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Jefferies 2015 Global Healthcare Conference

June 1, 2015

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Acceleron Forward-Looking Statements

This presentation contains forward-looking statements. Forward-looking statements are neitherhistorical facts nor assurances of future performance. Instead, they are based on our currentbeliefs, expectations and assumptions regarding the future of our business, future plans andstrategies, 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 thenegative of these terms or other similar expressions are intended to identify forward-lookingstatements, although not all forward-looking statements contain these identifying words.

We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-lookingstatements. Actual results or events could differ materially from the plans, intentions andexpectations disclosed in the forward-looking statements we make.

Risks and uncertainties are identified under the heading “Risk Factors” included in theCompany’s Annual Report on Form 10-K which was filed with the Securities and ExchangeCommission (SEC) on March 2, 2015, and other filings that the Company has made and maymake with the SEC in the future. The forward-looking statements contained in this presentationreflect the Company’s current views with respect to future events, and the Company does notundertake and specifically disclaims any obligation to update any forward-looking statements.

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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

• 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

Red Blood Cells

Luspatercept

RBC/Bone

Sotatercept

Vasculature

Dalantercept

Muscle/Bone

ACE-2491

Adipose

ACE-2791

Fibrosis

ACE-2531

Muscle

ACE-083 (local)

ACE-3891

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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 13th 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

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Luspatercept for Myelodysplastic Syndromes (MDS)

Phase 3 start expected 2015in collaboration with Celgene

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Poor Red Blood Cell Maturation in MDSInability 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

High EPO levels drive proliferation

But excessive Smad2/3 signaling inhibits RBC maturation

ReticBaso EBFU-E CFU-E Pro E RBCPoly E Ortho E

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Luspatercept is ligand trap that inhibits Smad2/3 signaling and promotes the

maturation of RBCs.

ReticBaso EBFU-E CFU-E Pro E RBCPoly E Ortho E

Luspatercept promotes differentiation and maturation by trapping Smad2/3 activating ligands

Poor Red Blood Cell Maturation in MDSImprovement of RBC maturation with luspatercept

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Luspatercept Opportunity in MDS

EPO or RBC Transfusions

Lower Risk MDS(87,000 patients US/EU5)

Revlimid®Vidaza®

Dacogen®

Patient Population

Treatment

AlgorithmLuspatercept

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Luspatercept in MDS: Encouraging Preliminary Phase 2 Data Data presented at 13th 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

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Luspatercept Opportunity in MDS

EPO or RBC Transfusions

Lower Risk MDS(87,000 patients US/EU5)

Revlimid®Vidaza®

Dacogen®

Patient Population

Treatment

AlgorithmLuspatercept

We estimate there are between

26,000 – 43,000RS+ patients in

US/EU5

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Luspatercept for Beta-Thalassemia

Phase 3 start expected 2015in collaboration with Celgene

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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

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Beta-Thalassemia

Beta-Thalassemia

Patient Population

Pathologies

and Current

Treatments

Non-TransfusionDependent

(20,000+ patients US/EU)

TransfusionDependent

(20,000 patients US/EU)

• Anemia, vasoocclusion, splenomegaly, foot ulcers and in 2nd 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

Data as of 10 Oct 14

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Exjade® (deferasirox): Iron Chelator as an Indicator of the Commercial Opportunity in β-Thalassemia

Source: Evaluate Pharma

$0

$100

$200

$300

$400

$500

$600

$700

$800

$900

$1,000

2006 2007 2008 2009 2010 2011 2012 2013 2014

ROW

US

$ m

illio

n

• Iron overload leads to liver fibrosis and heart failure and is a major cause of morbidity and mortality in beta-thalassemia

• Exjade, the predominant therapy to treat iron overload, had 2014 WW annual sales of >$900M

• Iron overload is measured by liver iron concentration

• In a phase 3 study that included transfusion dependent beta-thalassemia patients, Exjade reduced LIC by 2.4 mg/g dry weight after 12 months of treatment

• In a phase 3 study that included non-transfusion dependent beta-thalassemia patients, Exjade reduced LIC by 1.5 – 3.8 mg/g dry weight after 12 months of treatment

Exjade Annual Sales

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Reduced Liver Iron Concentration (LIC by MRI) in NTD PatientsLuspatercept -Thalassemia Phase 2 Clinical Trial

Data as of 10 Oct 2014

Baseline LIC ≥ 5 mg/g dry weight (dw)

-5

-4

-3

-2

-1

0

1

2

3

On iron chelator

No iron chelatorCh

ange

fro

m B

ase

line

at4

mo

nth

s in

LIC

(m

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dw

)

Dose (mg/kg)

0.2 0.4 0.6 1.0

Phase 3 study in NTD patients Exjade reduced LIC by 1.5 – 3.8 mg/g dry weight after 12 months of treatment

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Luspatercept in Beta-Thalassemia

Patient Population

Pathologies

and Current

Treatments

Non-TransfusionDependent

(20,000+ patients US/EU)

TransfusionDependent

(20,000 patients US/EU)

• Anemia, vasoocclusion, splenomegaly, foot ulcers and in 2nd decade iron overload

• Occasional transfusions for severe anemic episodes, iron chelation

• Dose dependent increases in hemoglobin

• Dose dependent decreases in liver iron concentration in 9/12 iron overloaded patients

• Significant healing of leg ulcers

• Life threatening anemia, rapid iron overload

• Regularly scheduled transfusions

• Iron chelation• Bone marrow transplants

• Substantial reductions in transfusion burden

• Liver iron concentration decreases in 4/5 iron overloaded patients

• Significant healing of leg ulcers

Luspatercept

activity in Ph2

clinical trials

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Luspatercept Opportunity in MDS

EPO or RBC Transfusions

Lower Risk MDS(87,000 patients US/EU5)

Revlimid®Vidaza®

Dacogen®

Patient Population

Treatment

AlgorithmLuspatercept

We estimate there are between

26,000 – 43,000RS+ patients in

US/EU5

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Building a Hematology Franchise with Celgene

• 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

Acceleron and Celgene are collaborating on the development and commercialization of sotatercept and luspatercept

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Dalantercept

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

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Tumor secretes pro-angiogenic

factors e.g. VEGF

VEGF induces EC proliferation

Step 1

ALK1 mediates vessel maturation

and pericyte coverage

Step 2

VEGF Receptor ALK1 ReceptorMature Vessel

Proliferation Maturation

Concept: Inhibit sequential steps in pathway to generate synergistic inhibition

Two Key Steps in AngiogenesisEndothelial Cell Proliferation and Vessel Formation/Maturation

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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

DiseaseWorldwide anti-VEGF

2014 Revenue1

NSCLC $1.2B

Colorectal $3.9B

RCC $2.8B

HCC $0.8B

1) EvaluatePharma

• 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

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DART Study Part 1 – Study Schema

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DART Study Part 1 – Best Overall Response

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DART Study Part 1 – Treatment Duration

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DART Study Part 1 – Response Rates

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• 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

Dart Study Part 1 Conclusions

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DART Study Part 2 Study SchemaOn Track For early 2016 Accrual

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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 beta-

thalassemia 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

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Acceleron’s 2020 Vision

• 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

20202015

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

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Thank You

Building one of the world’s great biotechnology companies

www.acceleronpharma.comNASDAQ: XLRN