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Executive Summary

Sevasemten is an orally administered first-in-class fast skeletal myosin inhibitor designed to protect dystrophic muscle against contraction-induced injury in Becker muscular dystrophy, potentially becoming the first approved therapy for this devastating disease.

Sevasemten

Fast skeletal myosin ATPase · Small molecule

Pivotal Wholly-owned

Target: Fast skeletal myosin ATPase

Full NameFast skeletal muscle myosin ATPase

PathwayMuscle contraction

See Target Biology →

Mechanism of Action[Pres '26 S8]

TypeFast skeletal myosin inhibitor

DescriptionSevasemten inhibits fast skeletal myosin ATPase to reduce the force of muscle contractions, thereby protecting dystrophic muscle fibers from contraction-induced damage that leads to progressive muscle breakdown and functional impairment

DifferentiationFirst-in-class fast skeletal myosin inhibitor with novel mechanism of action that addresses the root cause of muscle breakdown in Becker muscular dystrophy, with oral administration and generally safe and well tolerated profile

Indications: Becker muscular dystrophyDuchenne muscular dystrophy

Target Biology[Pres '26 S9]

In Becker muscular dystrophy, progressive contraction-induced muscle damage results in loss of skeletal muscle function and severe disability. Sevasemten targets fast myosin to protect dystrophic muscle against this contraction-induced injury, intended to minimize progressive muscle damage that leads to functional impairment.

Human Genetic Evidence: Becker is caused by mutations in the dystrophin gene leading to reduced/abnormal dystrophin protein, making muscle vulnerable to contraction-induced damage

Clinical Data

Phase 1 24-month Open Label Study[Pres '26 S9]

Phase 1 Completed n=N=12

Design: 24-month open label study

Arms: Sevasemten

Endpoints

Endpoint	Result
Primary: Safety and tolerability[Pres '26 S9] Safety and tolerability assessment	Durable response, 11 of 12 remain on therapy, longest exposure +4 years, well tolerated

Safety

Well tolerated with durable response, 11 of 12 patients remain on therapy with longest exposure over 4 years

Phase 2 16-week Placebo Controlled Exercise Challenge Study[Pres '26 S9]

Phase 2 Completed n=N=9

Design: 16-week placebo controlled exercise challenge study

Arms: Sevasemten, Placebo

Endpoints

Endpoint	Result
Primary: Biomarkers of muscle damage[Pres '26 S9] Reduction in biomarkers of muscle damage vs placebo	Significant reduction in biomarkers of muscle damage vs placebo

Biomarkers

Biomarker	Result	Significance
Muscle damage biomarkers[Pres '26 S9]	Significant reduction vs placebo	Indicates reduced muscle damage from contractions

Safety

Well tolerated

Phase 2 12-month Placebo Controlled Study[Pres '26 S9]

Phase 2 Completed n=N=40 Adults

Design: 12-month placebo controlled study

Arms: Sevasemten, Placebo

Endpoints

Endpoint	Result
Primary: Creatine kinase (CK)[Pres '26 S9] Reduction in CK levels	Met primary endpoint reduction in CK
NSAA stability[Pres '26 S9]	NSAA stable over time with trend toward improvement vs placebo

Biomarkers

Biomarker	Result	Significance
Creatine kinase (CK)[Pres '26 S9]	Significant reduction vs placebo	CK is a biomarker of muscle damage; reduction indicates muscle protection

Safety

Well tolerated

GRAND CANYON Pivotal Trial[Pres '26 S14]

Pivotal Ongoing n=N=175 Adults

Design: 18-month placebo controlled global registrational study

Arms: Sevasemten, Placebo

Endpoints

Endpoint	Result
Primary: NSAA at 18 months[Pres '26 S14] North Star Ambulatory Assessment score at 18 months	Powered at >98% for observing a significant difference assuming a mean NSAA difference of 1.7 points over placebo at 18 months
Timed function tests[Pres '26 S14]	Pending
Patient reported outcomes[Pres '26 S14]	Pending

Biomarkers

Biomarker	Result	Significance
Biomarkers of muscle damage[Pres '26 S14]	Pending	Will assess muscle protection effects

Safety

Ongoing assessment

MESA Open Label Extension[Pres '26 S11]

Extension Ongoing n=99% of eligible Becker trial participants enrolled

Design: Open-label extension study in adults/adolescents with Becker

Arms: Sevasemten

Endpoints

Endpoint	Result
Primary: Long-term safety and efficacy[Pres '26 S11] Long-term assessment	Sustained stability over 3 years vs predicted -4.4 point decline
NSAA score maintenance[Pres '26 S11]	NSAA score at 3 years: +0.2 vs predicted decrease of -4.4 points

Safety

Well tolerated long-term with high retention rate

Investment Analysis

Satya Bio Analysis — estimates based on public data and analyst judgment, not sourced from company materials

Bull Case

Thesis Point	Supporting Evidence	Confidence
First-ever therapy in Becker with zero competition and Orphan exclusivity	No FDA-approved therapies; FDA Type C confirmation of registration path	High
3 years of durability data from MESA OLE	NSAA stabilization diverging from natural history after 3 years	Medium
Duchenne expansion represents much larger market (10mg dose selected)	LYNX/FOX Phase 2 data, Phase 3 design H2 2026	Medium

Bear Case

Risk	Evidence	Mitigating Factors
NSAA endpoint may not translate to meaningful clinical benefit	Even 1-point NSAA decline can have detrimental effects, but regulatory acceptance uncertain	—
Limited commercial opportunity due to small patient population	Only ~6,000 Becker patients in US limits peak sales potential despite high pricing	—

Key Debates

Question	Bull View	Bear View	Resolution Catalyst
Will NSAA functional benefit translate to regulatory approval and commercial success?	NSAA preservation is clinically meaningful in progressive disease with no alternatives	Regulatory bar may be higher for functional endpoints in rare disease	GRAND CANYON pivotal trial results and FDA interactions
Can Edgewise successfully execute first commercial launch?	Strong commercial preparation, high physician awareness, clear unmet need	Inexperienced commercial organization in specialized rare disease market	Commercial execution following potential approval

Market Opportunity[Pres '26 S16]

Total Addressable Market

~$5 Billion total potential Becker market

Patient Population

~6,000 Becker patients in the US; >12,000 in major markets

Unmet Need: Zero FDA approved therapies for a devastating, genetic, life-shortening, debilitating and degenerative neuromuscular disease

Catalysts & Upcoming Events

Event	Timing	Importance	Key Metrics to Watch	Consensus
GRAND CANYON Pivotal Trial Readout	End of year 2026	critical	NSAA score difference vs placebo at 18 months, powered at >98% for 1.7 point difference	—
NDA Submission for Becker	H1 2027	critical	Successful regulatory filing based on GRAND CANYON results	—
Phase 3 Trial Planning and Initiation in Duchenne	H1 2026	high	Trial design and enrollment initiation	—
GRAND CANYON registrational cohort readout	Q4 2026	critical	18-month NSAA difference vs placebo, statistical significance, safety profile	—
Duchenne Phase 3 trial planning and initiation	H1 2027	high	Trial design based on Becker results, regulatory guidance, enrollment strategy	—
NDA submission for Becker	H1 2027	critical	FDA filing acceptance, priority review designation, PDUFA date	—