Forma Therapeutics Holdings Inc

Forma Therapeutics — Technical Presentation (December 2021)

15 slides from Forma Therapeutics's technical presentation, December 2021

  1. Slide 1: Activation of Pyruvate Kinase-R With Etavopivat Is Well Tolerated, Improves Anemia

    Activation of Pyruvate Kinase-R With Etavopivat (FT-4202) Is Well Tolerated, Improves Anemia, and Decreases Intravascular Hemolysis in Patients With Sickle Cell Disease Treated for up to 12 Weeks R. Clark Brown, Santosh Saraf, Kimberly Cruz, Modupe Idowu, Theodosia A. Kalfa, Ifeyinwa Osunkwo, Robert

  2. Slide 2: Disclosures

    Disclosures Consultancy: GBT, Imara, Novartis, Novo Nordisk; Research funding: GBT, Imara, Novartis, Forma Therapeutics Inc. 2

  3. Slide 3: Introduction: Sickle Cell Disease (SCD)

    Introduction Sickle Cell Disease (SCD) • SCD is a chronic and progressive inherited disorder characterized by impaired red blood cell (RBC) health and lifespan • SCD results in hemolytic anemia, painful VOCs, end-organ damage, diminished quality of life, and decreased survival • Sickle RBCs have hig

  4. Slide 4: Etavopivat-Mediated PKR Activation: Multimodal MoA

    Etavopivat-Mediated PKR Activation: Multimodal MoA Potential to Increase Hb and Decrease VOC by Improving RBC Health HYPOTHESIS #1: Glucose PKR activation may decrease 2,3-DPG, Oxy reducing HbS polymerization and -Hb sickling • Etavopivat (FT-4202) ATP is an investigational, 2,3-DPG HbS polymerizati

  5. Slide 5: Etavopivat Phase 1 Study Design and Status

    Etavopivat Phase 1 Study Design and Status Randomized, Placebo-Controlled, Multicenter (NCT03815695) Healthy Single Ascending Dose (Completed) Multiple Ascending Dose (MAD, Completed) volunteers Etavopivat vs placebo Etavopivat vs placebo, 2 weeks of treatment (N=90)1 100 mg 200 mg 300 mg 400 mg Key

  6. Slide 6: Etavopivat Phase 1 Study: Baseline Characteristics of Patients With SCD

    Etavopivat Phase 1 Study: Baseline Characteristics of Patients With SCD Etavopivat or Placebo Once Daily Etavopivat Once Daily Mean (SD) or n (%) for 2 Wks for 12 Wks Placebo (N=4) 300 mg (N=8) 600 mg (N=8) 400 mg (N=15) Age, years 26.5 (8.6) 27.4 (9.0) 32.6 (14.1) 32.3 (10.1) Male 3 (75%) 2 (25%) 1

  7. Slide 7: Etavopivat Once Daily for 2 Weeks Was Well Tolerated

    Etavopivat Once Daily for 2 Weeks Was Well Tolerated Placebo Etavopivat Once Daily for 2 Wks + 1 Wk Off Treatment Adverse Event (AE) (N=4) 300 mg (N=8) 600 mg (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 serious AE (SAE) 0 0 1 (12.5) Etavopivat was Relate

  8. Slide 8: Etavopivat 400 mg Once Daily for Up to 12 Weeks Was Well Tolerated

    Etavopivat 400 mg Once Daily for Up to 12 Weeks Was Well Tolerated Safety Profile Consistent with Underlying Disease Etavopivat 400 mg Once Daily up to 12 Wksb + 4 Wks Off Treatment Adverse Eventa, n (%) Gr 1–2 (in ≥2 patients) Gr 3–4 (in ≥1 patients) N=15 N=15 • On-treatment: 3 SAEs reported in 2 p

  9. Slide 9: 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 ​ Hemoglobin 11 LSM (±SE) Hemoglobin, g/dL *** *** 12-wk Cohort *** *** Responder Parameter *** *** N=15 10 Maximal Hb increase, mean (range), g/dL 1.5 (0.7-2.3) Hb increase >1 g/dL on treatment,a n (%) 11 (73.3) 9 *

  10. Slide 10: Increased RBC Lifespan and Decreased Hemolysis Sustained Over 12 Weeks

    Increased RBC Lifespan and Decreased Hemolysis Are Sustained Over 12 Weeks of Etavopivat Treatment Absolute Reticulocytes Indirect Bilirubin LDH 300 3.0 500 LSM (±SE) Indirect Bilirubin, mg/dL 2.5 LSM (±SE) ARC, 109/L 250 LSM (±SE) LDH, U/L 400 2.0 * * 200 ** ** ** ** *** ** * *** *** *** *** * ** 1

  11. Slide 11: Decreasing Trend in VOCs Observed With Etavopivat Once Daily for Up to 12 Weeks

    Decreasing Trend in VOCs Observed With Etavopivat Once Daily for Up to 12 Weeks Prior History Once Daily Etavopivat On Treatment Cohort N Annualized VOCa Rate Annualized VOCb Rate Exposure Duration (no. events) (no. events) (Patient Years) Etavopivat 2-wk cohorts 16 0.88 (13) 0.00 (0) 0.61 Etavopiva

  12. Slide 12: Summary

    Summary • Etavopivat daily for up to 12 weeks demonstrated a favorable safety profile in patients with SCD – Safety and tolerability established up to 600 mg daily for 2 weeks: a dose 50% higher than the highest dose in the Phase 2/3 Hibiscus Study • Etavopivat significantly increased RBC lifespan a

  13. Slide 13: Acknowledgments

    Acknowledgments • The authors thank the patients Investigator Site and their families, and the Marilyn Telen Duke University - Hematology, Durham, NC investigators and sites for Robert Hagar UCSF Benioff Children’s Hospital San Francisco, Oakland, CA participation in the study Santosh Saraf Universi

  14. Slide 14: Access This Presentation

    Access This Presentation The information available via the QR Code and website is intended to provide scientific information for individual reference. The presentation or content within should not be altered or reproduced in any way. https://epg-digital.com/u/ASH2021-Brown

  15. Slide 15: Disclosures

    Disclosures RCB: Consultancy: GBT, Imara, Novartis, Novo Nordisk; Research funding: GBT, Imara, Novartis, Forma Therapeutics Inc. SLS: Research funding: GBT, Novartis, Pfizer; Membership on Board of Directors/advisory committee: GBT, Novartis. KC: No conflicts of interest to disclose. MI: Research f

Forma Therapeutics Holdings — Technical Presentation (December 2021) on 6ix