$MYOK Positive Topline Results, Phase 2 PIONEER-HCM Study in oHCM

• Phase 2 Study Met Primary and Key Secondary Endpoints
• Results from First Patient Cohort of PIONEER-HCM Accepted for Oral Presentation at Heart Failure Society of America’s 21st Annual Scientific Meeting
• Enrollment Complete in Second, Low-Dose Patient Cohort; Topline Data Expected Q1 2018
• Company to Discuss Results on Conference Call Today at 8:30 a.m. EDT (5:30 a.m. PDT)

SOUTH SAN FRANCISCO, Calif., Aug. 07, 2017 —  MyoKardia, Inc. (Nasdaq:MYOK) (“MyoKardia” or the “Company”), a clinical stage biopharmaceutical company pioneering a precision medicine approach for the treatment of heritable cardiovascular diseases, today announced positive topline data from the first patient cohort of its Phase 2 PIONEER-HCM study of mavacamten in symptomatic, obstructive hypertrophic cardiomyopathy (oHCM) patients. This cohort met the primary endpoint of change in post-exercise peak left ventricular outflow tract (LVOT) gradient from baseline to week 12 as well as key secondary endpoints, including peak oxygen consumption (peak VO₂). Based on these results and subject to discussions in the coming months with the U.S. Food and Drug Administration (FDA), MyoKardia is planning for its next study, EXPLORER-HCM, to be a pivotal study. EXPLORER-HCM is expected to initiate by the end of this year.

“We are very encouraged by the observed physiological effects of mavacamten in this study,” said Stephen Heitner, M.D., director of the HCM Clinic at Oregon Health and Science University’s Knight Cardiovascular Institute, and the lead investigator in the PIONEER-HCM study. “These results continue to build the body of evidence linking the mechanistic hypothesis of mavacamten to potential clinical benefit in symptomatic, obstructive HCM patients.”

In this first patient cohort of PIONEER-HCM, 11 patients enrolled and 10 completed the study. A statistically significant improvement was observed in the primary endpoint, change in post-exercise peak LVOT gradient from baseline to week 12 (p=0.002).

After 12 weeks of treatment, all 10 subjects (100%) achieved a reduction in post-exercise peak LVOT gradient from a baseline mean of 125 mmHg. In eight of the 10 subjects, the post-exercise peak LVOT gradient was reduced below the diagnostic threshold for oHCM (≤ 30 mmHg), with the other two patients’ measurements below 50 mmHg. Clinically meaningful improvements (≤ 30 mmHg) in resting LVOT gradient were observed as early as week 2 in nine out of 10 subjects, providing the rationale for the addition of a second, low-dose cohort to the PIONEER study. Additionally, clinically and statistically significant improvements were observed in peak VO₂ (p=0.004).

The following table summarizes the results observed in post-exercise peak LVOT gradient and peak VO­₂:

	Baseline, mean (SD) n=11	Week 12, mean (SD) n=10	Change from Baseline to Week 12, mean (SD) n=10	p-value
Post-Exercise Peak LVOT Gradient, mmHg	125 (60.0)	19 (12.9)	-112 (63.8)	0.002
Peak VO2, mL/kg/min	20.7 (7.44)	24.6 (8.78)	+3.5 (3.25)	0.004

With respect to New York Heart Association Functional Classification, an exploratory endpoint of PIONEER-HCM, improvements from baseline were observed at week 12 (p=0.016), by at least one class in seven patients, with two of these patients improving by two classes.

Mavacamten was generally well-tolerated. One patient with a history of paroxysmal atrial fibrillation experienced a serious adverse event. In order to participate in the study, this patient had discontinued background beta blocker and disopyramide therapy, both of which are indicated for the management of atrial fibrillation. During the study, the patient experienced a recurrent episode of atrial fibrillation and was cardioverted. The patient had another episode of atrial fibrillation and was hospitalized and successfully treated with anti-arrhythmic therapy. The patient elected to stop study drug at week 4. All other adverse events (AEs) were mild to moderate, and a majority of the AEs were deemed to be unrelated to study drug.

After reviewing safety data from PIONEER-HCM, the Independent Data Monitoring Committee (IDMC) recommended continuation of the study.

In the coming months, MyoKardia intends to discuss the mavacamten clinical development plan in an End-of-Phase 2 meeting with the FDA and seek feedback on the potential for EXPLORER-HCM, its next study of mavacamten in symptomatic oHCM, to be a pivotal study with peak VO₂ as the primary endpoint. The key inclusion and exclusion criteria for EXPLORER-HCM are anticipated to be similar to those for PIONEER-HCM, and the Company expects to enroll between 200 and 250 patients in EXPLORER-HCM. The Company expects to initiate EXPLORER-HCM before the end of this year.

“We are delighted by the positive data released today from PIONEER-HCM,” said Marc Semigran, M.D., chief medical officer of MyoKardia. “We believe these results further demonstrate the potential of mavacamten in oHCM and we intend to move decisively and with urgency to develop this potential therapy for patients. We look forward to discussing with FDA the potential for EXPLORER-HCM to serve as a pivotal study.”

“Hypertrophic cardiomyopathy is an area of critical unmet medical need,” said Anthony Muslin, M.D., Head of Cardiovascular Research at Sanofi S.A. (Sanofi), collaboration partner with MyoKardia. “The PIONEER-HCM study of mavacamten and its early results mark a milestone in the development of a potentially transformative therapy for patients with this genetic heart disease.”

MyoKardia also announced today that the second, low-dose patient cohort in PIONEER-HCM has completed enrollment. Given the marked improvement observed in patients in the first cohort within the first two weeks of dosing, the Company added this patient cohort to explore lower daily doses of mavacamten. This second cohort did not require discontinuation of beta blocker therapy prior to enrollment. The Company expects to release topline data from this second patient cohort in the first quarter of 2018.

On behalf of the PIONEER-HCM investigators, Dr. Heitner will present results from the first cohort at the Heart Failure Society of America’s 21st Annual Scientific Meeting on Monday, September 18, 2017 in the “Big Trials of the Last Year” session.

Conference Call and Webcast

MyoKardia will host a conference call and live audio webcast on Monday, August 7, 2017 at 8:30 a.m. EDT / 5:30 a.m. PDT. The call may be accessed by phone by calling (844) 494-0193 from the U.S. and Canada or (508) 637-5584 internationally and using the conference ID 62326435. The webcast may be accessed live on the Investor Relations section of the Company’s website at http://investors.myokardia.com. A replay of the webcast will be available on the MyoKardia website for 90 days following the call.

PIONEER-HCM Study Design

PIONEER-HCM is a Phase 2 open-label study to assess the efficacy, safety, pharmacokinetics, pharmacodynamics, and tolerability of mavacamten in patients with symptomatic oHCM. oHCM patients with left ventricular ejection fraction (LVEF) ≥ 55%, LVOT gradient (resting gradient ≥ 30 mmHg, post-exercise peak LVOT gradient ≥ 50 mmHg) and New York Heart Association (NYHA) Class ≥ II were treated with mavacamten for 12 weeks, followed by a four-week washout phase. The primary endpoint of PIONEER-HCM is the change in post-exercise peak LVOT gradient from baseline to week 12. Additional endpoints include change from baseline to week 12 in peak VO₂, VE/VCO₂, NYHA Class, NT-proBNP, rest and exercise LVEF, and dyspnea score. Safety endpoints include treatment-related AEs and serious AEs, and changes from baseline in laboratory test results, vital signs, and electrocardiograms. PIONEER-HCM consists of two dosing cohorts: the first cohort, in which subjects received a 10 mg or 15 mg daily dose and were required to discontinue background therapy including beta blockers, and the second cohort, in which subjects will receive a lower daily dose and are not required to discontinue beta blocker therapy.

About Mavacamten (Formerly MYK-461)

Mavacamten is a novel, oral, allosteric modulator of cardiac myosin that reduced hypercontractility in a Phase 1 clinical study of HCM patients. MyoKardia has evaluated mavacamten in multiple Phase 1 clinical studies, primarily designed to evaluate safety and tolerability of oral doses of mavacamten, and provide pharmacokinetic and pharmacodynamic data. In April 2016, the U.S. FDA granted Orphan Drug Designation for mavacamten for the treatment of symptomatic oHCM, a subset of HCM. MyoKardia is currently studying mavacamten in the Phase 2 PIONEER-HCM study.

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 (HCM), and dilated cardiomyopathy (DCM). MyoKardia’s most advanced product candidate is mavacamten (formerly MYK-461). Mavacamten is a novel, oral, allosteric modulator of cardiac myosin that reduced hypercontractility in Phase 1 clinical studies of HCM patients. In April 2016, the FDA granted Orphan Drug Designation for mavacamten for the treatment of symptomatic oHCM, a subset of HCM. MyoKardia is currently studying mavacamten in PIONEER-HCM. MYK-491, MyoKardia’s second product candidate, is designed to increase the overall extent of the heart’s contraction in DCM patients by increasing cardiac contractility. MyoKardia is currently evaluating MYK-491 in a Phase 1 study in healthy volunteers. A cornerstone of the MyoKardia platform is the Sarcomeric Human Cardiomyopathy Registry (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 and Sanofi entered into a worldwide collaboration in 2014 for the research, development and potential commercialization of therapies to treat hypertrophic and dilated cardiomyopathy, as well as potential additional indications. The collaboration was a result of Sanofi’s Sunrise Initiative. 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 mavacamten (formerly MYK-461) and MYK-491, the Company’s expectations with respect to the timing of the release of topline data from the second patient cohort of PIONEER-HCM, the Company’s ability to continue to advance mavacamten in the PIONEER-HCM study and MYK-491 in its Phase 1 study in healthy volunteers and its expectations with respect to the timing of the release of data from this study, the Company’s ability to initiate its planned double-blind, placebo-controlled study of mavacamten (EXPLORER-HCM) in symptomatic oHCM and its expectations that it will be considered a pivotal study, the anticipated inclusion and exclusion criteria and number of patients expected to be enrolled in EXPLORER-HCM, the Company’s plans to expand the clinical investigation of mavacamten to patients with non-obstructive HCM in a planned Phase 2 study, and the timing of the initiation of these studies, the Company’s expectations with regard to its End-of-Phase 2 meeting with the FDA, as well as the requirements for registration of the Company’s product candidates, 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, 2017, which we expect to be filed on or about August 7, 2017, 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.

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