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Interim Results from Two Phase 2 Clinical Trials in Adults with Beta-Thalassemia

Interim Results from Two Phase 2 Clinical Trials in Adults with Beta-Thalassemia Ellis Neufeld, MD PhD. Data adapted from presentations at 19 th European Hematology Congress in Milan, Italy June 14, 2014. Studies supported by Acceleron Pharma and Celgene. Disclosure for Dr. Neufeld.

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Interim Results from Two Phase 2 Clinical Trials in Adults with Beta-Thalassemia

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  1. Interim Results from Two Phase 2 Clinical Trials in Adults with Beta-Thalassemia Ellis Neufeld, MD PhD Data adapted from presentations at 19th European Hematology Congress in Milan, Italy June 14, 2014 Studies supported by AcceleronPharma and Celgene

  2. Disclosure for Dr. Neufeld • Safety Committee for Acceleron for one of the studies I am presenting. Data limited to public information

  3. Background: ACE-536 and Sotatercept Sotatercept ACE-536 ECD ofActRIIA Modified ECD of ActRIIB Fc Domain of human IgG1 Antibody Fc Domain of human IgG1 Antibody • Protein therapeutics (biologics) • Both molecules act during late-stage erythropoiesis to increase release of mature red blood cells into circulation • Novel mechanism of action, distinct from EPO • May work by turning down the “brakes” on normal red cell formation. • Effective in mouse model of thalassemia. • ACE-536 and sotatercept are currently in Phase 2 studies in Europe in patients with transfusion-dependent and non-transfusion dep. beta-thal • Drugs administered by a subcutaneous injection once every 3 weeks Suragani, Nature Medicine Carrancio S, et al. Br J Haematol. 2014;165:870-82

  4. 3 2 1 0 −1 −2 −3 1 49 97 145 193 241 289 337 385 433 Mean Change in Hemoglobin - NTD PatientsSotatercept -Thalassemia Phase 2 Clinical Trial 0.75 mg/kg 0.5 mg/kg 0.3 mg/kg Hb change from baseline (g/dL) 0.1 mg/kg Days • Dose-dependent increase in hemoglobin • Effects are maintained while on treatment Interim data as of February 7, 2014

  5. Maximum Change in Hemoglobin (9 Weeks) – NTD PatientsSotatercept -Thalassemia Phase 2 Clinical Trial Maximum change in Hb during the first 9 weeks 100% 83% Patients (%) 67% 50% 33% 0.5 mg/kg(n = 6) 0.1 mg/kg(n = 6) 0.75 mg/kg(n = 4) 0.3 mg/kg(n = 6) 0.1 mg/kg(n = 6) 0.5 mg/kg(n = 6) 0.75 mg/kg(n = 4) 0.3 mg/kg(n = 6) 0% 0% 0% Hb values are not included if measured within 2 weeks after a transfusion.

  6. Reduction in Red Cell Burden for Transfused PatientsSotatercept -Thalassemia Phase 2 Clinical Trial Dose dependent reduction in transfusion burden in TD patients, including β-thalassemia major and β0/β0 genotype Patients (%) 67% 50% 33% 33% 0.5 mg/kg(n = 2) 0.1 mg/kg(n = 2) 0.75 mg/kg(n = 3)a 0.3 mg/kg(n = 3) 0.1 mg/kg(n = 2) 0.5 mg/kg(n = 2) 0.75 mg/kg(n = 3)a 0.3 mg/kg(n = 3) 0% 0% 0% 0% Change in transfusion burdenb aTransfusion burden evaluated up to the last known efficacy record, adjusted to 168 days. bChange in transfusion burden (units/168 days) from baseline.

  7. Mean Change in Hemoglobin - NTD PatientsACE-536 -Thalassemia Phase 2 Clinical Trial • Dose-dependent increase in hemoglobin • Effects are maintained while on treatment Planned ACE-536 Dose Mean Change in Hemoglobin (g/dL) Study Day Preliminary data as of 28 April 2014

  8. Max. Change in Hemoglobin ≥ 1 or 2 g/dL - NTD PatientsACE-536 -Thalassemia Phase 2 Clinical Trial 0.2 mg/kg 0.4 mg/kg 0.6 mg/kg 0.8 mg/kg Patients (%) n=3 n=5 n=6 n=6 n=5 n=3 n=6 n=6 ≥ 1.0 g/dL ≥ 2.0 g/dL Preliminary data as of 28 April 2014

  9. Transfusion Response - TD Patients (n=4)ACE-536 -Thalassemia Phase 2 Clinical Trial • Reduction in transfusion burden >50% observed in 100% (4/4) transfusion-dependent patients * Patient discontinued after 8.4 weeks on study Preliminary data as of 28 April 2014

  10. ConclusionsACE-536 and Sotatercept -Thalassemia Phase 2 Clinical Trials • Both drugs were safe and well-tolerated in adults with β-thalassemia. A few patients have had bone pain at higher doses. • Dose-dependent increases in hemoglobin demonstrated in non-transfusion dependent patients • Reduction in transfusion burden observed in transfusion-dependent patients • Further dose escalation is ongoing; longer-term extension studies are planned • Phase 3 studies are planned

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