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MyoKardia Shares Data from Ongoing Clinical Programs and Details Three New Research Programs at 2018 R&D Day

Interim PIONEER-OLE Data for Mavacamten Demonstrate Reductions in LVOT Obstruction; Ejection Fraction Maintained above Normal Range

First-in-Human Data for MYK-491 in Healthy Volunteers Presented; Phase 2a Multiple-ascending Dose Trial Initiated

Introduced MYK-224, ACT-1 and LUS-1: Each with Distinct Mechanisms Targeting Diseases of Cardiac Contractility

Detailed Ongoing Efforts to Improve HCM Disease Awareness

SOUTH SAN FRANCISCO, Calif., Oct. 30, 2018 (GLOBE NEWSWIRE) -- MyoKardia, Inc., (Nasdaq: MYOK), a clinical-stage biopharmaceutical company pioneering precision medicine for the treatment of cardiovascular diseases, announced a comprehensive update on its clinical-stage and emerging pipeline today at its 2018 R&D Day in New York City.  Among the highlights:

  • New data were presented for mavacamten in obstructive hypertrophic cardiomyopathy (oHCM) from the company’s ongoing open-label extension study of PIONEER-HCM patients
  • First-in-human data from MyoKardia’s Phase 1a clinical trial of MYK-491 in healthy volunteers confirming the desired activity profile for MYK-491 were also presented.  The company announced that enrollment has begun in the Phase 2a multiple-ascending dose trial of MYK-491 in patients with systolic heart failure and described plans for MYK-491’s future development in a targeted subset of systolic dysfunction. 
  • MyoKardia unveiled three new research programs: MYK-224, the company’s second candidate addressing HCM, which will enter a Phase 1 clinical study in 2019; ACT-1, a proprietary, wholly-owned cardiac muscle activator which is being developed for the treatment of genetic dilated cardiomyopathy (DCM); and LUS-1, the first known compound to specifically target impaired cardiac relaxation for patients with diseases of diastolic dysfunction, also wholly owned.

“We’re proud of the progress we’ve made in the two years since MyoKardia’s first R&D day, particularly the advancement of our two clinical programs.  Our commitment to continued leadership in discovering and developing first-in-class and best-in-class therapeutics to address the high unmet needs among patients suffering from cardiovascular diseases is apparent across our portfolio,” said Tassos Gianakakos, Chief Executive Officer.  “The additional clinical data shared today increases our confidence in mavacamten’s potential, and the introduction of three new research programs highlights our ability to efficiently discover and develop multiple targeted therapies for important diseases areas, with the end goal of changing the world for people suffering from serious cardiovascular disease.”

Pursuing HCM Disease-Area Leadership with a Rich Portfolio of Potential Therapies

  • Interim twelve-week data from open-label extension study of mavacamten affirm activity and safety observations from Phase 2 trial and personalized dosing approach in Phase 3:  MyoKardia shared interim data from the PIONEER Open-Label Extension (OLE) study of mavacamten for the treatment of symptomatic oHCM.  Twelve of twenty patients with oHCM who previously completed MyoKardia’s Phase 2 PIONEER-HCM trial have enrolled in PIONEER-OLE, and seven patients have completed a twelve-week assessment. 
    • Despite treatment with therapies such as beta blockers and calcium channel blockers, patients entered PIONEER-OLE with significant left ventricular outflow tract (LVOT) obstruction (mean LVOT gradient of 94.5mmHg upon provocation).
    • Following resumed mavacamten treatment with individualized dosing, evaluable patients in PIONEER-OLE achieved a statistically significant reduction in LVOT obstruction, to a mean provoked gradient of 22.3mmHg (p=0.031).  For reference, LVOT obstruction is defined as a gradient of 30.0mmHg or greater at rest and a gradient of greater than 50.0mmHg is considered to be hemodynamically significant.(1)  In MyoKardia’s Phase 2 PIONEER-HCM clinical trial of mavacamten, reductions in LVOT obstruction correlated to improvements in patients’ symptoms and exercise capacity.
    • All patients maintained ejection fractions well in the normal range of greater than 50 percent. 
    • There have been no significant adverse events reported.  The longest duration of treatment thus far has been 25 weeks.
    • MyoKardia plans to present additional data from PIONEER-OLE in the first quarter of 2019, including gradient and ejection fraction data from longer term exposures, NT-proBNP and NYHA functional classification changes.
  • Introducing MYK-224, a second therapeutic candidate aimed at HCM:  MyoKardia announced the expansion of its pipeline with MYK-224, a second HCM-targeted candidate with differentiated pharmaceutical properties.  Like mavacamten, MYK-224 is designed to correct excess contractility and address impaired diastolic function, without affecting myosin-actin cross-bridge kinetics or inducing an increase in calcium transient or energy burden.  MYK-224 has been optimized to enable rapid dose adjustment and simplify dose finding in patients.  MyoKardia plans to initiate a Phase 1 clinical trial in 2019 followed by a Phase 2a trial in 2020 addressing a complementary HCM population to mavacamten.

Targeted Approach to Tackling Diseases of Diastolic Dysfunction

  • Revealing LUS-1, a program aimed at tackling diastolic heart failure:  MyoKardia shared preclinical data from its emerging LUS-1 program, a first-of-its-kind class of agents targeted at improving diastolic compliance, or the ability of the heart to relax and fill.  Experience in preclinical studies and observations from clinical trials of mavacamten suggests that it may improve diastolic function and compliance.  Building on these data, MyoKardia has discovered compounds that improve diastolic compliance with minimal impact on contractility.  Preclinical data were shared that demonstrate that MyoKardia’s proprietary agents successfully uncouple contractility inhibition from improved diastolic compliance, with a net positive impact on stroke volume.  MyoKardia plans to share more mavacamten clinical data relating to its potential diastolic benefits at the upcoming American Heart Association Annual Meeting in November and will disclose additional preclinical data in relevant disease models for its LUS-1 program in 2019.

Developing a Portfolio of Precision Therapies to Address Systolic Heart Failure

  • MYK-491 advances to Phase 2a study: The protocol for the ongoing Phase 1b clinical study of MYK-491, MyoKardia’s lead compound targeting impaired cardiac contractility, was recently modified to incorporate a Phase 2a multiple-ascending dose trial in stable heart failure.  Enrollment of patients in the Phase 2a clinical trial has begun, with data anticipated in late 2019.  MyoKardia plans to report topline data from the Phase 1b portion of the Phase 1b/2a clinical trial of MYK-491 in the fourth quarter of 2018. 
  • MYK-491 healthy volunteer data support initial proof-of-mechanism:  MyoKardia detailed results of its Phase 1a study in healthy volunteers, showing that MYK-491 increased cardiac contractility by 5-20 percent across multiple echocardiographic parameters at higher drug concentrations, with minimal impact on diastolic function.  These data are consistent with preclinical data. 
  • MYK-491 future development: MyoKardia reviewed its clinical development program for MYK-491.  Along with its partner Sanofi, MyoKardia plans to study MYK-491 in patients with systolic dysfunction.  Upon successful completion of the ongoing Phase 2a study, MyoKardia and Sanofi expect to target patients based on shared phenotypic characteristics to address patient need.    
  • Debuting ACT-1, a second cardiac muscle activator program aimed at genetic DCM:  MyoKardia shared preclinical data for ACT-1, a non-myosin cardiac muscle activator intended to target a specific mutation underlying genetic forms of DCM.  In preclinical studies, ACT-1 was able to increase stroke volume and systolic function with no prolongation of systolic ejection time and no significant impact on diastolic relaxation.  ACT-1 has been designed specifically for genetic DCM patient segments, which will be supported based on longitudinal studies in genetic animal models.  MyoKardia plans to advance ACT-1 into clinical studies in late 2020/early 2021.

Partnering with the HCM Community to Transform the Care of Patients

MyoKardia is committed to building a community of stakeholders to better understand the substantial and progressively worsening long-term burden of HCM and the impact of disease progression on patients’ and their families’ lives. MyoKardia outlined several key strategic imperatives to support disease education of mavacamten in advance of potential mavacamten approval in the U.S.  These efforts include:

  • The Sarcomeric Human Cardiomyopathy Registry (SHaRe), which aims to advance the understanding of HCM through the development of a robust database of genetic and clinical information
  • Digital health initiatives incorporated into ongoing clinical trials
  • The HCM Care mobile app, an information resource for patients and physicians
  • MyoSeeds™ grant program to foster research in HCM and DCM
  • The formation of the first-of-its-kind HCM patient community in partnership with 23andMe

Anticipated Milestones in 2018 and 2019:


  • Presentation of new clinical and preclinical data highlighting the effects of mavacamten on diastolic function and showcasing findings from the Sarcomeric Human Cardiomyopathy Registry (SHaRe) at the 2018 Scientific Sessions of the American Heart Association (AHA), November 10-12, 2018 in Chicago, Illinois
  • Presentation of additional interim clinical data from the ongoing PIONEER-OLE study in the first quarter of 2019
  • Completion of enrollment in the pivotal Phase 3 EXPLORER-HCM trial in oHCM in the second half of 2019 and reporting of topline clinical data in the second half of 2020
  • Reporting of data from the Phase 2 MAVERICK-HCM trial in symptomatic non-obstructive HCM patients in the second half of 2019


  • Reporting of clinical data from the ongoing Phase 1b clinical trial of MYK-491 in stable heart failure patients in the fourth quarter of 2018
  • Reporting of clinical data from the ongoing Phase 2a clinical trial of MYK-491 in stable heart failure patients in late 2019


  • Initiation of Phase 1 clinical trial in healthy volunteers in the second half of 2019


  • Announcement of third quarter financial results on November 7, 2018 via press release.

Webcast Information
The live webcast for today’s event can be accessed under “Events & Presentations” in the Investor Relations section of the Company’s website at A replay of the webcast will be available on MyoKardia’s website for 90 days following the call.

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.

  1. ACC and ESC Guidelines

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 mavacamten and MYK-491, the Company's ability to enroll patients in its Phase 3 EXPLORER-HCM study of mavacamten in symptomatic oHCM and its PIONEER-OLE study, the Company’s ability to advance mavacamten in its ongoing Phase 2 MAVERICK-HCM study in nHCM, the Company’s ability to advance MYK-491 in its Phase 2a study in DCM patients, the Company’s ability to initiate its planned Phase 1 study of MYK-224, the Company’s expectations with respect to the release of data from these studies, the anticipated numbers of patients expected to be enrolled in these studies, the Company’s ability to advance additional research programs into clinical development, and the timing of these events, as well as the requirements for registration of the Company's product candidates, the Company’s ability to carry out initiatives to support market development of mavacamten, the Company’s projected cash runway and the anticipated amount and use of proceeds from the offering described herein, 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 June 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)

Tuesday, October 30, 2018 - 07:30