Scholar Rock : Conference Call to Discuss Results from Phase 3 SAPPHIRE Study of Apitegromab Presentation

Published: 2024-10-07 11:24:04 ET SRRK

Positive Topline Results from Pivotal Phase 3 SAPPHIRE Trial of Apitegromab in Spinal Muscular Atrophy (SMA)

October 7, 2024

Agenda

Introduction

Jay Backstrom, M.D., MPH, President & Chief Executive Officer

SAPPHIRE Results

Jing Marantz, M.D. Ph.D., Chief Medical Officer

Concluding Remarks

Jay Backstrom, M.D., MPH, President & Chief Executive Officer

Q&A Session

Forward-Looking Statements

Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock Holding Corporation and Scholar Rock, Inc. (collectively, "Scholar Rock"), including, without limitation, Scholar Rock's expectations regarding its growth, strategy, progress and timing of its clinical trials for apitegromab, and indication selection and development timing, including the timing of any regulatory submissions or commercial launch, the therapeutic potential, clinical benefits and safety of any product candidates, expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials, its cash runway, expectations regarding the achievement of important milestones, the ability of any product candidate to perform in humans in a manner consistent with earlier nonclinical, preclinical or clinical trial data, and the potential of its product candidates and proprietary platform. The use of words such as "may," "might," "could," "will," "should," "expect," "plan," "anticipate," "believe," "estimate," "project," "intend," "future," "potential," or "continue," and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, without limitation, whether the results from the Phase 3 SAPPHIRE trial will be sufficient to support regulatory approval, that the full results from the Phase 3 SAPPHIRE trial may differ from the topline data, that preclinical and clinical data, including the results from the Phase 2 or Phase 3 clinical trial of apitegromab, are not predictive of, may be inconsistent with, or more favorable than, data generated from future or ongoing clinical trials of the same product candidates; the data generated from Scholar Rock's nonclinical and preclinical studies and clinical trials; information provided or decisions made by regulatory authorities; competition from third parties that are developing products for similar uses; Scholar Rock's ability to obtain, maintain and protect its intellectual property; Scholar Rock's dependence on third parties for development and manufacture of product candidates including, without limitation, to supply any clinical trials; and Scholar Rock's ability to manage expenses and to obtain additional funding when needed to support its business activities and establish and maintain strategic business alliances and new business initiatives, and our ability to continue as a going concern; as well as those risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock's Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Scholar Rock's views only as of today and should not be relied upon as representing its views as of any subsequent date. All information in this presentation is as of the date of the presentation, and Scholar Rock undertakes no duty to update this information unless required by law.

This presentation discusses product candidates that are under clinical study, and which have not yet been approved for marketing by the FDA or any other regulatory agency. No representation or warranty, express or implied, is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied.

This presentation may also contain estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we compete are necessarily subject to a high degree of uncertainty and risk.

Apitegromab is an investigational drug candidate under evaluation. Apitegromab has not been approved for any use by the FDA or any other regulatory agency and the safety and efficacy of apitegromab has not been established.

Introduction

Jay Backstrom, M.D., MPH

President & Chief Executive Officer

Our Purpose: Create Possibilities for Those Living with Spinal Muscular Atrophy (SMA)

Muscle is everything. I want to live knowing that I have the strength to take care of myself if left alone.

- Lyza

Positive Phase 3 SAPPHIRE Trial: Transformative Benefit in SMA

MET PRIMARY

ENDPOINT:

1.8

CONSISTENT

30%

POINT

clinically meaningful

of apitegromab patients

IMPROVEMENT

benefit across

ACHIEVED ≥3

in HFMSE* vs. placebo

all age groups

POINT IMPROVEMENT IN

(p=0.0192)

(2-21)

HFMSE†

FAVORABLE

SAFETY profile consistent with >48 months experience in Phase 2 TOPAZ trial

Apitegromab has the potential to alter the course of SMA

SOC=Standard of care (i.e., nusinersen or risdiplam)

Phase 3 SAPPHIRE Topline Results

Jing Marantz, M.D., Ph.D.

Chief Medical Officer

S A P P H I R E - A P I T E G R O M A B I N S M A

Study Design

Randomized, double-blind,placebo-controlled, parallel arm design (n=188) Patients on standard of care (nusinersen or risdiplam)

SCREENING

MAIN POPULATION (n=156)

Ages 2-12

With nonambulatory Types 2 and 3 SMA

Stratified to ensure balanced allocation across the three arms:

TREATMENT (52 weeks)

Apitegromab (20 mg/kg IV q4w) + SOC

Apitegromab (10 mg/kg IV q4w) + SOC

1:1:1

Placebo (IV q4w) + SOC

ENDPOINTS

Primary Efficacy:

Mean HFMSE change from baseline at 12 months

Additional Efficacy Measures:

RULM, WHO, other outcome measures

Safety, PK/PD, ADA

Additional Study Objectives

Exploratory Population (n = 32, age 13-21)

Stratified by SOC, randomized 2:1 between apitegromab 20 mg/kg vs placebo Endpoints: Safety & exploratory efficacy

Separate open-label extension study (after patients complete 12-month treatment period)

Safety & exploratory long-term efficacy

ClinicalTrials.gov Identifier: NCT05156320

HFMSE=Hammersmith Functional Motor Scale Expanded; RULM=Revised Upper Limb Module; WHO: World Health Organization Motor Developmental Milestones; R=randomization;8 SMA=spinal muscular atrophy; SOC=standard of care; PK/PD=pharmacokinetics/pharmacodynamics; ADA=anti-drug antibodies.

S A P P H I R E - A P I T E G R O M A B I N S M A

Prespecified Statistical Analysis Plan

Primary Objective

To assess the efficacy of apitegromab compared with placebo using HFMSE in patients 2 through 12 years old

1:1:1

Apitegromab (20 mg/kg) + SOC

Apitegromab (10 mg/kg) + SOC

Placebo

+ SOC

Primary Confirmatory Test

Prespecified Analyses

Apitegromab combined dose (10 mg/kg and 20 mg/kg) + SOC vs.

Placebo + SOC

Apitegromab 20 mg/kg + SOC vs. Placebo + SOC

Boundary To Win

One p-value≤ 0.025 Other p-value> 0.05

Both p-value ≤ 0.05

The Hochberg procedure (Hochberg 1988) was used to test: 1) apitegromab combined dose (10 mg/kg and 20 mg/kg) vs placebo and 2) apitegromab 20 mg/kg dose vs placebo concurrently for the

primary endpoint as the primary confirmatory test. The hierarchical testing procedure was applied to account for multiple confirmatory tests for the primary endpoint and key secondary endpoints. The

testing procedure first evaluated the primary confirmatory test, followed by analyses of key secondary endpoints for apitegromab 20 mg/kg, and then the analyses of primary endpoint and key

secondary endpoints for apitegromab 10 mg/kg.

SOC=standard of care

S A P P H I R E - A P I T E G R O M A B I N S M A

98% of Patients Continue on Long-Term Extension

188 Patients Underwent Randomization

Ages 2-12

Ages 13-21

156

Apitegromab

Placebo + SOC

Apitegromab

Placebo + SOC

20 mg/kg + SOC

10 mg/kg + SOC

Group

20 mg/kg + SOC

Group

Completed SAPPHIRE Treatment Period

155 † (99%)

31 † (97%)

ONYX Long-Term Extension Trial (Ongoing)

185* (98%)

*1 patient from 2-12 age group opted not to enroll in the ONYX study.

† 1 subject (1%) in the 20 mg/kg apitegromab arm in the 2-12 age group withdrew consent. 1 subject (3%) in the 20 mg/kg apitegromab arm in the 13-21 age group withdrew consent. Neither

withdrew consent due to an adverse event.

SOC=standard of care.

Disclaimer

Scholar Rock Holding Corporation published this content on October 07, 2024, and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on October 07, 2024 at 15:23:03.579.