MyoKardia : Corporate Presentation, March 2020

Pioneering a Precision Approach to Cardiovascular Medicine

Corporate Presentation - March 2020

forward-looking statement

Statements we make in this presentation 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 danicamtiv, the availability of data from the Phase 3 EXPLORER-HCM study of mavacamten in symptomatic obstructive HCM and the timing of the full-data presentation of the data from the EXPLORER study, the full-data presentation of the data from the Phase 2 MAVERICK-HCM study in non- obstructive HCM, the initiation of the SRT study of mavacamten, the ability to provide an update on the regulatory path for mavacamten in nHCM, the initiation of a Phase 2 clinical study of mavacamten in HFpEF, the data presentation from the Phase 2a study of danicamtiv in DCM patients, the initiation of the Phase 2 study of danicamtiv in genetic DCM patients, the Company's ability to progress mavacamten for non-obstructive HCM and danicamtiv into later stage clinical trials, the availability of data from the Phase 1 study of MYK-224, the initiation of a Phase 2 study of MYK-224, 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, 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 Annual Report on Form 10-K for the year ended December 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.

Corporate Presentation - March 2020

2

today

Q2

2020

Phase 3 data for	Growing body of data
mavacamten in	fueling pipeline -
obstructive HCM	new indications
	(HFpEF) AND new
	discoveries

Corporate Presentation - March 2020

World-class team	Platform strategy	Global rights to
focused on our	for aggressive	entire portfolio
mission and vision	value creation
	starting with
	mavacamten and
	danicamtiv*
		* Formerly MYK-491	3

cardiovascular disease

the GREATEST

global health burden…

#1 cause of death globally(1)

92M people in the U.S. living with some form of heart disease(1)

$316B annual U.S. cost burden(1)

…yet a DECREASING rate of therapeutic innovation

<5% of products in development are for cardiovascular indications(2)

(23%)	fewer FDA approvals for
cardiovascular medicines
	compared to prior decade(2)
1 of 48	NMEs approved by FDA in 2019
was for a cardiovascular disease

indication(3)

Corporate Presentation - March 2020	1. PhRMA 2018 report on cardiovascular drug development	| 2. EvaluatePharma as of September 2018; 2010- 2018 compared to 2000-2009 |	4

3. CDER Annual New Drug Therapy Approvals

the MyoKardia solution

our strategy…

1 Precision approach to cardiovascular disease

2 Commitment to disease leadership

3 Growing pipeline guided by a cycle of learning

Corporate Presentation - March 2020

• in action

Understand underlying cause

Target cardiac muscle proteins to modulate function

Segment large patient populations

Apply learnings from clinical research to guide future portfolio

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segmenting large patient populations

6M people in the U.S. and

26M worldwide with heart failure

Hypertrophic	Patient subgroups	Dilated
Cardiomyopathy	Cardiomyopathy
(630,000)		(1M)

				Patient subgroups
Obstructive	Non-	Initial HFpEF	Genetic	Other DCM
obstructive
HCM	subgroup	DCM	subgroups
HCM

Diastolic Heart Failure or "HFpEF"		Systolic Heart Failure or "HFrEF"
(2M-3M)		(2M-3M)

Corporate Presentation - March 2020
NOTE: All figures approximate. Reflect estimated diagnosed and undiagnosed totals.	6

industry-leading cardiovascular disease pipeline

HCM and diseases of diastolic and systolic dysfunction

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

Obstructive HCM

Mavacamten	Non-obstructive HCM

Precision diastolic disease (targeted HFpEF)

MYK-224	HCM
		Precision diastolic
LUS-1
disease(s)
Danicamtiv	Genetic dilated cardiomyopathy (DCM)
ACT-1	Precision systolic diseases
(targeted HFrEF)
	Corporate Presentation - March 2020	7

building a position of disease-area leadership inHCM

HCM: a progressive, debilitating disease

Prevalence ~1/500(1)

530K

Undiagnosed

Increased		Chronic		Decreased		Long-term	Increasing
mortality		symptoms		functionality		complications	burden

100K

diagnosed(2)

1/3 non-

obstructive

2/3 HCM(3)

obstructive HCM(3)

current treatment options are inadequate and non-specific

Corporate Presentation - March 2020	Note: All figures approximate; reflect estimated totals 1. Maron et al, Circulation 1995 | 2. Maron et al, AJC 2016 | 3. Maron et al, Circulation 2006	9

targeting the underlying cause of HCM

Enlarged left

atrium

LVOT

obstruction

Decreased left ventricular

volume

Thickened heart

muscle and septum

Corporate Presentation - March 2020

• HCM is a disease of hypercontractility that leads to hypertrophy and impaired relaxation of the left ventricle
• • The heart is working harder, but unable to fill with sufficient blood to meet the body's needs
  • • In obstructive HCM, the thickening of the heart's walls may block the path out for oxygenated blood, while non-obstructiveHCM is driven more by diastolic dysfunction

Mavacamten is intended to reduce HCM symptoms, improve function and potentially slow disease progression by restoring contractility toward a normal state, alleviating obstruction and enabling improved compliance of the left ventricle

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mavacamten efficacy observations

Clinical results in obstructive HCM

gradient

Statistically significant reductions in post-exercise LVOT gradient achieved in PIONEER Phase 2 study (N=20) at 12 weeks:

• 100% below threshold for

surgical intervention (50mmHg)

93.7

Reductions repeated and sustained in PIONEER-OLE (N=11*) at 48 weeks:

• 100% reductions in gradient
• 82% patients below 50mmHg
• 55% patients below diagnostic threshold (30mmHg)

symptoms

PIONEER-HCM PHASE 2 & WEEK 48 PIONEER-OLE

Change from Baseline

	Phase 2	OLE
NYHA Class	Week 12	Week 48
	(N=20)	(N=12)
Improvement	80%	75%
of ≥1 classes
% achieving	65%	75%
Class I status

function

PIONEER-HCM PHASE 2

Change from Baseline

	Phase 2
Peak VO2	Week 12
	(N=20)
Improvement of	60%
≥1.5 mL/kg/min
Improvement of	40%
≥3.0 mL/kg/min

Corporate Presentation - March 2020	Heitner, et al; Annals of Internal Medicine 2019, Heitner, et al; AHA 2019	11
	* One of the 12 PIONEER-OLE patients was unable to complete post-exercise testing at the time of measure

mavacamten safety observations

Mavacamten has been well tolerated

SYMPTOMS

• ~135 patient-years of exposure to date	ejection fraction
• Most adverse events (AEs) observed have
WEEK 48 PIONEER-OLE
been mild, moderate and transient
MEAN (SD) LVEF

• Longest duration of exposure >1.5 years
• Safety vs. placebo (MAVERICK)
• • Serious adverse events (SAEs) occurred twice as frequently in the placebo arm vs. active
  • Fewer cardiovascular AEs occurred on active drug vs. placebo

100	Change from Baseline
72.0			*	70.6
*	*
75
%
50
25
0
Baseline	Week 12	Week 24	Week 36	Week 48
n=13	n=13	n=13	n=12	n=12

*p<0.05 for change from baseline

Threshold for normal ejection fraction

Corporate Presentation - March 2020

Heitner, et al; AHA 2019

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mavacamten biomarker data

Mavacamten may be moving the heart closer to a normal state

LA Volume

wall stress

			Normal	Baseline	Week 48
			Median	Median
		NT-proBNP
		N=13	N=12
	(pg/mL)			594	137
		<125
		Change from baseline
			-472(-2467,-157)*
					*p<0.01
filling pressure

left atrial volume

	Normal	Baseline	Week 48
	Mean (SD)	Mean (SD)
		N=13	N=12
(mL/m2)		40.9 (16.4)	31.5 (6.9)
16-34
Change from baseline
		-9.8 (13.5)*
			*p<0.05

septal wall thickness

Normal	Baseline	Week 48
Mean (SD)	Mean (SD)
E/e′
N=13	N=11
	12.8 (2.9)	9.1 (2.0)
<13
Change from baseline

16.7mm

18

14

10

6

15.3mm

*p<0.01

-3.4 (3.4)*

Corporate Presentation - March 2020

Baseline	Week 12	Week 24	Week 36	Week 48
n=13	n=13	n=13	n=12	n=12
Normal range: 6 mm to 10 mm				13
p <0.05 at weeks 12, 24, 36 for change from baseline	Heitner, et al; AHA 2019

pivotal EXPLORER trial - topline data Q2 2020

251 patients enrolled

Symptomatic (NYHA class II/III) Obstructive (LVOT gradient ≥ 50 mmHg)

Similar level of impairment at baseline to PIONEER patients (LVOT gradient, NYHA class, Peak VO2)

individualized dosing	meaningful endpoints
Start at 5mg, increase up to 15mg QD to	Composite functional endpoint
eliminate gradient

Aim to eliminate symptoms and

2 dose titration opportunities at weeks 8obstruction in a majority of patients and 14 based on blinded echo reads

Secondary endpoints NYHA, peak VO2, gradient, biomarkers

strong participation	+	supportive data	powered to detect a
	>95% 25% treatment effect

68 sites in 13 countries

Overenrolled, ahead of schedule

MAVERICK and OLE studies confirmed safety and tolerability; mechanism and dosing

21% placebo response rate for composite functional endpoint in MAVERICK validated powering assumptions

Placebo assumptions based on LIBERTY, confirmed by MAVERICK

Corporate Presentation - March 2020

14

tackling heart failure

1

a large and growing need

1 in 8

38%

20-45%

$31B

deaths in the U.S. list heart failure as a contributing cause (1)

increase in heart failure deaths from 2011-2017(2)

of individuals aged 45+ are at risk of developing heart failure (2)

annual U.S. cost of heart failure (1)

Survival

Heart failure has a similar 5-year mortality outlook as NSCLC(4)

1. -

1. -

1. -

0.4 -								HFpEF
								HFrEF
0.2 -							T4 NSCLC
							(Stage 3B or worse)
0.0 -
	0	1	2	3	4	5

Year

Corporate Presentation - March 2020	All figures U.S. 1. CDC Natl Center for Health Stats 2019 | 2. Sideny, et al. JAMA 2019 | 3. Benjamin EJ, et al. Circulation 2018 | 4.. Owan, et al NEJM 2006 |	16

heart failure with preserved ejection fraction

Definition

The clinical syndrome of heart failure, normal LVEF, and no other etiology (e.g. valve disease, coronary disease

• Also called "diastolic heart failure" based on hypothesis that if contractility is normal, diastolic function (relaxation, distensibility) must be abnormal

Corporate Presentation - March 2020

heterogenous causes

• Multiple abnormalities in cardiac, vascular, and metabolic physiology can lead to symptoms and morbidity
• • Contribution of diastolic dysfunction varies in different segments of the patient population

HFpEF

•	deconditioning	•	coronary disease
•	renal dysfunction	•	hypertension
•	diabetes mellitus	•	obesity

• COPD

diverse comorbidities

Shah & Pfeffer, Nat. Rec. Cardiol. 2012, 10.1038

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previous efforts to develop pharmacologic therapies have failed

TRIAL NAME	SAMPLE	THERAPEUTIC TARGET	PRIMARY ENDPOINT	OVERALL
	SIZE			RESULT
RELAX (sildenafil)	216	Systemic & pulmonary vasculature	Peak VO2	Negative
TOPCAT (spironolactone)	3,445	RAAS, myocardial fibrosis	CV death, cardiac arrest, HF hospitalization	Negative
ALDO-DHF (spironolactone)	422	RAAS, myocardial fibrosis	Peak VO2, diastolic function	Negative
I-PRESERVE (Irbesartan)	4,128	RAAS, systemic vasculature	All-cause mortality, CV hospitalization	Negative
CHARM-preserved (candesartan)	3,023	RAAS, systemic vasculature	CV death, HF hospitalization	Negative
DIG-PEF (digoxin)	6,800	Sympathetic tone	HF mortality, HF hospitalization	Negative
PEP-CHF (perindopril)	805	RAAS, systemic vasculature	All-cause mortality, HF hospitalization	Negative
SENIORS (nebivolol)	2,128	β-adrenergic blocker	All-cause mortality, CV hospitalization	Negative
PARAGON-HF (sacubitril/valsartan)	4,822	Neprilysn inhibitor, RAAS	CV death, HF hospitalization	Negative

Corporate Presentation - March 2020

RAAS = Renin-Angiotensin-Aldosterone System

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a precision approach

1Begin with proof-of- concept in a targeted population

Obstructive2

HCM

PIONEER EXPLORER

Apply our precision medicine	Leverage learnings to the
approach to adjacent patient	discovery of new molecules
2 populations	3 and new indications

Non-

obstructiveMYK-224

HCM

HFpEF
(diastolic)	LUS-1
HFrEF	ACT-1
(systolic)

MAVERICK

Corporate Presentation - March 2020

19

topline MAVERICK Phase 2 results

First study to show clinical benefit in non-obstructive HCM

Aorta

Left ventricular

outflow tract

Decreased left

ventricular

volume

Thickened heart

muscle and septum

Generally well tolerated

• Rate of AEs greater in active cohorts than placebo
• SAEs seen at half the frequency relative to placebo
• Reversible reductions in LVEF observed

NT-proBNP

• NT-proBNPlevels decreased with statistical significance (p=0.004) in active cohorts vs. placebo

Symptoms, function and biomarker improvements in patients with greatest impairment at baseline

• Two subgroups showed clinical benefit with meaningful trends across multiple endpoints of symptoms, function, circulating and echo biomarkers
• • Elevated filling pressure at baseline (N=25)
  • Pre-specifiedhigh risk population (N=19)

Corporate Presentation - March 2020

20

a segment of HFpEF patients share common

pathophysiology with HCM patients…

Established biomarkers enable HFpEF patient identification

SYMPTOMS

	Shortness of breath
	(↑dyspnea index)
	Fatigue
	(↓peak VO2, ↑NYHA)
HCM	Palpitations
(↑atrial fibrillation)

Chest discomfort

Edema

Premature mortality

Corporate Presentation - March 2020

PATHOPHYSIOLOGY

Myocardial diastolic dysfunction

(↓E/A, ↓e')

Elevated LV filling pressure

(↑NT-proBNP, ↑E/e')

LV wall hypertrophy, ↓ volume

(↓LVEDV)

Left atrial enlargement

(↑LAV)

Normal or hypercontractility

(↑LVEF, s')

Myocardial injury & fibrosis

(troponin, LGE, T1 mapping)

Abnormal myocardial energetics

(ECG ischemia)

targeted

HFpEF segments

21

… that may be alleviated by mavacamten

	SYMPTOMS
	Shortness of breath
	(↑dyspnea index)
	Fatigue
	(↓peak VO2, ↑NYHA)
HCM	Palpitations
(↑atrial fibrillation)

Chest discomfort

Edema

Premature mortality

PATHOPHYSIOLOGY

Myocardial diastolic dysfunction

(↓E/A, ↓e')

Elevated LV filling pressure

(↑NT-proBNP, ↑E/e')

LV wall hypertrophy, ↓ volume

(↓LVEDV)

Left atrial enlargement

(↑LAV)

Normal or hypercontractility

(↑LVEF, s')

Myocardial injury & fibrosis

(troponin, LGE, T1 mapping)

Abnormal myocardial energetics

(ECG ischemia)

targeted

HFpEF segments

Corporate Presentation - March 2020

22

advancing mavacamten in diseases of diastolic dysfunction

learnings from MAVERICK…

identification of patients who should benefit from mavacamten

appropriate dosing for non- obstructive patients

utilization of biomarkers of treatment effect to guide dosing

…inform our next steps

Non-obstructive HCM

• ~1/3 of the 100K diagnosed HCM patients

Meet with FDA on potential registration pathways; regulatory update 1H 2020

Targeted HFpEF

• ~3M patients in U.S. with heart failure with preserved ejection fraction (LVEF >55%)

• Subgroup: ~10-20% of broader HFpEF

Advance to Phase 2 1H 2020

Corporate Presentation - March 2020

23

targeting dilated cardiomyopathy

Enlarged

left atrium

Thin chamber

walls

Dilated

(distended) left

ventricle

• DCM is a disease of reduced contractility and elevated filling pressures
• • The left ventricle is enlarged and the heart muscle becomes too weakened to pump with enough force to meet the body's needs
  • • Fluid retention, shortness of breath and reduced exercise capacity result

Danicamtiv (MYK-491) is intended to increase contractility without detracting

from the heart's ability to relax and fill

Corporate Presentation - March 2020

24

advancing danicamtiv in diseases of systolic dysfunction

Emerging best-in-class profile…

Generally well-tolerated in Phase 1 and Phase 2a clinical studies

>10% increase in stroke volume, evidence of increased contraction

No meaningful changes in relaxation or filling pressures

…informs our path in genetic DCM

• 5-yearmortality approaches 50% in most

centers(1)

• Characterized by enlargement of the heart, fluid accumulation and shortness of breath

• Mutations present in about 30-40% of DCM patients; estimated prevalence of 250,000 to 500,000 people in the U.S. (2)

Phase 2 planned to begin Q2 2020 in patients with genetic DCM (sarcomeric mutations)

Corporate Presentation - March 2020

1.Levy, et al, NEJM, 2002, Roger, et al, JAMA, 2004 |2. Hershberger, et al; Nature, 2013

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building value across our portfolio

value-creating catalysts ahead

Q1	• MAVERICK-HCM full data	Q3
presentation at ACC 2020
2020	2020

• EXPLORER full data presentation *
• MYK-224Phase 1 data

	• Non-obstructive HCM regulatory
		update*
	• Initiate Phase 2 in targeted
		HFpEF population
Q2	•	Initiate VALOR-HCM
2020	•	EXPLORER-HCM topline data

• Danicamtiv Phase 2a data presentation*

• Initiate danicamtiv Phase 2 genetic DCM trial

Corporate Presentation - March 2020

			•	Advance mavacamten
	Q4
		for non-obstructive HCM
2020 •
Initiate MYK-224

Phase 2 trial

* Timing pending abstract acceptances, meeting timing with Agency

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driven by the heart

We are pioneering a precision medicine approach to change the world for people with serious cardiovascular disease through bold and innovative science

Patients first | Passion for science | Succeed together | Imagine and innovate | Lifelong learning

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thank you