Bimagrumab

Phase 2 study in obesity, evaluating treatment with once-weekly and once-monthly taldefgrobep alfa as monotherapy, is now fully enrolled; topline data expected in 2H 2026. Taldefgrobep is a novel inhibitor of the myostatin-activin signaling pathway, which directly targets both fat and muscle, offering the potential to achieve high-quality weight loss in people living with overweight and obesity. In previous clinical studies, taldefgrobep produced meaningful reductions in fat mass while increasing lean muscle mass in healthy adults and other non-obese populations; it has also demonstrated a highly favorable safety and tolerability profile in more than 700 trial participants. In nonclinical studies in obese mouse models, taldefgrobep, both as monotherapy and in combination with a GLP-1 agonist, generated significant reductions in fat mass and body weight, while increasing lean mass. March 19, 2026 -- Biohaven Ltd. (NYSE: BHVN) ("Biohaven"), a global clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of life-changing therapies to treat a broad range of rare and common diseases, today announced the completion of enrollment in a Phase 2 proof-of-concept (PoC) study with its myostatin-activin pathway inhibitor (MAPI), taldefgrobep alfa, which offers the potential to achieve high-quality weight loss in people living with obesity. Topline data from the study are expected in 2H 2026. Frank Greenway, M.D., Professor, Chief Medical Officer of the Clinical Trials Unit at Pennington Biomedical Research Center, Baton Rouge, LA stated, "We are at a watershed moment in the treatment of obesity, brought on by the introduction of highly effective therapies like the GLP-1 agonists. To realize optimal long-term health outcomes, however, we will need to look beyond maximizing weight reduction and remain vigilant around the importance of muscle mass in overall health and wellness. Investigational medications, like taldefgrobep, with the potential to meaningfully reduce body weight and adipose tissue, while increasing muscle mass can be an important addition to the anti-obesity armamentarium." The Phase 2 PoC study (NCT07281495) is a randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and tolerability of once-weekly and once-monthly taldefgrobep as monotherapy, via self-administered autoinjector, in adults living with overweight and obesity. It includes a 24-week double-blind treatment period followed by 24-week open-label extension period. The study is targeting approximately 150 participants for randomization. The primary outcome measure is percent change in total body weight from baseline to Week 24, and secondary outcome measures are percent change in total body fat mass and in total body lean mass. The study is being conducted at 20 clinical sites across the US. Peter Ackerman, M.D., Senior Vice President of Clinical Development at Biohaven stated, "We are excited to evaluate taldefgrobep, as both a once-weekly and once-monthly dosing regimen, in an obese patient population. We believe taldefgrobep could represent an important new agent, as monotherapy and in combination with the current standard of care, that can help optimize high-quality weight loss in people living with obesity." Dr. Ackerman added, "New investigational therapies with novel modes of action are critical to maximizing long-term health benefits in people living with overweight and obesity. While there have been great recent advancements in the field of obesity medicine, there is still a lot of work to do in optimizing the management of a complex, heterogeneous condition that affects nearly half of the world's population. Our team is grateful to the investigators, their staff, and all participants involved in this important study." In previous clinical studies, taldefgrobep demonstrated beneficial changes in fat mass and lean mass in non-obese populations. Participants in a Phase 1 trial who received taldefgrobep realized significant reductions in total body fat mass (>6%) with commensurate increases in lean muscle mass (up to 4%) after 29 days of dosing. In that study, taldefgrobep benefit in body composition change was not fully realized until four weeks beyond the final dose was administered, suggesting the drug may support extended dosing intervals. In the Phase 3 study BHV2000-301, examining patients with a neuromuscular disorder, taldefgrobep-treated participants achieved statistically significant reductions in total body fat accumulation (9.7%; p700 clinical trial participants and has been well tolerated with low rates of serious adverse events (SAEs) and adverse events (AEs) leading to early discontinuation. Rates of muscle- and GI-related AEs have been generally comparable to placebo. In nonclinical studies, taldefgrobep has demonstrated the ability to have direct beneficial effects on lean muscle mass and adipose tissue by interrupting the signaling through activin receptors (ActRII) caused by transforming growth factor-beta (TGF-ß) ligands, such as myostatin and multiple activins (A, E, etc.). In a diet-induced obese (DIO) mouse model, taldefgrobep monotherapy showed significant improvements in total body weight, fat mass, and lean mass relative to vehicle. In DIO mice, taldefgrobep in combination with a GLP-1 agonist showed additive benefit across these endpoints. Data from multiple Phase 2 studies conducted with bimagrumab, a myostatin-activin pathway inhibitor, demonstrates a strong proof of concept for this therapeutic approach to obesity. In the BELIEVE study, participants dosed with bimagrumab as monotherapy, achieved reductions in total body fat mass comparable to high-dose semaglutide (2.4 mg) at one year (-25.3% vs. -24.8%, respectively). In the same study, bimagrumab-treated individuals saw a greater reduction in metabolically active visceral adipose tissue (-40.2% vs. -29.5%) and improvement in lean muscle mass compared semaglutide (+2.7% vs. -7.9%, respectively). Unfortunately, the safety profile of bimagrumab (high rates of GI- and muscle-related AEs and worsening of cholesterol levels) has complicated further development of this asset for an indication in chronic weight management. Taldefgrobep alfa is a novel fusion protein designed to inhibit signaling through activin transmembrane receptors (ActRII). Taldefgrobep targets free myostatin, forming stable complexes which bind to ActRII in a manner that prevents downstream signaling from transforming growth factor-beta (TGF-ß) ligands (including myostatin and activins) important in body composition change. Taldefgrobep's novel mechanism of action offers the potential for meaningful reductions in fat mass, increased lean mass, and improvements in multiple metabolic parameters. Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, obesity, neuroscience, and oncology. Biohaven is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's clinical and preclinical programs include Kv7 ion channel modulation for epilepsy; MoDE™ and TRAP™ extracellular protein degradation for immunological diseases; TYK2/JAK1 inhibition for neuroinflammatory disorders; myostatin-activin pathway inhibition for neuromuscular and metabolic diseases; antibody recruiting bispecific molecules; and antibody drug conjugates for cancer. The content above comes from the network. if any infringement, please contact us to modify.

Stockholm-based Atrogi AB has dosed the first subjects in clinical trial evaluating the muscle physiological effects of its oral β2-adrenergic receptor therapy ATR-258 in overweight male volunteers, as per a company announcement. ATR-258 is a first-in-class, GRK-biased, long-acting β2-adrenergic receptor agonist designed to mimic the metabolic effects of exercise — driving fat loss while preserving or increasing skeletal muscle mass. The 8-week investigator-initiated study, led by Associate Professor Morten Hostrup at the University of Copenhagen, will measure the extent to which ATR-258 recapitulates the muscle-building effects of classical β2-agonists through biased downstream signaling. The trial is registered as NCT07421024 and is also listed on AllSci. The study plans to enrol 10 participants receiving daily oral dosing of Atrogi ATR-258, with endpoints focused on molecular and physiological readouts in skeletal muscle. A primary completion date of December 2026 is listed. This trial builds on a completed 69-subject Phase 1 study in healthy volunteers and patients with type 2 diabetes, the results of which were published in Cell in June 2025 and demonstrated safety and tolerability. Atrogi describes ATR-258 as an exercise mimicking drug with potential across metabolic disease and muscle atrophic conditions including sarcopenia, immobilization-induced wasting, and muscle loss during weight-loss therapy. Research context: β2-adrenergic signaling for muscle-sparing weight loss The β2-adrenergic receptor is a GPCR expressed in skeletal muscle and other tissues. Traditional β2-agonists such as clenbuterol are known to promote muscle hypertrophy and fat oxidation, but their clinical use for metabolic indications has been precluded by cardiovascular toxicity — tachycardia, arrhythmias, and desensitization with chronic dosing. ATR-258 is engineered to exploit biased agonism, preferentially engaging GRK-mediated signaling pathways rather than classical G protein coupling. The principle that selective pathway activation at GPCRs can separate therapeutic from adverse effects is well established in receptor pharmacology, as reviewed in literature on β2-adrenergic receptor activation. Atrogi’s Cell publication provided validation that GRK2-biased β2-AR agonism can decouple the metabolic and muscle-related benefits from cardiovascular risk, a result that underpins the current trial’s rationale. The Copenhagen study is designed to interrogate the specific downstream effectors — GRK, cAMP/PKA, and β-arrestin pathways — in human muscle tissue, generating mechanistic data that would be difficult to obtain outside a dedicated physiology-focused trial. The obesity treatment landscape has been reshaped by incretin-based therapies. Semaglutide (Wegovy, Novo Nordisk), approved in 2021, and tirzepatide (Zepbound, Eli Lilly), approved in 2023, deliver 15–22% body weight reductions. An oral formulation of semaglutide for obesity was approved in December 2025. All current pharmacotherapies operate primarily through appetite suppression and caloric intake reduction. None specifically target muscle preservation. Studies indicate that 25%-40% of total weight lost with GLP-1 agonists can be lean body mass, raising concerns about sarcopenia, frailty, and metabolic deterioration, particularly in older adults. No pharmacotherapy is currently approved for sarcopenia itself. ATR-258, as an oral obesity treatment that aims to simultaneously promote fat loss and muscle gain through a mechanistically distinct pathway, would address a gap that existing incretin therapies do not. No other GRK-biased β2-adrenergic receptor agonists are in active clinical development for obesity or muscle-sparing weight loss, according to public data. The closest conceptual competitor addressing muscle loss during weight reduction is bimagrumab, an anti-activin type II receptor antibody acquired by Eli Lilly. Bimagrumab operates through an entirely different mechanism — blocking myostatin/activin signaling to prevent muscle catabolism — and requires intravenous infusion. A Phase II trial combining bimagrumab with semaglutide showed lean mass preservation, but Lilly terminated one of its Phase II studies for the molecule in 2025 for strategic reasons. The broader obesity pipeline remains dominated by incretin-based approaches: Eli Lilly’s retatrutide (a triple GIP/GLP-1/glucagon agonist) is in late-phase development, and multiple companies are advancing oral GLP-1 formulations. These programs pursue appetite and energy balance modulation rather than direct muscle anabolism. ATR-258 potentially occupies a distinct position as an oral small molecule that attempts to achieve both fat loss and muscle gain through a single mechanism. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website