Scholar Rock Reports Apitegromab Meets Primary Endpoint in Phase 3 SAPPHIRE Study in Patients with Spinal Muscular Atrophy (SMA) Apitegromab met primary endpoint with statistically significant and clinically meaningful i

Scholar Rock Reports Apitegromab Meets Primary

Endpoint in Phase 3 SAPPHIRE Study in Patients with Spinal Muscular Atrophy (SMA)

Mass.--(BUSINESS WIRE)--October 7, 2024--Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing

innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors

play a fundamental role, today announced positive topline results from the Phase 3 SAPPHIRE clinical trial (NCT05156320)

evaluating the efficacy and safety of apitegromab, an investigational muscle-targeted therapy, in patients with SMA.

The study achieved its primary endpoint demonstrating a statistically

significant and clinically meaningful improvement for apitegromab versus placebo in motor function as measured by the gold standard HFMSE

in SMA patients on chronic dosing of standard of care therapies (either nusinersen or risdiplam). Based upon the similar pharmacological

profile of the 20 mg/kg and 10 mg/kg doses of apitegromab, the statistical analysis plan was prespecified to analyze both the combined

dose (10 mg/kg and 20 mg/kg) compared to placebo, and 20 mg/kg dose each compared to placebo. Statistical significance is achieved

per the prespecified statistical analysis plan (Hochberg multiplicity adjustment) where the p-value ( 0.025) is more rigorous

if only one prespecified analysis crosses the statistical significance boundary of 0.05.

Motor function outcomes were meaningful and consistent across the main

efficacy population and in the ages 13-21 exploratory population, favored apitegromab (n=22) compared to placebo (n=10). Thirty

percent of patients receiving apitegromab had >3 point improvement in HFMSE versus 12.5% of patients on placebo. Patients receiving

apitegromab demonstrated early motor function improvement compared to placebo from the first measured time point at 8 weeks, benefit expanded

at 52 weeks as measured by HFMSE. Following trial completion, 98 percent of SAPPHIRE patients (185/188) enrolled in the ongoing ONYX open-label

"We are thrilled that apitegromab met the primary endpoint in

our Phase 3 SAPPHIRE clinical study. The results clearly demonstrate robust and clinically meaningful improvement in motor function in

patients with SMA," said Jay Backstrom, M.D., MPH, President and Chief Executive Officer of Scholar Rock. "At Scholar

Rock, we are working with urgency to deliver the potentially transformative benefits of apitegromab to children and adults with SMA in

the US, Europe, and around the world."

Treatment with apitegromab was well-tolerated across all age groups.

There were no clinically relevant differences in the adverse event profile by dose, 10 mg/kg versus 20 mg/kg. No new safety findings were

observed in the SAPPHIRE clinical trial; the profile was consistent with that observed in the Phase 2 TOPAZ clinical trial, including

an extension study which had over four years of treatment as of the cut-off date. Serious adverse events (SAEs) were consistent with the

underlying disease and current standard of care received by patients; no SAEs were assessed as related to apitegromab. There were no study

drug discontinuations due to adverse events.

"We are grateful to the families and investigators who participated

in our trials. The positive Phase 3 SAPPHIRE trial, along with over 4 years of TOPAZ clinical trial data, clearly demonstrate the potentially

transformative benefit of apitegromab to drive clinically meaningful improvements in motor function as measured by HFMSE in a broad SMA

population, where motor function would normally be expected to generally decline over time," said Jing Marantz, M.D., Ph.D., Chief

Medical Officer at Scholar Rock. "We look forward to submitting our applications to the FDA and the EMA in Q1 2025."

The U.S. Food and Drug Administration (FDA) has granted Fast Track,

Orphan Drug, and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and

Orphan Medicinal Product designations, to apitegromab for the treatment of SMA. The Company plans to submit a U.S. Biologics License Application

(BLA) and a European Union marketing authorisation application (MAA) in Q1 2025.

"It's a great day for people living with SMA and their

families. These encouraging trial results mark a critical milestone for the SMA community," said Kenneth Hobby, President of Cure

SMA. "Declining motor function and hopes for reversing losses associated with muscle weakness are significant unmet needs, impacting

activities of daily living, from breathing, eating, self-care, to working and social interactions. We need an approved therapy that can

support motor function and further improve daily activities for people with SMA."

Analyses of the full Phase 3 SAPPHIRE data are ongoing, and Scholar

Rock plans to present detailed results at an upcoming medical conference in early 2025. Preliminary baseline characteristics from the

trial will be presented during a poster presentation at the upcoming 29th Annual Congress of the World Muscle Society on Friday,

October 11, 2024, being held in Prague, Czech Republic.

Conference Call Information

will hold an investor conference call today, October 7 at 8:00 am ET. To access the live conference call, participants may register

here. The live audio webcast of the call will be available under "Events and Presentations" in the Investor Relations section

of the Scholar Rock website at http://investors.scholarrock.com. To participate via telephone, please register here.

Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including

the dial-in number along with a unique passcode and registrant ID that can be used to access the call. An archived replay of the webcast

will be available on the Company's website for approximately 90 days.

Presentation at Annual Congress of the World Muscle Society

Scholar Rock will present baseline characteristics from the SAPPHIRE

trial in a poster presentation at the 29th Annual Congress of the World Muscle Society. Details of the presentation are as

Apitegromab in Spinal Muscular Atrophy: baseline characteristics of participants enrolled in the phase 3 SAPPHIRE study

type: Poster presentation

Thomas O. Crawford, M.D., Professor of Neurology and Pediatrics, Johns Hopkins University

time: Friday, October 11, 2024, 3:45 PM CET

Prague, Czech Republic

Apitegromab is an investigational fully human monoclonal antibody inhibiting

myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. It is the first muscle-targeted

treatment candidate to demonstrate clinical proof-of-concept in spinal muscular atrophy (SMA). Myostatin, a member of the TGF superfamily

of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle

mass and strength in multiple animal species, including humans. Scholar Rock believes that its highly selective targeting of pro-

and latent forms of myostatin with apitegromab may lead to a clinically meaningful improvement in motor function in patients with SMA.

The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and

the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab

for the treatment of SMA. Apitegromab has not been approved for any use by the FDA or any other regulatory agency.

SAPPHIRE was a randomized, double-blind, placebo-controlled Phase 3

clinical trial that evaluated the safety and efficacy of apitegromab in nonambulatory patients with Types 2 and 3 SMA who are receiving

current standard of care (either nusinersen or risdiplam). SAPPHIRE enrolled 156 patients aged 2-12 years old in the main efficacy population.

These patients were randomized 1:1:1 to receive for 12 months either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo by intravenous

(IV) infusion every 4 weeks. An exploratory population that enrolled 32 patients aged 13-21 years old was also evaluated. These patients

were randomized 2:1 to receive either apitegromab 20 mg/kg or placebo.

Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disease

that afflicts an estimated 30,000 to 35,000 people in the United States and Europe. The disease is characterized by the

loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk, and progressive muscle weakness. While there has been

progress in the development of therapeutics that address the loss of motor neurons, there continues to be a high unmet need for therapies

that directly address the progressive muscle weakness that leads to loss of motor function in SMA.

Scholar Rock is a biopharmaceutical company that discovers, develops,

and delivers life-changing therapies for people with serious diseases that have high unmet need. As a global leader in the biology of

the transforming growth factor beta (TGF ) superfamily of cell proteins and named for the visual resemblance of a scholar rock to

protein structures, the clinical-stage company is focused on advancing innovative treatments where protein growth factors are fundamental.

Over the past decade, Scholar Rock has created a pipeline with the potential to advance the standard of care for neuromuscular

disease, cardiometabolic disorders, cancer, and other conditions where growth factor-targeted drugs can play a transformational role.

to unlocking fundamentally different therapeutic approaches is powered by broad application of a proprietary platform, which has developed

novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity. By harnessing cutting-edge science in

disease spaces that are historically under-addressed through traditional therapies, Scholar Rock works every day to create

new possibilities for patients. Learn more about our approach at ScholarRock.com and follow @ScholarRock and on LinkedIn.

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