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MyoKardia Reports Positive Data from Phase 1b Single-Ascending Dose Clinical Trial of MYK-491 in Dilated Cardiomyopathy and Systolic Heart Failure Patients

MYK-491 Demonstrated Increase in Contractility Consistent with Data from Preclinical and Healthy Volunteer Studies

Multiple-Ascending Dose Phase 2a Clinical Trial in DCM and Systolic Heart Failure Patients Underway

SOUTH SAN FRANCISCO, Calif., Dec. 11, 2018 (GLOBE NEWSWIRE) -- MyoKardia, Inc. (Nasdaq: MYOK), a clinical-stage biopharmaceutical company pioneering precision medicine for the treatment of cardiovascular diseases, today announced topline results from the Phase 1b single-ascending dose study of MYK-491.  MYK-491 was generally well-tolerated and increases in cardiac contractility were observed.  MYK-491 is MyoKardia’s most advanced activator molecule designed to increase contractility of the heart (systolic function) with minimal adverse effects on myocardial relaxation (diastolic function).  MYK-491 is being developed in collaboration with Sanofi S.A. (Sanofi) for the treatment of dilated cardiomyopathy (DCM) and systolic heart failure in which the left ventricle is too distended and weak to adequately pump blood to meet the body’s needs.

“Patients with systolic heart failure may suffer from symptoms such as shortness of breath and fatigue that can progress to frequent hospitalizations and death.  By increasing the heart’s contractility without detracting from the heart’s ability to fill, we believe MYK-491 could potentially make a meaningful difference in patients’ lives,” said Marc Semigran, MyoKardia’s Chief Medical Officer.  “Topline data from single doses of MYK-491 are encouraging. Cardiac contractility increased across a number of standard echocardiographic parameters, with little discernible impact on measures of diastolic relaxation and MYK-491 was generally well tolerated.  Our Phase 2a multiple-ascending dose trial of MYK-491 is now underway, and we look forward to results from that study in late 2019.”

The Phase 1b clinical trial evaluated the safety, tolerability and preliminary pharmacokinetics and pharmacodynamics of single ascending doses of MYK-491.  Eight patients with stable heart failure were enrolled and randomized to receive a single dose of either MYK-491 or placebo, after which patients underwent extended observation, followed by a washout period.  This process was repeated until each patient had received at least three doses (MYK-491 or placebo).

Administration of MYK-491 resulted in approximately 10 percent relative increases from baseline in cardiac contractility across multiple echocardiographic measures, including stroke volume, left ventricular ejection fraction and fractional shortening.  In increasing the heart’s contractility, MYK-491 did not appear to meaningfully change duration of the contraction or the heart’s ability to relax and fill with oxygenated blood. systolic ejection time (SET), a measure of the time it takes to eject blood from the left ventricle, showed a modest increase and the impact of MYK-491 on left ventricular filling was minor across multiple measures of diastolic relaxation.  Overall, these data were consistent with results previously reported from the single-ascending dose trial of MYK-491 in healthy volunteers and supported advancement to Phase 2.

Absolute (Relative) Change from Baselineof
Echocardiogram Parameters at Higher Exposure
  Phase 1a
Healthy volunteers
Phase 1b
Patients with stable
heart failure
EF increase % 3.2 (5.1%) 3.6 (8.3%)
FS increase % 6.3 (20%) 2.3 (10%)
SV increase (mL) 8.2 (12%) 8.7mL (11%)
SET prolongation (msec) 26 30
Relaxation/Diastolic Function
E/e’ -0.06 0.15
E/A -0.05 0.06

1 Placebo-adjusted values

MYK-491 was generally well tolerated.  There were no serious or severe adverse events (AEs) reported.  All treatment-emergent AEs were mild or moderate in severity and occurred at most in one patient.  Sporadic, transient and mild elevations of circulating troponin proteins were observed at baseline and during treatment in both the placebo (two patients) and treatment arms (four patients).  One patient in the study experienced moderate cardiac discomfort, shortness of breath and low-level troponin elevation, all of which resolved without intervention.  No other cardiac-related AEs were observed.

The protocol for the Phase 1b clinical trial was modified to incorporate a Phase 2a multiple-ascending dose trial in patients with dilated cardiomyopathy and stable heart failure.  The Phase 2a study is designed to assess the safety of MYK-491 when dosed chronically to steady state and establish proof-of-concept.  Up to 40 patients will be randomized to receive either MYK-491 or placebo for one week, during which time patients will be monitored to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MYK-491.  Enrollment of patients in the Phase 2a clinical trial is ongoing, with data anticipated in the fourth quarter of 2019. 

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 patients with stable heart failure. MYK-491 is being developed in an ongoing collaboration between MyoKardia and Sanofi.

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 and rare 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 has formed a collaboration with Sanofi to support the commercialization of mavacamten outside the U.S. and for MYK-491’s worldwide late-stage development and commercialization.  MyoKardia’s mission is to change the world for patients with serious cardiovascular disease through bold and innovative science.

Forward-Looking Statements
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 September 30, 2018, 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)


MyoKardia, Inc.