apitegromab (SRK-015) / Scholar Rock - LARVOL DELTA

OPAL: A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy (clinicaltrials.gov) - P2 | N=52 | Not yet recruiting | Sponsor: Scholar Rock, Inc.

New P2 trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Myostatin Modulation in Spinal Muscular Atrophy: A Systematic Review of Preclinical and Clinical Evidence. (PubMed, Int J Mol Sci) - "Despite this, myostatin pathway inhibition remains a compelling approach, particularly when integrated into broader treatment paradigms aimed at enhancing motor unit stability and function in individuals with SMA. Further clinical research is essential to validate efficacy, determine optimal timing, and define the patient subgroups most likely to benefit from myostatin-targeted therapies."

Journal • Preclinical • Review • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Scholar Rock to Present Comprehensive Update at 2025 Annual Cure SMA Research and Clinical Care Meeting, Including Positive Results from Pivotal Phase 3 SAPPHIRE Trial (Businesswire) - "Scholar Rock...announced...that it will present data from its Phase 3 SAPPHIRE clinical trial (NCT05156320) in an oral presentation at Cure SMA’s Annual SMA Research & Clinical Care Meeting being held June 25-27, 2025, in Anaheim, California...Scholar Rock previously shared positive topline data from the trial in October 2024 and announced in March 2025 that the U.S. FDA accepted its BLA for apitegromab. The application has a priority review designation, and the FDA has assigned a PDUFA target action date of September 22, 2025."

P3 data • PDUFA • Muscular Atrophy

Scholar Rock Reports Positive Phase 2 EMBRAZE Trial Results Demonstrating Statistically Significant Preservation of Lean Mass with Apitegromab During Tirzepatide-Induced Weight Loss (Businesswire) - P2 | N=100 | EMBRAZE (NCT06445075) | Sponsor: Scholar Rock, Inc. | "Patients receiving apitegromab with tirzepatide over 24 weeks showed a 54.9% preservation of lean mass (+4.2 lbs of lean mass) versus tirzepatide alone (p=0.001). Patients receiving apitegromab with tirzepatide over 24 weeks lost 18.8 lbs of fat mass while those on tirzepatide alone lost 17.7 lbs of fat mass Patients receiving apitegromab with tirzepatide over 24 weeks lost 12.3% of body weight while those on tirzepatide alone lost 13.4% of body weight. Higher quality of weight loss observed for patients receiving apitegromab with tirzepatide (85% fat mass/15% lean mass) compared to tirzepatide alone (70% fat mass/30% lean mass). Apitegromab was generally well tolerated, and the encouraging safety profile was consistent with the safety profile observed in prior clinical studies."

P2 data • Obesity

Scholar Rock Reports First Quarter 2025 Financial Results and Highlights Business Progress (Businesswire) - "Topline data to be reported in June 2025 from the Phase 2 EMBRAZE proof-of-concept trial. The trial is designed to evaluate the safety and efficacy of apitegromab in preserving muscle mass in adults who are overweight or obese and receiving tirzepatide....IND application for SRK-439 to support the first in human study remains on track and is expected to be filed in Q3 2025."

IND • P2 data • Obesity

...EMA Accepts Marketing Authorisation Application (MAA) for Apitegromab as a Treatment for Spinal Muscular Atrophy (Businesswire) - "The Company has also submitted and received validation for its Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for apitegromab for the treatment of SMA. Validation confirms that the application is complete and the formal review process by EMA can begin...Apitegromab’s regulatory submissions are based on positive efficacy and safety data from the pivotal Phase 3 SAPPHIRE trial (NCT05156320)...as well as supportive data from the Phase 2 TOPAZ trial and long-term extension ONYX trial....European launch anticipated in 2026."

EMA filing • Launch Europe • Muscular Atrophy

FDA Grants Priority Review for Biologics License Application (BLA)...for Apitegromab as a Treatment for Spinal Muscular Atrophy (Businesswire) - "Scholar Rock...announced that the U.S. Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for apitegromab, an investigational muscle-targeted treatment that is being developed to provide clinically meaningful improvement in motor function for people living with spinal muscular atrophy (SMA) who are receiving an SMN-targeted treatment. The FDA will review the application under priority review and has assigned a Prescription Drug User Fee Act (PDUFA) target action date of September 22, 2025...Apitegromab’s regulatory submissions are based on positive efficacy and safety data from the pivotal Phase 3 SAPPHIRE trial (NCT05156320)...as well as supportive data from the Phase 2 TOPAZ trial and long-term extension ONYX trial....Scholar Rock is planning for a U.S. commercial launch upon approval in 2025..."

FDA filing • Launch US • PDUFA • Priority review • Muscular Atrophy

EAP of Apitegromab for Patients With Spinal Muscular Atrophy (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Scholar Rock, Inc.

New trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Scholar Rock Presents New Phase 3 SAPPHIRE Data at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference (Businesswire) - P3 | N=188 | SAPPHIRE (NCT05156320) | Sponsor: Scholar Rock, Inc. | "...The Phase 3 SAPPHIRE trial 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 patients with SMA on chronic dosing of standard of care therapies....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) in the main efficacy population (ages 2-12)....A greater proportion of patients treated with apitegromab had improvements of ≥3 points in their HFMSE scores compared to placebo with odds ratio of 3.0 (nominal p-value = 0.0256). Additionally, 30.4% of patients receiving apitegromab had ≥ 3-point improvement in HFMSE versus 12.5% of patients on placebo (nominal p-value= 0.0156)."

P3 data • Muscular Atrophy

SAPPHIRE: Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam (clinicaltrials.gov) - P3 | N=188 | Completed | Sponsor: Scholar Rock, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Apitegromab in other rare neuromuscular disorders (Businesswire) - "Presenting preclinical data on a combination treatment approach with apitegromab in DMD at the MDA Clinical and Scientific Conference. The poster presentation includes initial preclinical data on an investigational approach combining the murine equivalent of apitegromab and a dystrophin corrector for addressing muscle defects in a DMD mouse model."

Preclinical • Duchenne Muscular Dystrophy

Scholar Rock Reports Full Year 2024 Financial Results and Highlights Business Progress (Businesswire) - "Apitegromab: In anticipation of regulatory approvals, Scholar Rock is planning for a U.S. commercial launch in 4Q 2025, with European launch to follow....Plans to initiate Phase 2 OPAL clinical trial in SMA patients under two years of age in 3Q 2025....SRK-439: Topline data expected in the second quarter of 2025 from the Phase 2 EMBRAZE proof-of-concept trial....IND application for SRK-439 for the treatment of obesity in patients on standard of care GLP-1 RAs expected to be filed in 3Q 2025....The Company’s outstanding debt balance is unchanged at $50 million. The new facility provides the Company with access to an additional $50 million at its discretion through December 31, 2025. An additional $50 million would be available to the Company upon FDA approval of apitegromab in SMA..."

Commercial • IND • Launch US • New P2 trial • P2 data • CNS Disorders • Metabolic Disorders • Muscular Atrophy • Obesity

Scholar Rock to Present Additional Clinical Data from the Phase 3 SAPPHIRE Trial at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference (Businesswire) - "Scholar Rock...announced today that it will present additional data from its Phase 3 SAPPHIRE clinical trial (NCT05156320) at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference being held March 16-19 in Dallas, Texas."

P3 data • Muscular Atrophy

ONYX: Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab (clinicaltrials.gov) - P3 | N=238 | Active, not recruiting | Sponsor: Scholar Rock, Inc. | Trial completion date: Jan 2027 ➔ May 2029

Trial completion date • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Scholar Rock Submits Biologics License Application (BLA) to the U.S. FDA for Apitegromab as a Treatment for Patients with Spinal Muscular Atrophy (SMA) (Businesswire) - "Scholar Rock...today announced the submission of a Biologics License Application to the U.S. Food and Drug Administration (FDA) for apitegromab, a muscle-targeted therapy designed and developed to provide clinically meaningful improvement in motor function for people living with SMA who are receiving SMN-targeted treatments. The Company remains on track to file a Marketing Authorisation Application to the European Medicines Agency in 1Q 2025...The submission is supported by data from the Phase 3 SAPPHIRE trial and the Phase 2 TOPAZ trial...Scholar Rock plans to also study apitegromab in SMA patients under two years of age in the Phase 2 OPAL trial, with a planned initiation in mid-2025."

EMA filing • FDA filing • New P2 trial • Muscular Atrophy

Advance the anti-myostatin program in cardiometabolic disorders (Businesswire) - "Topline data expected in the second quarter of 2025 from the Phase 2 EMBRAZE proof-of-concept trial, 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 in overweight and obese adults who are taking a GLP-1 receptor agonist (GLP-1 RA). Trial outcomes will be used to guide clinical development of SRK-439."

P2 data • Metabolic Disorders • Obesity

EMBRAZE: Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Scholar Rock, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Scholar Rock Reports Second Quarter 2024 Financial Results and Highlights Business Progress (Businesswire) - "Remains on track to report topline data from pivotal Phase 3 SAPPHIRE trial in patients with Spinal Muscular Atrophy (SMA) in 4Q 2024...Phase 2 EMBRAZE proof-of-concept trial enrolling ahead of schedule, topline data expected in 2Q 2025...The Company plans to file an IND for SRK-439 for the treatment of obesity in 2025."

IND • P2 data • P3 data: top line • CNS Disorders • Metabolic Disorders • Muscular Atrophy • Obesity

Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: results from the 36-month TOPAZ study. (PubMed, Front Neurol) - P2 | "The most frequently reported treatment-emergent adverse events were pyrexia (48.6%), nasopharyngitis (45.7%), COVID-19 infection (40.0%), vomiting (40.0%), and upper respiratory tract infection (31.4%). The benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings."

Journal • Patient reported outcomes • Fatigue • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Pediatrics • Rare Diseases • Respiratory Diseases

EMBRAZE: Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Scholar Rock, Inc.

New P2 trial • Genetic Disorders • Obesity

Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3: The Phase 2 TOPAZ Study. (PubMed, Neurology) - No abstract available

Journal • P2 data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

TOPAZ: An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy (clinicaltrials.gov) - P2 | N=58 | Completed | Sponsor: Scholar Rock, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Effect of apitegromab on motor function and patient-reported outcomes at 36 months in patients aged 2–21 years with spinal muscular atrophy (MDA 2024) - P2 | "In the 52-week treatment period, 3 cohorts of patients received either 2- or 20-mg/kg apitegromab, alone (n=11) or in combination with nusinersen (n=47). Treatment with apitegromab was associated with sustained clinical benefit and improvements in patient- and caregiver-reported outcomes of function and perceived fatigue in patients with Types 2 or 3 SMA for 36 months. These results support further development of apitegromab in SMA."

Clinical • Patient reported outcomes • Fatigue • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3: The Phase 2 TOPAZ Study. (PubMed, Neurology) - P2 | "Apitegromab led to improved motor function in participants with later-onset types 2 and 3 SMA. These results support a randomized, placebo-controlled phase 3 trial of apitegromab in participants with SMA."

Journal • P2 data • CNS Disorders • Cough • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pain • Rare Diseases • Respiratory Diseases

Scholar Rock Announces FDA Clearance of IND Application to Initiate Phase 2 Proof-of-Concept Trial with Apitegromab to Treat Obesity (Businesswire) - "Scholar Rock...announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for its Phase 2 proof-of-concept trial of apitegromab to treat obesity in patients taking a GLP-1 receptor agonist (GLP-1 RA)....Trial initiation is on track for mid-2024, and data from the apitegromab Phase 2 trial are expected in mid-2025."

IND • New P2 trial • P2 data • Metabolic Disorders • Obesity