xlrn-20201113
0001280600false00012806002020-11-132020-11-13


UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C.  20549
 
___________________________
 
FORM 8-K
___________________________

CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
 
Date of Report (Date of earliest event reported):  November 13, 2020
 ___________________________
 
ACCELERON PHARMA INC.
(Exact name of Registrant as specified in its charter)
 

Delaware
001-36065
27-0072226
(State or other jurisdiction
of incorporation)
(Commission
File Number)
(I.R.S. Employer
Identification Number)

128 Sidney Street
Cambridge,
MA
02139
(Address of principal
executive offices)
(Zip Code)
 

Registrant’s telephone number, including area code:  (617) 649-9200
 
Not Applicable
(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
            Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
            Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
            Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
            Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Exchange Act:
Title of each classTicker Symbol(s)Name of each exchange on which registered
Common Stock, $0.001 per shareXLRNThe Nasdaq Global Market
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company           
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.           





Item 7.01    Regulation FD Disclosure.

On November 13, 2020, Acceleron Pharma Inc. (the "Company") issued a press release titled "Acceleron Presents New Data from the PULSAR Phase 2 Trial, Preclinical Research on Sotatercept in Pulmonary Arterial Hypertension (PAH) at the 2020 American Heart Association (AHA) Scientific Sessions." A copy of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K.

On November 13, 2020, the Company also issued a press release titled "Acceleron Presents Preliminary Interim Data from the SPECTRA Phase 2 Trial of Sotatercept in Pulmonary Arterial Hypertension (PAH) at the 2020 American Heart Association Scientific Sessions." A copy of the press release is attached as Exhibit 99.2 to this Current Report on Form 8-K.

The information contained in Item 7.01 of this Current Report on Form 8-K and Exhibits 99.1 and 99.2 hereto are being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or for any other purpose, and shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, regardless of any general incorporation language in any such filing, except as expressly set forth by specific reference in such a filing.

Item 8.01    Other Events.

On November 13, 2020, the Company will host a previously announced conference call and webcast to review the presentations of sotatercept at the 2020 AHA Scientific Sessions. A copy of the slide presentation to be presented during this conference call and webcast is attached as Exhibit 99.3 to this Current Report on Form 8-K and is incorporated herein by reference.

Item 9.01    Financial Statements and Exhibits.

(d)    Exhibits.

Exhibit NumberDescription of Exhibit
99.1
99.2
99.3
104Cover Page Interactive Data File (embedded within the Inline XBRL document)
2


SIGNATURES
 
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
 

ACCELERON PHARMA INC.
By:
/s/ Adam M. Veness, Esq.
Adam M. Veness, Esq.
Senior Vice President, General Counsel and Secretary
Date: November 13, 2020

3
Document
Exhibit 99.1
https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11.jpg

Acceleron Presents New Data from the PULSAR Phase 2 Trial, Preclinical Research on Sotatercept in Pulmonary Arterial Hypertension (PAH) at the 2020 American Heart Association (AHA) Scientific Sessions

– Treatment with sotatercept in the ongoing PULSAR Phase 2 trial was associated with improvements in cardiac and pulmonary function at week 24 –

– Presentation of echocardiography data from the PULSAR trial received AHA’s “Cardiopulmonary Best Abstract” Award –

– Preclinical research shows sotatercept inhibits cardiac remodeling, restores function in experimental model of severe PAH –

– Acceleron to host investor and analyst conference call and webcast with guest PAH key opinion leaders today, Friday, November 13, at 11:00 a.m. EST –


Cambridge, Mass. – November 13, 2020 – Acceleron Pharma Inc. (Nasdaq: XLRN), a leading biopharmaceutical company in the discovery, development, and commercialization of TGF-beta superfamily therapeutics to treat serious and rare diseases, today presented new cardiac and pulmonary function data from the ongoing PULSAR Phase 2 trial of sotatercept in patients with pulmonary arterial hypertension (PAH).

Echocardiography data obtained during the PULSAR trial and presented virtually during the American Heart Association (AHA) 2020 Scientific Sessions showed that patients on stable background PAH-specific therapies treated with sotatercept experienced improvement in a measure of cardiopulmonary function known as right ventricular-pulmonary arterial (RV-PA) coupling, which represents the match between the output of the RV and the resistance of the pulmonary vasculature. These patients also experienced improvement in RV function. In patients with PAH, RV function deteriorates as a result of the pulmonary vascular remodeling that is a hallmark of the disease.

“Progression of PAH may lead to RV failure, which is ultimately fatal in patients with this disease,” said Dr. Vallerie McLaughlin*, Professor of Medicine and Director of the Pulmonary Hypertension Program at the University of Michigan. McLaughlin’s presentation today of the PULSAR echocardiography data received AHA’s “Cardiopulmonary Best Abstract” award.

"The measurement of RV-PA coupling may offer important insights into how the RV is coping with increased pulmonary pressure. Although the assessment of RV-PA coupling noninvasively is a relatively new approach, these data are encouraging, as they demonstrate potential for RV remodeling,” McLaughlin continued. “Taken together with previously reported results of sotatercept’s hemodynamic and functional improvements—as measured by reduced pulmonary vascular resistance and increased six-minute walk distance—these outcomes suggest that sotatercept has the potential to become a paradigm-shifting new treatment option for patients with PAH.”

In the PULSAR Phase 2 double-blind, placebo-controlled study, 106 patients were randomized to receive placebo, 0.3 mg/kg of sotatercept, or 0.7 mg/kg of sotatercept subcutaneously every 21 days in combination with stable background PAH-specific therapies over a 24-week treatment period. The echocardiography results presented are from 94 patients and additional data analyses are ongoing. In addition to RV-PA coupling (measured in 51 patients) and RV function, patients treated with sotatercept experienced improvements in a number of other cardiopulmonary measures, including pulmonary artery systolic pressure and right ventricular fractional area change.



https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11.jpg
Sotatercept was generally well tolerated in the trial. Adverse events observed in the study were generally consistent with previously published data on sotatercept in other diseases.

“As we seek to deliver a much-needed, transformative therapy to patients with this debilitating disease, we are increasingly encouraged by a growing body of clinical and preclinical evidence that sotatercept does indeed have such potential,” said Habib Dable, President and Chief Executive Officer of Acceleron, who also referenced a preclinical research presentation at AHA showing that a murine version of sotatercept prevented RV remodeling and restored RV function in an animal model of severe disease.

“We look forward to confirming this early success with sotatercept in PAH in a comprehensive Phase 3 clinical development program, beginning with the registrational STELLAR trial, which we expect to initiate before the end of this year,” Dable added.

Sotatercept is an investigational therapy that is not approved for any use in any country.

The presentations referenced above are available on the “Publications” page under the “Science & Pipeline” section of Acceleron’s website, www.acceleronpharma.com.

*Dr. McLaughlin is an investigator in the PULSAR trial and a paid consultant to Acceleron.

About the PULSAR Trial

The PULSAR Phase 2 trial is a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of sotatercept in PAH patients. The primary endpoint of the trial is the change from baseline in pulmonary vascular resistance (PVR) over a 24-week treatment period. PVR, as measured by right heart catheterization, is the resistance that the heart must overcome to pump blood through the pulmonary circulatory system. The key secondary endpoint was six-minute walk distance (6MWD); a measure of functional capacity/endurance. Other exploratory analyses included change in amino-terminal brain natriuretic propeptide (NT-proBNP), a hormone secreted by cardiac muscle cells in response to stretching caused by increased blood volume in the heart; mean pulmonary arterial pressure, a hemodynamic measure of average pressure in the main pulmonary arteries, which is elevated in PAH patients; and WHO functional class. A total of 106 patients were randomized in a 3:3:4 ratio to receive placebo, sotatercept 0.3 mg/kg, or sotatercept 0.7 mg/kg subcutaneously every 21 days with standard-of-care therapies in combination.

Following the 6-month double-blind treatment period, participants in the trial were eligible to continue in the 18-month extension period.

As of October 28, 2020, 93 of 97 patients who opted to participate in the 18-month extension period of the trial were still enrolled; 94 patients have now been treated with sotatercept for at least 12 months.

Conference Call and Webcast Information

The Company will host a webcast and conference call today, November 13, 2020, at 11:00 a.m. EST, to review the presentations of sotatercept at AHA.

The webcast will be accessible under “Events & Presentations” in the Investors/Media page of the company's website at www.acceleronpharma.com. Individuals can participate in the live conference call by dialing 877-312-5848 (domestic) or 253-237-1155 (international) and referring to the “AHA Sotatercept Conference Call.”

A replay of the webcast will be available on the Acceleron website approximately two hours after the event.



https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11.jpg
About Sotatercept

Sotatercept is an investigational reverse-remodeling 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. The PULSAR Phase 2 trial evaluating sotatercept in combination with approved PAH-specific medicines in patients with PAH achieved its primary endpoint of improvement in pulmonary vascular resistance and its key secondary endpoint of improvement in 6-minute walk distance. Sotatercept was generally well tolerated in the trial. Adverse events observed in the study were generally consistent with previously published data on sotatercept in other diseases. Following the PULSAR results, sotatercept was granted Breakthrough Therapy designation from the FDA and Priority Medicines designation from the EMA in PAH. Sotatercept is also being evaluated in the SPECTRA Phase 2 exploratory trial

In preclinical research published in Science Translational Medicine, 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 Company recently presented details of its Phase 3 development plan, including the design for the registrational STELLAR trial, which is expected to be initiated before the end of 2020. Acceleron is planning two additional Phase 3 studies in patients with PAH: the HYPERION trial, exploring early intervention with sotatercept, and the ZENITH trial assessing later-stage intervention.

Sotatercept is an investigational therapy that is not approved for any use in any country. Sotatercept is part of a licensing agreement with Bristol Myers Squibb.

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, REBLOZYL® (luspatercept-aamt) is the first and only erythroid maturation agent approved in the United States, Europe, and Canada for the treatment of anemia in certain blood disorders. REBLOZYL is part of a global collaboration partnership with Bristol Myers Squibb. The Companies co-promote REBLOZYL in the United States and 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 (PAH), having recently presented positive topline results of the PULSAR Phase 2 trial. The Company is currently planning multiple Phase 3 trials with the potential to support its long-term vision of establishing sotatercept as a backbone therapy for patients with PAH at all stages of the disease.



https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11.jpg
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.

Source: Acceleron Pharma Inc.

Investors:
Jamie Bernard, IRC, 617-649-9650
Associate Director, Investor Relations

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





Document
Exhibit 99.2
https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11a.jpg

Acceleron Presents Preliminary Interim Data from the SPECTRA Phase 2 Trial of Sotatercept in Pulmonary Arterial Hypertension (PAH) at the 2020 American Heart Association Scientific Sessions

– Treatment with sotatercept in first set of patients in the ongoing SPECTRA Phase 2 trial was associated with substantial improvements in hemodynamics, exercise tolerance and exercise capacity at week 24 –

– Sotatercept was generally well tolerated, consistent with the previously reported safety profile in PAH and in other diseases –

– Acceleron to host investor and analyst conference call and webcast with guest PAH key opinion leaders today, Friday, November 13, at 11:00 a.m.. EST –


Cambridge, Mass. – November 13, 2020 – Acceleron Pharma Inc. (Nasdaq: XLRN), a leading biopharmaceutical company in the discovery, development, and commercialization of TGF-beta superfamily therapeutics to treat serious and rare diseases, today presented a set of preliminary interim data from the ongoing SPECTRA Phase 2 trial of sotatercept in patients with pulmonary arterial hypertension (PAH).

Initial data from the trial, which is designed to assess resting and exercise hemodynamics and peak oxygen uptake—as recorded by invasive cardiopulmonary exercise testing (iCPET)—show that patients treated with sotatercept experienced substantial improvements in multiple hemodynamic measures as well as in exercise tolerance and exercise capacity. These early outcomes, obtained from the first 10 patients participating in the trial, were shared as part of an Invited Talk entitled, “SPECTRA and Beyond: Signs of Disease Modification?” presented virtually during the American Heart Association (AHA) 2020 Scientific Sessions.

Among the largest resting hemodynamic improvements observed were reductions in pulmonary vascular resistance (PVR; as measured in dynes-sec/cm5) from a mean of 576 at baseline to 369 at week 24 (35.9% reduction) and mean pulmonary arterial pressure (mPAP) as measured in mmHg from 43.4 to 30.6. (29.5% reduction)

“The SPECTRA trial’s innovative design is meant to help us better understand and detect sotatercept’s potential effects on underlying disease pathology,” said Aaron Waxman, M.D., Ph.D.*, Director, Pulmonary Vascular Disease Program at Boston’s Brigham and Women’s Hospital, who delivered the Invited Talk at the AHA. “Despite the limited number of patients evaluated to date, it’s difficult not to be encouraged by the range and extent of positive changes seen in key hemodynamic and exercise capacity measures thus far.”

In this single-arm, open-label multi-center exploratory study, a total of up to 25 patients with advanced PAH (classified as WHO functional class III) on stable combination background therapy are to be treated with an initial cycle of 0.3 mg/kg of sotatercept delivered subcutaneously, followed by subsequent cycles of 0.7 mg/kg of sotatercept through a 24-week treatment period. The protocol includes iCPET at baseline and at week 24 to assess change from in peak oxygen uptake or VO2 max (the primary endpoint) as well as changes from baseline in a range of secondary endpoints, including mPAP and VO2 at anaerobic threshold.

During his AHA talk, Dr. Waxman also provided an in-depth profile of the first patient treated in the SPECTRA trial: a 25 year-old woman diagnosed with idiopathic PAH nearly five years prior to enrollment. This patient, who was classified as WHO functional class III and on combination background therapy, experienced substantial hemodynamic and functional improvements. Perhaps most notably, this patient


https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11a.jpg
was reclassified from WHO functional class III at baseline to class I at week 24. The patient retained functional class I status in follow-up testing at 48 weeks.

Sotatercept was generally well tolerated in the trial. Adverse events observed in the study were generally consistent with previously published data on sotatercept in PAH and in other diseases.

“We’re thrilled to see such positive preliminary outcomes from the SPECTRA trial, which serves as another important exploration of sotatercept and the potential of its unique mechanism to alter the course and treatment of PAH,” said Habib Dable, President and Chief Executive Officer of Acceleron. “These results, combined with new PULSAR trial data presented at AHA and the topline PULSAR findings announced earlier this year, position us well to initiate a robust Phase 3 development program to realize our vision of sotatercept as a backbone therapy for patients with PAH across all stages of disease.”

Sotatercept is an investigational therapy that is not approved for any use in any country.

The presentation referenced above is available on the “Publications” page under the “Science & Pipeline” section of Acceleron’s website, www.acceleronpharma.com.

*Dr. Waxman is principal investigator in the SPECTRA trial and a paid consultant to Acceleron.

About the SPECTRA Trial

The SPECTRA Phase 2 trial is a single arm, open-label, multi-center exploratory study to determine the effects of sotatercept plus standard of care in adults with WHO functional class III PAH. The primary endpoint of the trial is the change from baseline in peak oxygen uptake (VO2 max) at 24 weeks, as recorded by invasive cardiopulmonary exercise testing (iCPET). Secondary hemodynamic endpoints as well as endpoints of exercise capacity and tolerance assessed via iCPET and right heart catheterization include change from baseline at 24 weeks in: ventilatory efficiency (VE/VCO2 slope); cardiac index (L/min/m2); mean pulmonary artery pressure (mPAP); pulmonary vascular resistance (PVR); arteriovenous oxygen content difference (Ca-vO2); ventilatory efficiency; “dead space” assessment (VE/VCO2 slope); and oxygen consumption at anaerobic threshold (VO2 at AT).

A total of up to 25 patients are to receive stable background combination PAH therapy plus sotatercept at a starting dose level of 0.3 mg/kg delivered subcutaneously for one cycle, escalating to 0.7 mg/kg at cycle 2 for the remainder of the treatment period. Following the 6-month open-label treatment period, participants in the trial are eligible to continue in the 18-month extension period, which includes iCPET conducted at 48 weeks.

Conference Call and Webcast Information

The Company will host a webcast and conference call today, November 13, 2020, at 11:00 a.m. EST, to review the presentations of sotatercept at AHA.

The webcast will be accessible under “Events & Presentations” in the Investors/Media page of the company's website at www.acceleronpharma.com. Individuals can participate in the live conference call by dialing 877-312-5848 (domestic) or 253-237-1155 (international) and referring to the “AHA Sotatercept Conference Call.”

A replay of the webcast will be available on the Acceleron website approximately two hours after the event.



https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11a.jpg
About Sotatercept

Sotatercept is an investigational reverse-remodeling 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. The PULSAR Phase 2 trial evaluating sotatercept in combination with approved PAH-specific medicines in patients with PAH achieved its primary endpoint of improvement in pulmonary vascular resistance and its key secondary endpoint of improvement in 6-minute walk distance. Sotatercept was generally well tolerated in the trial. Adverse events observed in the study were generally consistent with previously published data on sotatercept in other diseases. Following the PULSAR results, sotatercept was granted Breakthrough Therapy designation from the FDA and Priority Medicines designation from the EMA in PAH. Sotatercept is also being evaluated in the SPECTRA Phase 2 exploratory trial

In preclinical research published in Science Translational Medicine, 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 Company recently presented details of its Phase 3 development plan, including the design for the registrational STELLAR trial, which is expected to be initiated before the end of 2020. Acceleron is planning two additional Phase 3 studies in patients with PAH: the HYPERION trial, exploring early intervention with sotatercept, and the ZENITH trial assessing later-stage intervention.

Sotatercept is an investigational therapy that is not approved for any use in any country. Sotatercept is part of a licensing agreement with Bristol Myers Squibb.

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, REBLOZYL® (luspatercept-aamt) is the first and only erythroid maturation agent approved in the United States, Europe, and Canada for the treatment of anemia in certain blood disorders. REBLOZYL is part of a global collaboration partnership with Bristol Myers Squibb. The Companies co-promote REBLOZYL in the United States and 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 (PAH), having recently presented positive topline results of the PULSAR Phase 2 trial. The Company is currently planning multiple Phase 3 trials with the potential to support its long-term vision of establishing sotatercept as a backbone therapy for patients with PAH at all stages of the disease.



https://cdn.kscope.io/a8627546479c0b86ee5fcb65bca2cf6f-image_11a.jpg
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.

Source: Acceleron Pharma Inc.

Investors:
Jamie Bernard, IRC, 617-649-9650
Associate Director, Investor Relations

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






xlrn-20201113ex993
Exhibit 99.3 AHA 2020 Virtual: Updates from the PULSAR and SPECTRA Trials of Sotatercept in PAH November 13, 2020 Sotatercept is an investigational therapy that is not approved for any use in any country.


 
Acceleron Forward-Looking Statements THIS PRESENTATION CONTAINS FORWARD-LOOKING STATEMENTS ABOUT THE COMPANY’S STRATEGY, FUTURE PLANS AND PROSPECTS, including statements regarding the development and commercialization of sotatercept in pulmonary arterial hypertension (“PAH”) and of the Company’s other compounds, the timeline for clinical development and regulatory approval of the Company’s compounds and the expected timing for reporting of data from ongoing clinical trials. The words “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “may,” “plan,” “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 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 regulatory approval of the Company’s compounds in one indication or country may not be predictive of approval in another indication or country, that the development of the Company's compounds may take longer and/or cost more than planned, that the Company may be unable to successfully complete the clinical development of the Company’s compounds, that the Company may be delayed in initiating, enrolling or completing any clinical trials, that the Company's compounds may not receive regulatory approval or become commercially successful products, and that Breakthrough Therapy or Priority Medicines (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 the Company's most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q, 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 ARE BASED ON MANAGEMENT’S CURRENT VIEWS, PLANS, estimates, assumptions and projections with respect to future events, and the Company does not undertake and specifically disclaims any obligation to update any forward-looking statements. This presentation is for investor relations purposes only – Not for product promotional purposes. 2


 
Our Special Guest Presenters on Today’s Call Vallerie McLaughlin, MD Aaron Waxman, MD, PhD Professor of Cardiovascular Medicine; Director, Pulmonary Vascular Disease Program, Director of the Pulmonary Hypertension Program, Brigham and Women’s Hospital; University of Michigan Associate Professor of Medicine, Harvard Medical School Investigator in the PULSAR trial and a paid consultant to Acceleron Principal investigator in the SPECTRA trial and a paid consultant to Acceleron 3 This presentation is for investor relations purposes only – Not for product promotional purposes.


 
Habib Dable Chief Executive Officer This presentation is for investor relations purposes only – Not for product promotional purposes.


 
Sotatercept: Significant Progress in 2020 PRECLINICAL REGULATORY CLINICAL CLINICAL Upcoming Phase 3 Trial Starts Planned BREAKTHROUGH THERAPY DESIGNATION SCIENCE TRANSLATIONAL MEDICINE RESEARCH ARTICLE PRIME – PRIORITY MEDICINES This presentation is for investor relations purposes only – Not for product promotional purposes. 5


 
Presentations at AHA Scientific Sessions 2020 November 13-17, 2020  A virtual experience CLINICAL PRESENTATIONS • Sotatercept Improves Right Ventricular - Pulmonary Arterial Coupling and Right Ventricular Function in the PULSAR Study: A Phase 2, double-blind, placebo controlled, randomized study to compare the efficacy and safety of sotatercept versus placebo when added to standard of care for the treatment of pulmonary arterial hypertension (PAH)  Cardiopulmonary Best Abstract Award • SPECTRA and Beyond: Signs of Disease Modification? PRECLINICAL PRESENTATIONS • Sotatercept Analog RAP-011 Inhibits Right Ventricular Remodeling and Restores Function in a Mouse Model of Pressure Overload This presentation is for investor relations purposes only – Not for product promotional purposes. 6


 
Vallerie McLaughlin, MD Professor of Cardiovascular Medicine; Director of the Pulmonary Hypertension Program, University of Michigan Investigator in the PULSAR trial and a paid consultant to Acceleron 7 This presentation is for investor relations purposes only – Not for product promotional purposes.


 
Sotatercept improves right ventricular – pulmonary arterial coupling and right ventricular function in the PULSAR study A Phase 2, double-blind, placebo controlled, randomized study to compare the efficacy and safety of sotatercept versus placebo when added to standard of care for the treatment of pulmonary arterial hypertension (PAH) 1Vallerie McLaughlin, 2Mardi Gomberg-Maitland, 3Solaiappan Manimaran, 3Jonathan Lu, 4Simon Gibbs. 1University of Michigan, AnnArbor, MI; 2GWMFA,George Washington University, Washington DC; 3Acceleron Pharma, Cambridge, MA; 4Imperial College London, London, UK. #AHA20


 
Disclosures Financial relationships with relevant commercial interests for three years preceding this presentation: Dr. McLaughlin reports grants and personal fees from Acceleron, Actelion, Bayer, Gossamer, and United Therapeutics; personal fees from Altavant, Caremark, CiVi Biopharma and Neuroderm and grants from Reata Pharm. and SonoVie, outside the presented work 9


 
Right ventricular dysfunction in PAH • Right ventricular dysfunction is a central feature of PAH and the main factor affecting prognosis1 • Energy transfer between ventricle contractility and arterial afterload is termed coupling. Energy transfer specifically between the right ventricle (RV) and pulmonary artery is termed right ventricle–pulmonary artery (RV–PA) coupling2 Severe RV dilation* Mild/Normal RV dilation* *Left-hand video shows short axis and right-hand shows long axis apical four chamber ECHO ECHO: echocardiography; PAH: pulmonary arterial hypertension; RV: right ventricular; RV–PA: right ventricular–pulmonary arterial 1. Tello K, et al. Herz 2019; 44: 509–16 2. Hsu S. Circ Heart Fail 2019; 12: doi.org/10.1161/CIRCHEARTFAILURE.118.005715 10 3. Groeneveldt JA, et al. Curr Opin Pul Med 2019; 25: 410–17


 
Echocardiographic estimation of RV–PA coupling • RV–PA coupling can be estimated non-invasively as a ratio of TAPSE/PASP values* • A TAPSE/PASP ratio of ≥0.31 mm/mm Hg is associated with a better prognosis and reduced risk of clinical worsening1 PASP = TRV2 × 4 + RA pressure RV–PA coupling = TAPSE/PASP *The cut-off value of 0.31 mm/mm Hg for RV–PA coupling has not been validated in a large cohort PASP: pulmonary arterial systolic pressure; RA: right atrium; RV–PA: right ventricular–pulmonary arterial; TAPSE: tricuspid annular plane systolic excursion; TRV: tricuspid regurgitation velocity 11 1. Tello K, et al. Circ Cardiovasc Imaging 2019; e009047


 
Sotatercept and the role of BMPR-II/TGF-β signaling • Sotatercept is a novel, first-in-class fusion protein comprising the extracellular domain of human activin receptor type IIA linked to the Fc domain of human immunoglobulin G1 • Sotatercept is proposed to act by rebalancing signaling between pro- and anti-proliferative pathways, thereby reversing the characteristic vascular remodeling seen in PAH Sotatercept is an investigational product that is not approved for any use in any country ACTRIIA: activin receptor type 2A; ALK: activin receptor-like kinase; BMP/BMPR: bone morphogenetic protein/BMP receptor; Fc, fragment crystallizable; GDF: growth differentiation factor; 12 PAH: pulmonary arterial hypertension; pSmad; phosphorylated Smad; TGF-β: transforming growth factor-beta


 
PULSAR study design A Phase 2, randomized, double-blind, placebo-controlled study to compare the safety and efficacy of sotatercept versus placebo when added to standard of care (SOC) for the treatment of PAH in 106 patients at 43 sites across eight countries (NCT03496207) Inclusion criteria • WHO Group 1 PAH • WHO Functional Class II or III • Baseline right-heart catheterization with PVR ≥5 Wood units • Baseline 6-minute walk distance Randomization (6MWD) 150–550 m 3:3:4 stratified • Stable treatment with SOC therapies by baseline including mono-, double, and triple WHO FC therapies: • An endothelin-receptor antagonist, a phosphodiesterase 5 inhibitor, a soluble guanylate cyclase Trial currently in open-label stimulator, and/or a prostacyclin extension phase (including IV) End of placebo-controlled treatment period (EOP)† †EOP represents data obtained at the end of the placebo-controlled treatment period (24 weeks) 6MWD: six-minute walk distance; ECHO: echocardiography; FC: functional class; IV: intravenous; NT-proBNP: N-terminal pro-brain natriuretic peptide; PAH: pulmonary arterial hypertension; PVR: pulmonary vascular resistance; SOC: standard of care; TAPSE: tricuspid annular plane systolic excursion; TGF-β: transforming growth factor beta; WHO: World Health Organization 1. Badesch, DB, et al. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. Presentation at: ATS 2020 Virtual. American Thoracic Society International Conference; 24 June-10 13 November, 2020.


 
PULSAR study design A Phase 2, randomized, double-blind, placebo-controlled study to compare the safety and efficacy of sotatercept versus placebo when added to standard of care (SOC) for the treatment of PAH in 106 patients at 43 sites across eight countries (NCT03496207) Inclusion criteria Primary endpoint Topline results • WHO Group 1 PAH • Change in PVR from baseline Results presented at the American to week 24 • WHO Functional Class II or III Thoracic Society 2020 congress • Baseline right-heart catheterization with demonstrated improvements in: PVR ≥5 Wood units Key secondary endpoints • PVR (34% overall reduction) • Baseline 6-minute walk distance • Change from baseline to week 24 • 6MWD (6MWD) 150–550 m in 6MWD, NT-proBNP, and TAPSE • NT-proBNP • Stable treatment with SOC therapies • Pulmonary arterial pressure including mono-, double, and triple therapies: Key exploratory endpoints Sotatercept was generally well tolerated and safety findings were consistent with • An endothelin-receptor antagonist, • Change from baseline to week 24 in other patient populations1 a phosphodiesterase 5 inhibitor, a TGF-β ligands and other PAH soluble guanylate cyclase biomarkers, and ECHO parameters stimulator, and/or a prostacyclin (including IV) †EOP represents data obtained at the end of the placebo-controlled treatment period (24 weeks) 6MWD: six-minute walk distance; ECHO: echocardiography; FC: functional class; IV: intravenous; NT-proBNP: N-terminal pro-brain natriuretic peptide; PAH: pulmonary arterial hypertension; PVR: pulmonary vascular resistance; SOC: standard of care; TAPSE: tricuspid annular plane systolic excursion; TGF-β: transforming growth factor beta; WHO: World Health Organization 1. Badesch, DB, et al. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. Presentation at: ATS 2020 Virtual. American Thoracic Society International Conference; 24 June-10 14 November, 2020.


 
Methods • Echocardiography was performed by the local lab at each site and centrally read • Calculation of RV-PA coupling is dependent on paired results for three parameters (TRV, RAP, TAPSE) at baseline and at Placebo + SOC (n=30) EOP† • Data analyses on the remaining patients is ongoing • Unavailable values were not imputed for the echocardiography parameters Placebo + SOC (n=19) Primary analysis data cut-off date 14 January 2020 †EOP represents data obtained at the end of the placebo-controlled treatment period (24 weeks) *Nine patients discontinued before End of Period EOP: End of placebo-controlled treatment period; RAP: right atrial pressure; RVEDA: right ventricular end-diastolic area; RVESA; right ventricular end-systolic area; RVFAC: right ventricular 15 fractional area change; RV–PA: right ventricular – pulmonary artery; SOC: standard of care; TAPSE: tricuspid annular plane systolic excursion; TRV: tricuspid regurgitation velocity


 
PULSAR study: Baseline characteristics (1/2) Sotatercept Sotatercept Placebo Total 0.3 mg/kg 0.7 mg/kg n=32 n=106 n=32 n=42 Female, n (%) 26 (81) 29 (91) 37 (88) 92 (87) Age, mean (range), years 46 (21–71) 48.5 (23–80) 48.5 (19–77) 48 (19–80) Time since diagnosis, mean (range), years 7.2 (0.3–22) 7.6 (0.7–26) 6.2 (0.8–24) 7.4 (0.3–26) PAH classification, n (%) Idiopathic 19 (59) 13 (41) 29 (69) 61 (58) Heritable 7 (22) 5 (16) 5 (12) 17 (16) Associated with 3 (9) 9 (28) 6 (14) 18 (17) connective-tissue disease Drug or toxin-induced 1 (3) 4 (13) 2 (5) 7 (7) Associated with corrected 2 (6) 1 (3) 0 (0) 3 (3) congenital shunts Primary analysis data cut-off date 14 January 2020 16 PAH: pulmonary arterial hypertension


 
PULSAR study: Baseline characteristics (2/2) Sotatercept Sotatercept Placebo Total 0.3 mg/kg 0.7 mg/kg n=32 n=106 n=32 n=42 WHO functional class, n (%) II 17 (53) 15 (47) 24 (57) 56 (53) III 15 (47) 17 (53) 18 (43) 50 (47) Standard-of-care PAH therapy, n (%) Parenteral prostacyclin 10 (31) 11 (34) 18 (43) 39 (37) Monotherapy 3 (9) 3 (9) 4 (10) 10 (9) Double therapy 12 (38) 11 (34) 14 (33) 37 (35) Triple therapy 17 (53) 18 (56) 24 (57) 59 (56) Pulmonary vascular resistance, 797 ± 57.0 789 ± 50.8 756 ± 63.5 779 ± 33.9 dyn·s/cm5 6-minute walk distance, m 409 ± 11.3 386 ± 15.7 398 ± 14.1 398 ± 8.1 NT-proBNP, pg/mL 870 ± 214.5 999 ± 227.6 871 ± 248.2 908 ± 135.4 Primary analysis data cut-off date 14 January 2020 Mean ± standard error unless otherwise noted 17 NT-proBNP: amino-terminal brain natriuretic propeptide; PAH: pulmonary arterial hypertension; WHO: World Health Organization


 
PULSAR results: Invasive hemodynamics (n=102) Primary analysis data cut-off date 14 January 2020 Bar graphs represent mean ± standard deviation †EOP represents data obtained at the end of the placebo-controlled treatment period (24 weeks) CO: cardiac output; EOP: end of placebo-controlled treatment period; mPAP: mean pulmonary arterial pressure; mPAWP: mean pulmonary arterial wedge pressure; 18 PVR: pulmonary vascular resistance; SOC: standard of care


 
PULSAR results: Echocardiography (n=94) Placebo + SOC Sotatercept 0.3 mg/kg + SOC Sotatercept 0.7 mg/kg + SOC LS mean difference LS mean difference Endpoint LS mean‡ LS mean P value LS mean P value (95% CI) (95% CI) RVEDA (cm2) −0.00 (0.68) −2.5 (0.66) −2.5 (−4.4, −0.55) 0.0122 −4.7 (0.61) −4.6 (−6.5, −2.8) <0.0001 RVESA (cm2) −0.50 (0.63) −3.1 (0.61) −2.6 (−4.3, −0.83) 0.0043 −4.8 (0.56) −4.3 (−6.0, −2.6) <0.0001 RVFAC (%) 1.9 (1.2) 5.0 (1.1) 3.1 (−0.13, 6.4) 0.0598 6.2 (1.1) 4.3 (1.2, 7.5) 0.0078 Primary analysis data cut-off date 14 January 2020 Bar graphs represent mean ± standard deviation †EOP represents data obtained at the end of the placebo-controlled treatment period (24 weeks) ‡Standard error is represented in parentheses for all LS mean values CI: confidence interval; EOP: end of placebo-controlled treatment period; LS: least squares; RVEDA: right ventricular end-diastolic area; RVESA; right ventricular end-systolic area; 19 RVFAC: right ventricular fractional area change; SOC: standard of care


 
PULSAR results: Echocardiography † Placebo + SOC Sotatercept 0.3 mg/kg + SOC Sotatercept 0.7 mg/kg + SOC LS mean difference LS mean difference Endpoint, n LS mean, n‡ LS mean, n P value LS mean, n P value (95% CI) (95% CI) PASP (mm Hg), 54 4.8 (4.1), 20 −24.3 (4.7), 16 −29.1 (−41.6, −16.6) <0.0001 −21.9 (4.6), 18 −26.7 (−39.3, −14.2) <0.0001 TAPSE (mm), 91 −0.00 (0.05), 29 0.00 (0.06), 27 0.00 (−0.13, 0.18) 0.7334 −0.10 (0.05), 35 −0.10 (−0.22, 0.08) 0.3584 Primary analysis data cut-off date 14 January 2020 Bar graphs represent mean ± standard deviation †EOP represents data obtained at the end of the placebo-controlled treatment period (24 weeks) ‡Standard error is represented in parentheses for all LS mean values 20 CI: confidence interval; LS: least squares; PASP: pulmonary artery systolic pressure; SOC: standard of care; TAPSE: tricuspid annular plane systolic excursion


 
PULSAR results: RV–PA coupling (n=51) 0.31 mm/mm Hg cut-off§ Placebo + SOC (n=19) Sotatercept 0.3 mg/kg + SOC (n=15) Sotatercept 0.7 mg/kg + SOC (n=17) Placebo + SOC Sotatercept 0.3 mg/kg + SOC Sotatercept 0.7 mg/kg + SOC LS mean difference LS mean difference Endpoint LS mean‡ LS mean P value LS mean P value (95% CI) (95% CI) RV–PA coupling −0.02 (0.03) 0.13 (0.03) 0.15 (0.06, 0.24) 0.0015 0.09 (0.03) 0.10 (0.02, 0.2) 0.0198 (mm/mm Hg) Primary analysis data cut-off date 14 January 2020 Bar graphs represent mean ± standard deviation †EOP represents data obtained at the end of the placebo-controlled treatment period (24 weeks) ‡Standard error is represented in parentheses for all LS mean values §Cut-off values for RV–PA coupling have not been validated in a large cohort CI: confidence interval; LS: least squares; RV–PA: right ventricular–pulmonary artery; 21 PASP: pulmonary artery systolic pressure; SOC: standard of care; TAPSE: tricuspid annular plane systolic excursion


 
Conclusions • In this limited subgroup of the PULSAR study: o Treatment with sotatercept was associated with statistically significant improvements in RV–PA coupling and RV function when compared with placebo o Significant improvement from baseline to week 24 in both sotatercept dose groups versus placebo was observed in RV–PA coupling, RVEDA, RVESA, and PASP o For RVFAC, significance was seen at the sotatercept 0.7 mg/kg dose level and was trending at the sotatercept 0.3 mg/kg dose level but did not quite reach the 0.05 significance level o No changes were seen in TAPSE or in cardiac output • Sotatercept was generally well tolerated and safety findings were consistent with other patient populations • Sotatercept has the potential to be a new treatment option for PAH patients, with consistent and encouraging effects on RV–PA coupling and RV function in a post hoc analysis PAH: pulmonary arterial hypertension; PASP: pulmonary arterial systolic pressure; RV: right ventricular; RVEDA: right ventricular end-diastolic area; RVESA: right ventricular end-systolic area; 22 RVFAC: right ventricular fractional area change; RV–PA: right ventricular–pulmonary artery; TAPSE: tricuspid annular plane systolic excursion


 
PULSAR study: Acknowledgements • We thank all the patients, their families, and all the PULSAR study investigators who participated in the trial – PULSAR study investigators: Y. Adir, H. Alnuaimat, M. Andrade-Lima, J. Arakaki, R. Argula, A. Baloira, D. Baratz, J. Barberá, A. Bar-Shai, C. Berastagui, L. Bertoletti, M. Delcroix, D. Blanco, A. Bourdin, F. Campos, M. Chakinala, C. Church, J. Cifrian Martinez, J. Coghlan, T. Demarco, S. Eisenmann, P. Engel, P. Escribano-Subias, J. Feenstra, J. Feldman, M. Halank, L. Howard, O. Hussein, A. Keogh, M. Kramer, T. Lange, M. Lavender, M. Lazaro Salvador, G. Meyer, J. Michaelson, D. Montani, W. Nseir, K. Olsson, C. Opitz, C. Pison, D. Poch, F. Rahaghi, Y. Raviv, G. Reeves, F. Rischard, J. Robinson, Z. Safdar, R. Saggar, J. Schreiber, M. Segel, J. Segovia Cubero, D. Shitrit, N. Sood, L. Spikes, S. Steiglitz, JL. Vachiery, J. Wheatley, H. Wirtz • We also thank all members of the PULSAR trial steering committee including; D. Badesch, R. De Souza, M. Hoeper, M. Humbert, I. Preston and A. Waxman • The study was sponsored by Acceleron Pharma, Cambridge, MA, USA – Acceleron personnel: A. Atanasov, C. Barron, B. Budda, E. Davis, K. de Jong, R. Gerber, S. Harrison, J. Lu, J. Reynolds, J. Oram, C. Sanmarco, M. Troy, N. Yuen • The authors received editorial assistance from InterComm LTD, supported by Acceleron Pharma 23


 
Aaron Waxman, MD, PhD Director, Pulmonary Vascular Disease Program, Brigham and Women’s Hospital; Associate Professor of Medicine, Harvard Medical School Principal investigator in the SPECTRA trial and a paid consultant to Acceleron 24 This presentation is for investor relations purposes only – Not for product promotional purposes.


 
SPECTRA and Beyond: Signs of Disease Modification? Aaron B Waxman, MD, PhD Director, Pulmonary Vascular Disease Program Brigham and Women’s Hospital, Cardiovascular Medicine, Pulmonary and Critical Care #AHA20


 
Disclosures Financial relationships with relevant commercial interests for three years preceding this presentation: • Acceleron Pharma Sotatercept is an investigational product that is not approved for any use in any country 26


 
Sotatercept and the role of BMPR-II/TGF-β signaling • Sotatercept is a novel, first-in-class fusion protein comprising the extracellular domain of human activin receptor type IIA linked to the Fc domain of human immunoglobulin G1 • Sotatercept is proposed to act by rebalancing signaling between pro- and anti-proliferative pathways, thereby reversing the characteristic vascular remodeling seen in PAH PAH Sotatercept Anti-proliferative Pro-proliferative Anti-proliferative Pro-proliferative Activins/GD BMPs BMPs Fs ALK ALK 1/2/3/6 ALK4/5/ ALK4/5/ 1/2/3/6 7 X BMPR- 7 BMPR- II II ACTRIIA/B ACTRIIA/B X pSmad1/5/8 Gremlin- Gremlin- 1 1 Noggin Noggin Sotatercept is an investigational product that is not approved for any use in any country ACTRIIA: activin receptor type 2A; ALK: activin receptor-like kinase; BMP: bone morphogenetic protein; GDF: growth differentiation factor; PAH: pulmonary arterial hypertension; pSmad; 27 phosphorylated Smad


 
SPECTRA study design A Phase 2a Single-Arm, Open-Label, Multicenter Exploratory Study to Assess the Effects of Sotatercept for the Treatment of PAH in up to 25 patients at 4 sites across the USA • WHO PH Group I (PAH) Open-label treatment period Extension period Post-treatment follow-up • Idiopathic or heritable (24 weeks) (18 months) (8 weeks) • Drug- or toxin-induced • CTD-associated • STP shunt-associated Cycle 1: Sotatercept 0.3 mg/kg + SOC • PAH WHO Functional Class III n=25 Sotatercept Follow-up visits for • Right heart catheterization with PVR 0.7 mg/kg + safety at 4 and 8 ≥ 4 Wood units SOC weeks post last dose Cycle 2 onward: • 6-minute-walk distance 100 -550 m Stratified by Sotatercept 0.7 mg/kg + SOC baseline • Hgb ≤ 16 g/dL n=25 WHO FC • Stable combination PAH therapy iCPET iCPET iCPET baseline primary endpoint 48 weeks CTD: connective-tissue disease; Hgb: hemoglobin; iCPET: invasive cardiopulmonary exercise testing; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; SOC: standard of care; WHO: World Health Organization 28 https://clinicaltrials.gov/ct2/show/NCT03738150 [Accessed 23 September 2020].


 
SPECTRA study: iCPET assessments • Primary endpoint: Change from baseline in peak oxygen uptake (VO2 max) at 24 weeks • Secondary endpoints from iCPET measured as change from baseline at 24 weeks: • Ventilatory efficiency (VE/VCO2 slope) • Cardiac index (L/min/m2) • Mean pulmonary artery pressure, (mPAP, mmHg) • Arteriovenous O2 content difference (Ca-vO2) • VE/VCO2 slope (ventilatory efficiency, “dead space” assessment) • VO2 at (O2 consumption at anaerobic threshold) 29


 
How do we perform iCPET? 30 iCPET: invasive cardiopulmonary exercise testing; RA: right atrium; VO2: peak oxygen uptake


 
SPECTRA study: Baseline characteristics Total N=10 Female, n 6 Age, median (range), years 45 (25-66) Time since diagnosis, median (range), years 3.2 (0.6-13.1) PAH classification, n Idiopathic 5 Associated with connective-tissue disease 4 Heritable 1 Standard-of-care PAH therapy, n Parenteral prostacyclin 7 Double therapy 5 Triple therapy 5 Supine resting pulmonary vascular resistance, median (range), dyn·s/cm5 564 (370-870) 6-minute walk distance, median (range), m 359 (254-506) Data cut-off date 21 Sept 2020 31 PAH: pulmonary arterial hypertension


 
SPECTRA study results: Supine Resting Hemodynamics Baseline Week 24/EOS# (n=10) (n=10) Mean Pulmonary Arterial Pressure (mPAP), mmHg 43.4 ± 9.7 30.6 ± 9.7 Pulmonary Arterial Wedge Pressure (PAWP), mmHg 10.0 ± 4.0 9.1 ± 4.8 Cardiac Output (CO), L/min 4.7 ± 0.7 4.8 ± 1.4 Pulmonary Vascular Resistance (PVR), dyn·sec/cm5 576 ± 139 369 ± 121 Data cut-off date 21 Sept 2020 Mean ± SD #EOS: End of study visit, n=1, performed after 3 doses of study drug 32


 
SPECTRA Study: Safety Treatment Emergent Adverse Events (TEAE) reported: • 9/10 patients reported at least one TEAE • Arthralgia, dizziness, fluid overload, gingival bleeding, hematochezia, hemoglobin increased, infusion site pain, palpitations, pyrexia, upper respiratory tract infection, weight increased • Two SAEs reported (fluid overload, resolved; hematochezia, resolved), both considered not related to study drug and no dose interruption or reduction required. • One discontinuation due to AE (patient felt worsening pain at Remodulin® site injection) Data cut-off date 21 Sept 2020 AE: adverse event; SAE: serious adverse event: TEAE: treatment-emergent adverse event 33


 
SPECTRA Study: Case Report of First Patient (1/2) • 25-year-old female, idiopathic PAH for 4.7 years, receiving tadalafil and ambrisentan for the treatment of PAH. At baseline, subject was classified as WHO FC III and 6MWD was 285.5 m. • The subject’s medical history includes gastroesophageal reflux disease, sleep disorder, depression, endometriosis, restless leg syndrome and dust allergy. Resting supine hemodynamics Baseline Week 24 Week 48 mPAP, mmHg 39 13 11 mRAP, mmHg 8 2 2 PAWP, mmHg 8 4 3 CO, L/min 3.73 4.24 3.42 DPG, mmHg 20 3 5 PVR, dynes-sec/cm5 665 170 187 • At 24 weeks, subject was classified as WHO FC I and 6MWD was 468.7 m (183.2 m increase from baseline). • At 48 weeks, subject remained WHO FC I and 6MWD was 443.7 (158.2 m increase from baseline). Data cut-off date 21 Sept 2020 6MWD: 6-minute-walk distance; CO: cardiac output; DPG: diastolic pressure gradient; FC: functional class; mPAP: mean pulmonary arterial pressure; mRAP: mean right arterial pressure; 34 PAH: pulmonary arterial hypertension; PAWP: pulmonary arterial wedge pressure; PVR: pulmonary vascular resistance; WHO: World Health Organization


 
SPECTRA Study Case Report of First Patient (2/2) Peak Exercise Hemodynamics (iCPET) Baseline Week 24 Week 48 Work, W 39 66 85 mPAP, mmHg 41 27 23 TPG, mmHg 37 25 22 PAWP, mmHg 4 2 1 CO, L/min 7.0 7.84 7.4 PVR, dynes-sec/cm5 423 255 237 Pulmonary artery compliance, mL/mmHg 2.2 3.9 2.3 VO2 max, mL/kg/min 10.7 17.7 20 VO2 max, % predicted 33% 54% 62% Ca-vO2, mL/dL 9 10.4 15.3 VE/VCO2 slope 55 27 30 Data cut-off date 21 Sept 2020 Ca-vO2: arteriovenous O2 content difference; CO: cardiac output; iCPET: invasive cardiopulmonary exercise testing; mPAP: mean pulmonary arterial pressure; PAWP: pulmonary arterial 35 wedge pressure; PVR: pulmonary vascular resistance; TPG: transpulmonary pressure gradient; VO2: oxygen consumption; VE/VCO2: ventilatory efficiency


 
Conclusions • The ongoing SPECTRA study has shown substantial improvements in hemodynamics as well as exercise tolerance and capacity in the limited number of subjects studied to date. • Sotatercept was generally well tolerated, consistent with the previously reported safety profile in PAH1. • Additional data on sotatercept will be presented during AHA 2020: • McLaughlin V, et al. “Sotatercept improves right ventricular – pulmonary arterial coupling and right ventricular function in the PULSAR study”, Dickinson W. Richards Memorial Lecture, Cardiopulmonary Best Abstract Award, presentation number 287 • Joshi S, et al. “Sotatercept analog RAP-011 inhibits right ventricular remodeling and restores function in a mouse model of pressure overload”, poster number MP282 1 Badesch, DB, et al. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. Presentation at: ATS 2020 Virtual. American Thoracic Society International Conference; 36 24 June-10 November, 2020.


 
SPECTRA study: Acknowledgements • We thank all the patients, their families, and all the SPECTRA study investigators who participated in the trial – SPECTRA study investigators: Aaron B. Waxman, MD, PhD, Franz Rischard, MD, Michael Risbano, MD, and Robert Frantz, MD. – The study was sponsored by Acceleron Pharma, Cambridge, MA, USA – Acceleron personnel: Jonathan Lu, Rebecca Young, Solaiappan Manimaran, Jennifer Barnes, Musa Mutyaba, Erica Davis, Atanas Atanasov, Saba Qamar, Carrie Barron, Jay Backstrom, Janethe Pena 37


 
Summary | Jay T. Backstrom, MD, MPH EVP, Head of Research & Development This presentation is for investor relations purposes only – Not for product promotional purposes.


 
AHA 2020: Key Highlights from the Sotatercept Presentations • Echo data received “Cardiopulmonary Best Abstract” • Sotatercept associated with measures of improved right ventricular function • Preliminary hemodynamic data consistent with PULSAR ― Reduction in PVR and mPAP ― Improvement in exercise tolerance and capacity Sotatercept is an investigational therapy that is not approved for any use in any country. This presentation is for investor relations purposes only – Not for product promotional purposes. 39


 
Upcoming Priorities for Sotatercept Program in PAH Initiation of STELLAR PULSAR open-label Additional results HYPERION Phase 3 (early Phase 3 trial planned extension study expected from the intervention) trial and for YE:2020 update expected in SPECTRA trial in ZENITH Phase 3 (later 1H:21 1H:21 intervention) trial initiation in expanded PAH populations planned in mid:2021 Sotatercept is an investigational therapy that is not approved for any use in any country. This presentation is for investor relations purposes only – Not for product promotional purposes. 40


 
Sotatercept Phase 3 Clinical Development Plan and Vision REGISTRATIONAL LABEL EXPANSION SOTATERCEPT VISION BACKBONE THERAPY IN PAH Phase 3 Early Intervention Study Main Phase 3 Study ZENITH Phase 3 Later Intervention Study Sotatercept is an investigational therapy that is not approved for any use in any country. This presentation is for investor relations purposes only – Not for product promotional purposes. 41


 
Question & Answer Session Habib Dable Vallerie McLaughlin, MD* President & Chief Executive Officer Professor, Cardiovascular Medicine; Director, Pulmonary Hypertension Program, University of Michigan Jay T. Backstrom, MD, MPH EVP, Head of Research & Development Aaron Waxman, MD, PhD** Director, Pulmonary Vascular Disease Program, Brigham & Women’s Hospital; Sujay Kango Associated Professor of Medicine, EVP, Chief Commercial Officer Harvard Medical School Janethe Pena, MD, PhD Todd James VP, Medical Research, Pulmonary SVP, Corporate Affairs & Investor Relations *Investigator in the PULSAR trial and a paid consultant to Acceleron. **Principal investigator in the SPECTRA trial and a paid consultant to Acceleron. This presentation is for investor relations purposes only – Not for product promotional purposes. 42