Positive Phase 2 Topaz Trial Extension Data Demonstrate Sizable and Sustained Motor Function Improvement at 24 Months with Apitegromab for Non-Ambulatory Patients with Types 2 and 3 Spinal Muscular Atrophy (SMA) - Sizabl

Positive Phase 2 Topaz Trial Extension Data

Demonstrate Sizable and Sustained Motor Function

Improvement at 24 Months with Apitegromab for Non-Ambulatory Patients with Types 2 and

Muscular Atrophy (SMA)

CAMBRIDGE, Mass., June 17, 2022 (BUSINESS WIRE) -- Scholar

Rock (NASDAQ: SRRK), a Phase 3, clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein

growth factors play a fundamental role, today announced new data from the Phase 2 TOPAZ trial extension period evaluating patient outcomes

after 24-months of treatment, which support sustained and continued improvement with apitegromab for non-ambulatory patients with Types

2 and 3 SMA receiving an SMN therapy. Detailed results are being presented by Thomas Crawford, M.D. of Johns Hopkins Medicine and

the lead principal investigator of the TOPAZ trial, during a podium presentation at the Cure SMA Research & Clinical Care Meeting

today at 11:20 a.m. PST.

"The 24-month results provide long-term data and evidence, underscoring

the findings of the 12-month primary treatment period of the TOPAZ trial in which patients receiving apitegromab experienced sizable motor

function gains," said George Nomikos, M.D., Ph.D., Senior Vice President of Clinical Sciences, Head of Muscle Therapeutic Area of

Scholar Rock. "This durability and continued increase in motor function support the transformative potential of apitegromab for

patients suffering with SMA."

"These data support apitegromab's potential to meaningfully

improve the lives of non-ambulatory patients with Types 2 and 3 SMA," said Nagesh Mahanthappa, Ph.D., Founding Chief Executive Officer

& President of Scholar Rock. "As a company, we are dedicated to the SMA community and are urgently enrolling patients in our

ongoing pivotal Phase 3 SAPPHIRE trial."

TOPAZ evaluated apitegromab across a broad age range (2-21 years) of

patients with Types 2 and 3 SMA. All 35 non-ambulatory patients (Cohorts 2 and 3) and 12 of 23 ambulatory patients (Cohort 1) were receiving

nusinersen maintenance therapy. The primary efficacy endpoint for the non-ambulatory population was mean change from baseline in HFMSE.

Additional endpoints included mean change from baseline in RULM, an assessment specifically designed for upper limb function in patients

with SMA. The HFMSE is a validated measure for the assessment of gross motor function in SMA, while the RULM is validated to evaluate

upper limb motor performance by evaluating tasks which correspond to the ability to perform various everyday activities with their hands

For this 24-month evaluation, an observed case analysis was conducted,

which pooled all the non-ambulatory patients (Cohorts 2 and 3) and was based upon the available data for given timepoints. This analysis

population included patients receiving either low dose (2 mg/kg) or high dose (20 mg/kg) apitegromab (inclusive of patients in Cohort

3 who switched from 2 mg/kg to 20 mg/kg in Year 2) and did not exclude any patients who had missed apitegromab doses due to study site

access restrictions from COVID-19.

Non-ambulatory patients (age range of 2 to 21 years old) with

valid HFMSE assessments had sizable, sustained gains in HFMSE scores at 24 months from baseline (prior

to first dose of apitegromab), while RULM scores continued to increase at 24 months. The mean change from baseline results for non-ambulatory

*Three patients in the non-ambulatory group underwent scoliosis

surgery in year 2, which has been reported to negatively impact HFMSE scores for a considerable period afterwards1.

This analysis excluded post-surgery data of these patients.

Dose response continued to be observed across the 24 months of apitegromab

administration based upon HFMSE scores and pharmacodynamic data (target engagement as measured by serum latent myostatin concentrations),

with signs that that there may be further HFMSE increases as non-ambulatory patients originally receiving the low dose switched to the

high dose treatment.

Data at 24-months for ambulatory patients with Type 3 SMA (Cohort

1) suggest stability of Revised Hammersmith Scale (RHS) scores in patients receiving 20 mg/kg of apitegromab and nusinersen. The mean

RHS change from baseline at 24-months was 0.7 points (95% CI: -3.1, 1.7) for the apitegromab and nusinersen subgroup (n=10) and 2.8

points (95% CI: -8.4, 2.8) for the apitegromab monotherapy subgroup (n=11). A subset of individuals in Cohort 1(n=21) had RHS improvements,

as reflected by 42.9% (9/21) and 23.8% (5/21) of patients having 1-point and 3-point RHS increases from baseline at 24 months

Of the 55 patients who completed the 24-month TOPAZ extension period,

54 have opted to continue treatment in the 36-month extension period.

Consistent with the 12-month safety data, no serious safety

risks were identified as part of the analysis of the cumulative 24-month data. The incidence and severity of adverse events were

consistent with the underlying patient population and background therapy. The five most common treatment-emergent adverse events

(TEAEs) were headache, pyrexia, upper respiratory tract infection, cough, and nasopharyngitis. No deaths or serious

adverse reactions have been observed with apitegromab. A total of 14 serious TEAEs have been reported over the 24-month

treatment period, all assessed by the respective trial investigator as unrelated to apitegromab.

1 Dunaway Young, Sally

et al. Scoliosis Surgery Significantly Impacts Motor Abilities in Higher-functioning Individuals with Spinal Muscular Atrophy'.

Journal of Neuromuscular Disease. 1 Jan. 2020: 183-192.

podium presentation at SMA Research & Clinical Care Meeting are as follows:

Title: TOPAZ Extension:

24-Month Efficacy and Safety of Apitegromab in Patients with Later-Onset Spinal Muscular Atrophy (Type 2 and Type 3 SMA)

Presenter: Thomas Crawford,

M.D., lead principal investigator of the TOPAZ trial and Professor of Neurology and Pediatrics; Johns Hopkins University.

Clinical Drug Development

Session: June 17 at 11:20 - 11:40 a.m. PST (Abstract #28)

Conference Call/Webcast:

Scholar Rock will host a conference call

and audio webcast to discuss topline 24-month data from the Phase 2 TOPAZ clinical trial on June 17, 2022 at 8:30 a.m. Eastern Time. To

participate in the call, please dial 833-519-1308 (domestic) or 914-800-3874 (international) and refer to conference ID: 6495684. A webcast

of the call will also be available on the Investors & Media section of the Scholar Rock website at http://investors.scholarrock.com.

An archived replay of the webcast will be available on Scholar Rock's website at: https://scholarrock.com/ for approximately

180 days following the presentation.

About the Phase 2 TOPAZ Trial

The TOPAZ trial is an ongoing proof-of-concept, open-label phase 2

trial evaluating the safety and efficacy of apitegromab in patients with Types 2 and 3 SMA. In the main treatment period, patients were

dosed intravenously every four weeks as monotherapy or with nusinersen, an approved SMN therapy. The trial enrolled 58 patients in the

U.S. and Europe. The primary efficacy endpoints were mean change from baseline in Revised Hammersmith Scale (RHS) score at 12 months for

the ambulatory population (Cohort 1), and mean change from baseline in HFMSE score at 12 months for non-ambulatory population (Cohorts

2 and 3). The trial also includes multiple 12-month extension periods designed to evaluate longer-term patient outcomes.

About the Phase 3 SAPPHIRE Trial

SAPPHIRE is an ongoing randomized, double-blind, placebo-controlled,

phase 3 clinical trial evaluating the safety and efficacy of apitegromab in non-ambulatory patients with Types 2 and 3 SMA who are receiving

SMN therapy (either nusinersen or risdiplam). Approximately 156 patients aged 2-12 years old are anticipated to be enrolled in the main

efficacy population. These patients will be 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 of approximately 48 patients aged 13-21 years old will

also separately be evaluated. These patients will be randomized 2:1 to receive either apitegromab 20 mg/kg or placebo. In this subpopulation

of older individuals with SMA, the safety and tolerability of apitegromab will be characterized, and efficacy will also be evaluated

in an exploratory, nonpowered manner. SAPPHIRE is expected to enroll 55 sites in the U.S. and Europe. For more information about SAPPHIRE,

visit www.clinicaltrials.gov.

Apitegromab is a selective inhibitor of the

activation of myostatin and is an investigational product candidate for the treatment of patients with 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 inhibiting myostatin activation with apitegromab may promote 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. The efficacy and safety of apitegromab have not been established and apitegromab has not been approved for any

use by the FDA or any other regulatory agency.

Spinal muscular atrophy (SMA) is a rare, and often fatal, genetic disorder

that typically manifests in young children. An estimated 30,000 to 35,000 patients are afflicted with SMA in the United States and Europe.