bimagrumab (BYM338) / Novartis, Eli Lilly - LARVOL DELTA

MTRX31 induces bodyweight loss in diet-induced obesity mice at thermoneutrality by switching metabolism from fat to carbohydrate oxidation (EASD 2026) - "Materials and : : Male C57BL/6J mice fed high-fat diet (60%) or standard chow from week 6 of age for 15 weeks were dosed with MTRX31 (1 and 5 mg/kg; s.c. TIW), tirzepatide (5 nmol/kg, s.c. QD), bimagrumab (20 mg/kg, s.c, QW) or combinations for 8 weeks (n=10). Altogether, MTRX31 demonstrates potent and long lasting anti-obesogenic properties. Bodyweight loss is associated with strong reduction in fat while preserving lean mass and strength suggesting muscle function preservation. Improvement in metabolic capacity/parameters and a switch from fat to carbohydrates oxidation support a differentiated mode-of-action from incretins or uncouplers thus providing alternative monotherapy solutions for individuals living with obesity, as well as options for combinations with existing treatments or for maintenance therapies after cessation of incretin therapy."

Preclinical • Metabolic Disorders • Obesity

Cardiometabolic changes during 6-month withdrawal from bimagrumab and/or semaglutide in adults with obesity: BELIEVE study extension (EASD 2026) - P2 | "After 6-month withdrawal, VAT, hsCRP and BP benefits persisted in participants treated with bima, sema or combo. Improvements in LDL-c and HbA1c on sema returned to BL post-treatment. LDL-c increased on bima and decreased to below BL post- treatment."

Clinical • Metabolic Disorders • Obesity • CRP

PG-110, a trispecific actrii/myostatin/gip antibody, improves the quality of semaglutide-induced weight loss beyond body composition compared with bimagrumab (EASD 2026) - "PG-110 enhanced semaglutide-induced fat-selective weight loss while preserving lean mass and improving muscle function, muscle quality, glycemic control, and liver health. Compared with bimagrumab, PG-110 demonstrated integrated benefits beyond body composition, supporting simultaneous targeting of ActRII, myostatin, and GIP pathways as a promising strategy for improving the quality of GLP-1-induced weight loss."

Late-breaking abstract • Trispecific • Metabolic Disorders • Obesity • ACVR2A

Efficacy and Safety of Bimagrumab in Adults With Obesity and Metabolic Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Diabetes Obes Metab) - "Bimagrumab effectively reversed adverse effects on body composition in obese individuals, resulting in significant fat reduction, increased skeletal muscle mass, and improved glycemic control, suggesting that bimagrumab is a promising new target for personalized metabolic therapy."

Journal • Retrospective data • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Putting the brakes on muscle growth: Myostatin as regulator of disuse atrophy. (PubMed, Exp Physiol) - "Finally, these mechanistic insights have stimulated therapeutic strategies targeting the myostatin-ActRIIB axis, notably bimagrumab, a monoclonal antibody against ActRIIB and inhibitor of downstream myostatin signalling. Evidence from human and rodent studies suggests that myostatin inhibition may represent a promising strategy to counteract skeletal muscle disuse atrophy caused by inactivity. Collectively, the current evidence highlights myostatin as a central molecular integrator of mechanical unloading-induced muscle atrophy."

Journal • Review • Muscular Atrophy • Targeted Protein Degradation • ACVR2A

MyoScreen, a Human Skeletal Muscle Platform, Reveals Novel Targets and Muscle-Preserving Small Molecules (ICNMD 2026) - "Collectively, the data indicates that selective ALK5/TGFβR1 inhibition drives skeletal muscle hypertrophy and a transition toward a more mature and metabolically active phenotype, highlighting ALK5/TGFβR1 as a potential intracellular target for muscle-preserving therapies. These findings also establish MyoScreen as a clinically translatable human muscle platform that robustly models disease-relevant muscle states and recapitulates myofiber rescue by established standards such as bimagrumab. Importantly, this platform approach enables efficient discovery and in-depth characterization of next-generation drug candidates aimed at preserving muscle health."

Cachexia • Chronic Kidney Disease • Diabetes • Genetic Disorders • Immunology • Metabolic Disorders • Muscular Atrophy • Muscular Dystrophy • Myositis • Nephrology • Obesity • Renal Disease • Sarcopenia • Type 2 Diabetes Mellitus • ACVR2A • TGFB1 • TGFBR1 • TNFA

Imaging-Derived Sarcopenic Obesity and Cardiovascular Outcomes: Insights Into Heart Failure Risk and Muscle Biology. (PubMed, J Am Coll Cardiol) - "These results establish sarcopenic obesity as a clinically meaningful cardiovascular risk phenotype and point to viable therapeutic targets."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Muscular Atrophy • Obesity • Sarcopenia • ACVR2B

Advances in Clinical Management Strategies for Sarcopenia: From Exercise and Nutrition to Pharmacotherapy and Comprehensive Interventions. (PubMed, Mol Neurobiol) - "These include agents acting on the myostatin/activin signaling pathway (e.g., Bimagrumab), androgen receptors (e.g., LPCN 1148), metabolic and endocrine pathways (e.g., active vitamin D, metformin), as well as anti-inflammatory and immunomodulatory approaches (e.g., probiotics, anti-TNF-α agents). Despite notable progress, the field continues to face challenges including disease heterogeneity, inconsistent diagnostic criteria, poor long-term adherence to interventions, and inadequate functional translation of drug therapies. Future research should prioritize advancing precision medicine, optimizing personalized regimens, exploring novel biomarkers, and integrating and disseminating effective interventions into community and clinical practice to comprehensively improve the clinical management of sarcopenia."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Musculoskeletal Diseases • Nephrology • Oncology • Renal Disease • Sarcopenia • AR

HM500197, a De Novo–Designed Long-Acting Peptide Myostatin Inhibitor, Improves Skeletal Muscle Mass and Body Composition in Diet-Induced Obese Mice (ADA 2026) - "Introduction and Objective: Incretin therapies effectively reduce body weight and improve metabolic parameters but are frequently accompanied by lean mass loss, underscoring inhibition of the myostatin (MSTN)/activin pathway—exemplified by bimagrumab (Bima)—as a rational therapeutic strategy. HM500197 significantly increased skeletal muscle mass relative to Bima and prevented muscle loss during caloric restriction-induced weight reduction, supporting its potential to improve weight loss quality and serve as an optimal combination partner for incretin therapies."

Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity • INHBB

FBL-140, a Best-in-Class ActR2A/B mAb Designed for Infrequent SC Dosing for Treatment of Obesity (ADA 2026) - "Bimagrumab + semaglutide therapy induced 22% weight loss (93% from fat), but 30 mpk i.v. bimagrumab was required for full activity, associated with high Cmax and dose-related adverse effects... Quarterly s.c. dosing, enabled by FBL-140's strong manufacturability and PK, offers a unique opportunity for lean mass preserving weight loss for patients with obesity."

Late-breaking abstract • Metabolic Disorders • Obesity

ActRIIA Plays a Predominant Role over ActRIIB in Human Myoblast Differentiation (ADA 2026) - "Myoblasts differentiated for 4-6 days with GDF8 or activin A alone or in the presence of anti-ActRIIA, anti-ActRIIB and dual anti-ActRIIA/IIB Bimagrumab antibodies... These results indicate that ActRIIA plays a more prominent role than ActRIIB in the differentiation of human myoblasts. This provides a strong rationale for more presicse targeting ActRII receptors to preserve muscle in obesity treatment."

Late-breaking abstract • Metabolic Disorders • Obesity • ACVR2A

Obese Rhesus Monkeys Recapitulate Human Efficacy Profiles of Semaglutide, Bimagrumab, and Retatrutide (ADA 2026) - "Obese rhesus monkeys exhibit human-like fat distribution and treatment responses to Semaglutide, Bimagrumab, and Retatrutide. Notably, the selective fat loss and lean mass gain induced by Bimagrumab closely mirror clinical findings, supporting this model as a robust translational platform for preclinical anti-obesity drug development."

Clinical • Metabolic Disorders • Obesity

Development of FBL-140, a Best-in-Class, Once-Monthly Subcutaneous ActR2A/B Antagonist Antibody for Obesity and Related Comorbidities (ADA 2026) - "Bimagrumab in BELIEVE was not optimized for convenient, subcutaneous (s.c.) dosing, and low affinity for ActR2A limits fat mass efficacy at lower doses... FBL-140 demonstrates a class-leading PK and manufacturability profile achieving full target engagement and efficacy, with modeling and simulation predicting once-monthly, low-volume s.c. injection in humans."

Metabolic Disorders • Obesity • ACTR2

Body Composition and Functional Outcomes of HM17321, a CRFR2-Selective UCN2 Analog, Alone and in Combination with Myostatin/Activin Inhibition in DIO Mice (ADA 2026) - "Clinical studies combining incretin therapies with myostatin/activin pathway inhibition, such as bimagrumab (Bima), suggest benefits for WLQ. HM17321 induced fat-selective BWL with functional lean mass gain in both sexes, supporting its potential as a novel foundational WLQ therapy. These findings provide proof-of-concept for additional benefits of incorporating myostatin/activin pathway inhibition for body weight and body composition, warranting longer-term evaluation."

Combination therapy • Preclinical • Metabolic Disorders • Obesity

Myo-004 Induces Body-Weight Loss in DIO at Thermoneutrality by Switching Metabolism from Fat to Carbohydrate Oxidation (ADA 2026) - "Our mitochondrial-targeted small molecules provide an alternative mode-of-action to modulate metabolism to combat obesity. Male C57BL/6J mice fed high-fat diet (60%) or standard chow from week 6 of age for 15 weeks were dosed with Myo-004 (1 and 5 mg/kg; s.c. TIW), tirzepatide (5 nmol/kg, s.c. QD), bimagrumab (20 mg/kg, s.c, QW) or combinations for 8 weeks (n=10). Altogether, Myo-004 demonstrates potent anti-obesogenic properties that are long lasting in the DIO model at thermoneutrality. Bodyweight loss is associated with strong reduction in fat while preserving lean mass as well as grip-strength suggesting muscle function preservation. Improvement in metabolic capacity (increased RER) and a switch between fat and carbohydrates oxidation support a differentiated mode-of-action from incretins or uncouplers thus providing alternative solutions for individuals living with obesity or for maintenance therapies after incretins therapy cessation."

Metabolic Disorders • Obesity

HM17321, a CRFR2 Selective UCN2 Analog, Prevents Muscle Loss and Functional Decline in Sarcopenic Mice (ADA 2026) - "HM17321 attenuated sarcopenia across multiple etiologies by preserving muscle mass, function, and structural integrity. These findings support the potential of HM17321 as a therapeutic approach for sarcopenia."

Preclinical • Metabolic Disorders • CLSPN,

Body Composition and Functional Outcomes of HM17321, a CRFR2-Selective UCN2 Analog, Alone and in Combination with Myostatin/Activin Inhibition in DIO Mice (ADA 2026) - "Clinical studies combining incretin therapies with myostatin/activin pathway inhibition, such as bimagrumab (Bima), suggest benefits for WLQ. HM17321 induced fat-selective BWL with functional lean mass gain in both sexes, supporting its potential as a novel foundational WLQ therapy. These findings provide proof-of-concept for additional benefits of incorporating myostatin/activin pathway inhibition for body weight and body composition, warranting longer-term evaluation."

Combination therapy • Preclinical • Metabolic Disorders • Obesity

In Vitro and In Vivo Characterization of CC-18, a Novel GLP-1R/ActRIIA/ActRIIB Dual Pathway-Targeting Fusion Protein That Reduces Weight while Increasing Muscle in Preclinical Models (ADA 2026) - "Interestingly, ActRII blockade with bimagrumab impaired GLP-1R signaling, reducing Emax to 52%, an effect not observed with CC-18... CC-18 conferrs robust and durable metabolic benefits via coordinated GLP-1R activation and ActRII blockade, supporting its further development as a promising dual-mechanism metabolic therapy."

Preclinical • Metabolic Disorders • Obesity • ACVR2A

Bimagrumab trial shows total fat loss with muscle gain (MSN News) - "In a double-blind, placebo-controlled phase 2 trial involving 507 adults with obesity, bimagrumab treatment resulted in 6–9.3 kg of weight loss over 48 weeks, with 100% of the loss coming from fat mass. Appendicular lean mass and total body lean mass increased slightly, marking a rare outcome in weight-loss interventions. This occurred without greater calorie restriction than placebo, highlighting the drug’s unique metabolic effects....Discontinuation rates exceeded 25%, higher in bimagrumab groups, underscoring the need for risk–benefit assessment."

P2 data • Obesity

Hepatic stellate cell-derived Follistatin-like 3 ameliorates alcohol-induced liver injury via inhibition of Activin type II receptor signaling pathway (EASL 2026) - "Hepatic stellate cell-derived FSTL3 may act as an intrinsic protective factor in ALD by antagonizing Activin A-mediated SMAD2/3 signaling pathway. Enhancing FSTL3 activity or blocking the hepatic Activin type II receptor using antagonists such as bimagrumab may offer a therapeutic approach to limit liver injury and influence early disease mechanisms in ALD."

Hepatology • Liver Failure • CDKN1A

Body composition (DXA) changes during 6-month withdrawal from semaglutide and/or bimagrumab treatment of adults with obesity: The BELIEVE study extension (ECO 2026) - "Sema 2.4 treatment resulted in greater decreases in body weight vs. bima 30 at W72, whereas bima 30 resulted in similar fat loss and greater reduction in VAT; the combination resulted in additive fat loss. Following 6-month treatment withdrawal, lean mass returned to BL post-bima, as expected."

Clinical • Acne Vulgaris • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Inflammation • Obesity • CRP

Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies. (PubMed, Metabol Open) - "Oral GLP-1 agonists, including orforglipron, offer comparable efficacy to injectables while potentially improving global accessibility by eliminating cold-chain requirements and simplifying manufacturing. Multi-receptor agonists represent the most transformative developments: triple agonists such as retatrutide achieve weight reductions of 20-24%, while dual GLP-1/glucagon agonists like survodutide and mazdutide show strong efficacy with particular promise for metabolic-associated steatotic liver disease. Maridebart cafraglutide, combining GLP-1 agonism with glucose-dependent insulinotropic polypeptide (GIP) antagonism, enables once-monthly dosing. The amylin pathway has re-emerged through long-acting analogs (cagrilintide, eloralintide) and unimolecular co-agonists (amycretin), achieving weight reductions up to 24% via distinct neuroendocrine circuits."

Journal • Review • Genetic Disorders • Hepatology • Obesity • Pediatrics

Targeting the activin/myostatin - actrii pathway to preserve skeletal muscle mass in obesity: mechanistic insights and therapeutic perspectives. (PubMed, Rev Endocr Metab Disord) - No abstract available

Journal • Review • Genetic Disorders • Obesity • Sarcopenia • ACVR2A

BMPR2 Dosage Gates BMP9/10 Signaling Output in Pulmonary Artery Endothelium. (PubMed, Cells) - "Under BMPR2-limiting conditions, BMP9/10 responses became sensitive to Activin type II receptor blockade by bimagrumab, consistent with a context-dependent contribution of Activin type II receptors...Together, these findings support a receptor-dosage model where physiological BMPR2 expression is required to sustain homeostatic BMP9/10 signaling in pulmonary artery endothelium. This framework provides a basis for interpreting context-dependent pathway effects in PAH."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CASP3 • CASP7

Cardiac Safety of Chronic Inhibition of the Myostatin-Activin Pathway with Bimagrumab in Healthy Older Adults. (PubMed, J Clin Endocrinol Metab) - "Six months of myostatin-activin pathway inhibition with bimagrumab had no effect on cardiac structure or function in healthy older adults compared to placebo. These results support consideration of bimagrumab as a skeletal muscle sparing intervention in adults undergoing weight loss with GLP-1 receptor agonists."

Clinical • Journal • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus