U.S. markets closed

Acceleron Announces Publication in Science Translational Medicine Describing the Underlying Biology Behind Sotatercept’s Potential as a Novel Therapy in Pulmonary Arterial Hypertension

Preclinical research of murine version of sotatercept reveals significant role of key TGF-beta superfamily proteins, including activin and growth differentiation factor ligands, in pulmonary vascular disease; points to therapeutic strategy in pulmonary arterial hypertension (PAH)

Acceleron Pharma Inc. (Nasdaq: XLRN), a biopharmaceutical company dedicated to the discovery, development, and commercialization of TGF-beta superfamily therapeutics to treat serious and rare diseases, today announced that research published in the journal Science Translational Medicine describes how a murine version of the investigational agent sotatercept acts to restore balance in key signaling pathways whose disruption drives the disease pathology of pulmonary arterial hypertension (PAH).

The research may provide a mechanistic rationale for the positive topline results reported earlier this year from the PULSAR Phase 2 clinical trial of sotatercept in patients with PAH.

The article reports that in experimental human cell-based tissue and animal models of pulmonary hypertension and PAH, sotatercept exhibited consistent effects across multiple components of disease, including suppressed proliferation of pulmonary arterial smooth muscle and microvascular endothelial cells, reduced pulmonary pressures, lessened right ventricular hypertrophy, improved right ventricular function, and attenuated vascular remodeling. The anti-remodeling effects were not seen with a PAH standard-of-care therapy included in the study as a comparator. The researchers concluded that sotatercept exerted its beneficial effects on these pathologic hallmarks by selectively binding the TGF-beta superfamily ligands activin A, activin B, and growth differentiation factor (GDF) 8 and GDF11. Signaling of these ligands, which may induce cellular proliferation, has been found to be upregulated in PAH—which in turn may impair signaling of bone morphogenetic protein receptor type 2 (BMPR-II), which is thought to be protective.

"Dysregulated BMP and TGF-beta signaling has long been implicated in the pathology of PAH," said Paul B. Yu, M.D., Ph.D., Associate Physician, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Associate Professor of Medicine, Harvard Medical School, and the study’s principal investigator. "Here we demonstrate that the murine version of sotatercept rebalances this signaling to improve hemodynamics and attenuate vascular remodeling, at the same time revealing how large a role activin A, activin B, GDF8, and GDF11 play as drivers of pulmonary vascular disease. Targeting these ligands with sotatercept to restore balanced signaling could represent a promising therapeutic approach."

"The publication of Paul Yu’s elegant research highlights the importance of TGF-beta superfamily biology to the underlying pathology of pulmonary vascular disease and provides biological support for sotatercept’s activity in PAH," said Jay T. Backstrom, M.D., M.P.H., Executive Vice President and Head of Research and Development at Acceleron. "Based on our recent clinical trial results establishing proof-of-concept, we have great enthusiasm for sotatercept’s potential as a novel therapy for patients with PAH. This research brings added confidence in and clarity to the underlying biology behind sotatercept’s hypothesized mechanism of action as we shape our clinical development plans in the pulmonary space."

About Sotatercept

Sotatercept is an investigational agent designed to be a selective ligand trap for members of the TGF-beta superfamily to rebalance BMPR-II signaling, which is a key molecular driver of PAH. Recent topline analysis of the PULSAR Phase 2 trial of sotatercept in patients with PAH revealed the trial met the primary as well as key and other secondary endpoints, with adverse events consistent with previously published data on sotatercept in other diseases. Sotatercept, which is part of a licensing agreement with Bristol Myers Squibb, is also being evaluated in the exploratory, open-label SPECTRA Phase 2 trial in patients with PAH. For more information, please visit www.clinicaltrials.gov

Sotatercept, which has been granted Breakthrough Therapy designation from the U.S. Food and Drug Administration and Priority Medicine (PRIME) designation from the European Medicines Agency in PAH, is an investigational therapy that is not approved for any use in any country.

About PAH

PAH is a rare and chronic, rapidly progressing disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. PAH results in significant strain on the heart, often leading to limited physical activity, heart failure, and reduced life expectancy. The 5-year survival rate for patients with PAH is approximately 57%. Available therapies generally act by promoting the dilation of pulmonary vessels without addressing the underlying cause of the disease. As a result, PAH often progresses rapidly for many patients despite standard of care treatment. A growing body of research has implicated imbalances in BMP and TGF-beta signaling as a primary driver of PAH in familial, idiopathic, and acquired forms of the disease.

About Acceleron

Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. Acceleron’s leadership in the understanding of TGF-beta superfamily biology and protein engineering generates innovative compounds that engage the body's ability to regulate cellular growth and repair.

Acceleron focuses its commercialization, research, and development efforts in hematologic and pulmonary diseases. In hematology, Acceleron and its global collaboration partner, Bristol Myers Squibb, are co-promoting REBLOZYL® (luspatercept-aamt), the first and only approved erythroid maturation agent, in the United States for the treatment of anemia in certain blood disorders. The Companies are also developing luspatercept for the treatment of anemia in patient populations of MDS, beta-thalassemia, and myelofibrosis. In pulmonary, Acceleron is developing sotatercept for the treatment of pulmonary arterial hypertension, having recently reported positive topline results of the Phase 2 PULSAR trial.

For more information, please visit www.acceleronpharma.com. Follow Acceleron on social media: @AcceleronPharma and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements about Acceleron’s strategy, future plans and prospects, including statements regarding the development of sotatercept in PAH, the timeline for clinical development and regulatory approval of sotatercept in PAH, the expected timing for reporting of data from ongoing clinical trials, and the potential of Acceleron’s compounds as therapeutic drugs. The words "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "may," "plan," "possible," "potential," "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.

Actual results could differ materially from those included in the forward-looking statements due to various factors, risks and uncertainties, including, but not limited to, that preclinical testing of Acceleron’s compounds and data from clinical trials may not be predictive of the results or success of ongoing or later clinical trials, that regulatory approval of Acceleron’s compounds in one indication or country may not be predictive of approval in another indication or country, that the development of Acceleron’s compounds will take longer and/or cost more than planned, that Acceleron will be unable to successfully complete the clinical development of Acceleron’s compounds, that Acceleron may be delayed in initiating, enrolling or completing any clinical trials, that Acceleron’s compounds will not receive regulatory approval or become commercially successful products, and that Breakthrough Therapy or PRIME designation may not expedite the development or review of sotatercept. These and other risks and uncertainties are identified under the heading "Risk Factors" included in Acceleron’s most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q, and other filings that Acceleron has made and may make with the SEC in the future.

The forward-looking statements contained in this press release are based on management's current views, plans, estimates, assumptions, and projections with respect to future events, and Acceleron does not undertake and specifically disclaims any obligation to update any forward-looking statements.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200513005780/en/

Contacts

Acceleron Pharma Inc.

Investors:
Todd James, 617-649-9393
Senior Vice President, Corporate Affairs and Investor Relations

Media:
Matt Fearer, 617-301-9557
Director, Corporate Communications