highlights from ash 2019...2019/12/09 · highlights from ash 2019 december 10, 2019 2 this...

Highlights from ASH 2019December 10, 2019

2 This presentation is for investor relations purposes only –Not for product promotional purposes.

Acceleron Forward-Looking Statements

THIS PRESENTATION CONTAINS FORWARD-LOOKING STATEMENTS ABOUT THE COMPANY’S STRATEGY, FUTURE PLANS andprospects, including statements regarding the development and commercialization of the Company's compounds, the timeline forclinical development and regulatory approval of the Company’s compounds and the expected timing for reporting of data fromongoing clinical trials, and the potential of REBLOZYL® (luspatercept-aamt) as a therapeutic drug. The words “anticipate,” “believe,”“could,” “estimate,” “expect,” “goal,” “intend,” “may,” “plan,” “potential,” “project,” “should,” “target,” “will,” “would,” and similarexpressions are intended to identify forward-looking statements, although not all forward-looking statements contain theseidentifying words.

ACTUAL RESULTS COULD DIFFER MATERIALLY FROM THOSE INCLUDED IN THE FORWARD-LOOKING STATEMENTS DUE TO VARIOUSfactors, risks and uncertainties, including, but not limited to, that preclinical testing of the Company's compounds and data fromclinical trials may not be predictive of the results or success of ongoing or later clinical trials, that the results of any clinical trial maynot be predictive of the results or success of other clinical trials of the same product candidate, that regulatory approval of theCompany’s compounds in one indication or country may not be predictive of approval in another indication or country, that thedevelopment of the Company's compounds will take longer and/or cost more than planned, that the Company will be unable tosuccessfully complete the clinical development of the Company’s compounds, that the Company may be delayed in initiating,enrolling or completing any clinical trials, and that the Company's compounds will not receive regulatory approval or becomecommercially successful products. These and other risks and uncertainties are identified under the heading "Risk Factors" included inthe Company's most recent Annual Report on Form 10-K, and other filings that the Company has made and may make with the SECin the future.

THE FORWARD-LOOKING STATEMENTS CONTAINED IN THIS PRESENTATION ARE BASED ON MANAGEMENT’S CURRENT VIEWS,plans, estimates, assumptions and projections with respect to future events, and the Company does not undertake and specificallydisclaims any obligation to update any forward-looking statements.

3

Today’s Agenda

WELCOME Todd James, IRC, Acceleron, VP of IR and Corp. Comm.

OPENING REMARKS Habib Dable, Acceleron, CEO

REBLOZYL & ASH 2019 Jay T. Backstrom, MD, MPH, Acceleron, EVP, Head of R&D

MDS Rami Komrokji, MD, Moffitt Cancer Center

BETA-THALASSEMIAThomas Coates, MD, Children’s Hospital Los Angeles, University of Southern California

MYELOFIBROSIS Srdan Verstovsek, MD, PhD, MD Anderson Cancer Center

COMMERCIAL Sujay Kango, Acceleron, CCO

QUESTION & ANSWER SESSION

This presentation is for investor relations purposes only –Not for product promotional purposes.

Opening RemarksHabib DableChief Executive Officer

REBLOZYL® Now Approved1


1. REBLOZYL® (luspatercept-aamt) is not approved to treat patients with myelodysplastic syndromes, myelofibrosis, or non-transfusion-dependent beta-thalassemia in any country. All REBLOZYL activities are in collaboration with Bristol-Myers Squibb.

6

Jay T. Backstrom, MD, MPHExecutive Vice President, Head of Research and Development, Acceleron

REBLOZYL1 U.S. and E.U. Regulatory Activities

7

Phase 3

Phase 3

April 4, 2020FDA PDUFA

Target Action Date

EMA decision on MAA expected in 2H 20201. All REBLOZYL (luspatercept-aamt) regulatory activities are in collaboration with Bristol-Myers Squibb

FDA PDUFA: US Food and Drug Administration Prescription Drug User Fee Act; RS+: Ring sideroblasts; EMA: European Medicines Agency; MAA: Marketing Authorization Application

NOW APPROVED

Treatment of anemia in adult patients with beta-thalassemia, who require regular RBC transfusions

Treatment of anemia in adult patients with very low- to intermediate-risk MDS,

who are RS+ and require RBC transfusions


Additional REBLOZYL1 Trials

Beta-Thalassemia (NTD)

Phase 2

Phase 3

Lower-Risk MDS, First-line

Phase 2

Myelofibrosis


1. All REBLOZYL (luspatercept-aamt) activities are in collaboration with Bristol-Myers Squibb2. A Phase 3 double-blind, randomized study to compare the efficacy and safety of luspatercept (ACE-536) versus placebo in subjects

with myeloproliferative neoplasm-associated myelofibrosis on concomitant JAK 2 inhibitor therapy and who require red blood cell transfusions

Pivotal Phase 3 trial start expected in 20202

Fully EnrolledTopline results

YE:2020

Enrollment OngoingTopline results expected by

Late 2021/Early 2022

9

Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled Medalist Trial of Luspaterceptto Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-RiskMyelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions (Fenaux)

Luspatercept Significantly Reduces Red Blood Cell (RBC) Transfusion Burden, Regardless of Gene Mutation Frequency, Spectrum, andPrognostic Significance, Among Patients (Pts) with LR-MDS Enrolled in the Medalist Trial (Platzbecker)

Hematologic Improvement–Neutrophil and –Platelet in the Medalist Trial: Multilineage Data from a Phase 3, Randomized, Double-Blind,Placebo- Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk MyelodysplasticSyndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions (Garcia-Manero)

MEDALIST


All REBLOZYL (luspatercept-aamt) activities are in collaboration with Bristol-Myers Squibb

Evaluating Luspatercept Responders in the Phase 3, Randomized, Double-Blind, Placebo-Controlled Believe Trial of Luspatercept in AdultBeta-Thalassemia Patients (Pts) Who Require Regular Red Blood Cell (RBC) Transfusions (Viprakasit)

Effects of Luspatercept on Iron Overload and Impact on Responders to Luspatercept: Results from the Believe Trial (Porter)

BELIEVE

A Phase 2 Study of Luspatercept in Patients with Myelofibrosis-Associated Anemia (Gerds)

Myelofibrosis

Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled

MEDALIST Trial of Luspatercept to Treat Anemia in IPSS-R Very Low-, Low-, or Int-Risk RBC Transfusion-Dependent

MDS with Ring Sideroblasts

Pierre Fenaux1,2, Ghulam J. Mufti3, Rena Buckstein4, Valeria Santini5, María Díez-Campelo6, Carlo Finelli7, Mario Cazzola8, Osman Ilhan9, Mikkael A. Sekeres10, Rami S. Komrokji11, Alan F. List11, Amer M. Zeidan12,

Amit Verma13, Abderrahmane Laadem14, Rodrigo Ito14, Jennie Zhang14, Anita Rampersad14, Daniel Sinsimer14, Peter G. Linde15, Guillermo Garcia-Manero16, Uwe Platzbecker17

1Service d’Hématologie Séniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France; 2Université Paris 7, Paris, France; 3Department of Haemato-Oncology, King’s

College London, London, UK; 4Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 5MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of

Florence, Florence, Italy; 6Hematology Department, Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, Salamanca, Spain; 7Department of Oncology and

Hematology, S. Orsola-Malpighi University Hospital, Bologna, Italy; 8Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; 9Department of Hematology, Ankara University

School of Medicine, Ankara, Turkey; 10Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA; 11Moffitt Cancer Center, Tampa, FL, USA; 12Department of

Internal Medicine, Yale School of Medicine and Yale Cancer Center, Yale University, New Haven, CT, USA; 13Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, USA; 14Bristol-Myers Squibb, Summit, NJ, USA; 15Acceleron Pharma, Cambridge, MA, USA; 16Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA;

17Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Hematology and Cellular Therapy, Leipzig, Germany

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Rami Komrokji, MDMoffitt Cancer Center, Senior Member & Professor of Oncologic Sciences, Section Head- Leukemia and MDS,Vice Chair-Malignant Hematology Department

INTRODUCTION

• Chronic anemia is the most common cytopenia in LR-MDS and is associated with a

number of complications, including fatigue, falls, and decreased quality of life1,2

• Treatments for anemia include ESAs and RBC transfusions; however, RBC

transfusion dependence is associated with reduced survival3 and responses to

ESAs are limited2

• Treatment options are lacking for patients with transfusion-dependent LR-MDSa for

whom ESA treatment is ineffective or is not an option2,4

a IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS.

ESA, erythropoiesis-stimulating agent; IPSS-R, Revised International Prognostic Scoring System;

LR; lower-risk; MDS, myelodysplastic syndromes; RBC, red blood cell.

1. Stauder R, et al. Blood. 2018;131:505-514.

2. Fenaux P, Adès L. Blood. 2013;121:4280-4286.

3. Hiwase DK, et al. Blood. 2013;122:abstract 1518.

4. Adès L, et al. Lancet. 2014;383:2239-2252.

STUDY DESIGN

Inclusion Criteria

• MDS with RS (WHO): ≥ 15% RS or ≥ 5% with

SF3B1 mutation

• < 5% blasts in bone marrow

• Non-del(5q) MDS

• IPSS-R Very low-, Low-, or Intermediate-risk

• Prior ESA response

– Refractory, intolerant

– ESA naive: EPO > 200 U/L

• Average RBC transfusion burden

≥ 2 U/8 weeks

• No prior treatment with disease-modifying

agents (e.g. IMiD agents, HMAs)

Randomized

2:1

Luspatercept 1.0 mg/kg (s.c.) every 21 days(n = 153)

Placebo (s.c.) every 3 weeks(n = 76)

Dose titrated up to a maximum of 1.75 mg/kg

Disease and response assessment

Week 24 and every 6 months

Treatment discontinued for lack of clinical benefit or disease

progression per IWG criteria

Patients followed ≥ 3 years post final dose for AML progression,

subsequent MDS treatment, and overall survival; crossover

between groups was not allowed

Primary analysis data cutoff date May 8, 2018; current data cutoff date July 1, 2019.

Patients randomized between March 2016 and June 2017 at 65 sites in Belgium, Canada, France, Germany, Italy, Netherlands, Spain,

Sweden, Turkey, UK, and USA.

RBC-TI ≥ 8 WEEKS ACHIEVED ANY TIME DURING TREATMENT PERIOD

Data cutoff: July 1, 2019.

• Primary endpoint previously reported: 37.9% luspatercept versus 13.2% placebo patients achieved

RBC-TI ≥ 8 weeks during Weeks 1–24 (P < 0.0001)1

1. MEDALIST authors. Blood. 2018;132:abstract 1.

0

10

20

30

40

50

60

Luspatercept(n = 153)

Placebo(n = 76)

Pati

en

ts A

ch

iev

ing

R

BC

-TI ≥ 8

Weeks A

ny T

ime

Du

rin

g t

he T

reatm

en

t P

eri

od

(%

)n = 73

n = 12

47.7%

15.8%

P < 0.0001a

OR (95% CI):a 5.978 (2.840–12.581)

a Determined using a Cochran-Mantel-Haenszel test stratified for average baseline transfusion requirement (≥ 6 U/8 weeks vs < 6 U/8weeks) and baseline IPSS-R score (Very low or Low vs Intermediate).

CI, confidence interval; OR, odds ratio.

LUSPATERCEPT PATIENTS ACHIEVING RBC-TI ≥ 8 WEEKS (N = 73)ANALYSIS OF MULTIPLE RESPONSE PERIODS


• Of the 73 luspatercept-treated patients achieving RBC-TI ≥ 8 weeks during the entire treatment period:

– 51 (69.9%) had ≥ 2 separate response periods

– 28 (38.4%) had ≥ 3 separate response periods

– 15 (20.5%) had ≥ 4 separate response periodsResponse according to IWG 2006 criteria.

Transfusion events are not representative of changes in RBC units transfused.

RBC transfusion event

RBC-TI < 8 weeks

RBC-TI ≥ 8 weeks

−16 −8 240 8 16 32 40 7248 56 64 80 88 12096 104 112 128 136 168144 156 160 184176

Time (weeks)

−16 −8 240 8 16 32 40 7248 56 64 80 88 12096 104 112 128 136 168144 156 160 184176

Time (weeks)

TREATMENT EXPOSURE AND CUMULATIVE DURATION OF RESPONSE


ParameterLuspatercept

(n = 153)

Placebo

(n = 76)

Treatment duration, median (range), weeks 50.9 (6.0–172.0) 24.0 (7.0–103.0)

In patients achieving RBC-TI ≥ 8 weeks during the entire treatment phase 109.1 (18.0–172.0)a 53.6 (24.0–103.0)b

Patients remaining on treatment as of July 1, 2019 data cutoff, n (%) 41 (26.8) 0

Cumulative duration of RBC-TI ≥ 8 weeks (sum of all periods of RBC-TI ≥ 8 weeks),c

median (95% CI), weeks79.9 (53.7–112.3)a 21.0 (10.9–NE)b

a In the 73 patients in the luspatercept arm who achieved RBC-TI ≥ 8 weeks during the entire treatment phase. b In the 12 patients in the placebo arm who achieved RBC-TI ≥ 8

weeks during the entire treatment phase. c Cumulative duration of RBC-TI ≥ 8 weeks is defined as the sum of all durations of RBC-TI for patients achieving RBC-TI ≥ 8 weeks during

the entire treatment phase.

• Of the 153 luspatercept-treated patients, 12 (7.8%) remained transfusion free after the first dose of

luspatercept through Week 48

• Patients receiving luspatercept had longer duration of treatment, duration of the longest single period

of RBC-TI ≥ 8 weeks, and cumulative duration of RBC-TI ≥ 8 weeks

ACHIEVEMENT AND DURATION OF CLINICAL BENEFIT OVER THE ENTIRE TREATMENT PERIOD


Clinical Benefit and Duration Luspatercept Placebo

Clinical benefita – all patients, n/N (%) 98/153 (64.1) 20/76 (26.3)

Baseline transfusion burden ≥ 6 U/8 weeks 37/66 (56.1) 9/33 (27.3)

Baseline transfusion burden ≥ 4 to < 6 U/8 weeks 22/41 (53.7) 3/23 (13.0)

Baseline transfusion burden < 4 U/8 weeks 39/46 (84.8) 8/20 (40.0)

Duration of clinical benefitb – all patients, median (range), weeks 92.3 (8–172) 26.8 (8–103)

Baseline transfusion burden ≥ 6 U/8 weeks 66.0 (8–148) 23.9 (8–103)

Baseline transfusion burden ≥ 4 to < 6 U/8 weeks 96.1 (13–150) 45.7 (45–51)

Baseline transfusion burden < 4 U/8 weeks 91.7 (21–172) 26.8 (18–76)

a Defined as achieving RBC-TI ≥ 8 weeks and/or mHI-E per IWG 2006 criteria1 over the entire treatment phase.b Duration of clinical benefit is defined as the time from start of response (RBC-TI ≥ 8 weeks and/or mHI-E) to end of treatment.

.

• Durable clinical benefit with luspatercept was achieved regardless of baseline transfusion burden

1. Cheson BD, et al. Blood. 2006;108:419-425.

SAFETYSUMMARY


Summary of TEAEs, n (%)Luspatercept

(n = 153)

Placebo

(n = 76)

Patients with ≥ 1 TEAE 134 (87.6) 63 (82.9)

Patients with ≥ 1 TEAE resulting in treatment discontinuation 21 (13.7) 6 (7.9)

Specific TEAEsa resulting in discontinuation

Fatigue 2 (1.3) 0

Diarrhea 0 0

Asthenia 1 (0.7) 0

Dizziness 0 0

Nausea 0 0

Back pain 0 0

Headache 1 (0.7) 0

Dyspnea 0 0

a TEAEs occurring more frequently in the luspatercept arm.

.• The overall frequency of SAEs was 41.8% in the luspatercept arm and 30.3% in the placebo arm

– After adjusting for exposure, the incidence of SAEs per 100 patient-years was comparable between the luspatercept (EAIR

42.3/100 patient-years) and placebo (EAIR 55.7/100 patient-years) arms

– The overall EAIR of SAEs was comparable between the luspatercept arm and placebo arm

• Incidence of grade 3 TEAEs was balanced between treatment arms

EAIR, exposure-adjusted incidence rate; TEAE, treatment-emergent

adverse event; SAE, serious adverse event.

SAFETYDISEASE PROGRESSION


Summary of Disease Progression, n (%)Luspatercept

(n = 153)

Placebo

(n = 76)

Progression to HR-MDS or AML 8 (5.2) 4 (5.3)

HR-MDS 5 (3.3) 2 (2.6)

AML 3 (2.0) 2 (2.6)

AML, acute myeloid leukemia; HR-MDS, higher-risk myelodysplastic syndromes.

SUMMARY

• In this longer-term analysis of the MEDALIST study, more luspatercept-treated patients achieved RBC-TI ≥ 8 weeks any time during treatment versus placebo (47.7% vs 15.8%)

– Approximately 70% of responders in the luspatercept arm had multiple response periods

• Luspatercept-treated patients had durable cumulative duration of RBC-TI and clinical benefit regardless of baseline transfusion burden

• Those TEAEs occurring more frequently with luspatercept resulted in very few discontinuations and decreased in incidence over time

• Luspatercept is a potential new therapy for the treatment of anemia in patients with LR-MDS with RS

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A phase 3 study evaluating the efficacy and safety of luspatercept versus epoetin alfa

in patients with LR-MDS who are ESA-naive and require RBC transfusions

Evaluating Luspatercept Responders in the Phase 3, Randomized, Double-Blind, Placebo-Controlled BELIEVE Trial of Luspatercept in Adult Beta-Thalassemia Patients

(Pts) Who Require Regular Red Blood Cell (RBC) Transfusions

Vip Viprakasit1*, Ali Taher2, Olivier Hermine3,4*, John Porter5*, Antonio Piga, MD6, Kevin H. M. Kuo, MD, MSc, FRCPC7, Thomas Coates, MD8,9, Ersi Voskaridou10*, Hong Keng Liew11*, Silverio Perrotta12*, Abderrahim Khelif13*, Antonis Kattamis,

MD14, Abderrahmane Laadem15, Jeevan K. Shetty16*, Wen-Ling Kuo15*, Dimana Miteva16*, Tatiana Zinger16*, Daniel Sinsimer15*, Peter G. Linde17 and Maria Domenica Cappellini, MD18

1Siriraj Hospital, Mahidol University, Bangkok, Thailand; 2Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 3Imagine Institute, INSERM U1163,

University of Paris, Paris, France; 4Department of Hematology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; 5University College London; University College London

Hospitals, London, United Kingdom; 6Department of Clinical and Biological Sciences, University of Turin, Orbassano, Torino, Italy; 7University Health Network, Toronto, ON, Canada8Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA; 9USC Keck School of Medicine, Los Angeles, CA; 10Thalassemia and Sickle Cell Center of

Laiko General Hospital, Athens, Greece; 11Hospital Sultanah Bahiyah, Alor Setar, Malaysia; 12Università della Campania, Luigi Vanvitelli, Caserta, Italy; 13Farhat Hached University Hospital,

Sousse, Tunisia; 14First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece; 15Celgene Corporation, Summit, NJ; 16Celgene International, Boudry,

Switzerland; 17Acceleron Pharma, Cambridge, MA; 18Fondazione IRCCS Ca’ Granda Policlinico Hospital, University of Milan, Milan, Italy

23

Thomas Coates, MDProfessor of pediatrics and pathology, Division of Hematology / Oncology, Children’s Hospital Los Angeles, University of Southern California

24

• Thalassemias are a group of hereditary blood disorders resulting from defects in hemoglobin (Hb) production

• Beta (β) thalassemia is caused by mutations in the HBB gene locus, affecting β-globin production resulting in either deficient or absent β-globin

• Imbalance of α- and β-globin leads to precipitation of excess alpha chains, leading to ineffective erythropoiesis and hemolysis

• Anemia is the primary manifestation of symptomatic β-thalassemia syndromes

BETA-THALASSEMIA

Data cutoff used for this analysis was January 7, 2019. a β-thalassemia or Hb E/β-thalassemia (compound β-thalassemia with mutation and/or multiplication of α-globin genes was allowed).b Patients could receive RBC transfusions and ICT to maintain their baseline Hb level. c The trial is fully enrolled and patients continue to receive treatment or follow-up.

BSC, best supportive care; Hb, hemoglobin; ICT, iron chelation therapy; RBC, red blood cell; s.c., subcutaneously.

Figure 1. Study Design of the BELIEVE Trial

Current studystatusc

Luspaterceptb

1 mg/kg s.c. every 21 days + BSC(n = 224)

Placebob

s.c. every 21 days + BSC(n = 112)

Post-treatmentfollow-up(3 years)

Ra

nd

om

ize

d

2:1

Stu

dy

un

blin

din

g

12-weekscreeningperiod

12-weekhistoricaltransfusions

Double-blind period(48 weeks)

Crossover from placebo toluspatercept permitted

Open-label(up to

5 years)

May be titrated up to 1.25 mg/kg

a-thalassemia

patients

regular RBC transfusions(defined as:

6–20 RBC units in the24 weeks prior to

randomization with no> 35-day transfusion-free period during that

time) (N = 336)

≥ 18 years, requiring

β

Figure 2. Achievement of RBC Transfusion Reduction in ITT Population

ITT, intent to treat; RBC, red blood cell.

0

10

20

30

40

50

60

70

80

90

Any 12 Weeks Any 12 Weeks Any 24 Weeks Any 24 Weeks

Pati

en

t sA

ch

ievi n

gR

ed

uc

tio

nin

Tra

nsfu

si o

nB

urd

en

( %)

Luspatercept (n = 224) Placebo (n = 112)

76.3%

(n = 171)

34.8%

(n = 39)

44.6%

(n = 100)

8.0%

(n = 9)

45.1%

(n = 101)

20.5%

(n = 46)2.7%

(n = 3)0.9%

(n = 1)

P < 0.0001

P < 0.0001 P < 0.0001

P < 0.0001

Data cutoff: January 7, 2019.

Figure 2. Response Periods for Patients in Luspatercept Arm Achieving ≥33% Reduction in RBC Transfusion

Burden Over Any 24 Weeks

Responders may have multiple and potentially overlapping response periods. The duration of response of a continuous response was defined as Last Day of Respsonse –

First Day of Response + 1. Analysis performed in the intent-to-treat population (n = 224 in the luspatercept arm). Data cutoff: January 7, 2019.

Table 3. Duration of Clinical Benefit for Luspatercept-Treated Patients

Characteristic Luspatercept (n = 224a)

Patients achieving clinical benefit,b n (%) 101 (45.1)

Duration of clinical benefit, median (range), weeks 76.3 (24.0–128.1)

Patients with no loss of response, n (%) 39 (17.4)

Patients achieving RBC-TI, n (%)

RBC-TI ≥ 8 weeks 25 (11.2)

RBC-TI ≥ 24 weeks 5 (2.2)

RBC-TI ≥ 48 weeks 3 (1.3)

Duration of RBC-TI, median (range), weeks

Duration of response in patients achieving RBC-TI ≥ 8 weeks 10.6 (8.0–106.3)

Duration of response in patients achieving RBC-TI ≥ 24 weeks 94.6 (32.1–106.3)

Duration of response in patients achieving RBC-TI ≥ 48 weeks 100 (94.6–106.3)

Mean reduction in RBC units transfused in clinical benefit responders vs baseline,c RBC units (U per 24 weeks)

Reduction in any 24 week period 6.69 (0.28)

Patients with > 15 RBC U/24 weeks at baseline 8.36 (0.35)

a Luspatercept intent-to-treat population. b Clinical benefit was defined as the time of first response (≥ 33% reduction in RBC transfusion over any 24 weeks) to discontinuation due to any cause at that episode. c For each patient, the 24 week period in which they received the fewest RBC transfusions was counted.

RBC, red blood cell; TI, transfusion independence. Data cutoff: January 7, 2019.

Table 4. AEs Occurring More Frequently in the Luspatercept Arm

AEs Luspatercept (n = 223a) Placebo (n = 109b)

Bone pain, n (%)

Incidence 45 (20.2) 9 (8.3)

Discontinuation due to bone pain 1 (0.4) 0

Arthralgia

Incidence 47 (21.1) 16 (14.7)

Discontinuation due to arthralgia 2 (0.9) 0

Dizziness

Incidence 27 (12.1) 5 (4.6)

Discontinuation due to dizziness 0 0

a Luspatercept safety population. b Placebo safety population.

AE, adverse event. Data cutoff: January 7, 2019.

SUMMARY

• Most patients with beta-thalassemia who achieved clinical benefit with

luspatercept experienced multiple episodes of clinically meaningful transfusion

burden reduction and had durable clinical benefit over the follow-up period

• The incidence of AEs with luspatercept was consistent with the previously

reported 48-week safety profile, was not associated with dose level, and

decreased over time with no impact on treatment modification or continuation

• Patients continue to be monitored for safety

31

An ongoing phase 2 study to determine the efficacy and safety of luspatercept in adult

patients with non-transfusion dependent beta-thalassemia

ABSTRACT 557

A Phase 2 Study of Luspatercept in Patients With Myelofibrosis-Associated

Anemia

Aaron T. Gerds1, Alessandro M. Vannucchi2, Francesco Passamonti3, Marina Kremyanskaya4, Jason Gotlib5, Jeanne M. Palmer6, Kelly McCaul7, Vincent Ribrag8, Adam J. Mead9, Claire Harrison10, Ruben Mesa11,

Jean-Jacques Kiladjian12, Giovanni Barosi13, Robert Peter Gale14,15, Abderrahmane Laadem15, Joseph Pariseau15, Torsten G. Gerike15, Jennie Zhang15, Peter G. Linde16, Joseph G. Reynolds16, Srdan Verstovsek17

1Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA; 2Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Florence, Italy; 3Department of Medicine and Surgery, University of Insubria, Varese, Italy; 4Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA;

5Stanford Cancer Institute, Stanford, CA, USA; 6Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA; 7Avera Cancer Institute, Sioux Falls, SD, USA; 8Institut Gustave Roussy, Villejuif, France; 9Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 10Guy's and St Thomas' NHS Foundation Trust, London, UK; 11Mays Cancer Center, UT Health San Antonio

Cancer Center, San Antonio, TX, USA; 12Hôpital Saint-Louis et Université Paris Diderot, Paris, France; 13IRCCS Policlinico San Matteo Foundation, Pavia, Italy; 14Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK; 15Bristol-Myers Squibb, Summit, NJ, USA;16Acceleron Pharma, Cambridge, MA,

USA; 17Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Presented at the 61st Annual Meeting of the American Society of Hematology (ASH); December 7–10, 2019; Orlando, FL, USA.

33

Srdan Verstovsek, MD, PhDDepartment of Leukemia, Division of Cancer MedicineMD Anderson Cancer Center

MYELOFIBROSIS

Myelofibrosis patient characteristics at diagnosis and 1 year after diagnosis

At Diagnosis

(n = 340)

After 1 Year of

Diagnosis

(n = 386)

Hemoglobin < 10 g/dL 38% 64%

Platelet count < 100 × 109/L 18% 31%

Circulating blasts ≥ 1% 45% 66%

Requires transfusions 24% 45%

Constitutional symptoms 29% 34%

Splenomegaly > 10 cm 21% 46%

Unfavorable karyotype 10% 18%

Tefferi A, et al. Mayo Clin Proc, 2012;87:25-33.

ANEMIA IN MYELOFIBROSIS

No anemia

N=159; median survival 7.9 years

Mild anemia


Moderate anemia


Severe anemia


• Severe anemia (Hgb level of <8

g/dL or transfusion dependence)

associated with >1.5-fold increase

in risk of death, compared to

moderate anemia.

• DIPSS-plus prognostic tool places

extra emphasis on transfusion

requirement (2 points) and non-TD

anemia (Hgb < 10g/dL; 1 point).

Nicolosi et al; Leukemia 2018

Baseline Anemia:

Mild = Hgb ≥10 g/dl but below lower limit of normal

Moderate = Hgb between 8 g/dl and <10 g/dl;

Severe = Hgb <8 g/dl or transfusion dependent.

RBC transfusion

dependent

within last

12 weeksb

No RBC

transfusions

within last

12 weeks

STUDY DESIGN

Day 169

Disease

response

assessment

Follow-up

3 years post

last dose

a A stable daily dose of RUX for at least 16 weeks at enrollment. b 2–4 RBC U/28 d transfused within last 12 weeks.

d, day; RUX, ruxolitinib; U, unit.

Receiving

stable dose

of RUXa

Cohort 3A

(n = 14)Cohort 1

(n = 22)

Cohort 3B

(n = 19)

Not

receiving

RUXa

Cohort 2

(n = 21)

If clinical benefit

Continue study

treatment

If no clinical benefit

Discontinue study

treatment

Luspatercept

1.0 mg/kg with

titration up to

1.75 mg/kg

every 21 d

for 168 d

(N = 76)

Primary phase of the

treatment period

Extension phase of

the treatment period

• No RBC transfusions (Cohorts 1 & 3A)

– No RBC transfusions within 12 weeks before enrollment

– Hb levels ≤ 9.5 g/dL (recorded on 3 separate occasions, with ≥ 14 d between each measurement)

• RBC transfusions (Cohorts 2 & 3B)

– RBC transfusion dependent (2–4 RBC U/28 d within 12 weeks before enrollment)

– No transfusion-free interval > 6 weeks

BASELINE PATIENT CHARACTERISTICS

Characteristic

No RBC Transfusionsa RBC Transfusion Dependenta

Overall(N = 76)

Not Receiving RUXb Receiving RUXb Not Receiving RUXb Receiving RUXb

Cohort 1(n = 22)

Cohort 3A(n = 14)

Cohort 2(n = 21)

Cohort 3B(n = 19)

Age, median (range), years 69.0 (50–89) 64.5 (51–81) 75.0 (59–88) 72.0 (59–83) 71.0 (50–89)

Male, n (%) 13 (59) 7 (50) 15 (71) 9 (47) 44 (58)

Most recent pathology, n (%)

Primary MF 15 (68) 7 (50) 13 (62) 8 (42) 43 (57)

Post-ET MF 7 (32) 3 (21) 6 (29) 6 (32) 22 (29)

Post-PV MF 0 4 (29) 2 (10) 5 (26) 11 (15)

Time since initial MF diagnosis

≤ 2 years, n (%) 10 (46) 2 (14) 6 (29) 1 (5) 19 (25)

> 2 years, n (%) 12 (55) 12 (86) 15 (71) 18 (95) 57 (75)

DIPSS risk categoryc

Intermediate-1 1 (5) 4 (29) 1 (5) 1 (5) 7 (9)

Intermediate-2 18 (82) 9 (64) 15 (71) 18 (95) 60 (79)

High 2 (9) 1 (7) 5 (24) 0 8 (11)

Baseline Hb level, median (range), g/dL 8.8 (6.7–10.0) 8.6 (6.7–9.1) N/A N/A N/A

Baseline RBC transfusion burden, median (range), U/28 d N/A N/A 2.7 (1–5) 2.3 (2–4) N/A

a In the 12 weeks prior to treatment. b A stable daily dose of RUX for ≤ 16 weeks at enrollment. c DIPSS category unknown for 1 patient.

DIPSS, Dynamic International Prognostic Scoring System; N/A, not applicable.

Preliminary findings – data cutoff: Aug 5, 2019

BASELINE PATIENT CHARACTERISTICS (cont.)

Characteristic


Overall(N = 76)


Cohort 1(n = 22)

Cohort 3A(n = 14)

Cohort 2(n = 21)

Cohort 3B(n = 19)

Baseline serum erythropoietin, median (range), U/L 52 (7–1,997) 158 (30–2,395) 140 (16–1,594) 87 (6–915) 97 (6–2,395)

Platelet count, median (range), × 109/L 167 (33–434) 260 (54–667) 128 (38–880) 118 (75–335) 150 (33–880)

Prior therapy received, n (%)c

ESAs 6 (27) 2 (14) 6 (29) 2 (11) 16 (21)

Danazol 3 (14) 0 7 (33) 0 10 (13)

Thalidomide 0 0 1 (5) 0 1 (1)

Lenalidomide 0 0 2 (10) 0 2 (3)

RUXd 2 (9) N/A 6 (29) N/A N/A

RUX daily dose received, median (range), mg/de N/A 20 (5–50) N/A 20 (5–40) N/A

Duration of prior RUX therapy, median (range), weeks N/A 57 (22–315) N/A 69 (30–411) N/A


a In the 12 weeks prior to treatment. b A stable daily dose of RUX for ≤ 16 weeks at enrollment. c Not received within the 16 weeks prior to enrollment. d The patients who received prior

RUX in Cohorts 1 and 2 did not receive RUX within the 16 weeks prior to enrollment. e Within the 16 weeks prior to enrollment.

TREATMENT EXPOSURE

Characteristic


Overall(N = 76)


Cohort 1(n = 22)

Cohort 3A(n = 14)

Cohort 2(n = 21)

Cohort 3B(n = 19)

Treatment duration, median (range), weeks 24.0 (2.1–60.1) 24.2 (10.7–85.6) 24.0 (11.4–53.7) 24.0 (3.0–82.0) 24.0 (2.1–85.6)

Number of doses received, median (range) 8 (1–19) 8 (3–26) 8 (4–18) 8 (1–28) 8 (1–28)

Dose escalations, n (%)

1.33 mg/kg 19 (86) 11 (79) 21 (100) 14 (74) 65 (86)

1.75 mg/kg 14 (64) 9 (64) 17 (81) 10 (53) 50 (66)

On treatment at time of data cutoff, n (%) 7 (32) 3 (21) 3 (14) 6 (32) 19 (25)

RUX daily dose received, median (range), mg/dc N/A 20 (5–50) N/A 20 (5–40) N/A


a In the 12 weeks prior to treatment. b A stable daily dose of RUX for ≤ 16 weeks at enrollment. c Within the 16 weeks prior to enrollment.

• RUX daily dose remained stable throughout the 24-week treatment period in both

Cohorts 3A and 3B

ACHIEVEMENT OF THE PRIMARY AND SECONDARY EFFICACY ENDPOINTS

a For patients not receiving RBC transfusions: Hb increase ≥ 1.5 g/L at every assessment from baseline for ≥ 12 consecutive weeks, within the first 24 weeks

on study. For patients receiving RBC transfusions: RBC transfusion free for ≥ 12 consecutive weeks, within the first 24 weeks on study.b For patients not receiving RBC transfusions: mean Hb increase ≥ 1.5 g/dL from baseline for ≥ 12 consecutive weeks. For patients receiving RBC

transfusions: ≥ 50% reduction in RBC transfusion burden from baseline.

14%10%

21%

32%

18%

38%

64%

53%

0%

10%

20%

30%

40%

50%

60%

70%

Cohort 1 Cohort 2 Cohort 3A Cohort 3B

Pa

tie

nts

Ac

hie

vin

g E

nd

po

int

(%)

Primary endpoint Secondary endpointa b

Patients Not Receiving RUX

Number of responders 3 4 2 8 3 9 6 10

• The median duration of RBC transfusion independence ≥ 12 weeks was 32 and 39 weeks for Cohorts 2 and 3B

Patients Receiving RUX

(No transfusions) (No transfusions)(Transfusions) (Transfusions)

SAFETY

Patient Safety Assessment



Cohort 1(n = 22)

Cohort 3A(n = 14)

Cohort 2(n = 21)

Cohort 3B(n = 19)

≥ 1 treatment-related TEAE (any grade), n (%) 14 (64) 7 (50) 5 (24) 4 (21)

≥ 1 treatment-related grade 3–4 TEAE, n (%) 0 2 (14) 0 1 (5)

≥ 1 treatment-related SAE, n (%)c 1 (5) 0 0 1 (5)

TEAE leading to death, n (%)d 1 (5) 0 3 (14) 3 (16)

TEAE leading to treatment discontinuation, n (%)e 0 2 (14) 2 (10) 3 (16)


• The most common treatment-related TEAEs (any grade) were hypertension (12% of patients), bone pain (9%), and diarrhea (5%)

• Three grade 3 TEAEs were considered treatment related: single cases of hypertension, diarrhea, and dehydration

– No treatment-related grade 4 or 5 TEAEs were reported

• Grade 3 hypertension was reported in 3 (4%) patients; none led to treatment discontinuation

– No grade 4 hypertension events were reported

• One transformation to blast phase occurring after the end of treatment visit, but was not considered related to treatment

a In the 12 weeks prior to treatment. b A stable daily dose of RUX for ≤ 16 weeks at enrollment. c individual cases of diarrhea, enteritis, and urinary tract infection. d The 7 TEAEs leading

to death were multiple organ dysfunction syndrome, pneumonia, septic shock, post-procedural hemorrhage, subdural hematoma, myelofibrosis, and ischemic stroke. e TEAEs were

individual cases of anemia, splenomegaly, fatigue, general physical health deterioration, pyelonephritis, sepsis, urinary tract infection, and diverticular perforation.

SAE, serious adverse event.

SUMMARY

• The initial results from this ongoing study suggest clinical activity of

luspatercept in patients with MF-associated anemia

• Luspatercept improved anemia in those receiving and not receiving RBC

transfusions, with more profound effects in patients treated with RUX

• The majority of adverse events were grade 1–2 in severity, consistent

with previous studies of luspatercept in myelodysplastic syndromes and

β-thalassemia

43

A Phase 3 double-blind, randomized study to compare the efficacy and safety of

luspatercept versus placebo in subjects with myeloproliferative neoplasm-associated

myelofibrosis on concomitant JAK 2 inhibitor therapy and who require red blood cell

transfusions

REBLOZYL CommercialSujay KangoChief Commercial Officer

45

Acceleron Commercial Footprint in Beta-Thalassemia Focused around Centers of Excellence (CoEs) and Key Accounts


UCSF Benioff

Children’s

Hospital of Los

Angeles

Texas Children's

Hospital

(Houston)

Children’s

Health Dallas

Children’s

Hospital of

Philadelphia

Children’s

Healthcare of

Atlanta

Boston

Children’s

Hospital

Weill Medical

College

Hospital of the

University of

Pennsylvania

Lurie

Children’s

Hospital

of

Chicago

Lower patient density Higher patient density

Centers of Excellence Acceleron Commercial Footprint

✓ 20 top caliber field team (including field management)

✓ 80 new products/indications total combined launches

✓ Average 13+ years in hematology/oncology experience

46

Joint Launch Execution with Celgene/BMS Ongoing as Planned


▪ Joint launch training meeting with Celgene/BMS held on Nov 4-8th

▪ Final REBLOZYL package insert (PI) received on Nov 11th

▪ Sales team initiated promotional activities on Nov 12th with approved PI

▪ CoEs and Key accounts engaged in the first month of launch

▪ Early indicators suggest no access barriers

▪ Strong collaboration amongst Acceleron and Celgene/BMS teams

47

Successful ASH execution for REBLOZYL


▪ ASH Executed successfully jointly with BMS

▪ High level of interest based on Acceleron, BMS booth traffic

▪ Education Sessions-Product Theater in approved indication

▪ Partnerships with Cooley’s Anemia Foundation (CAF) and Thalassemia International Federation (TIF)

▪ Collaborative dialogue with multiple tertiary academic centers

▪ Internal preparation on potential MDS approval underway

48

ASH 2019 Question & Answer Session


Habib Dable Chief Executive Officer, Acceleron

Jay Backstrom, MD, MPH EVP, Head of Research and Development, Acceleron

Rami Komrokji, MD Moffitt Cancer Center, Senior Member & Professor of Oncologic Sciences, Section Head- Leukemia and MDS, Vice Chair-Malignant Hematology Department

Thomas Coates, MD Professor of Pediatrics and Pathology, Division of Hematology / Oncology, Children’s Hospital Los Angeles, University of Southern California

Srdan Verstovsek, MD, PhD Department of Leukemia, Division of Cancer MedicineMD Anderson Cancer Center

Sujay Kango Chief Commercial Officer, Acceleron

Todd James, IRC VP, Investor Relations and Corporate Communications, Acceleron

highlights from ash 2019...2019/12/09 · highlights from ash 2019 december 10, 2019 2 this...

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