Apitegromab in SMA - Positive Phase 3 trial data showed a 18 point improvement versus placebo in Hammersmith Functional Motor Scale-Expanded (HFMSE) in SMA patients[23] - 30% of apitegromab patients achieved ≥3-point improvement in HFMSE compared to 125% of placebo patients[23] - FDA accepted BLA under Priority Review with a target action date of September 22, 2025[25] - MAA Validated with anticipated EU approval in 2026[14] - The company is initiating Phase 2 OPAL Trial in Q3 to study apitegromab in patients under 2 years old[14, 27] Pipeline Expansion - EMBRAZE trial achieved primary endpoint with positive Phase 2 proof-of-concept in obesity[14] - Apitegromab combined with tirzepatide resulted in a 549% reduction in lean mass loss versus tirzepatide alone[36] - The company is on track to file IND for SRK-439 in 2H 2025[14, 39, 43] Financial Status - The company had $295 million cash as of June 30, 2025[14]

Business Overview - Scholar Rock's strategy focuses on selectivity in targeting latent growth factors to develop therapeutics across multiple disease areas[12, 15, 17, 19] - The company is advancing a pipeline of product candidates in neuromuscular disorders, cardiometabolic disorders, immuno-oncology, fibrosis, and anemia[20, 23] - Scholar Rock anticipates transformative execution in the next 12-24 months, driven by upcoming milestones and commercialization efforts[12] Apitegromab (Spinal Muscular Atrophy) - Topline readout from the Phase 3 SAPPHIRE trial in SMA is expected in Q4 2024, with a potential SMA launch in Q4 2025 if successful and approved[30] - 48-month data from the TOPAZ clinical trial showed substantial and sustained improvements in motor function outcomes in pooled nonambulatory SMA patients[39, 46, 52] - In the TOPAZ trial, pooled nonambulatory patients showed mean change from baseline in HFMSE of 2.8 at 6 months, 3.6 at 12 months, 4.2 at 24 months, 4.0 at 36 months, and 5.3 at 48 months[40] - In the TOPAZ trial, pooled nonambulatory patients showed mean change from baseline in RULM of 0.6 at 6 months, 1.3 at 12 months, 2.3 at 24 months, 2.4 at 36 months, and 3.6 at 48 months[47] Apitegromab (Obesity) & SRK-439 - A Phase 2 proof-of-concept EMBRAZE study of apitegromab in obesity is enrolling, with topline data expected in Q2 2025[23, 30, 60, 63] - SRK-439, a novel anti-myostatin antibody, is being advanced to IND submission, with preclinical data showing potential for healthier weight loss in combination with GLP-1 receptor agonists[23, 30, 75] - Preclinical data showed that SRK-439 increased lean mass and attenuated regain of fat mass after GLP-1 RA withdrawal in an obesity mouse model[78] - In preclinical studies, SRK-439 demonstrated greater potency than an anti-ActRII antibody at maintaining lean mass during GLP-1 RA-induced weight loss[77, 88]

Investment Rating - The industry investment rating is "Positive" (maintained) [1] Core Insights - The report highlights recent positive developments in the high-quality weight loss sector, particularly focusing on myostatin pathway clinical trial results from Regeneron and Scholar Rock, which demonstrate significant reductions in lean body mass loss when combined with GLP-1 medications [4][12] - The pharmaceutical and biotechnology sector experienced a decline of 4.35% in the third week of June 2025, underperforming the CSI 300 index by 3.9 percentage points, ranking 29th among 31 sub-industries [5][16] - The report emphasizes the potential of Activin receptor drugs, such as Eli Lilly's Bimagrumab and Lai Kai's LAE-102, to retain lean body mass and even promote muscle gain, with promising safety and pharmacokinetic data [4][12] Summary by Sections 1. Recent Developments in Weight Loss Sector - Regeneron's myostatin antibody Trevogrumab combined with semaglutide showed a 50.8% reduction in lean body mass loss over 24 weeks, compared to a 7.9 lbs loss with semaglutide alone [4][12] - Scholar Rock's myostatin antibody Apitegromab combined with Tirzepatide demonstrated a 54.9% reduction in lean body mass loss [4][12] 2. Market Performance - The pharmaceutical and biotechnology sector's decline of 4.35% in June's third week was the largest among all sectors, with the vaccine sector experiencing the smallest drop of 0.4% [5][21] - Other sub-sectors, such as blood products and medical consumables, also faced declines, with the largest drop seen in other biological products at 6.7% [5][21] 3. Recommended Stocks - Recommended stocks include major pharmaceutical and biotechnology companies such as Heng Rui Medicine, East China Medicine, and Innovent Biologics, among others [6]

Core Insights - Scholar Rock's Phase 2 EMBRAZE trial results indicate that apitegromab combined with tirzepatide can significantly preserve lean mass during weight loss, with a notable reduction in lean mass loss compared to tirzepatide alone [1][2][3] Group 1: Trial Results - The trial showed that 30% of the weight loss from tirzepatide was attributed to lean mass loss, while the addition of apitegromab reduced this to 14.6% [3][4] - Patients receiving the apitegromab-tirzepatide combination lost 12.3% of their body weight, compared to 13.4% for those on tirzepatide with placebo [4] - The combination therapy resulted in a higher quality of weight loss, with patients losing 85% fat and 15% lean mass, compared to 70% fat and 30% lean mass in the placebo group [4] Group 2: Market Reaction - Following the positive trial results, Scholar Rock's stock price increased by 18%, reaching $36.77 [6]

Investment Rating - The report maintains a "Positive" investment rating for the industry [1] Core Insights - The report highlights the significant potential of blocking the Activin receptor (ActR) signaling pathway to promote muscle growth, particularly in treating muscle atrophy-related diseases [4][9] - There is a substantial unmet clinical need for muscle-targeted therapies, especially for patients with spinal muscular atrophy (SMA) and those experiencing muscle loss due to aging or weight management [4][29] - The market for muscle-targeted therapies is projected to be large, with current SMA therapies generating approximately $4.5 billion in sales, indicating a significant opportunity for new treatments [4][33] Summary by Sections 1. ActR Pathway - The ActR pathway plays a crucial role in regulating muscle, blood, and bone through members of the TGFβ superfamily, including Myostatin [9] - Blocking the ActR pathway can effectively treat muscle atrophy by inhibiting Myostatin, which negatively regulates muscle growth [4][10] 2. Clinical Applications of ActR Pathway Blockade: Spinal Muscular Atrophy (SMA) - SMA is a genetic neuromuscular disease caused by mutations in the SMN1 gene, leading to severe muscle atrophy and respiratory failure [22][23] - Current SMA therapies primarily target SMN protein, but they have limitations, highlighting the need for combined therapies that also address muscle atrophy [25][29] 3. Clinical Applications of ActR Pathway Blockade: Weight Management - Muscle loss is a significant issue not only in genetic diseases but also in aging populations, with a 1% annual muscle loss in individuals over 60 [36] - The widespread use of GLP-1RA medications has been linked to 25-40% muscle loss in users, creating a demand for therapies that preserve or enhance muscle mass during weight management [36] 4. Targeted ActRII Pathway Drugs - Apitegromab, developed by Scholar Rock, is a monoclonal antibody targeting latent Myostatin, showing promising results in Phase 3 trials for SMA and expected to submit for FDA approval [38][39] - Taldefgrobep, developed by BIOHAVEN, targets active Myostatin but did not meet primary endpoints in its Phase 2 trial for SMA, although it showed trends of benefit in certain subgroups [57][62] - GYM329, developed by Roche, specifically targets latent Myostatin and is currently undergoing clinical trials for various indications, demonstrating potential for muscle mass increase [69]