Acceleron Forward-Looking Statements This presentation contains forward-looking statements about the Company's strategy, future plans and prospects, including statements regarding the development of the Company's compounds, including sotatercept, luspatercept, dalantercept, ACE-083, ACE-2494, the Company’s IntelliTrap™ drug discovery platform, and the Company's TGF-beta superfamily program generally, the timeline for clinical development and regulatory approval of the Company's compounds, the expected timing for the reporting of data from ongoing trials, and the structure of the Company's planned or pending clinical trials. The words “anticipate,” “appear,” “believe,” “continue,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks that the Company's cash, cash equivalents and investments will be insufficient to fund operations into the second half of 2019, that preclinical testing of the Company's compounds and data from clinical trials may not be predictive of the results or success of ongoing or later clinical trials, that data may not be available when the Company expects it to be, that the Company or its collaboration partner, Celgene, will be unable to successfully complete the clinical development of the Company’s compounds, that the development of the Company's compounds will take longer or cost more than planned, that the Company or Celgene may be delayed in initiating or completing any clinical trials, and that the Company's compounds will not receive regulatory approval or become commercially successful products.
Other risks and uncertainties include those identified under the heading "Risk Factors" included in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 25, 2016, 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. 2
We Are Building One of the Industry’s Most Robust Pipelines Preclinical
Luspatercept Myelodysplastic Syndromes β-Thalassemia
Sotatercept Dalantercept ACE-083
Renal Cell Carcinoma
FSH Muscular Dystrophy Muscle / Bone Loss
ACE-3891
Muscle
ACE-1332 ACE-2798
Fibrosis
ACE-2536 ACE-2395
Undisclosed
ACE-661
Undisclosed
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MEDALIST Study BELIEVE Study
Phase 2
Phase 3
Hematology
Chronic Kidney Disease
ACE-2494
Phase 1
Fibrosis
Oncology
Neuromuscular diseases Fibrotic diseases
Undisclosed
Four internally discovered therapeutic candidates in clinical trials Fifth to file IND by end of year Goal of new molecule to enter clinic every 12-18 months with at least 8 therapeutic candidates in clinic by 2020
Collaborating with the Leader in Hematology
Luspatercept & Sotatercept Collaboration Highlights Celgene funds 100% of development costs Acceleron will receive tiered royalties in the low-to-mid 20% range $330M of milestones still outstanding for development and regulatory achievements plus $230M for commercial achievements Companies will co-promote in North America, Celgene promotes rest of world Celgene funds 100% of Acceleron’s commercialization costs for North American co-promote
Celgene’s Franchise in Hematology 2015 Hematology Sales of >$6.7B Granted regulatory approvals in nearly 70 countries
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Luspatercept: Innovation in Hematology Current anemia therapies (erythropoiesis-stimulating agents (ESA)/EPO) generate $6B-$8B in annual sales, primarily in end-stage renal disease patients
ESAs have shown limited to no efficacy treating a variety of anemias Luspatercept’s mechanism of action is distinct from ESAs and is being developed initially in anemias that are non-responsive to ESAs Initially targeting Myelodysplastic Syndromes (MDS) and beta-thalassemia – Each indication has blockbuster potential – Several opportunities for follow-on indications
Luspatercept is being co-developed with Celgene, the leading global marketer of hematology therapies
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Luspatercept in MDS
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Myelodysplastic Syndrome (MDS): Disease Overview
DISEASE
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PREVALENCE
CURRENT TREATMENTS
bone marrow failure disorder resulting in low blood cell count
NCI estimates >10,000 people are diagnosed with MDS in the U.S. each year
Erythropoiesis-Stimulating Agent (ESA) treatment, RBC transfusion, immunomodulatory drugs/ chemotherapeutics
Nearly all patients have anemia, creating significant symptom burden
≈ 100,000 lower-risk MDS patients in the U.S. and E.U.
RBC transfusions are burdensome and increase risk of iron overload
Luspatercept Target Population in Ongoing MDS Phase 3 Study Represents Roughly 50% of All Lower Risk MDS Patients Lower Risk MDS patients (100K pts US/EU) del5q (~15%)
lenalidomide
Non-del5q (~85%)
ESA
Luspatercept
(EPO≤200)
(EPO>200 and RS+)
Luspatercept
2nd Line
(RS+)
lenalidomide azacitadine decitabine 8
1St Line
3rd Line
Therapeutic Goal in MDS: Reduce/Eliminate RBC Transfusions Luspatercept Activity in Low-Risk MDS ERYTHROID RESPONSE (IWG HI-E )
69% (9/13) LTB* patients achieved IWG HI-E response for mean hemoglobin increase 68% (13/19) HTB patients achieved IWG HI-E criteria of a reduction of ≥4 units RBC over 8 weeks TRANSFUSION INDEPENDENCE
50% (11/22**) patients who were transfused prior to study achieved RBC transfusion independence (TI) ≥ 8 weeks Duration of TI ranges from 9-50+ weeks with many ongoing
responses
Results presented at ASH December 2015 * Low transfusion burden (LTB) patients (< 4 Units/8 wk, Hb < 10 g/dL) 9
** RBC-TI: RBC transfusion independent ≥ 8 weeks; includes 19 HTB patients and 3 LTB patients evaluable for transfusion independence (at least 2 Units over 8 weeks pre-treatment)
Increase in Mean Hemoglobin in LTB Patients 69% (9/13) LTB patients achieved IWG HI-E response for mean Hb increase – IWG HI-E response criteria of ≥1.5 g/dL Hb increase for ≥8 weeks Baseline from Change Hemoglobin Hgb Change from Baseline (g/dL) (g/dL)
Acce le ron Pharma - Protocol: A536-05 Pre liminary Data as of Aug 31, 2015
Figure 1.C4 Hemoglobin Mean Change From Baseline(Low Transfusion Burden)
44.0 3.5
33.0
IWG HI-E Responders (n=9)
2.5
22.0
All (n=13)
1.5
IWG HI-E Non-Responders (n=4)
11.0 0.5
HI-E Responders High Dose Group
00.0 0
1
0
Non-Responders
2
1
3
2
4
3
5
4
6
5
Months
7
6
7
8
9
8
9
10
# of subjects:
Resp Non-Resp High
9
9
6
9
6
6
9
9
6
8
6
6
9
7
6
9
9
9
7
8
8
6
5
4
4
4
4
4
4
4
4
3
4
3
4
4
3
4
Months
9
4
3
4
4
4
2
2
1
1
13
13
10
13
10
10
13
13
10
11
10
9
13
11
9
13
12
13
13
11
10
10
7
6
Note: Direct rollover patients use both 03/05 data and Interrupted patients use 05 data only Results # of subjects = Number of Observations at T ime point in dose group Patient calculated study days which are +/- 3 days of a scheduled study day are windowed to that study day Baseline=Mean of 2 or more pretreatment Hgb values between (-28