Muscle preservation has emerged as the most studied side of the GLP-1 era. Up to 40% of incretin-driven weight loss in the highest-loss patients lands on lean mass, and Nature Reviews Endocrinology has flagged sarcopenia and frailty as under-recognized GLP-1 side effects — particularly in adults over 65 and patients with pre-existing low muscle mass.
Covered here: Regeneron's REGN1033 (trevogrumab) Phase 2 COURAGE trial with semaglutide showing the myostatin antibody preserves lean mass during GLP-1-driven weight loss; Ascletis's ASC47, an adipose-targeting thyroid hormone receptor beta (THRβ) agonist that delivered up to 111.8% greater relative weight loss when combined with semaglutide in obesity participants vs semaglutide monotherapy (ECO 2026 May 14 poster session); Lilly's bimagrumab follow-on through the Versanis acquisition; and a 2026 Journal of Cachexia, Sarcopenia and Muscle scoping review documenting peptide candidates across MIF1/MIF2 myostatin inhibitors and GH-axis peptides like CJC-1295, ipamorelin, and tesamorelin.
Stories here cover the combination-with-incretin strategies, the myostatin program readouts, and the broader sarcopenia therapeutic landscape. See #myostatin, #sarcopenia, and #glp-1-side-effects.
Follow-through analyst commentary Tuesday August 25, 2026 on the Monday Roche (SIX: ROG) and Hanmi Pharm HM17321 urocortin-2 (UCN2) obesity licensing deal positioned Roche as now targeting a top-three global obesity commercial position behind Eli Lilly (Zepbound, Mounjaro, Foundayo, and upcoming retatrutide) and Novo Nordisk (Wegovy, Ozempic, Wegovy Pill, Wegovy HD, CagriSema under review). Deal recap: $190 million upfront, up to $2.3 billion in milestones, plus tiered royalties; Genentech gets global rights excluding South Korea. HM17321 mechanism: a proprietary urocortin-2 (UCN2) analog peptide that selectively activates the corticotropin-releasing factor 2 receptor (CRFR2), a mechanism distinct from the incretin pathway (GLP-1, GIP) that anchors every currently-approved obesity drug. Roche obesity portfolio positioning: HM17321 combines with Roche's existing CT-388 (a dual GIP/GLP-1 receptor agonist acquired in the December 2023 Carmot Therapeutics acquisition for $2.7 billion, currently in Phase 2 for obesity and type 2 diabetes) and the emerging Roche obesity pipeline including RG7500 orforglipron precursor and other early-stage assets. The multi-mechanism portfolio provides a differentiated commercial positioning to compete across weight-loss efficacy (Roche's incretin agonist candidates match Lilly and Novo) and muscle-preservation (HM17321's differentiated UCN2 mechanism designed for lean mass preservation). Roche's obesity ambition contrasts with prior investor skepticism about its late-cycle entry into the category; Tuesday's analyst commentary suggests the multi-mechanism strategy could position Roche credibly for 2028-2030 commercial launches assuming pipeline programs advance to registration.
Hanmi Pharm (KRX: 128940) signed Monday August 24, 2026 an exclusive licensing agreement with Genentech (a member of the Roche Group) for HM17321, a proprietary urocortin-2 (UCN2) analog peptide for obesity. Deal terms: $190 million upfront payment, up to $2.3 billion in development, regulatory, and commercial milestone payments, plus tiered royalties on sales. Territory: Genentech secures global rights excluding South Korea, where Hanmi retains the license. Mechanism: HM17321 selectively activates the corticotropin-releasing factor 2 receptor (CRFR2), a peptide-hormone receptor pathway distinct from the incretin pathway (GLP-1 receptor, GIP receptor) that anchors every currently-approved obesity drug including semaglutide, tirzepatide, orforglipron, and the broader GLP-1 receptor agonist class. Urocortin-2 is a naturally occurring 38-amino-acid peptide of the corticotropin-releasing factor family. Differentiated profile: HM17321 is positioned as a potential first-in-class treatment designed to simultaneously promote weight loss and preserve lean body mass, an important differentiator against the semaglutide-tirzepatide-retatrutide GLP-1 class where roughly 25% of the total weight lost is lean muscle mass. Development pathway: Hanmi received FDA IND clearance to initiate a Phase 1 clinical trial in November 2025. Hanmi is responsible for completing the Phase 1 clinical trial, after which Genentech will take over development starting with Phase 2 clinical trials. The deal represents one of the largest 2026 obesity licensing transactions and adds a substantially different mechanism to Roche's obesity portfolio that also includes CT-388 (dual GIP/GLP-1 agonist from the Carmot Therapeutics acquisition).
Pep2Tango Therapeutics presented preclinical data on PTT-A, a novel long-acting unimolecular peptide tetra-agonist activating the GLP-1, GIP, amylin, and calcitonin receptors simultaneously, in a Medscape 'Moving Beyond GLP-1s' feature drawing from the ADA 2026 session 'Novel Strategies for Obesity Pharmacology' (oral abstracts 85-OR and 299-OR, Diabetes journal supplement). In 21-day chronic studies in diet-induced obese rats, the higher PTT-A dose achieved 19% body weight reduction versus the vehicle, compared to 12% each for tirzepatide and cagrilintide + semaglutide (CagriSema). Body composition analysis showed fat-mass loss without lean-mass loss, distinguishing PTT-A's profile from tirzepatide's documented muscle-loss pattern. PTT-A also showed robust glucose lowering, plasma lipid improvement, insulin sensitization, and liver-fat benefits.
Hanmi Pharmaceutical presented HM500197 (LA-MSTN) at ADA 2026 (June 5-8, New Orleans) as the world's first peptide-based myostatin inhibitor, positioned as a muscle-preserving adjunct to GLP-1 weight-loss therapy. The molecule was designed on Hanmi's HARP (Hanmi AI-driven Research Platform) integrating AI and structural modeling. Hanmi paired the LA-MSTN unveiling with a second next-generation candidate, HM17321, in a broader eight-abstract slate spanning the company's obesity pipeline. The myostatin angle addresses a major shortcoming of the current GLP-1 class — 25-40% of weight loss coming from lean tissue rather than fat — which Stanford's Maharjan team flagged at ENDO 2026 with the 560-step daily activity drop and which underlies the broader bone-health and frailty concerns now being studied across the GLP-1 class.
Ascletis Pharma will present multiple poster sessions at ECO 2026 covering programs beyond the already-presented ASC30. ASC47, an adipose-targeting thyroid hormone receptor beta (THRβ) agonist designed for muscle-preserving weight loss, demonstrated up to 111.8% greater relative weight loss when combined with semaglutide vs semaglutide monotherapy in obesity participants. ASC36, a once-monthly next-generation amylin receptor agonist peptide, posted a 32-day average observed half-life — six times longer than Zealand's petrelintide. ASC35, a once-monthly next-generation GLP-1R/GIPR dual agonist peptide, showed a 14-day average observed half-life (six times longer than tirzepatide) and 71% more relative weight loss than tirzepatide in a diet-induced obesity mouse model. Session Thursday May 14, 18:00-19:15 TRT.
Scholar Rock's apitegromab — a selective pro/latent myostatin antibody approved for SMA — continues to draw obesity-pipeline attention with EMBRAZE Phase 2 data showing 54.9% relative lean mass preservation when combined with tirzepatide vs tirzepatide alone (4.2 lbs / 1.9 kg additional lean mass preserved, p=0.001). Body composition shifted from 70% fat/30% lean with tirzepatide alone to 85%/15% with the combination. SRK-439 next-gen selective myostatin inhibitor is in preclinical development with attenuation of fat-mass rebound after GLP-1 withdrawal as a key signal.
Regeneron's COURAGE Phase 2 data presented at EASD 2025 continue to drive obesity-pipeline conversations. Semaglutide alone produced 6.5% lean mass loss at 26 weeks; sema + trevogrumab 200 mg cut that to 3.3% (~half), and the triplet with garetosmab (anti-activin A) pushed to 2.0% lean mass loss with 92.6% fat-mass loss. The triplet had higher discontinuation for tolerability. Full COURAGE completion is expected late 2026, with Phase 3 initiation likely 2027.