$MYOK Announces Presentations at #AHA Scientific Sessions 2016

Clinical Data from Phase 1 SAD Trials of MYK-461 in Hypertrophic Cardiomyopathy Patients and Healthy Volunteers

New Animal Model Research Advances Understanding of HCM Pathophysiology

SOUTH SAN FRANCISCO, Calif., Nov. 04, 2016  — MyoKardia, Inc. (Nasdaq:MYOK), a clinical stage biopharmaceutical company pioneering a precision medicine approach for the treatment of heritable cardiovascular diseases, today announced presentations at American Heart Association (AHA) Scientific Sessions 2016 highlighting the Company’s clinical and animal model research in hypertrophic cardiomyopathy (HCM), novel insights from its SHaRe registry and precision cardiovascular approach, as well as two of MyoKardia’s cofounders presenting research in understanding HCM causes and outcomes. AHA Scientific Sessions 2016 will be held Nov. 12-16 in New Orleans.

Clinical Data from Phase 1 SAD Trials of MYK-461 in Hypertrophic Cardiomyopathy

Data from MyoKardia’s two Phase 1 single ascending dose trials of MYK-461 in HCM patients and healthy volunteers will be presented by Martin S. Maron, M.D., Director of the Hypertrophic Cardiomyopathy Center at Tufts Medical Center in Boston. Topline data from the studies were released in July 2016.

The studies were designed to establish the safety and tolerability of single oral doses of MYK-461. Secondary objectives included establishing the preliminary pharmacokinetic and pharmacodynamics profiles of MYK-461. Clinical proof of mechanism was observed overall as a dose-dependent reduction in cardiac contractility following single oral doses, in both healthy volunteers and HCM patients.

MyoKardia is currently studying MYK-461 in PIONEER-HCM, a Phase 2 open-label single-arm pilot study to evaluate safety, tolerability and efficacy of MYK-461 in subjects with symptomatic, obstructive HCM (oHCM). The U.S. Food and Drug Administration has granted the company Orphan Drug Designation for MYK-461 for the treatment of symptomatic oHCM.

The poster presentation, “Obstructive Hypertrophic Cardiomyopathy: Initial Single Ascending Dose Data in Healthy Volunteers and Patients,” is part of the “Hypertrophic Cardiomyopathy: New Insights” session. The presentation is on Nov. 15, 10:45 AM to 12:00 PM, in the Science and Technology Hall, Clinical Science Section.

New Animal Model Data Advances Understanding of HCM Pathophysiology

Previous MyoKardia research, including results published in a recent paper in the leading medical journal Science, has provided evidence of the ability of MYK-461 to prevent and reverse development of HCM in multiple animal models. A new study highlighted at AHA sheds further light on how mutations in sarcomere genes lead to the physiology of HCM. The findings of the MyoKardia study provide the first evidence integrating molecular, cellular and organ-level studies that hypercontractility, subclinical ischemia and fibrosis contribute to the early pathogenesis of HCM.

Ferhaan Ahmad, M.D., Ph.D., Director of the Cardiovascular Genetics Program at the University of Iowa, will present “A Minipig Genetic Model of Hypertrophic Cardiomyopathy.” The presentation is part of the “Molecular Basis of Cardiac Hypertrophy” session on Nov. 15, from 1:30 to 2:45 PM, and is being held in the Science and Technology Hall, Clinical Science Section.

The experiments highlighted by Dr. Ahmad were performed on proprietary genetic pig models of HCM, which were created by Exemplar Genetics, a wholly-owned subsidiary of Intrexon Corporation. MyoKardia and Exemplar Genetics have formed a multi-year collaboration, in which MyoKardia may direct the development of additional pig models of disease by Exemplar Genetics, each with distinct genetic defects known to cause heritable cardiomyopathies. Researchers anticipate this model, and future models created under the collaboration, will be valuable for advancing our understanding of disease pathophysiology and for the further development of novel therapeutics to treat heritable cardiomyopathies.

Presentations Highlight SHaRe, Precision Medicine

• Eric Green, M.D., Ph.D., senior director of translational research at MyoKardia, will present “Translating Insights from Human Genetics into Precision Therapeutics” during the “Precision Medicine 2016: Changing Genetic Destiny: New Approaches to Therapy” session at AHA. The presentation is scheduled for Nov. 14, 2:30 to 2:45 PM.
• A discussion of HCM databases that includes the Sarcomeric Human Cardiomyopathy Registry, or SHaRe, will be included in the “Genotype-Phenotype Correlations: Identification and Prevention” presentation at AHA. The presentation, part of the “Precision to Population: Optimizing Outcomes in HF” session, will be delivered by Carolyn Ho, M.D., Associate Professor, Harvard Medical School. It is scheduled for Nov. 15, 11:00 to 11:15 AM.

MyoKardia Co-Founders Leslie Leinwand and Christine Seidman Present Research on Cardiomyopathy Causes and Outcomes

• MyoKardia co-founders Leslie Leinwand, Ph.D., Molecular, Cellular, and Developmental Biology Professor and the chief scientific officer of the BioFrontiers Institute at the University of Colorado, Boulder; and Christine Seidman, M.D., a professor of genetics and the Thomas W. Smith professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, will each be presenting in separate sessions at AHA.
• Dr. Leinwand will present “Functional Changes in Motor and Structural Proteins Causing HCM” during the “Cellular and Molecular Aspects of Hypertrophic Cardiomyopathy” session, which focuses on the latest research in cellular and molecular aspects of HCM. The presentation is Nov. 15, 10:45 to 11:00 AM.
• Dr. Seidman will present “Genomics and Heart Failure: The Secret Within,” at AHA. The presentation is part of a session entitled “From Precision to Population: Optimizing Outcomes in HF,” that focuses on the role of precision medicine in heart failure. It is scheduled for Nov. 15, 10:45 to 11:00 AM.

About MYK-461 and PIONEER-HCM

MYK-461 is an orally administered small molecule designed to reduce left ventricular contractility by allosterically modulating the function of cardiac myosin, the motor protein that drives heart muscle contraction. MyoKardia has evaluated MYK-461 in three Phase 1 clinical trials, primarily designed to evaluate safety and tolerability of oral doses of MYK-461, as well as provide pharmacokinetic and pharmacodynamic data. In April 2016, the U.S. FDA granted the company Orphan Drug Designation for MYK-461 for the treatment of symptomatic oHCM, a subset of HCM.

MyoKardia is currently studying MYK-461 in PIONEER-HCM, a Phase 2 open-label single-arm pilot study to evaluate safety, tolerability and efficacy of MYK-461 in patients with symptomatic oHCM. The primary endpoint of PIONEER-HCM is the level of reduction in post-exercise left ventricular outflow tract (LVOT) gradient over 12 weeks of drug treatment. PIONEER-HCM will also explore the relationship between reduction in contractility and LVOT gradient, endpoints measuring functional capacity (i.e., exercise) and clinical symptoms in addition to gathering safety and tolerability data on MYK-461 in an outpatient setting.

About HCM and oHCM

It is estimated that one in every 500 people in the United States has HCM, the most prevalent form of heritable cardiomyopathy. HCM is defined as an otherwise unexplained thickening of the walls of the heart, known as hypertrophy. The consequences include reduced left ventricular volumes and cardiac output, reduced ability of the left ventricle to expand, and elevated filling pressures. These can all contribute to reduced effort tolerance and symptoms that include shortness of breath and chest pain. HCM is a chronic disease and for the majority of patients, the disease progresses slowly and can be extremely disabling. HCM substantially increases the risk of developing atrial fibrillation that can lead to stroke or malignant ventricular arrhythmias that can cause sudden cardiac death. There are currently no approved drug products indicated for the treatment of HCM. Patients are typically prescribed one or more drugs (including beta blockers, non-dihydropyridine calcium channel blockers and disopyramide) indicated for the treatment of hypertension, heart failure or other cardiovascular disorders more generally.

oHCM is a physiological complication of HCM in which the thickened heart muscle obstructs the LVOT. Approximately two thirds of all HCM patients have obstruction, either at rest or with provocation like exercise. Measured most commonly by non-invasive imaging (echocardiography), oHCM is defined as ≥30 mm Hg pressure gradient across the LVOT. Symptoms of oHCM can include shortness of breath, chest pain, dizziness, fainting, and palpitations. The presence of obstruction in an HCM patient further increases risk of progression to severe symptoms, and risk of death from heart failure or stroke.

The degree of LVOT obstruction in oHCM patients is a primary criterion for surgical and other invasive interventions (recommended for symptomatic patients with LVOT gradients measured at ≥50 mmHg). Relief of obstruction has been associated with improved symptoms, function and clinical outcomes. Surgical or other invasive interventions, including septal myectomy, an open heart procedure, may be appropriate. There are no approved drug products indicated for this condition. The primary endpoint of the Phase 2 PIONEER-HCM study is to assess level of reduction in LVOT gradient over 12 weeks of drug treatment. The trial is also exploring relationships among reductions in contractility, LVOT gradient and endpoints that include safety, tolerability, functional capacity and clinical symptoms.

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 treatment of heritable cardiomyopathies, a group of rare, genetically-driven forms of heart failure that result from biomechanical defects in cardiac muscle contraction. MyoKardia has used its precision medicine platform to generate a pipeline of therapeutic programs for the chronic treatment of the two most prevalent forms of heritable cardiomyopathy—hypertrophic cardiomyopathy, or HCM, and dilated cardiomyopathy, or DCM. MyoKardia’s most advanced product candidate, MYK-461, is an orally-administered small molecule designed to reduce excessive cardiac muscle contractility leading to HCM and has been evaluated in three Phase 1 clinical trials. MyoKardia is now studying MYK-461 in a Phase 2 PIONEER-HCM pilot study in symptomatic oHCM, for which the FDA has granted MYK-461 Orphan Drug Designation. A cornerstone of the MyoKardia platform is the Sarcomeric Human Cardiomyopathy Registry, or SHaRe, a multi-center, international repository of clinical and laboratory data on individuals and families with genetic heart disease, which MyoKardia helped form in 2014. MyoKardia believes that SHaRe, currently consisting of data from approximately 10,000 individuals, is the world’s largest registry of patients with heritable cardiomyopathies. MyoKardia’s mission is to change the world for patients with serious cardiovascular disease through bold and innovative science. For more information, please visit www.myokardia.com.

Investor Contact:
Beth DelGiacco
Stern Investor Relations, Inc.
212-362-1200
beth@sternir.com

Media Contact:
Steven Cooper
Edelman
415-486-3264
steven.cooper@edelman.com