PatentVest Pulse is the pathway-intelligence series from PatentVest, the integrated IP strategy, IP law, and IP portfolio management firm built around a proprietary research and data platform covering 150M+ patent publications, clinical pipeline data, and deal flow across every major therapeutic area.

Most IP reports tell you what has been filed. This one tells you what the filings mean. Where the thickets are forming, which estates are anchored to clinical assets versus sitting latent, where freedom-to-operate is about to get expensive, which players are assembling licensing-in positions, and which are quietly building a royalty claim against every molecule that reaches the market.

Report #4 in this series mapped the triple-agonist pathway — the drugs racing to push obesity pharmacotherapy past 25% weight loss into surgical-substitute range. Report #5 maps the layer that sits on top of those drugs. If the triple agonist story is about how much weight comes off, the myostatin and ActRII story is about what comes off with it. Twenty percent of the weight a patient loses on semaglutide is lean mass. The category we map here is the engineered response to that statistic — the body-composition modifier that converts that twenty percent from muscle into fat.

If you are running a myostatin or ActRII obesity program, evaluating one to license in, building a competitive follow-on, or making a decision about how to position your GLP-1 franchise against the muscle-preservation argument, the IP structure underneath this category is the largest variable in your outcome over the next decade. This report is the starting point.

When a patient loses 50 pounds on Ozempic or Mounjaro, somewhere between 20 and 30 of those pounds is fat, and somewhere between 12 and 15 of them are lean body mass — everything in the body that isn't fat or bone, including muscle, organs, glycogen, and water. For a healthy 45-year-old losing weight over twelve months, that loss is mostly appropriate adaptation; the body is shedding what it no longer needs to support a smaller frame. For an 80-year-old, a chronic kidney disease patient, or any of the millions of people now planning to stay on a GLP-1 indefinitely, the loss of muscle becomes a real clinical problem.

Myostatin and ActRII inhibitors are the engineered response. Myostatin is the body's natural hormone for keeping muscle from growing too much; activin A does a similar job and also suppresses fat burning. Block them, and the math of a GLP-1 changes. Where semaglutide alone produces 15% weight loss that is roughly 70% fat and 30% lean, semaglutide plus a myostatin-blocking antibody produces about the same weight loss that is 90 to 95% fat — or, in the most aggressive combinations now in trials, 22% weight loss that is over 90% fat. Three large Phase 2 trials in the past twelve months have established that the science works. Eli Lilly paid $1.9 billion in 2023 to buy Versanis Bio. AstraZeneca paid up to $300 million in October 2025 to buy SixPeaks Bio. Twenty programs are now in development behind them. This report maps every one, every deal, and the patent layer that sits underneath.

• The "GLP-1 sarcopenia" problem is real but contested. SURMOUNT-1's DEXA substudy (published February 2025) found that tirzepatide-induced weight loss is approximately 25% lean body mass at 72 weeks. Semaglutide's STEP-1 substudy was meaningfully worse, at approximately 45%. Whether this is harmful sarcopenia or appropriate adaptive physiology depends on the patient. For a 50-year-old with BMI 35 losing 20% of body weight, the loss is consistent with classical body-composition principles. For an 80-year-old or a CKD patient, the lean mass loss can tip into clinically meaningful sarcopenia.
• Bimagrumab plus semaglutide hit 22.1% weight loss with 92.8% from fat. The BELIEVE Phase 2b trial (n=507, 72 weeks) published in Nature Medicine in early 2026 produced the cleanest readout in the category. Bimagrumab monotherapy alone caused 10.8% weight loss with a 2.5% lean mass gain. Combined with semaglutide 2.4 mg, total weight loss reached 22.1%, with visceral fat down 58.2%. This is the headline data point for the entire space.
• Apitegromab preserved 55% of lean mass loss on top of tirzepatide. Scholar Rock's EMBRAZE Phase 2 trial readout in June 2025 (n=100, 24 weeks) showed apitegromab 10 mg/kg preserved an additional 4.2 lbs (1.9 kg) of lean mass versus tirzepatide alone, with weight loss only modestly lower (12.3% vs 13.4%). The trial established myostatin-selective monoclonals as the cleaner, lower-risk side of the category.
• Regeneron's triplet hit 80.9% lean mass preservation. The COURAGE trial (n=999) read out full data at EASD in September 2025. Trevogrumab (anti-myostatin) plus semaglutide alone preserved roughly 51% of would-be lean mass loss. Adding garetosmab (anti-activin A) on top — the "triplet" arm — preserved 80.9%, with 92.6% of weight loss coming from fat mass and 27.3% more total fat loss than semaglutide alone. The triplet also carried 28.3% discontinuation — the highest tolerability cost in the class.
• Bimagrumab is the only drug in the class that works alone. Pan-ActRII receptor blockers (bimagrumab, Laekna's LAE-102, Keros's KER-065, SixPeaks/AstraZeneca's bispecific) reduce fat as well as preserve muscle, because activin A signaling on adipocytes suppresses lipolysis. Pure anti-MSTN antibodies (apitegromab, trevogrumab, taldefgrobep, emugrobart) preserve muscle but do not enhance fat loss on top of a GLP-1.
• The Lilly-Versanis acquisition gave Lilly the broadest method-of-use position in the field. The Versanis patent estate (US20190345251 and the EP4358995A1 family) claims the use of myostatin, activin, or ActRII antagonists for obesity and body composition — language broad enough that, if it withstands obviousness challenges, gives Lilly a colorable royalty claim against any anti-MSTN or ActRII molecule used in obesity. Combined with bimagrumab's underlying composition patents (priority ~2009, base U.S. expiry ~2029–2030 plus up to five years patent-term extension), Lilly is positioned as the IP center of gravity.
• AstraZeneca's $300M SixPeaks acquisition (October 2025) is the second major validation. SixPeaks Bio, a Versant-incubated Basel biotech, was acquired by AstraZeneca for $170M upfront, $30M deferred, and up to $100M in regulatory milestones. The asset is a bispecific ActRIIA/ActRIIB antibody engineered to avoid the BMP9/BMP10 cross-talk that killed Acceleron's ACE-031 program in 2013.
• The Veru FDA precedent (September 2025) reset the regulatory path for the entire category. Veru's meeting with the FDA on enobosarm established that incremental weight loss on top of a GLP-1 is an acceptable primary endpoint for muscle-preservation programs. Body composition as a primary endpoint is still not approvable on its own; incremental weight loss with muscle preservation as a secondary is the path.
• Twenty programs are in development. Twelve of them have a GLP-1 combination strategy. Bimagrumab (Lilly), apitegromab and SRK-439 (Scholar Rock), trevogrumab and garetosmab (Regeneron), taldefgrobep (Biohaven), emugrobart (Roche/Chugai), LAE-102 (Laekna with Lilly), KER-065 (Keros), and several preclinical programs. None of the assets produce meaningful weight loss alone; all are positioned as adjuncts.
• Activin E is the next frontier. Human genome-wide association studies have identified loss-of-function variants in INHBE (the gene for activin E) that protect from abdominal obesity. iBio's IBIO-610 is the first dedicated anti-activin E antibody in development, planning Phase 1 in 2027. Lilly, Novo, and Regeneron all have undisclosed INHBE-related filings.

1.0 Why This Pathway, Why Now

The obesity drug market crossed $50 billion in 2024 on the back of two molecules: semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). The strategic conversation inside every pharma since mid-2024 has been about what comes next. Report #4 in this series mapped the triple-agonist answer — retatrutide and the twenty-six programs chasing surgery-level weight loss. This report maps the other answer: the layer that sits on top of any GLP-1 and changes the quality of the weight loss, not the amount.

By April 2026, more than fifteen million Americans had been on a GLP-1 receptor agonist for obesity or type 2 diabetes. The clinical conversation has shifted decisively from acute weight loss to chronic maintenance. Once you accept indefinite chronic dosing, the question of what gets lost during that loss becomes a clinical issue with a long time horizon. Twelve months of GLP-1 therapy in a 50-year-old looks one way. Sixty months in a 65-year-old looks different. Sixty months in an 80-year-old looks different again.

The data on what actually gets lost is now sufficient to anchor a category. The SURMOUNT-1 DEXA substudy reported that tirzepatide-induced weight loss at 72 weeks was approximately 25% lean body mass. Semaglutide is meaningfully worse — the STEP-1 substudy and a 2026 SEMALEAN prospective cohort study both place the lean mass fraction at roughly 35–45%. The directional signal is unambiguous: a meaningful fraction of GLP-1 weight loss is muscle, and for the population subgroups that matter most, it is enough muscle to drive clinical outcomes.

Myostatin and ActRII inhibitors are the engineered response. The mechanism is straightforward: myostatin is the body's principal hormone for restricting muscle growth, and activin A is a related ligand that signals through the same receptor family with effects on both muscle and adipose tissue. Block them — either by binding the ligands themselves with a monoclonal antibody or by blocking their receptor — and protein synthesis in muscle rises, atrophy-related ubiquitin ligases fall, lipolysis in fat tissue increases, and the math of a GLP-1's weight loss tilts toward fat and away from lean.

2.0 The Muscle Paradox

Before bimagrumab, the myostatin pathway had a twenty-year reputation for killing drug programs. The arc from villain to engine is the second most interesting scientific story in metabolic disease in the last decade, after the glucagon arc mapped in Report #4.

For twenty years, pharma tried to use myostatin-blocking drugs to grow muscle in patients who were losing it from disease — muscular dystrophy, ALS, inclusion body myositis, age-related sarcopenia. Every major program failed. The drugs grew muscle volume on MRI but didn't make patients stronger or more functional. The pathway was written off as biologically interesting but clinically useless. Then in 2021, an academic study in obese diabetics tested one of these failed drugs (bimagrumab) for the first time in a metabolic indication. Patients gained muscle and lost fat at roughly the same rate, so they looked the same on the scale but had transformed their bodies underneath. That observation reframed the entire mechanism.

2.1 The Sarcopenia Graveyard (2004–2019)

The biological case for blocking myostatin was unusually strong, anchored on three unambiguous human observations. In 2004, the New England Journal of Medicine reported the case of a German child carrying a homozygous loss-of-function mutation in the myostatin gene who was visibly muscular from birth. Belgian Blue and Piedmontese cattle, breeds famously selected for double-muscling, were both homozygous for naturally occurring myostatin mutations. The signal was clear: lose myostatin function, gain muscle.

Wyeth ran the first major clinical program. Stamulumab (MYO-029) reached Phase 1/2 in adult muscular dystrophy patients in 2008. It was safe and well-tolerated. It did not improve strength. Pfizer followed with domagrozumab in Duchenne muscular dystrophy; it was terminated in August 2018 after failing the four-stair-climb endpoint. Acceleron's ACE-031 reached Phase 2 in DMD before being halted in 2013 over epistaxis and telangiectasias. And in 2016, Novartis's bimagrumab read out the RESILIENT trial in sporadic inclusion body myositis — the drug had increased muscle volume on MRI by a meaningful margin, but did not improve 6-minute walk distance. By 2019, the received wisdom was that myostatin inhibition reliably grew muscle volume but failed to improve clinical function.

2.2 The Heymsfield Accident (2021)

The reframing started accidentally, in a single Phase 2 trial in a different indication. In 2021, Steven Heymsfield and colleagues at Pennington Biomedical Research Center published a study in JAMA Network Open testing bimagrumab in adults with type 2 diabetes and obesity. The trial enrolled 75 patients on stable diabetes medication, randomized to bimagrumab or placebo for 48 weeks.

What stood out was the body composition data. Patients on bimagrumab lost an average of 7.5% of their total body fat (−20.5% in absolute terms) while gaining 3.6% in lean body mass. Total body weight changed by less than two percent on average — they looked roughly the same on the scale — but the composition of their bodies had been re-engineered. Visceral adipose tissue fell by approximately 25%. That trial was the inflection point. Atlas Venture and Medicxi, working with Aditum Bio, spun bimagrumab out of Novartis into Versanis Bio in August 2021 with a $70 million Series A. Two years later, Lilly announced the acquisition of Versanis for up to $1.925 billion.

2.3 The 2025–2026 Triple Validation

Three trials in the past twelve months established the category as real.

In June 2025, Scholar Rock reported topline results from EMBRAZE: apitegromab preserved 54.9% of the lean mass that the tirzepatide-only group lost, with tolerability matching placebo. In September 2025, Regeneron presented full COURAGE data at EASD: the triplet of trevogrumab plus garetosmab plus semaglutide preserved 80.9% of lean mass, produced 27.3% deeper fat loss than semaglutide alone, but carried 28.3% discontinuation. In early 2026, Lilly published BELIEVE in Nature Medicine: 507 patients, 72 weeks, bimagrumab plus semaglutide producing 22.1% weight loss with 92.8% from fat and visceral adipose down 58.2%.

Three trials, three positive readouts, three different mechanisms, three different background GLP-1s. The pattern was unambiguous. The category was no longer hypothetical.

3.0 The Twenty Programs

The myostatin/ActRII field is meaningfully smaller than the triple-agonist field mapped in Report #4 — roughly twenty programs versus twenty-seven — but more concentrated among large-pharma players. The field is anchored on four U.S. and European pharmaceutical companies (Lilly, Regeneron, Roche, AstraZeneca via SixPeaks), two well-financed U.S. biotechs (Scholar Rock, Biohaven), and a smaller number of Chinese and Korean entrants.

3.1 Three Features Worth Mentioning

• The ActRII versus MSTN-selective wedge is the most important strategic distinction in the field. Pan-ActRII receptor blockers (bimagrumab, LAE-102, KER-065, SixPeaks/AZ, Supercede) reduce fat mass on top of preserving muscle, because activin A signaling on adipocytes suppresses lipolysis. Pure anti-MSTN antibodies (apitegromab, trevogrumab, taldefgrobep, emugrobart, SRK-439, IBIO-600) preserve muscle but do not enhance fat loss versus a GLP-1 alone. The commercial winner will likely be whichever class delivers the right tolerability-versus-efficacy ratio for chronic indefinite dosing.
• The category contains two of the only oral routes in obesity pharmacotherapy. Supercede SPCD-4-79 is the only oral small-molecule ActRII inhibitor. The PeptiDream / Kawasaki oral macrocyclic peptide is the only oral peptide myostatin inhibitor in IND-stage development. In a market where every clinically advanced obesity drug requires injection, the first oral muscle-preservation agent to demonstrate sufficient bioavailability will collapse a meaningful compliance barrier.
• Activin E is the next frontier. iBio's IBIO-610 is the first clinical anti-activin E antibody. Activin E signals through ALK7 on adipocytes and is functionally a fat-mobilizer; loss-of-function variants in the INHBE gene are protective against abdominal obesity by human GWAS. If activin E blockade produces meaningful fat loss as monotherapy, it would be the first "third-mechanism" obesity drug in the lineage of incretins and ActRII blockade.

4.0 Asset Profiles

Individual drug profiles organized by phase and strategic centrality. Each profile covers mechanism, clinical status, key data, differentiation, and IP positioning.

4.1 Bimagrumab — Eli Lilly & Co. (via Versanis Bio)

Bimagrumab (BYM338, LY3985863) is a fully human monoclonal antibody that binds the type II activin receptors ACVR2A and ACVR2B with high affinity, preventing their engagement by all of the relevant ligands — myostatin, activin A, activin B, and GDF11. Originally developed at Novartis, it failed its registrational trial in sporadic inclusion body myositis in 2016. Atlas Venture and Medicxi spun it into Versanis Bio in 2021. Eli Lilly acquired Versanis in August 2023 for up to $1.925 billion.

4.2 Apitegromab — Scholar Rock, Inc. (SRRK)

Apitegromab (SRK-015) is a fully human IgG4 monoclonal antibody that selectively binds the pro-form and latent-form complexes of myostatin — not mature active myostatin, not GDF11, not activin A. The result is the highest-selectivity anti-myostatin antibody in the field. Its lead indication is spinal muscular atrophy (PDUFA September 30, 2026 after BLA resubmission), with obesity as a parallel clinical development track.

4.3 Trevogrumab and Garetosmab — Regeneron Pharmaceuticals, Inc. (REGN)

Trevogrumab (REGN1033) is a fully human anti-myostatin monoclonal antibody. Garetosmab (REGN2477) is a fully human anti-activin A monoclonal antibody. The two molecules are clinically combined in the COURAGE Phase 2 obesity program. Garetosmab is independently approved-pending for fibrodysplasia ossificans progressiva under Priority Review (OPTIMA Phase 3: >99% reduction in heterotopic ossification).

CoM base expiry: late 2033–2034 with possible PTE to 2038–2039. The post-COURAGE combination filings are the most strategically contested layer of the IP map.

4.4 Taldefgrobep alfa — Biohaven Pharmaceutical (BHVN)

Taldefgrobep alfa (BHV-2000) is a recombinant fusion protein consisting of an anti-myostatin adnectin (fibronectin tenth type III domain scaffold) joined to a human IgG1 Fc fragment. The molecule is approximately 80 kDa versus a full antibody's ~150 kDa. The ownership chain: BMS originated it → partnered to Roche for SMA (RG-6206) → Roche returned to BMS → BMS licensed worldwide rights to Biohaven in February 2022, retaining tiered high-teens royalties.

The Phase 3 RESILIENT trial in SMA missed its primary endpoint in November 2024. Biohaven pivoted to obesity: Phase 2 monotherapy trial (NCT07281495, n=150) enrollment complete March 2026, topline expected H2 2026. This is the most-watched Phase 2 of 2H 2026 — a pure anti-myostatin monotherapy readout without GLP-1 confounding.

4.5 Emugrobart — Roche / Chugai Pharmaceutical

Emugrobart (GYM-329, RG-6237) is a recombinant humanized anti-myostatin "sweeping antibody" built on Chugai's recycling-antibody platform. The MANATEE Phase 2/3 in SMA was discontinued in March 2025/2026 after Part 1 failed to show benefit over risdiplam alone. Roche's rationale for continuing the obesity Phase 2: obesity has higher circulating myostatin and different pathophysiology than neuromuscular disease. Phase 2 obesity data expected 2026.

4.6 LAE-102 — Laekna Pharmaceuticals (2105.HK)

LAE-102 is a selective anti-ACVR2A monoclonal antibody — distinct from bimagrumab in that it does not bind ACVR2B. The selectivity hypothesis: ACVR2A blockade is sufficient for muscle preservation and fat mobilization without engaging ACVR2B-mediated cardiac and vascular signaling. Phase 1 MAD (China) produced preliminary positive data at ADA 2025. Clinical collaboration with Eli Lilly announced November 2024 — Lilly provides funding and clinical expertise via Catalyze360-ExploR&D; Laekna retains worldwide rights. This is Lilly's hedge against bimagrumab's pan-ActRII pharmacology.

4.7 KER-065 / Rinvatercept — Keros Therapeutics (KROS)

KER-065 is a chimeric activin A/myostatin/TGF-beta ligand trap engineered to avoid BMP9/BMP10 cross-reactivity. Phase 1 healthy-volunteer study: increases in lean mass and bone mineral density, decreases in fat mass, well-tolerated. Phase 2 in DMD initiated Q2 2026. Obesity Phase 2 deprioritized following Keros's April 2025 strategic review, which concluded with a $375M capital return rather than a sale. KER-065 retains obesity optionality.

4.8 SRK-439 — Scholar Rock

Scholar Rock's next-generation selective anti-pro/latent-myostatin antibody, designed specifically for obesity with a less frequent dosing schedule than apitegromab. IND cleared Q4 2025; first-in-human SAD initiated late 2025 in healthy volunteers. SAD/MAD readout expected 2026. Phase 2 obesity GLP-1 combination trial contingent on positive PK and target engagement.

4.9 IBIO-600 — iBio, Inc. / AstralBio (IBIO)

A long-acting anti-myostatin monoclonal antibody engineered for extended half-life via Fc modification. Australian TGA clearance April 2026. First participant dosed June 2, 2026 — iBio became a clinical-stage company. Phase 1 SAD in approximately 32 overweight/obese adults with nine-month follow-up. In-licensed from AstralBio in January 2025 for $750K upfront (stock) and up to $28M in milestones. The broader iBio/AstralBio pipeline also includes a MSTN × Activin A bispecific (IND-equivalent H1 2027) and IBIO-610, an anti-activin E antibody (IND-equivalent 2H 2026).

4.10 PeptiDream Oral Macrocyclic Myostatin Peptide

A series of macrocyclic and bridged-macrocyclic peptide inhibitors of myostatin developed by PeptiDream in collaboration with Kawasaki Medical School. Selective for myostatin over GDF11. Designed for daily or weekly oral dosing. Preclinical data showed the oral peptide preserved lean mass in diet-induced obese mice on background semaglutide. The only oral peptide myostatin inhibitor in clinical-stage development. PeptiDream is actively seeking a licensing partner.

4.11 SixPeaks Bio Bispecific — AstraZeneca (AZN)

A bispecific monoclonal antibody targeting both ACVR2A and ACVR2B simultaneously, engineered to avoid the BMP9/BMP10 cross-reactivity that contributed to the Acceleron ACE-031 vascular signal. Founded 2022 by Versant Ventures' Ridgeline Discovery Engine in Basel. Emerged from stealth May 2024 with $30M Series A plus up to $80M non-dilutive AstraZeneca support. AstraZeneca exercised its acquisition option on October 22, 2025: $170M upfront, $30M deferred, up to $100M in regulatory milestones — $300M total. Clinical entry expected 2026–2027.

4.12 ImmuneOnco IMC-010 — GLP-1R × ACVR2A Bispecific

A bispecific monoclonal antibody combining GLP-1R agonism with ACVR2A antagonism in a single molecule — the only single-molecule GLP-1 plus muscle-preservation combination in the clinical pipeline. If the format is tractable, it would be the most differentiated commercial product in the field. First patient dosed December 2024.

4.13 EL-22 and EL-32 — PMGC / NorthStrive / MOA Life Plus

Engineered probiotic bacteria expressing myostatin antigen (EL-22) or dual myostatin and activin A antigens (EL-32) on their surface — the most architecturally distinctive modality in the field. EL-22 completed Korean Phase 1 in healthy volunteers (safe and well-tolerated). FDA pre-IND meeting in Q2 2025 with positive feedback supporting a U.S. Phase 2 in combination with a GLP-1 RA. EL-32 in preclinical.

4.14 Supercede Therapeutics SPCD-4-79

An orally bioavailable small-molecule inhibitor of the ActRII receptor pair (ACVR2A and ACVR2B). Preclinical data in diet-induced obese mice: monotherapy reduced fat mass, liver mass, liver fat, and body weight; combination with semaglutide drove up to 74% fat mass reduction and 36% body weight reduction. The only oral small-molecule ActRII inhibitor in development.

5.0 What Breaks Next (The Muscle Thesis at Population Scale)

Three Phase 2 readouts established that the science works. The commercial question is whether the muscle-preservation thesis holds up at population scale — in the real-world patient cohort, with real-world adherence, real-world dosing, and the trial-to-clinic compression that broke the triple agonist headline numbers down from 28.7% to a 17–22% real-world average.

5.1 Real-World Lean Mass Loss Is More Variable Than Trial DEXA Suggests

The trial DEXA numbers are clean and tightly controlled. SURMOUNT-1's tirzepatide arm lost 25% of body weight as lean mass at 72 weeks; STEP-1's semaglutide arm lost roughly 45%. In the real world, the variability is broader. The 2026 medRxiv body-composition digital phenotyping paper analyzing routine clinical care reported that tirzepatide drives greater lean body mass decline in real-world patients than in SURMOUNT-1. Some patients lose almost no lean mass on a GLP-1; some lose 50% or more.

The 2026 SEMALEAN prospective cohort study added a complicating layer: the percentage of sarcopenic obesity in the cohort fell from 49% at baseline to 33% at twelve months, because patients lost so much fat that even with some lean loss, their muscle-to-fat ratio improved. The muscle-preservation argument may only hold in older, frailer, or longer-term patients — which is a smaller commercial market than the headline "everyone on a GLP-1" framing implies.

5.2 The DEXA Interpretation Problem

DEXA does not measure muscle. It measures lean soft tissue — skeletal muscle, smooth muscle, viscera, glycogen-bound water, extracellular fluid, connective tissue, and skin. In an obese patient losing 20% of body weight on a GLP-1, the liver de-steatoses, the splanchnic mass shrinks, glycogen stores deplete, edema resolves. All of this registers on DEXA as "lean mass loss," but none of it is sarcopenia. The 2025 SURPASS-3 MRI substudy in Lancet Diabetes & Endocrinology measured discrete skeletal muscle volume directly: muscle volume loss was roughly proportional to total weight loss, intramuscular adipose infiltration fell, and the remaining muscle was qualitatively cleaner.

5.3 The Tolerability Cost of Triplet Regimens

The COURAGE triplet's discontinuation rate was 28.3% — more than four times higher than semaglutide alone in trial conditions. Garetosmab carries the activin A blockade safety signature: epistaxis, skin abnormalities, and a numerical mortality imbalance flagged by the FDA in the LUMINA-1 FOP trial. The strategic implication: the highest-efficacy regimens may not be the highest-commercial-share regimens. The selective myostatin antibodies (apitegromab, trevogrumab-mono, taldefgrobep) preserve roughly half of lean mass loss with substantially cleaner tolerability.

5.4 The FDA Endpoint Question and the Veru Precedent

The most important regulatory development of 2025 for the muscle-preservation category was the September 2025 FDA meeting on Veru's enobosarm, which established that incremental weight loss on top of a GLP-1 is an acceptable primary endpoint for muscle-preservation programs. Every Phase 3 in the category will now follow this playbook: head-to-head "GLP-1 alone versus GLP-1 plus muscle-preservation agent," with incremental percent body weight reduction as primary and DEXA-based lean mass preservation as secondary.

5.5 Who Wins, Who Loses

The triple agonists (Report #4) compete on absolute weight loss; the muscle-preservation combinations compete on body composition and long-term functional outcomes. Both categories may grow together rather than substitute. The losers are the pure GLP-1 monotherapies that have nothing on the lean-mass side. Lilly is integrating bimagrumab into its obesity portfolio and will offer the combination as a higher-priced premium product. Novo Nordisk, having no internal muscle-preservation asset, is exposed to the relative deterioration unless it executes a Versanis-scale acquisition. The most exposed mid-cap obesity players are those with dual GLP-1/GIP or dual GLP-1/glucagon assets that have neither the triple agonist's headline weight loss nor the muscle preservation's body composition argument.

6.0 Deals, Money, and Who Owns What

The Lilly-Versanis deal ($1.9B, July 2023) was the category's foundational transaction — Lilly's most aggressive bet on the body-composition layer, adding the muscle-preservation modality to a portfolio that already included tirzepatide and retatrutide. The September 2025 termination of the bimagrumab + tirzepatide T2D Phase 2b before enrollment introduces ambiguity; the BELONG readout in 2H 2026 will resolve it.

AstraZeneca's SixPeaks acquisition ($300M, October 2025) was AZ's entry into the category at an earlier stage than Lilly's Versanis play. Combined with AZ's ~$18B China-sourced incretin portfolio from CSPC in late 2025, the company now holds both halves of the muscle-preservation-plus-incretin combination.

Notably absent: Novo Nordisk. No disclosed muscle-preservation asset, no announced license, no announced acquisition. In a category where Lilly has a $1.9B position and AstraZeneca has a $300M position, Novo's silence is conspicuous. The market expects movement on this axis in 2026–2027.

7.0 Efficacy Comparison: Lean Mass Preservation and the Quality of Loss

7.1 The Tolerability-Versus-Efficacy Tradeoff

The field separates into three tiers by efficacy-tolerability profile. Tier 1 (Highest efficacy, highest tolerability cost): Pan-ActRII combinations and the COURAGE triplet — 22% weight loss / 93% fat fraction / 80% lean preservation, but with discontinuation rates in the 20–30% range. Tier 2 (Strong efficacy, clean tolerability): Selective MSTN antibodies (apitegromab + tirzepatide, trevogrumab + sema) — 12–13% weight loss / 85% fat fraction / 50–55% lean preservation, tolerability matching GLP-1 alone. Tier 3 (Pending): Phase 1 readouts across 2026–2027.

Our best guess: the selective MSTN antibodies will dominate the broader market, while the pan-ActRII combinations will dominate the high-acuity segment where the efficacy is worth the cost.

8.0 IP Strategy by Player

The patent landscape around myostatin, ActRII, and activin A inhibition spans an estimated 600 to 900 publications across 150 to 200 INPADOC families. Three layers of IP history compress into the current commercial picture: a 1997–2005 foundational layer rooted at Johns Hopkins, Wyeth, Acceleron, and MetaMorphix; a 2008–2018 antibody composition-of-matter wave; and a 2021–2026 obesity method-of-use and GLP-1 combination layer where the most strategically important new claims are being filed and contested.

8.1 The Broadest Position: Lilly via Versanis

Lilly's bimagrumab composition estate (WO2010/125003 family, priority ~2009) runs to a U.S. base expiry of approximately 2029–2030 with up to five years patent term extension. The Versanis-era obesity method-of-use family (US20190345251 and EP4358995A1, priority ~2018) claims the use of myostatin, activin, or ActRII antagonists for obesity and body composition — language broad enough that, if it withstands obviousness challenges, gives Lilly a colorable royalty claim against any anti-MSTN or ActRII molecule used in obesity, not just bimagrumab. The estate provides a defensible position across composition, indication, and combination layers through approximately 2038–2039.

8.2 The Combination Patentability Question

The most important strategic IP question in the field is whether the use of an anti-myostatin or ActRII antagonist in combination with a GLP-1 receptor agonist for obesity is patentable as a method of use. The 2002 Lee & McPherron body-composition paper plus 2014 academic publications showing GLP-1 plus ActRII synergy create a non-trivial obviousness wall against the broadest possible combination claims. The field will likely settle on narrow per-regimen claims (specific antibody-pair-with-specific-GLP-1-with-specific-dose-ratio). Lilly is best positioned. Regeneron has defensible narrow combination claims. Scholar Rock benefits from platform-level manufacturing IP that gives it leverage in any cross-license negotiation.

8.3 Where the White Space Is

• Activin E composition and method. iBio's IBIO-610 is the only dedicated clinical activin E asset, but the INHBE method-of-use space is wide open. Lilly, Novo, and Regeneron all have undisclosed INHBE filings. The first comprehensive activin E composition + method estate built around a clinical asset will be a Versanis-equivalent IP position for the next decade.
• Bispecific architectures combining incretin agonism with myostatin blockade. ImmuneOnco's IMC-010 (GLP-1R × ACVR2A) may sidestep existing combination claims if structured as a single molecule. The first five bispecific filings combining incretin agonism with myostatin pathway blockade will be disproportionately valuable.
• Long-acting formulation and delivery claims. The chronic indefinite-dosing nature of obesity therapy makes once-monthly, once-quarterly, and implantable dosing valuable. iBio's HLE platform and the broader long-acting Fc-engineering space are early filings; the implantable depot space is essentially uncovered.
• Indication expansion. Sarcopenic obesity in older patients, post-bariatric maintenance, chronic kidney disease, cancer cachexia — each is a separate label expansion opportunity. The methods-of-use filings on those indications will be worth more in 2030–2035 than the composition claims.

9.0 Open Questions and What We're Watching

Five things will determine how this pathway plays out over the next eighteen months.

10.0 The IP Layer Decoded: What the Filings Actually Tell You

10.1 If You Are a Sponsor With an Active Program

Three questions matter more than any other. First, does your composition-of-matter claim survive the prior-art layer from Wyeth/Pfizer (stamulumab, domagrozumab), Acceleron (ACE-031, sotatercept, luspatercept), and the original Lee & McPherron Johns Hopkins estate? Second, does your obesity method-of-use claim avoid the Lilly/Versanis broad combination filing or carve out specific defensible regimen claims? The cheapest path to a defensible method-of-use position is narrow specificity: a particular antibody at a particular dose with a particular GLP-1 at a particular dose ratio. Third, have you filed continuation and divisional applications on the second-wave method-of-use applications — cardiovascular outcomes, MASH, sarcopenic obesity in older patients, post-bariatric maintenance, chronic kidney disease, cancer cachexia? Each is a separate label expansion opportunity.

10.2 If You Are Evaluating a Molecule to License In

The composition claim tells you what molecule you are buying — necessary but insufficient. A serious diligence pass must answer: whether the estate covers the formulation you intend to commercialize; whether it blocks the most likely fast-follower design-arounds; whether freedom-to-operate is clear against Lilly/Versanis's obesity method-of-use family and post-COURAGE Regeneron combination filings; and whether the estate is structured to support geographic expansion. The China estate is rarely as deep as the U.S./EU estate; supplementary protection certificate strategies in the EU are particularly underdeveloped in this category.

10.3 If You Are an Investor Evaluating the Category

Scholar Rock at a ~$5.9B market cap in mid-2026 prices in SMA approval plus an obesity option value of perhaps $2–3B. If apitegromab launches in SMA in September 2026 and the obesity strategy reaches Phase 3 in 2027, the stock could rerate to $8–12B — a credible 50–100% return scenario. Biohaven (BHVN) at $9.26 in mid-2026 prices in essentially zero credit for the taldefgrobep obesity Phase 2; a positive H2 2026 readout could double the stock. Keros (KROS) is the post-capital-return runoff trade with KER-065 as embedded optionality. The cleanest pure-play exposure is Scholar Rock and Biohaven, with Scholar Rock being the higher-quality risk and Biohaven being the higher-leverage option.

10.4 The Five Patent-Layer Bets Worth Watching

• GLP-1 + MSTN/ActRII combination method-of-use filings. Lilly via Versanis holds the broadest filing; Regeneron has parallel narrower filings. The 2026–2027 prosecution decisions at the USPTO and EPO are the most strategically important regulatory events in the category.
• Bispecific architectures. IMC-010 (GLP-1R × ACVR2A) and SixPeaks/AstraZeneca's GLP-1-peptide + ActRII-antibody conjugate may sidestep existing combination claims if structured as single molecules. The first five bispecific filings combining both mechanisms will be disproportionately valuable.
• Activin E composition and method. IBIO-610 is the first dedicated activin E clinical asset. The INHBE method-of-use space is wide open. The first comprehensive activin E estate built around a clinical asset will be a Versanis-equivalent IP position.
• Tissue-selective delivery and engineered antibody architectures. Adipose-preferential or muscle-preferential targeting would unlock therapeutic windows no current molecule can achieve.
• Long-acting formulation and delivery claims. The chronic indefinite-dosing nature of obesity therapy makes once-monthly, once-quarterly, and implantable dosing valuable. The implantable depot and device space is essentially uncovered.

11.0 The Bottom Line

The science is settled. Three Phase 2 readouts in the past twelve months — BELIEVE, EMBRAZE, COURAGE — have established that blocking myostatin and/or activin A while a patient is on a GLP-1 changes the composition of weight loss in clinically meaningful ways. Bimagrumab plus semaglutide produced 22.1% weight loss that was 92.8% fat. Apitegromab on top of tirzepatide preserved 55% of lean mass loss with no tolerability cost. The Regeneron triplet preserved 80.9% with a real tolerability cost. The Lilly-Versanis $1.9 billion acquisition in 2023 validated the category commercially; the AstraZeneca-SixPeaks $300 million acquisition in October 2025 confirmed it.

The commerce is harder. Real-world adherence on chronic GLP-1 maintenance is already a binding constraint at 50% one-year persistence. Stacking a second injection on top of a GLP-1 increases the compliance burden in ways that have not yet been measured in real-world studies. The strongest-efficacy regimens carry tolerability costs that may not survive the chronic indefinite-dosing demands of obesity care. The cleanest commercial path is probably the selective MSTN antibodies with their tolerability matching placebo, even if the lean preservation magnitudes are lower.

The IP is what survives. The bimagrumab composition patent expires in 2029–2030 with PTE possibly extending to 2034–2035. The Versanis obesity method-of-use filing runs to 2038–2039. The Regeneron COURAGE-derived combination patents will prosecute through 2026–2027 with expiry in the late 2030s. The Scholar Rock platform manufacturing patents run through the mid-to-late 2030s. The molecules will eventually face biosimilar competition. The combination claims, the formulation claims, and the indication-expansion claims are the IP positions that will still be generating revenue in 2040. Lilly is best positioned through the Versanis estate. Regeneron is best positioned with narrow defensible combination claims. Scholar Rock has the platform leverage. Pfizer and Bristol Myers Squibb sit on latent positions that could be activated rapidly through a single acquisition.

The story of the GLP-1 era was whether the drugs work. The story of the muscle-preservation era is which quality of weight loss patients actually want, and who owns the right to provide it.

PatentVest Pulse. Pathway Intelligence Report, Beyond GLP-1 Series, Report #5 of 12. June 2026. © PatentVest.
PatentVest is an integrated IP strategy, IP law, and IP portfolio management firm. Contact: [email protected]