Edgewise Therapeutics : EDG-5506 ARCH 2 YR Topline Results April 2024

2-Year Topline Results from the ARCH Study of Sevasemten in Adults with Becker Muscular Dystrophy

April 16, 2024

NASDAQ: EWTX

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Forward looking statement

This presentation contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this presentation that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding Edgewise's expectations relating to its clinical trials and clinical development of sevasemten; statements regarding the potential of, and expectations regarding, Edgewise's product candidates and programs, including EDG-5506 and EDG-7500; statements regarding Edgewise's milestones, including timing of data from its CANYON trial; statements regarding whether data from GRAND CANYON could support a marketing application; and statements by Edgewise's chief medical officer and Barry J. Byrne, M.D., Ph.D.. Words such as "believes," "anticipates," "plans,"

"expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained

herein are based upon Edgewise's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company including the potential for Edgewise's product candidates to cause serious adverse events; Edgewise's ability to develop, initiate or complete clinical trials for, obtain approvals for and commercialize any of its product candidates; Edgewise's ability to take advantage of potential benefits associated with designations granted by FDA and/or to maintain qualifications for applicable designations over time; the timing, progress and results of clinical trials for EDG-5506 and EDG-7500; Edgewise's ability to enroll and maintain patients in clinical trials; Edgewise's ability to raise any additional funding it will need to continue to pursue its business and product development plans; the timing, scope and likelihood of regulatory filings and approvals; the potential for any clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; the potential that the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials; Edgewise's ability to develop a proprietary drug discovery platform to build a pipeline of product candidates; Edgewise's manufacturing, commercialization and marketing capabilities and strategy; the size of the market opportunity for Edgewise's product candidates; the loss of key scientific or management personnel; competition in the industry in which Edgewise operates; Edgewise's reliance on third parties; Edgewise's ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled "Risk Factors" in documents that Edgewise files from time to time with the U.S. Securities and Exchange Commission. These forward-looking statements are made as of the date of this presentation, and Edgewise assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

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Dr. Kevin Koch

Chief Executive Officer

Dr. Joanne Donovan

Chief Medical Officer

Dr. Barry Byrne

UF Health Center &

Powell Gene

Therapy Center

AGENDA

1. Introduction to Edgewise Therapeutics
2. Contextualizing functional measurements in Becker
3. Results from the 2-year ARCH Becker trial
4. Opportunity in Becker
5. Closing remarks

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Opening Remarks

Kevin Koch, CEO

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Leaders in muscle disease science

FOCUSED ON MUSCLE SCIENCE

• Global leader in muscle disease therapeutic development
• Deep knowledge of integrated muscle physiology
• Novel & holistic therapeutic approach to protect muscle

RAPIDLY ADVANCING PORTFOLIO

• Advancing sevasemten to become the foundational therapy for muscular dystrophies
• Developing EDG-7500 to target select cardiovascular diseases
• Novel cardiometabolic targets in discovery

UNWAVERING PATIENT COMMITMENT

• Mission-drivenfocus on unmet needs in severe muscle conditions
• Patients & families are critical voices in all development programs

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Our goal is to positively impact the course of Becker muscular dystrophy

• Becker is a severe, underappreciated condition with major unmet medical need and no standard of care

● No therapy has ever been approved specifically for Becker

• Can lead to relentlessly progressive loss of motor function
• Individuals with Becker lose mobility, function and independence in the prime of their lives

Source: NIH Genetics Home Reference - Duchenne and Becker muscular dystrophy; Romitti PA et. al., Pediatrics, 2015; Bushby KM, et. al., Lancet, 1991; Salari N, et. al., J Orthop Surg Res, 2022; : J Med Genet	6
2016;53:145-151; Lancet, 337 (8748), 1022-1024; J Orthop Surg Res 17, 96 (2022)

In Becker, fast muscle fibers are disproportionately injured by normal, everyday contractions

Healthy muscle contraction		Becker muscle contraction

	mechanical
	stress
	fiber
	breakdown
Dystrophin connects contractile proteins to the	Contraction-induced muscle injuries occur in the
membrane and surrounding matrix to protect against	absence of full-length dystrophin.
contraction-induced injury.

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Sevasemten's protective effects against contraction-induced injury in dystrophic muscles demonstrated in mdx mouse models

Contracting at 100% without sevasemten		Contracting at 85% with sevasemten

In mdx mouse muscle, even a few contractions cause visible injury

By minimally decreasing contraction while preserving function, contraction-induced injury is prevented

Both videos have been sped up 3x
Reference: Russell AJ, et al. J Clin Invest. 2023;133(10):e153837. doi:10.1172/JCI153837	8

Sevasemten: A first-in-class fast myofiber (type II) myosin inhibitor designed to protect against contraction-induced muscle injury

Sevasemten Therapeutic Hypothesis

Protected sarcomere

Sevasemten	Prevention of
	contraction-induced
Duchenne	muscle injury
Excessive
contraction
induced muscle	Collapsed sarcomere
damage
Becker
Progressive	Contraction-induced
muscle injury
disease
pathology

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Contextualizing North Star

Ambulatory Assessment (NSAA)

in Becker Muscular Dystrophy

Barry Byrne, MD, PhD

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