The domestically developed weight loss and muscle growth compound LAE102 is making significant strides toward becoming a best-in-class (BIC) contender. On September 29, 來凱醫藥-B (02105) released Phase I clinical trial results of its LAE102 compound, revealing that patients in the 6 mg/kg dosage group experienced an average lean body mass increase of 1.7% and a decrease in fat mass by 2.2% over five weeks; lean body mass adjusted for placebo increased by 4.6%, with an average fat mass reduction of 3.6%.
It's important to note the increasing global activity in weight loss-related deal-making: from Eli Lilly's $1.92 billion acquisition of Versanis Bio (Bimagrumab) to Novo Nordisk and Septerna's $2.2 billion deal for an oral small molecule, and Pfizer's $4.9 billion acquisition of Metsera (GLP-1 and insulin platforms). This surge not only underscores the emphasis on the extent of weight loss but also highlights unprecedented priorities for medication adherence and safety.
LAE102 is aligned with this emerging market trend, as evidenced by the latest SAD and MAD study data. It demonstrates efficacy in fat loss and muscle gain at low doses, while reducing gastrointestinal reactions, muscle cramps, and acne, common side effects of similar drugs. Furthermore, the weekly subcutaneous administration adds to its patient-friendly profile.
Looking ahead, it is anticipated that we will see even more impressive fat loss and muscle gain data from LAE102, potentially leading to a landmark international deal that underscores its BIC potential.
01 LAE102 Shows Promising Muscle Gain Data What level of muscle gain data does LAE102 present? Though only the Week 5 results have been disclosed, LAE102 achieved a 1.7% lean body mass increase at a baseline BMI of 29.4 kg/m² in overweight patients, and a 4.6% increase adjusted for placebo, indicating BIC potential. Currently, drug development for fat loss and muscle gain follows several mainstream paths, including ActRIIA/B receptor inhibitors, myostatin inhibitors, insulin, oral GLP-1, and THR-β agonists. Among these, only ActRIIA/B receptor inhibitors have effectively minimized muscle loss or even led to muscle gain, while other pathways usually see fat content reduction comprising 70-85% of total weight loss, indicating considerable lean body mass/muscle loss.
The most representative drug in the ActRIIA/B receptor inhibitor category is Eli Lilly's Bimagrumab (Bima), which in 2025 will present its two-year study results showing a 10.8% weight reduction (entirely from fat) and a lean body mass increase of 2.5%. This is not Bima's peak performance, as earlier studies indicated that, in patients with T2D and obesity (baseline BMI of 32.9 kg/m²), Bima led to an adjusted 4.4% increase in lean body mass after 48 weeks. Furthermore, the latest ADA conference disclosed that the Bima + Semaglutide combination achieved a 22.1% weight reduction after 72 weeks (92.9% from fat), with only a 2.9% loss in muscle mass.
Despite the differing baseline BMI, LAE102 has demonstrated superior muscle gain effects at lower doses and earlier follow-ups, laying a solid foundation for potentially outstanding results in longer follow-up periods.
For comparison, looking at the data from other myostatin targeting agents like Scholar Rock's Apitegromab and Regeneron's Trevogrumab: 1) The EMBRAZE study showed that in the 24th week, 14.6% of weight loss in the Apitegromab + Teriparatide group came from lean mass loss, while the Teriparatide monotherapy group saw 30.2%. The combination therapy retained an additional 54.9% of lean body mass; 2) The COURAGE study showed that in the 26th week, 16.8% of weight loss in the Regeneron Trevogrumab + Semaglutide group came from lean mass loss, while this figure was 33% in the Semaglutide monotherapy group.
Currently, both LAE102 and Bima showcase compelling data on muscle gain and muscle loss reduction, further supporting the notion that the ActRIIA/B receptor inhibition path is a promising BIC route for innovating weight loss and muscle gain drugs. As more experiential data emerges, asset prices in this space are expected to rise.
Additionally, the grip strength testing data for the Bima treatment group at the 48-week mark showed significant improvement from baseline levels, alleviating past market concerns regarding the functional use of muscles gained via ActRIIA/B receptor inhibition and further substantiating the potential for ActRIIA/B and GLP-1 combinations to foster healthier weight loss and muscle gain outcomes.
02 Safety Enhances Market Potential The safety of GLP-1-related weight loss and muscle gain combo drugs has been a focal point for the market. Regeneron’s GLP-1 + Trevogrumab + Garetosmab triplet therapy led to a 30% discontinuation rate among patients, casting a shadow over its prospects. In contrast, LAE102's MAD study safety data mirrors the favorable safety and tolerability from earlier SAD research, with most adverse events being mild (grade 1) laboratory abnormalities, and no reports of diarrhea, muscle cramps, or acne.
This superior safety data positions LAE102 as a potential BIC contender, possibly overshadowing Bima in terms of its Week 5 follow-up data. Bima's safety outcomes from the 2025 ADA conference indicate that muscle cramps, diarrhea, and acne were the primary concerns, while those related to Semaglutide included nausea, diarrhea, constipation, and fatigue, with significantly increased rates of adverse reactions in the combination group, leading to a 9% discontinuation rate due to adverse events over the 72 weeks.
Regarding the incidence rates of serious adverse events, they were recorded at 12.5% and 10.7% for Bima and Semaglutide monotherapies, respectively, with the combination showing a rate of 9.1%. The high rates of serious adverse events may impact Bima's market prospects, especially among patients who are already responsive to GLP-1 treatments or in healthy cohorts.
What enables LAE102 to maintain such safety? There may be two reasons: 1) Dosage advantage: Bima's clinical application involves higher dosing (30 mg/kg), which has been linked to safety concerns in studies concerning diabetic and obese patients, revealed by increased rates of gastrointestinal events and muscle cramps—a trend that led to the withdrawal of Bima from overseas diabetes clinical trials. Conversely, LAE102 achieved remarkable muscle gain effects at a lower dose (6 mg/kg), and SAD trials utilized 8 mg/kg for subcutaneous and 16 mg/kg for intravenous injections, demonstrating sustained pathway blockade, which may explain LAE102's superior safety; 2) Mechanistic strength: Bima represents a strong B but weak A dual receptor inhibitor profile, whereas LAE102 is viewed as a strong A. Although pathway mechanisms are not definitively established, preclinical animal model data and new studies indicate that ActRIIA inhibitors tend to yield more muscle gain effects compared to ActRIIB inhibitors, providing insight into the dosage differences that yield similar outcomes between Bima and LAE102.
From a patient compliance perspective, both LAE102 and Bima involve subcutaneous injection; however, Bima has yet to disclose subcutaneous data. Additionally, due to the dose difference, the development of subcutaneous formulations for Bima requires a careful balance of dosage and safety considerations. LAE102’s promising initial safety data in the MAD study alleviates some uncertainties surrounding subsequent development and commercialization.
Safety is paramount for a drug to achieve significant impact in chronic diseases, with IL-4Rα monoclonal antibody Dupilumab serving as a prime example, demonstrating excellent long-term safety and outperforming JAK family inhibitors in the autoimmune skin disease market. Similarly, LAE102 is poised to leverage its strong safety profile to engage the broad population of both GLP-1 tolerant and intolerant patients, establishing itself as the preferred partner for GLP-1 drugs, and creating vast market potential.
03 GLP-1 Combination as the Ultimate Strategy For ActRII pathway drugs, the ultimate strategy hinges on whether the GLP-1 combination can effectively preserve muscle while maintaining or enhancing lean body mass increments compared to monotherapy data. Clearly, Bima showed promising results in its Phase 2 BELIEVE study, where at 72 weeks, the combination of Bima (30 mg/kg) and Semaglutide (2.4 mg) led to a notable improvement in weight reduction compared to Semaglutide alone (-22.1% vs -15.7%), with markedly reduced fat mass loss (-2.9% vs -7.4%), as well as a significantly higher proportion of patients achieving weight loss ≥20% and fat mass loss ≥30% compared to Semaglutide monotherapy.
In terms of metabolic indices, the combination of Bima+Semaglutide markedly improved multiple cardiac metabolic markers, including inflammatory protein hsCRP, triglycerides, HDL-C, and more. This data supports an optimistic outlook for a potential BIC combo therapy involving Eli Lilly's Teriparatide with LAE102, grounded in current Phase I study findings asserting that inhibiting ActRIIA contributes to significantly better fat reduction compared to equivalent dosing impacts from ActRIIB inhibition, alongside the prospect that LAE102 could dramatically lower fat while preventing muscle loss when combined with GLP-1.
Moreover, early insights from various Eli Lilly Phase I studies suggest consistency in pharmacokinetic/pharmacodynamic data among Western populations, which reinforces the likelihood of replicated success in overseas clinical trials based on China’s outstanding Phase I safety and efficacy results.
Lastly, it is noteworthy that Teriparatide previously outperformed Semaglutide in head-to-head trials, and the combination of LAE102 and Teriparatide presents exciting possibilities for enhanced efficacy.
In conclusion, LAE102 from 來凱醫藥-B is systematically proving its efficacy and effectiveness criteria, stepping closer to fulfilling its prior assertions. With the GLP-1 weight loss market becoming increasingly competitive, the niche represented by the ActRIIA/B pathway for muscle gain and fat loss stands apart as a promising blue ocean opportunity within the broader weight loss market. A favorable competitive landscape directly contributes to the premium pricing of related assets. Should LAE102 indeed realize its BIC potential, a significant market transaction would seem inevitable.