PULSAR Phase 2 Trial Topline Results Announcement - January 27, 2020
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PULSAR Phase 2
Trial Topline Results
Announcement
January 27, 2020
1
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 sotatercept in PAH and of the
Company’s other compounds and the expected timing for reporting of data from ongoing clinical trials, and the potential of the Company’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 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 the results of any clinical trials may not be
predictive of the results or success of other 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 will take
longer and/or cost more than planned, that the Company will 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, and that the Company's
compounds will not receive regulatory approval or become commercially successful products. 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, 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.
2 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.
2017 R&D Day: A Strategy and Vision Presented in PAH
SOTATERCEPT
In conjunction with announcing the sotatercept collaboration
amendment with Celgene, we presented:
▪ The high unmet medical need in PAH
▪ The scientific rationale for targeting proteins within the TGF-beta
superfamily in PAH
▪ Initial preclinical results from our collaborators at the Brigham and
Women’s Hospital
▪ Our belief in the potential to combine sotatercept with background
PAH-specific therapies
4 This presentation is for investor relations purposes only –
Not for product promotional purposes.
Significant Program Progress Made to Date
▪ Multiple preclinical presentations at major medical meetings
▪ PULSAR trial designed and initiated
▪ SPECTRA trial designed and initiated
▪ PULSAR trial patient enrollment completed ahead of plan
▪ Sotatercept granted FDA’s Orphan Drug Designation in PAH
5
Sotatercept Phase 2 Trials in Patients with Pulmonary
Arterial Hypertension (PAH)
Topline Results Announced Enrollment Ongoing
6 This presentation is for investor relations purposes only –
Sotatercept is an investigational therapy that is not approved for any use in any country. Not for product promotional purposes.
Janethe Pena, MD, PhD
Vice President, Medical Research, Pulmonary
This presentation is for investor relations purposes only –
Not for product promotional purposes.
Marc Humbert, MD, PhD*
Professor of Respiratory Medicine at the Université Paris-Saclay in Le Kremlin-
Bicêtre, France; Director of the Department of Respiratory and Intensive Care
Medicine, French Pulmonary Hypertension Reference Centre, Hôpital Bicêtre,
Assistance Publique Hôpitaux de Paris, France
*Dr. Humbert is an investigator in the PULSAR trial and a paid consultant to Acceleron.
8 This presentation is for investor relations purposes only –
Not for product promotional purposes.
Pulmonary arterial hypertension: A severe pulmonary vascular
disease
• Definition: chronic pre-capillary pulmonary hypertension
• Cause: progressive structural remodeling of the small pulmonary arteries
• Consequence: right heart failure and death
Normal PAH
9 Galiè N et al. Eur Heart J 2016 & Eur Respir J 2015
Pulmonary arterial hypertension: a rare, but not an orphan, disease
• Rare: prevalence 15–50/million (incidence 6/million/year)
• Pathophysiology: pulmonary artery endothelial cell dysfunction
• Drugs: 14 agents approved in the last 25 years (orphan drug status)
• Lung/heart–lung transplantation: if refractory to medical therapy
PGI2: -
NO: -
ET-1: +
SMCs
Endothelial cell
10 Adapted from: Humbert M et al. Circulation 2014Current PAH treatment
Targeting 3 major endothelial cell dysfunctional pathways
11
Humbert et al. N Engl J Med 2004 Humbert et al. Circulation 2014Targeting endothelial dysfunction in PAH
ET, endothelin; IP, prostacyclin receptor; NO, nitric oxide; PDE5, phosphodiesterase type 5; PGI2, prostacyclin; sGC, soluble
12 guanylate cyclase.
Humbert M et al. Circulation 2014;130:2189–208.Targeting the Prostacyclin, Endothelin and NO Pathways
The Nobel Prize in The Nobel Prize in
Physiology or Physiology or Medicine
Medicine 1982 1998
"for their discoveries concerning "for their discoveries concerning nitric oxide as a
prostaglandins and related biologically active signalling molecule in the cardiovascular system"
substances"
Ser
Ser
Leu Cy Ser Cys
s
N
Met
Asp ET-1
Lys
Glu Cys Val Tyr Phe Cys His Leu Asp Ile Ile Trp
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Sune K. Bengt I. John R. Vane
Robert F. Furchgott Louis J. Ignarro Ferid Murad
Bergström Samuelsson
1/3 of the prize 1/3 of the prize 1/3 of the prize
1/3 of the prize 1/3 of the prize 1/3 of the prize
Sweden Sweden United Kingdom
USA USA USA
Karolinska Institutet Karolinska Institutet The Wellcome
Stockholm, Sweden Stockholm, Sweden Research SUNY Health Science Center University of California University of Texas Medical
Laboratories Brooklyn, NY, USA School of Medicine School at Houston
Los Angeles, CA, USA Houston, TX, USA
Beckenham, United
Kingdom
b. 1916 b. 1934 b. 1927 b. 1916 b. 1941 b. 1936
d. 2004 d. 2004
13
Humbert et al. N Engl J Med 2004Targeting the Prostacyclin, Endothelin and NO Pathways 14 Barst et al. N Engl J Med 1996; Rubin et al. N Engl J Med 2002; Galiè et al. N Engl J Med 2005
Unmet need in the modern management era
Despite drug discovery and development PAH remains a devastating condition
15
Humbert M et al. Circulation 2010;122:156–63How to do better? • Better use of currently available therapies (strategies) – Early detection and management – Risk stratification – Goal-oriented therapy (with initial/ sequential combination) – Initial combination therapy • Development of novel therapies – New treatments targeting other pathways (BMPR-II…) 16
Pulmonary arterial hypertension
Treatment algorithm
17 Galiè et al; Eur Respir J 2019Targeting novel pathways in PAH
• Pulmonary artery endothelial cell dysfunction is a major abnormality identified in PAH
• Three dysfunctional pathways are targetable with 14 approved in the last 20 years (orphan drug status)
• Lung/heart–lung transplantation should be considered in eligible patients refractory to medical therapy
• Strong translational research has identified a large number of novel targets in recent years
• A major challenge will be to prioritize drug discovery and development
• Improving right heart function is another priority
Inflammation
Mitochondrial metabolism Growth factors
Dysregulated angiogenesis BMPR2/TGF beta signaling
Extracellular matrix Calcium signaling
Vasoactive peptides
Neurohormonal activation
Adapted from: Humbert M et al. Circulation 2014;130:2189–208.
18
BMPR2, bone morphogenetic protein receptor type 2; TGF, transforming growth factorVallerie McLaughlin, MD*
Professor of Cardiovascular Medicine;
Director of the Pulmonary Hypertension Program
University of Michigan
*Dr. McLaughlin is an investigator in the PULSAR trial and a paid consultant to Acceleron.
19 This presentation is for investor relations purposes only –
Not for product promotional purposes.PULSAR Phase 2 Trial Design & Topline Results
This presentation is for investor relations purposes only –
Not for product promotional purposes.PULSAR Trial Inclusion Criteria
Key Inclusion Criteria
▪ Adults ≥18 years old
▪ WHO Group I PAH
▪ Functional Class II/III
▪ Baseline right heart catheterization with PVR ≥5 Wood Units
▪ Baseline 6MWD: 150 – 550 meters
WHO: World Health Organization; PVR: Pulmonary vascular resistance; 6MWD: 6-minute walk distance
215th World Symposium on PH: Hemodynamic Definition of PH/PAH
PH PAH
Mean PAP ≥25 mm Hg plus
Mean PAP ≥25 mm Hg
PAWP ≤15 mm Hg plus
at rest during RHC
PVR >3 Wood units
RHC: right heart catheterization PAP: pulmonary arterial pressure PAWP: pulmonary artery wedge pressure PVR: pulmonary vascular resistance
Hoeper MM et al. J Am Coll Cardiol. 2013;62:D42-D50.
22 This presentation is for investor relations purposes only –
Not for product promotional purposes.PAH Functional Class Assessments
NYHA: New York Heart Association WHO: World Health Organization
NYHA WHO
FUNCTIONAL FUNCTIONAL DESCRIPTIONS
CLASS CLASS
1 I No symptoms of pulmonary arterial hypertension with exercise or at rest
No symptoms at rest but uncomfortable and short of breath with normal activity such
2 II as climbing a flight of stairs, grocery shopping, or making the bed
Activities greatly limited by shortness of breath, fatigue, or near fainting. Patients in
3 III this class have a difficult time doing normal chores around the house and have to take
breaks while doing activities of daily living.
Symptoms at rest and severe symptoms with any activity. Patients may faint especially
4 IV while bending over with their heads lowered. Most patients in this class are also
volume overloaded with edema in their feet and ankles from right heart failure
23 This presentation is for investor relations purposes only –
Not for product promotional purposes.PULSAR Phase 2 Trial Design
Double-Blind Extension Period
106 subjects Treatment Period Re-randomize 18 months
Randomized 6 months PBO group
(3:3:4) (1:1)
Placebo (PBO) plus 0.3 mg/kg Sotatercept
Standard of Care (SOC) plus SOC
N = 32
0.7 mg/kg Sotatercept
plus SOC
Screening 0.3 mg/kg Sotatercept
28 days plus SOC
N = 32 0.3 mg/kg Sotatercept
plus SOC
0.7 mg/kg Sotatercept
plus SOC 0.7 mg/kg Sotatercept
N = 42 plus SOC
Long-term safety and
24-week Primary and efficacy endpoints
Secondary Endpoints
24 This presentation is for investor relations purposes only –
Not for product promotional purposes.PULSAR Phase 2 Trial Endpoints
Primary Endpoint
▪ Change from baseline in pulmonary vascular resistance (PVR)
Key Secondary Endpoint
▪ Change from baseline in 6-minute walk distance (6MWD)
Other Secondary Endpoint
▪ Change from baseline in NT-proBNP
▪ Change in World Health Organization (WHO) functional class
The trial was powered to detect an 18% reduction in the primary endpoint of
PVR and a 24-meter improvement in the secondary endpoint of 6MWD.
25 This presentation is for investor relations purposes only –
Not for product promotional purposes.PULSAR Phase 2 Trial Topline Results Summary
Primary Endpoint
▪ In patients on stable background PAH-specific therapies, sotatercept demonstrated a
statistically significant reduction in PVR at week 24 versus placebo.
Key Secondary Endpoint
▪ The trial achieved a statistically significant improvement in the key secondary endpoint
of 6MWD.
Other Secondary Endpoint
▪ The trial also achieved a statistically significant improvement in NT-proBNP and WHO
functional class.
Safety
▪ Generally well tolerated and adverse events were generally consistent with previously
published data on sotatercept in other diseases
26 This presentation is for investor relations purposes only –
Not for product promotional purposes.KOL View on PULSAR Topline Results
*Drs. McLaughlin and Humbert are investigators in the PULSAR trial and are paid consultants to Acceleron.
27 This presentation is for investor relations purposes only –
Not for product promotional purposes.Summary
Habib Dable
Chief Executive Officer
This presentation is for investor relations purposes only –
Not for product promotional purposes.Summary
High unmet medical need for new PULSAR topline results establish proof-of-
treatment options for patients with PAH. concept for Acceleron’s lead pulmonary
program (sotatercept) in PAH.
The PULSAR Phase 2 trial met its primary Sotatercept was generally well
(PVR) and key secondary (6MWD) endpoints tolerated in the trial and adverse events
The trial also achieved a statistically were generally consistent with
significant improvement in other secondary previously published data on
endpoints, including NT-proBNP and WHO sotatercept in other diseases.
functional class.
29 This presentation is for investor relations purposes only –
Sotatercept is an investigational therapy that is not approved for any use in any country. Not for product promotional purposes.A Significant Step Toward our Goal with Sotatercept in
PAH
Currently Approved
PAH-Specific Medicines
Multiple Pathways
Primarily Promote Vasodilation
Endothelin Receptor
Antagonists (ERAs)
+
PDE-5 Inhibitors
+ SOTATERCEPT
A novel investigational
sGC Stimulators
+ medicine
Prostacyclin
+
Initial goal: A combination approach with the potential to
reverse vascular remodeling in patients with PAH
30
Sotatercept is an investigational therapy that is not approved for any use in any country.Priorities for Sotatercept Program in PAH
▪ End of Phase 2 meeting with health authorities
▪ Presentation and publication of PULSAR Phase 2 trial results
▪ Planning for further global development of sotatercept in PAH
▪ SPECTRA Phase 2 trial preliminary results expected by YE2020
▪ Results from PULSAR trial long-term extension period
31 This presentation is for investor relations purposes only –
Sotatercept is an investigational therapy that is not approved for any use in any country. Not for product promotional purposes.Question & Answer Session
Habib Dable President and Chief Executive Officer
Janethe Pena, MD, PhD Vice President, Medical Research, Pulmonary
Marc Humbert, MD, PhD* Professor of Respiratory Medicine at the Université Paris-Saclay
Vallerie McLaughlin, MD* Professor of Cardiovascular Medicine at the University of Michigan
Jay T. Backstrom, MD, MPH Executive Vice President, Head of R&D
Sujay Kango Senior Vice President and Chief Commercial Officer
Todd James Vice President, Investor Relations and Corporate Communications
*Drs. McLaughlin and Humbert are investigators in the PULSAR trial and are paid consultants to Acceleron.
32 This presentation is for investor relations purposes only –
Not for product promotional purposes.You can also read
