CAMBRIDGE, Mass.--( BUSINESS WIRE )--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 reported financial results and corporate updates for the third quarter ended September 30, 2024. “ We were thrilled to announce positive and statistically significant topline data from the pivotal Phase 3 SAPPHIRE trial, a major achievement that underscores apitegromab’s potential to redefine the standard of care for patients with SMA,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer of Scholar Rock. “ The positive SAPPHIRE trial validates our approach to targeting pro-and latent myostatin and demonstrates apitegromab’s potentially transformative benefit. Based on these results, we plan to submit a BLA and MAA in the first quarter of 2025 and are working diligently to prepare for the commercial launch of apitegromab, and if approved, to deliver the potentially transformative benefits of apitegromab to children and adults living with SMA.” Dr. Backstrom continued, “ The robust results from SAPPHIRE also reinforce the broader potential of our selective myostatin inhibition strategy across our pipeline, with potential readthrough to our cardiometabolic program as we evaluate apitegromab in obesity in our Phase 2 EMBRAZE proof-of-concept trial. We were pleased to announce in September that the EMBRAZE trial is fully enrolled, and we expect to report initial data in the second quarter of next year.” Company Highlights and Upcoming Milestones SMA Program Apitegromab is an investigational, fully human monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle and is being developed as a potential first muscle-targeted therapy for the treatment of SMA. Apitegromab is the first muscle-targeted therapy to show clinical proof-of-concept in SMA. Reported positive topline data from Phase 3 SAPPHIRE clinical trial . 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). In the main efficacy population (ages 2-12), the mean difference in change from baseline in HFMSE was 1.8 points (p=0.0192) for all patients receiving apitegromab 10 mg/kg and 20 mg/kg (n=106) compared to placebo (n=50). Patients receiving 20 mg/kg of apitegromab (n=53) showed a 1.4 point mean difference compared to placebo (p=0.1149). The prespecified analysis of the 10 mg/kg dose showed that patients receiving 10 mg/kg of apitegromab (n=53) showed a mean difference in change from baseline in HFMSE of 2.2 points compared to placebo (nominal p=0.0121). Based upon PK/PD data from the SAPPHIRE trial, similar levels of target engagement were observed for the 10 mg/kg and 20 mg/kg dose groups. Scholar Rock plans to submit a U.S. BLA and a European Union MAA in 1Q 2025. Presented preliminary baseline characteristics from SAPPHIRE during a poster presentation at the 29 th Annual Congress of the World Muscle Society in October in Prague, Czech Republic. 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. The ONYX open-label, multi-center extension study remains ongoing. The study is evaluating the long-term safety and efficacy of apitegromab in patients who completed the TOPAZ or SAPPHIRE trials. More than 90 percent of patients on combination therapy in the TOPAZ trial have completed 4 years of apitegromab treatment and enrolled into ONYX. Following trial completion, 98 percent of SAPPHIRE patients (185/188) enrolled in the ongoing ONYX open-label expansion study. On track to initiate OPAL clinical trial in SMA patients under two years old in mid-2025. Cardiometabolic Program SRK-439 is a novel, preclinical, investigational myostatin inhibitor that binds to pro- and latent myostatin with high affinity and is selective for myostatin (i.e., no GDF11 or Activin A binding), and is initially being developed for the treatment of obesity. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass during weight loss. Completed enrollment of Phase 2 EMBRAZE proof-of-concept trial with apitegromab in combination with a GLP-1 receptor agonist (GLP-1 RA) in obesity in September. The Phase 2 trial is a randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of apitegromab, a highly selective investigational myostatin inhibitor, to preserve muscle mass as an adjunctive therapy in overweight and obese adults who are taking a GLP-1 RA. Data are expected in the second quarter of 2025 and will be used to guide clinical development of SRK-439. The Company plans to file an IND for SRK-439 for the treatment of obesity in 2025. Immuno-Oncology Program SRK-181 is an investigational selective inhibitor of latent TGFβ1 activation and is being developed with the aim of overcoming resistance to checkpoint therapy, such as anti-PD-(L)1 antibodies, in patients with advanced cancer. New SRK-181 data from the Phase 1 DRAGON proof-of-concept trial presented at the SITC 39 th Annual Meeting in November. The presentation, “ DRAGON Trial: Durable remission rate with the latent TGFβ1 inhibitor linavonkibart (SRK-181) and pembrolizumab in patients with immune checkpoint inhibitor resistant advanced cancers,” highlighted new clinical and biomarker results. Highlights since the Company’s last update on the DRAGON trial include one additional complete response, seen in the clear cell renal cell (ccRCC) cohort (ORR=23.3%) and durable responses in multiple cohorts. Additionally, biomarker results continue to support proof of mechanism; new data shows suppressed granulocytic myeloid-derived suppressor cells (gMDSC) levels in the tumor microenvironment of responders. Notably new biomarker data in the ccRCC cohort supports a potential patient selection strategy with positive correlations between clinical response and baseline CD8+ infiltration status, elevated baseline Treg levels, and elevated baseline TGFβ1 levels in the tumor compartment. Enrollment of the DRAGON trial was completed in December 2023, and patients who remain on the study continue to be treated. Other Corporate Updates Appointed Beth Shafer, Ph.D., to the newly created role of Chief Business Officer. Ms. Shafer brings over 20 years of biopharmaceutical industry leadership and expertise to Scholar Rock, where she will drive the Company’s long-term corporate and business development strategy. Raised $345 million in upsized follow-on offering. In October, the Company completed an upsized follow-on offering raising aggregate gross proceeds of $345 million. Third Quarter 2024 Financial Results For the quarter ended September 30, 2024, net loss was $64.5 million or $0.66 per share compared to a net loss of $42.4 million or $0.53 per share for the quarter ended September 30, 2023. The Company did not record any revenue for the quarter ended September 30, 2024, or for the quarter ended September 30, 2023. Research and development expense was $48.7 million for the quarter ended September 30, 2024, compared to $30.3 million for the quarter ended September 30, 2023. The increase was primarily attributable to costs associated with the ONYX and EMBRAZE trials, and the development of SRK-439. General and administrative expenses were $16.1 million for the quarter ended September 30, 2024, compared to $13.3 million for the quarter ended September 30, 2023. The increase was due to employee-related costs. As of September 30, 2024, Scholar Rock had cash, cash equivalents and marketable securities of approximately $139.1 million ($463.5 million, on a pro forma basis, including the approximately $324.4 million raised in the October 2024 equity offering). Along with cash available to the Company, runway is extended into 4Q 2026. “ Supported by our recent upsized public offering on the heels of successful SAPPHIRE data, Scholar Rock is advancing our mission from a position of strength as we move forward with preparations for our first commercial launch in the fourth quarter of 2025,” said Ted Myles, Chief Operating Officer and Chief Financial Officer of Scholar Rock. “ We are working tirelessly to obtain approval for apitegromab and deliver it to patients with SMA as soon as possible, as well as continuing to advance our portfolio of highly selective myostatin inhibition programs.” Conference Call Information Management will provide an update on the Company and discuss third quarter 2024 results via conference call on Tuesday, November 12 at 8:15 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 in advance 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. About Scholar Rock 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 (TGFβ) 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. This commitment 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. The efficacy and safety of apitegromab, SRK-181, and SRK-439 have not been established and apitegromab, SRK-181, and SRK-439 have not been approved for any use by the FDA or any other regulatory agency. Scholar Rock ® is a registered trademark of Scholar Rock, Inc. Availability of Other Information About Scholar Rock Investors and others should note that we communicate with our investors and the public using our company website www.scholarrock.com , including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on Twitter and LinkedIn. The information we post on our website, Twitter or LinkedIn could be deemed material information. As a result, we encourage investors, the media and others interested to review the information we post there regularly. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding its growth, strategy, progress and timing of its clinical trials for apitegromab and SRK-181 and its preclinical programs, including SRK-439, and indication selection and development timing, including the timing of any regulatory submissions, 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 relating to commercial launch in the US in the fourth quarter of 2025, 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, that preclinical and clinical data, including 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, or Part A or Part B of the Phase 1 clinical trial of SRK-181, 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; Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline; 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 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 September 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 press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law. Scholar Rock Holding Corporation Condensed Consolidated Statements of Operations (unaudited) (in thousands, except share and per share data) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Operating expenses Research and development $ 48,719 $ 30,337 $ 134,185 $ 86,939 General and administrative 16,061 13,335 48,512 36,324 Total operating expenses 64,780 43,672 182,697 123,263 Loss from operations (64,780 ) (43,672 ) (182,697 ) (123,263 ) Other income (expense), net 301 1,313 2,857 3,600 Net loss $ (64,479 ) $ (42,359 ) $ (179,840 ) $ (119,663 ) Net loss per share, basic and diluted $ (0,66 ) $ (0,53 ) $ (1,86 ) $ (1,49 ) Weighted average common shares outstanding, basic and diluted 97,050,637 80,606,438 96,587,149 80,115,143 Scholar Rock Holding Corporation Condensed Consolidated Balance Sheets (unaudited) (in thousands) September 30, 2024 December 31, 2023 Assets Cash, cash equivalents and marketable securities $ 139,065 $ 279,938 Other current assets 13,862 8,256 Total current assets 152,927 288,194 Other assets 26,206 22,841 Total assets $ 179,133 $ 311,035 Liabilities and Stockholders' Equity Current liabilities $ 39,372 $ 32,741 Long-term liabilities 60,565 53,076 Total liabilities 99,937 85,817 Total stockholders' equity 79,196 225,218 Total liabilities and stockholders' equity $ 179,133 $ 311,035

Phase 2Clinical ResultPhase 1Phase 3Financial Statement

04 Nov 2024

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Scholar Rock Announces New Preclinical Data for SRK-439 Showing Significant Lean Mass Increase and Enhanced Fat Mass Loss with Metformin

CAMBRIDGE, Mass.--( BUSINESS WIRE )--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 new preclinical data that support the potential of SRK-439, a highly selective investigational antimyostatin antibody, to increase lean mass and lower fat mass gain when taken with metformin. These data will be presented by Melissa Fulham, Ph.D., of Scholar Rock, at the ObesityWeek conference in San Antonio, Texas on November 5. “ These new data build upon a robust body of evidence demonstrating the potential of selective myostatin inhibition as an important therapeutic approach,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer at Scholar Rock. “ These latest SRK-439 data support our hypothesis that a highly selective approach to targeting myostatin inhibition could have positive effects on body composition in people living with obesity and associated comorbidities like diabetes, and also underscore the value within Scholar Rock’s platform. We are looking forward to providing more updates on the exciting advancements in our cardiometabolic program, including our Phase 2 EMBRAZE trial topline data in the second quarter of 2025.” Preclinical study design The research study tested a murine equivalent of SRK-439 in a diet-induced obesity (DIO) mouse model. All mice were given a high-fat diet, followed by either metformin (50 mg/kg daily) or control (water) for four weeks. Following that four-week period, mice in metformin and control groups were given either an IgG control antibody (10 mg/kg weekly) or SRK-439 (10 mg/kg weekly for younger mice and 3 mg/kg weekly for older mice) for another four weeks. To assess whether effects were persistent across age ranges, this study design was repeated in two age groups: both young (10-week-old) and mature (22-week-old) DIO mice. Quantitative nuclear magnetic resonance (qNMR) was used to analyze change in lean mass at baseline, after four weeks of metformin treatment, and every two weeks following treatment with SRK-439 or IgG control. Changes in body composition in the presence or absence of metformin The group that received SRK-439 on the background of metformin showed a significant increase in lean mass versus the group receiving metformin alone, and this result was consistent across age groups. Key findings supporting the potential for SRK-439 in advancing healthier weight management include: Young animals treated with SRK-439 and metformin demonstrated a 2-fold increase in lean mass over the duration of the study compared to the lean mass increase in the metformin group and in IgG controls (31.6% increase from baseline vs. 15.1%, p<0.0001). In older metformin-treated animals, the increase in lean mass in the SRK-439 treated animals compared to IgG controls was 50-fold (10.2% lean mass increase from baseline versus 0.2% in IgG controls, p<0.0001), owing primarily to the limited lean mass growth in the IgG control group over the duration of the study due to the age of the animals. In young mice, the combination treatment of SRK-439 and metformin also resulted in lower fat mass gain (68.2% increase from baseline) than metformin alone (114% increase from baseline; p<0.05). In older mice, SRK-439 showed a trend toward reduced fat mass gain when combined with metformin, as compared to metformin alone (10.6% increase from baseline vs 18.4%; not statistically significant). “ These new preclinical data show that selectively inhibiting myostatin in combination with metformin increased lean mass—and this effect was robust even in the older treatment group that was more weight stable,” said Mo Qatanani, PhD, Chief Scientific Officer at Scholar Rock. " In addition, we observed that when we combined SRK-439 and metformin in younger mice, the effect of lowering fat mass gain was greater than with either therapy alone. Taken together, this is compelling evidence suggesting that SRK-439 has the potential to improve body composition and contribute to healthier weight management in the context of both obesity and type 2 diabetes. These exciting data advance the science of obesity research and continue to differentiate Scholar Rock’s pipeline and anti-myostatin programs.” Poster Presentation Information Title: SRK-439 Selectively Inhibits Myostatin to Promote Healthy Body Composition During Metformin Therapy Presentation type: Poster presentation Presenter: Melissa Fulham, Ph.D., Senior Scientist II, Scholar Rock Date and time: Tuesday, November 5, 2024, 2:30 PM CT Location: Henry B. González Convention Center, San Antonio, TX For conference information, visit https://obesityweek.org/ . The slides from the presentation are available in the Publications & Posters section of Scholar Rock’s website. About EMBRAZE EMBRAZE is a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept trial evaluating the efficacy, safety and pharmacokinetics of apitegromab in adults with a body mass index (BMI) of >27 (overweight) or a BMI of >30 (obese) and taking a GLP-1 RA (tirzepatide or semaglutide). The target enrollment of EMBRAZE is 100 subjects aged 18-65 who are overweight or obese without diabetes. As part of the study design, the treatment period is 24 weeks, and all subjects will receive a GLP-1 RA. In addition, all subjects will be randomized 1:1 to receive either apitegromab or placebo by intravenous (IV) infusion every four weeks during the 24-week treatment period. The primary endpoint is change from baseline at Week 24 in lean mass assessed by dual-energy X-ray absorptiometry. Secondary endpoints include additional weight loss measures, safety and tolerability, and pharmacokinetic outcomes. Exploratory endpoints at Weeks 24 and 32 include cardiometabolic parameters (e.g. HbA1c), body composition, and physical function. About SRK-439 SRK-439 is a novel, preclinical, investigational myostatin inhibitor that binds to pro- and latent myostatin with high affinity and is selective for myostatin (i.e., no GDF11 or Activin-A binding), and is initially being developed for the treatment of cardiometabolic disorders, including obesity. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass during weight loss. The efficacy and safety of SRK-439 have not been established and SRK-439 has not been approved for any use by the FDA or any other regulatory agency. About Apitegromab 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 TGFβ 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. About Scholar Rock 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 (TGFβ) 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. This commitment 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. Availability of Other Information About Scholar Rock Investors and others should note that we communicate with our investors and the public using our company website www.scholarrock.com , including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on Twitter and LinkedIn. The information that we post on our website or on Twitter or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. Scholar Rock® is a registered trademark of Scholar Rock, Inc. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, 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, 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 press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.

Phase 2Orphan DrugClinical ResultFast Track

10 Sep 2024

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Scholar Rock Completes Enrollment in Phase 2 EMBRAZE Proof-of-Concept Trial of Apitegromab in Obesity

CAMBRIDGE, Mass.--( BUSINESS WIRE )--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 it has completed enrollment in the Phase 2 EMBRAZE trial designed to show proof-of-concept of apitegromab, an investigational selective myostatin inhibitor antibody, to safely preserve lean muscle mass in individuals on GLP-1 receptor agonist (GLP-1 RA) therapy for obesity. Results from this trial are expected in the second quarter of 2025 and will inform the development of SRK-439, a novel, investigational selective myostatin inhibitor, which the Company plans to advance specifically for the treatment of cardiometabolic disorders, including obesity. EMBRAZE is a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating the efficacy, safety and pharmacokinetics of apitegromab in adults who are overweight or obese without diabetes and taking a GLP-1 RA. The trial fully enrolled participants aged 18-65 to assess the primary endpoint of change in lean mass by DEXA scan at 24 weeks. Initiation of enrollment was announced in May 2024. “ We believe the rapid enrollment of the EMBRAZE trial speaks to the unmet need to preserve lean muscle mass for patients experiencing significant weight loss on GLP-1 therapies. As a leader in myostatin inhibition, Scholar Rock is uniquely positioned to play a meaningful role in the cardiometabolic space. Preserving muscle has the potential to improve the quality of weight loss as well as attenuate the weight regain often observed when people come off GLP-1 therapy,” said Jing Marantz, M.D., Ph.D., Chief Medical Officer at Scholar Rock. “ We anticipate reporting results from EMBRAZE in the second quarter of 2025 and plan to use the data to further inform Scholar Rock’s development of SRK-439, which was designed specifically for the treatment of obesity.” The Company also announced today that it will present new preclinical SRK-439 data in a poster presentation entitled, “ SRK-439 Selectively Inhibits Myostatin to Promote Healthy Body Composition During Metformin Therapy” at The Obesity Society’s Annual Meeting at ObesityWeek®, November 3-6, in San Antonio, Texas. Preclinical data presented earlier showed that SRK-439 maintained lean mass and improved fat mass loss when used in combination with a GLP-1 RA in diet-induced obesity (DIO) mice. Preclinical data also supported the potential for SRK-439 to increase lean mass and attenuate fat mass regain, thus contributing to a favorable body composition following withdrawal from GLP-1 RA treatment. The Company plans to file an IND for SRK-439 in 2025. Apitegromab is being developed as potentially the first muscle-targeted therapy for the treatment of spinal muscular atrophy (SMA) and is the only muscle-targeted therapy to show clinical proof-of-concept in SMA. The Company is on track to report topline data in the fourth quarter of 2024 from the pivotal Phase 3 SAPPHIRE clinical trial in patients with SMA. If the trial is successful and apitegromab is approved by the U.S. Food and Drug Administration (FDA), the Company expects to initiate a commercial product launch in 2025. About Apitegromab 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 TGFβ 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. 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. About the Phase 3 SAPPHIRE Trial in Spinal Muscular Atrophy SAPPHIRE is an ongoing randomized, double-blind, placebo-controlled, Phase 3 clinical trial evaluating the safety and efficacy of apitegromab in nonambulatory patients with Types 2 and 3 SMA who are receiving SMN-targeted therapy (either nusinersen or risdiplam). SAPPHIRE targeted enrolling approximately 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 targeted enrolling up to 48 patients aged 13-21 years old will also separately be evaluated. These patients were randomized 2:1 to receive either apitegromab 20 mg/kg or placebo. For more information about SAPPHIRE, visit www.clinicaltrials.gov . Apitegromab has not been approved for any use by the US FDA or any other health authority, and its safety and efficacy have not been established. About the Phase 2 EMBRAZE Trial in Obesity EMBRAZE is a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept trial evaluating the efficacy, safety and pharmacokinetics of apitegromab in adults with a body mass index (BMI) of >27 (overweight) or a BMI of >30 (obese) and taking a GLP-1 RA (tirzepatide or semaglutide). The target enrollment of EMBRAZE is 100 subjects aged 18-65 who are overweight or obese without diabetes. As part of the study design, the treatment period is 24 weeks, and all subjects will receive a GLP-1 RA. In addition, all subjects will be randomized 1:1 to receive either apitegromab or placebo by intravenous (IV) infusion every four weeks during the 24-week treatment period. The primary endpoint is change from baseline at Week 24 in lean mass assessed by dual-energy X-ray absorptiometry. Secondary endpoints include additional weight loss measures, safety and tolerability, and pharmacokinetic outcomes. Exploratory endpoints at Weeks 24 and 32 include cardiometabolic parameters (e.g. HbA1c), body composition, and physical function. About SRK-439 SRK-439 is a novel, preclinical, investigational myostatin inhibitor that has high in vitro affinity for pro- and latent myostatin and maintains myostatin specificity (i.e., no GDF11 or Activin-A binding), and is initially being developed for the treatment of cardiometabolic disorders, including obesity. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass during weight loss. The efficacy and safety of SRK-439 have not been established and SRK-439 has not been approved for any use by the FDA or any other regulatory agency. About Scholar Rock 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 (TGFβ) 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. Scholar Rock is the only company to show clinical proof-of-concept for a muscle-targeted treatment in spinal muscular atrophy (SMA). This commitment 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. Availability of Other Information About Scholar Rock Investors and others should note that we communicate with our investors and the public using our company website www.scholarrock.com , including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on Twitter and LinkedIn. The information that we post on our website or on Twitter or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. Scholar Rock® is a registered trademark of Scholar Rock, Inc. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding its growth, strategy, progress and timing of its clinical trials for apitegromab and its preclinical programs, including SRK-439, and indication selection and development timing, including the therapeutic potential, clinical benefits and safety thereof, expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials, 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,” “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, that preclinical and clinical data, including the results from the Phase 2 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, including, without limitation, the Phase 3 clinical trial of apitegromab in SMA; Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline; 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 press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.

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Indication	Highest Phase	Country/Location	Organization	Date
Obesity	Preclinical	US	Scholar Rock, Inc.	13 Oct 2023

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