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MyoKardia Presents Results from Phase 1a Clinical Trial of MYK-491 at the European Society of Cardiology Heart Failure Congress in Athens, Greece

First-in-Human Data for MYK-491 in Healthy Volunteers Demonstrated Well-Tolerated Increases in Cardiac Contractility

Topline Results from Phase 2a Clinical Trial of MYK-491 in Patients with Stable Heart Failure with Reduced Ejection Fraction Anticipated in Second Half 2019

SOUTH SAN FRANCISCO, Calif. and ATHENS, Greece, May 28, 2019 (GLOBE NEWSWIRE) -- MyoKardia, Inc., (MYOK), presented data today at the European Society of Cardiology Heart Failure Congress from its Phase 1a single-ascending dose study of MYK-491 in healthy volunteers. MYK-491 is MyoKardia’s most advanced activator molecule, designed to increase contractility of the heart (systolic function) with minimal effects on myocardial relaxation (diastolic function). 

First-in-human data from the Phase 1a clinical trial of MYK-491 in healthy volunteers showed the drug to be well tolerated.  MYK-491 increased cardiac contractility by 5-20 percent across multiple echocardiographic parameters at higher drug concentrations, with minimal impact on diastolic function.  MYK-491 is currently being studied in a Phase 2a multiple-ascending dose clinical trial for the treatment of patients with systolic heart failure, in which the heart is unable to contract sufficiently to meet the demands of the body.

“In developing MYK-491, we set out to target the underlying heart muscle proteins to increase contraction, with minimal impact on the heart’s ability to relax and fill with oxygenated blood between beats. Data from our Phase 1a study in healthy volunteers demonstrate that MYK-491 is achieving this desired effect, and these results have been confirmed by data from our Phase 1b study in patients with stable heart failure,” said June Lee, M.D., Executive Vice President, Chief Development Officer.  “We are now looking forward to assessing MYK-491’s safety and activity in patients when administered over several days in our multiple-ascending dose study.  The data from our ongoing proof-of-concept Phase 2a trial, combined with translational research efforts, will inform our late-stage development plans, and we look forward to reporting those results later this year.”

Single-Ascending Dose Trial in Healthy Volunteers
The Phase 1 randomized, double-blind placebo-controlled study was designed to assess safety, tolerability, pharmacokinetics and pharmacodynamics of single-ascending oral doses of MYK-491.  Sixty-four healthy adult volunteers (48 active, 16 placebo) were enrolled and randomized to receive placebo or single-ascending doses of MYK-491 ranging from 3mg-550mg.

MYK-491 was generally well tolerated with no dose-limiting toxicities observed. Transient and spontaneously resolving arrhythmias were reported.  The most common adverse event (AE) reported was headache, and there was no trend for increased AE frequency associated with higher dose concentrations.  Pharmacokinetic results indicated MYK-491 may be amenable to once- or twice-daily dosing.

Dose- and concentration-dependent increases in stroke volume (SV) and other indicators of enhanced systolic function were observed, including increases in left ventricular fractional shortening (FS) and ejection fraction (EF) as well as decreases in end-systolic left ventricular dimensions.  At the highest dose cohort, a modest prolongation of systolic ejection time (SET) and no discernible impact on relaxation and diastolic function (as measured by mitral annular and peak filling velocities during diastole) were observed.

Absolute (Relative) Change from Baseline1 of
Select Left Ventricular Echocardiography Parameters
  Phase 1a
Healthy Volunteers
Higher Concentration Cohort
EF increase % 3.2 (5%)
FS increase % 6.3 (20%)
SV increase (mL) 8.2 (12%)
SET prolongation (msec) 26
Relaxation/Diastolic Function
E/e’ -0.06
E/A -0.05

1 Placebo-adjusted values

These data were reported today by Jean-Francois Tamby, M.D., Vice President, Clinical Sciences, MyoKardia at the European Society of Cardiology Heart Failure Congress in a poster titled, “MYK-491, a Novel Cardiac Myosin Activator, Increases Cardiac Contractility in Healthy Volunteers” (Abstract 60668).  MyoKardia previously detailed results from the Phase 1a study of MYK-491 at its October 2018 R&D Day. 

About MYK-491
MYK-491 is an oral, small molecule, allosteric activator of myosin.  In the heart, myosin is the motor protein that binds to actin to generate the force and movement of contraction.  In patients with dilated cardiomyopathy and systolic heart failure, in which the left ventricle of the heart is too distended and weak to adequately pump blood to meet the body’s needs, MYK-491 is intended to increase myosin-actin engagement, thereby targeting the biomechanical defects underlying disease and improving cardiac contractility.  Based on data from preclinical research across multiple animal models and Phase 1 studies, MYK-491 may hold potential for controlled increases in the heart’s contractility with minimal impact on relaxation.  MYK-491 is currently being studied in a Phase 2a multiple-ascending dose trial in patients with stable heart failure.  

About MyoKardia
MyoKardia is a clinical-stage biopharmaceutical company pioneering a precision medicine approach to discover, develop and commercialize targeted therapies for the treatment of serious cardiovascular diseases. MyoKardia’s initial focus is on the development of small molecule therapeutics aimed at the cardiac muscle proteins that modulate cardiac muscle contraction and underlie diseases of systolic and diastolic dysfunction. Based on an in-depth understanding of disease biology, MyoKardia applies a precision medicine approach to develop its therapeutic candidates for patient populations with shared characteristics, such as causal genetic mutations or disease subtypes. MyoKardia’s most advanced product candidate is mavacamten (formerly MYK-461), a novel, oral, allosteric modulator of cardiac myosin intended to reduce hypercontractility. Mavacamten has advanced into a pivotal Phase 3 clinical trial, known as EXPLORER-HCM, in patients with symptomatic, obstructive hypertrophic cardiomyopathy (HCM). MyoKardia is also developing mavacamten in a second indication, non-obstructive HCM, in the Phase 2 MAVERICK-HCM clinical trial. MYK-491, MyoKardia’s second product candidate, is designed to increase cardiac output among patients with systolic heart dysfunction by increasing the overall extent of the heart’s cardiac contractility. MyoKardia is currently evaluating MYK-491 in a Phase 1b/2a study in stable heart failure patients.

MyoKardia’s mission is to change the world for patients with serious cardiovascular disease through bold and innovative science.

Forward-Looking Statement
Statements we make in this press release may include statements which are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements regarding the clinical and therapeutic potential of MYK-491 and the availability of data from the MYK-491 Phase 2a multiple ascending dose trial, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, risks associated with the development and regulation of our product candidates, as well as those set forth in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2019, and our other filings with the SEC. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Michelle Corral
Senior Director, Corporate Communications and Investor Relations
MyoKardia, Inc.

Hannah Deresiewicz (investors)
Stern Investor Relations, Inc.

Steven Cooper (media)