Jefferies 2015 Global Healthcare Conference June 1, 2015

Transcription

1 Jefferies 2015 Global Healthcare Conference June 1, 2015 Page 0

2 Acceleron Forward-Looking Statements This presentation contains forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results and other future conditions. The words anticipate, believe, estimate, expect, forecast, goal, intend, may, plan, predict, project, target, potential, will, would, could, should, continue, contemplate, or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forwardlooking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Risks and uncertainties are identified under the heading Risk Factors included in the Company s Annual Report on Form 10-K which was filed with the Securities and Exchange Commission (SEC) on March 2, 2015, and other filings that the Company has made and may make with the SEC in the future. The forward-looking statements contained in this presentation reflect the Company s current views with respect to future events, and the Company does not undertake and specifically disclaims any obligation to update any forward-looking statements. Page 1

3 Acceleron Drug Discovery Platform Acceleron is unlocking the body s ability to regulate the growth and repair of various cells and tissues including red blood cells, muscle, adipose, bone and the vasculature Red Blood Cells Luspatercept Acceleron is a leader in the field of developing therapeutic candidates that regulate cellular growth and repair Powerful biology and a therapeutically rich field Unique knowledge of how to optimally design therapeutic candidates to regulate different cell types RBC/Bone Sotatercept Vasculature Dalantercept Muscle ACE-083 (local) ACE-3891 Muscle/Bone ACE-2491 Adipose ACE-2791 Fibrosis ACE-2531 Page 2

4 Recent Business Highlights Luspatercept granted two Fast Track designations by FDA Treatment of patients with non-transfusion dependent beta-thalassemia Treatment of patients with transfusion dependent beta-thalassemia Celgene and Acceleron have selected luspatercept to move into phase 3 trials in both MDS and beta-thalassemia by year-end Presented luspatercept data at the 13 th International Symposium on Myelodysplastic Syndromes Converted previously transfused patients to become transfusion independent Confirmed value of biomarker-selected patients Presented encouraging dalantercept PFS data at ASCO-GU Dalantercept plus axitinib objective response and progression-free survival rates exceeded that of historical axitinib monotherapy Page 3

5 Luspatercept for Myelodysplastic Syndromes (MDS) Phase 3 start expected 2015 in collaboration with Celgene Page 4

6 Poor Red Blood Cell Maturation in MDS Inability of EPO to correct RBC maturation Anemia, a hallmark of MDS, is challenging to treat, particularly after failure of ESAs Many MDS patients have a deficiency in the maturation of erythroid precursors caused by excessive Smad2/3 signaling which leads to anemia EPO is produced at high levels in an attempt to correct the anemia BFU-E CFU-E Pro E Baso E Poly E Ortho E Retic RBC High EPO levels drive proliferation But excessive Smad2/3 signaling inhibits RBC maturation Page 5

7 Poor Red Blood Cell Maturation in MDS Improvement of RBC maturation with luspatercept Luspatercept is ligand trap that inhibits Smad2/3 signaling and promotes the maturation of RBCs. BFU-E CFU-E Pro E Baso E Poly E Ortho E Retic RBC Luspatercept promotes differentiation and maturation by trapping Smad2/3 activating ligands Page 6

8 Luspatercept Opportunity in MDS Patient Population Lower Risk MDS (87,000 patients US/EU5) EPO or RBC Transfusions Treatment Algorithm Luspatercept Revlimid Vidaza Dacogen Page 7

9 Luspatercept in MDS: Encouraging Preliminary Phase 2 Data Data presented at 13 th International Symposium on MDS Patient population: Lower risk MDS patients Patients were non-responsive, refractory or deemed ineligible to receive an ESA In lower risk MDS patients, the higher dose groups of luspatercept demonstrated robust clinical activity with just 3 months of treatment in a subset of patients with ringed sideroblasts 63% achieved the IWG hematologic improvement-erythroid (HI-E) threshold of efficacy 39% of patients who previously received transfusions became transfusion independent For 90% of these patients, the onset of transfusion independence began within the first 6 weeks of treatment All maintained transfusion independence for 10 weeks in this 3-month treatment study Page 8

10 Luspatercept Opportunity in MDS Patient Population Lower Risk MDS (87,000 patients US/EU5) Treatment Algorithm EPO or RBC Transfusions Luspatercept We estimate there are between 26,000 43,000 RS+ patients in US/EU5 Revlimid Vidaza Dacogen Page 9

11 Luspatercept for Beta-Thalassemia Phase 3 start expected 2015 in collaboration with Celgene Page 10

12 Luspatercept Granted Fast Track Designation for Beta-Thalassemia FDA has granted Fast Track designations to luspatercept for two separate indications Treatment of patients with transfusion dependent beta-thalassemia Treatment of patients with non-transfusion dependent beta-thalassemia Fast Track program of the FDA Facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs Provides the opportunity for more frequent interaction with FDA Allows a sponsor to submit sections of the BLA on a rolling basis Page 11

13 Beta-Thalassemia Beta-Thalassemia Patient Population Non-Transfusion Dependent (20,000+ patients US/EU) Transfusion Dependent (20,000 patients US/EU) Pathologies and Current Treatments Anemia, vasoocclusion, splenomegaly, foot ulcers and in 2 nd decade iron overload Occasional transfusions for severe anemic episodes, iron chelation Life threatening anemia, rapid iron overload Regularly scheduled transfusions Iron chelation Bone marrow transplants Page 12 Data as of 10 Oct 14

14 $ million Exjade (deferasirox): Iron Chelator as an Indicator of the Commercial Opportunity in β-thalassemia Iron overload leads to liver fibrosis and heart failure and is a major cause of morbidity and mortality in betathalassemia $1,000 $900 Exjade Annual Sales Exjade, the predominant therapy to treat iron overload, had 2014 WW annual sales of >$900M Iron overload is measured by liver iron concentration $800 $700 $600 $500 $400 ROW US In a phase 3 study that included transfusion dependent betathalassemia patients, Exjade reduced LIC by 2.4 mg/g dry weight after 12 months of treatment In a phase 3 study that included nontransfusion dependent betathalassemia patients, Exjade reduced LIC by mg/g dry weight after 12 months of treatment $300 $200 $100 $ Source: Evaluate Pharma Page 13

15 Change from Baseline at 4 months in LIC (mg/g dw) Reduced Liver Iron Concentration (LIC by MRI) in NTD Patients Luspatercept -Thalassemia Phase 2 Clinical Trial Baseline LIC 5 mg/g dry weight (dw) On iron chelator No iron chelator Dose (mg/kg) Phase 3 study in NTD patients Exjade reduced LIC by mg/g dry weight after 12 months of treatment Page 14 Data as of 10 Oct 2014

16 Luspatercept in Beta-Thalassemia Patient Population Non-Transfusion Dependent (20,000+ patients US/EU) Transfusion Dependent (20,000 patients US/EU) Pathologies and Current Treatments Anemia, vasoocclusion, splenomegaly, foot ulcers and in 2 nd decade iron overload Occasional transfusions for severe anemic episodes, iron chelation Life threatening anemia, rapid iron overload Regularly scheduled transfusions Iron chelation Bone marrow transplants Luspatercept activity in Ph2 clinical trials Dose dependent increases in hemoglobin Dose dependent decreases in liver iron concentration in 9/12 iron overloaded patients Significant healing of leg ulcers Substantial reductions in transfusion burden Liver iron concentration decreases in 4/5 iron overloaded patients Significant healing of leg ulcers Page 15

17 Luspatercept Opportunity in MDS Patient Population Lower Risk MDS (87,000 patients US/EU5) Treatment Algorithm EPO or RBC Transfusions Luspatercept We estimate there are between 26,000 43,000 RS+ patients in US/EU5 Revlimid Vidaza Dacogen Page 16

18 Building a Hematology Franchise with Celgene Acceleron and Celgene are collaborating on the development and commercialization of sotatercept and luspatercept Celgene funds 100% of current and future development costs for both programs Acceleron will receive tiered royalties in the low-to-mid 20% range on worldwide sales $320M of milestones still outstanding for development and regulatory achievements plus $230M for commercial achievements Companies will co-promote sotatercept and luspatercept in North America, Celgene promotes rest of world Celgene funds 100% of Acceleron s commercialization costs for North American co-promote Page 17

19 Dalantercept Novel anti-angiogenic agent based on the Activin Receptor-Like Kinase 1 (ALK1) Page 18

20 Two Key Steps in Angiogenesis Endothelial Cell Proliferation and Vessel Formation/Maturation Tumor secretes pro-angiogenic factors e.g. VEGF Step 1 VEGF induces EC proliferation Step 2 ALK1 mediates vessel maturation and pericyte coverage Concept: Inhibit sequential steps in pathway to generate synergistic inhibition Proliferation VEGF Receptor Maturation ALK1 Receptor Mature Vessel Page 19

21 Combination Therapy of Dalantercept with Anti-VEGF Agents Presents Large and Diverse Commercial Opportunity There are several approved VEGF pathway inhibitors that collectively generated 2014 annual worldwide sales in excess of $10 billion Disease NSCLC Colorectal RCC HCC Worldwide anti-vegf 2014 Revenue 1 $1.2B $3.9B $2.8B $0.8B There is significant opportunity to leverage the large and established base of VEGF pathway inhibitors in combination with dalantercept to more fully inhibit angiogenesis and improve patient outcomes Our initial clinical trial to study the combination of dalantercept with a VEGF pathway inhibitor is underway in RCC Page 20 1) EvaluatePharma

22 Page 21 DART Study Part 1 Study Schema

23 Page 22 DART Study Part 1 Best Overall Response

24 Page 23 DART Study Part 1 Treatment Duration

25 Page 24 DART Study Part 1 Response Rates

26 Dart Study Part 1 Conclusions In this pretreated advanced RCC population, the combination of dalantercept and axitinib was well tolerated with a generally non-overlapping safety profile. The combination of dalantercept and axitinib was associated with clinically meaningful activity including partial responses (25%) and prolonged disease control (57.1%) in patients with 1 to 3 prior lines of therapy. Dalantercept plus axitinib showed clinical activity in all patients previously treated with checkpoint inhibitors (N=3; 2 with PR and 1 with SD). The preliminary median PFS of 8.3 months in all dose levels combined compares favorably to the historical mpfs with axitinib of 4.8 months in a VEGFR TKI pre-treated advanced RCC population. 10 Page 25

27 Page 26 DART Study Part 2 Study Schema On Track For early 2016 Accrual

28 Key Value Drivers Focused effort on initiating Phase 3 studies with luspatercept in MDS and beta-thalassemia Health authority meetings to finalize phase 3 programs in MDS and betathalassemia expected mid-year Plan to begin phase 3 studies in MDS and beta-thalassemia by end of year Important progress with dalantercept Update on dalantercept RCC study presented at ASCO Continue to present new data / programs at major medical conferences Recent data presented/to be presented at meetings including ERA-EDTA, EHA, World Muscle Society and ASH Continued investment in R&D and expansion of the clinical pipeline Exciting discoveries in our research organization Page 27

29 Acceleron s 2020 Vision Our highly productive discovery and development platform is creating one of the most impressive pipelines in the industry with the potential to transform Acceleron into one of the world s leading biotechnology companies Approvals in up to 5 indications Multiple phase 3 studies 8 protein therapeutics in clinical trials Sales and marketing organization in U.S. Cash flow positive Page 28

30 Thank You Building one of the world s great biotechnology companies Page 29 NASDAQ: XLRN