001 vs BL Absolute Reticulocytes @ 12 weeks % change vs baseline: -32% (p < 0.05) @ 12 weeks %change vs baseline: -32% (p < 0.0001) @ 12 weeks %change vs baseline: -15% (p < 0.05)
Slide 30: | ciedvn tne 2016 g forma
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Slide 31: Pulmonary hypertension and Early Mortality
Pulmonary hypertension and Early Mortality Mehari et al., JAMA 2012; 307:1254-6.
Slide 32: Ultrasound of the heart used to diagnose pulmonary hypertension
Ultrasound of the heart used to diagnose pulmonary hypertension Tricuspid regurgitant jet velocity (TRV) measurement used to estimate of pulmonary pressures: Sensitivity 79-100 % Specificity 60-98 % McGoon, M. et al. Chest 2004 Gladwin et all NEJM 2004
Slide 33: Hazard ratios of death with elevated pulmonary artery systolic pressure
jhe Estimated pulmonary artery systolic pressure and sickle cell disease: a meta-analysis and systematic review Table IV. Hazard ratios of death associated with elevated pulmonary artery systolic pressure estimated by echocardiography in patients with sickle cell disease. ePASP cut-off Follow-up Dea
Slide 34: Log ee (
Log ee ( os Si j ‘GrENELLE UNESCO ® | © Hepa neck SE ARR, TouMonpamasse = ne Xx. al Magee = a Ne & forma
Slide 35: TRV associated with measures of hemolytic anemia and predicted mortality
656 patient study TRV associated with measures of hemolytic anemia (retic, LDH, Hb) and predicted mortality in multivariate analysis (HR 6.81) Best TRV cut-off by ROC analysis was 2.5 m/sec (AUC 0.7;P=0.0001)
Slide 36: Three-year probability of death by tricuspid regurgitant velocity
10th 25th SOth 75th — 90th Probability of death at 36 months (%) 1 12 14 16 18 2 2.2 24 2.6 28 3 3.2 34 TRY (ms) Figure 4 Three-year pr ility in pati ‘ is i ‘cuspid rig i velocity. & forma
Slide 37: Risk factors for mortality in adult patients with sickle cell disease
EUROPEAN Ferrata Storti HEMATOLOGY Foundation [ASSOCIATION Haematologica 2017 Volume 102(4):626-636 Risk factors for mortality in adult patients with sickle cell disease: a meta-analysis of studies in North America and Europe Poulami Maitra,* Melissa Caughey,? Laura Robinson,’ Payal C. Desai,* Susan
Slide 38: Probability of Surviving
Probabilty of Surviving Probabilty of Surviving Age (year) B Tricuspid Regurgitant Jet Velocity (m/s) Probabilty of Surviving Time (in years) tl death Time (in years) til death Hemoglobin (g/dL) D Creatinine (mg/dL) ~ *, 234 a 3 H Be Ef g se<nos<=7075| 2 a | 7675 <HGB<=87 >-valu based on no Ore 9182
Slide 39: Hemolysis drives inflammation and sets up vaso-occlusion
Hemolysis drives inflammation and sets up vaso-occlusion Kato, Steinberg, Gladwin JCI 2017
Slide 40: Sunnd, Gladwin, Novelli. Annual Reviews of Pathology. 2019
Sunnd, Gladwin, Novelli. Annual Reviews of Pathology. 2019 Decreased DPG, P50, intracellular polymerization and decreased HbS concentration (activation of Gardos) Increased ATP Reduction in hemolytic anemia Increasing Hb levels Increased ATP Improved RBC deformability Reduced PS exposure Reduced inf
Slide 41: Q&A
Q&A Frank Lee President, Chief Executive Officer, and Director Patrick Kelly, M.D. SVP, Chief Medical Officer David Cook, Ph.D. SVP, Chief Scientific Officer Ifeyinwa (Ify) Osunkwo, M.D., M.P.H. Director, Sickle Cell Disease Enterprise and Professor of Medicine Levine Cancer Institute Professor of M
Slide 42: Meeting Summary and Close
Frank Lee President, Chief Executive Officer, and Director Meeting Summary and Close
Slide 43: Forma - Key Takeaways
Forma - Key Takeaways Increased Hb levels and reduced hemolysis; encouraging trend in VOCs First comprehensive data set demonstrating global improvements in SCD RBC health Favorable tolerability and safety profile consistent with underlying disease FT-7051 Phase 1 mCRPC Olutasidenib, NDA ready SCD p
Slide 44: Thank you to our patients, caregivers, and investigators
Thank you to our patients, caregivers, and investigators
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