The domestically produced fat-reducing and muscle-building innovative molecule LAE102 is making significant strides on its path to becoming Best in Class.
On September 29, LAEKNA-B (02105) released the Phase I clinical MAD study data for LAE102, showing that in the fifth week, patients in the 6mg/kg dosage group had an average lean body mass increase of 1.7% and an average fat mass reduction of 2.2%; after adjusting for placebo, the lean body mass increased by 4.6%, and the average fat mass decreased by 3.6%.
It is noteworthy that the global weight loss field has seen a surge in licensing deals, from Eli Lilly's $1.92 billion acquisition of Versanis Bio (Bimagrumab) to Novo Nordisk and Septerna's $2.2 billion deal (oral small molecules), and Pfizer's $4.9 billion acquisition of Metsera (GLP-1 and amylin platform). This trend reflects an important shift: while the extent of weight loss is crucial, medication adherence and safety have taken on unprecedented importance.
LAEKNA-B's LAE102 perfectly meets the necessary conditions for this transaction trend. Combining SAD study and the latest MAD study data, it not only demonstrates fat-reducing and muscle-building efficacy at low doses but also reduces the gastrointestinal reactions, muscle cramps, and acne side effects commonly associated with similar drugs. Additionally, the once-weekly subcutaneous administration is very patient-friendly.
Perhaps in the near future, we will see more mature and outstanding fat-reducing and muscle-building data for LAE102 and a market-surprising overseas transaction to validate its Best in Class potential.
01 LAE102 Monotherapy Muscle-Building Data Shines
What level of muscle-building data does LAEKNA-B's LAE102 achieve?
Although only the fifth-week data has been disclosed so far, LAE102 has shown a 1.7% increase in lean body mass and a 4.6% increase adjusted for placebo in overweight patients with a baseline BMI of 29.4 kg/m2, indicating its Best in Class potential.
It is important to note that there are several mainstream pathways for the development of global fat-reducing and muscle-building drugs, including ActRIIA/B receptor inhibitors, myostatin ligand inhibitors, amylin, oral GLP-1, and THR-β agonists. Among these, only the ActRIIA/B receptor inhibitor pathway has achieved the maximum reduction in muscle loss and even muscle gain, while the other pathways generally see fat content reduction accounting for 70-85% of weight loss, meaning there is still a considerable degree of lean body mass/muscle loss.
The most representative drug in the ActRIIA/B receptor inhibitor pathway is Eli Lilly's ActRIIA/B antibody Bimagrumab (referred to as Bima). Data from the 2b phase disclosed at the 2025 ADA conference showed that subjects receiving Bima monotherapy lost 10.8% of their weight over 72 weeks (with 100% of the weight loss coming from fat) and increased lean body mass by 2.5%. This is not even Bima's optimal data; another earlier treatment in a clinical trial for T2D with obesity (baseline BMI of 32.9 kg/m2) showed that after 48 weeks of Bima monotherapy, there was a 4.4% increase in lean body mass adjusted for placebo
The latest disclosure from ADA 2025 shows that the Bima + Semaglutide combination therapy group achieved a weight loss of 22.1% (92.9% from fat) at week 72, with only a 2.9% loss in muscle.
Despite differences in baseline BMI, LAE102 demonstrated a stronger muscle gain effect at lower doses and earlier follow-up results, laying a solid foundation for achieving better results in subsequent longer follow-up periods.
Let's compare the data of two targeted muscle growth inhibitors, Scholar Rock's Apitegromab and Regeneron's Trevogrumab:
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In the EMBRAZE study, at week 24, 14.6% of the overall weight loss in the Apitegromab + Tirzepatide group came from lean body mass loss, while this figure was 30.2% in the Tirzepatide monotherapy group, with the combination group retaining an additional 54.9% of lean body mass;
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The COURAGE study showed that at week 26, 16.8% of the overall weight loss in the Regeneron Trevogrumab + Semaglutide group came from lean body mass loss, while this figure was 33% in the Semaglutide monotherapy group.
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Currently, the muscle gain and muscle loss reduction data for LAE102 from LAEKNA and Bima from Eli Lilly fully support the potential BIC route of ActRIIA/B receptor inhibition for global fat loss and muscle gain innovative drug development. There are currently few global clinical stage assets, and as more people experience confirmatory data readouts, asset prices are bound to rise.
Additionally, the grip strength test data for the Bima treatment group at 48 weeks showed significant enhancement compared to baseline levels, which not only dispelled past market concerns about the functionality of muscle gained from ActRIIA/B receptor inhibitors but also further demonstrated that the combination of ActRIIA/B receptor inhibitors with GLP-1 can help patients achieve healthier fat loss and muscle gain, potentially making it the best companion for GLP-1 drugs.
02 Safety Opens Up Space
The safety of GLP-1 fat loss and muscle gain companion drugs has always been a focus of market attention. Regeneron's GLP-1 + Trevogrumab + Garetosmab (activin A antibody) triple therapy led to a 30% discontinuation rate among patients, resulting in a bleak outlook.
The safety data for LAE102 from the MAD study reported by LAEKNA continued the good safety and tolerability seen in the earlier SAD study, with most adverse events during treatment being mild (grade 1) laboratory abnormalities, and no reports of diarrhea, muscle cramps, or acne-related adverse reactions.
The outstanding safety data for LAE102 clearly shows BIC potential, and although it is only the fifth week of follow-up data, it seems to overshadow Bima.
From the safety data of the BELIEVE study released at the 2025 ADA conference, the main safety concerns related to Bima were muscle cramps, diarrhea, and acne, while those related to Semaglutide included nausea, diarrhea, constipation, and fatigue. In the combination therapy group, the rates of adverse reactions such as nausea, diarrhea, and acne were significantly increased, leading to 9% of participants in this study discontinuing treatment due to adverse events within the 72-week period
In terms of the incidence of serious adverse events, the rates in the Bima monotherapy and semaglutide monotherapy groups were 12.5% and 10.7% respectively (both from the highest dose group), while the incidence of serious adverse events in the Bima and semaglutide combination group was 9.1%. The higher incidence of serious adverse events may affect the market prospects of Bima in patient populations that already have a strong response to GLP-1 or in healthy patient populations.
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(Safety data of Bima at 48 weeks)
Why is LAEKNA able to achieve such safety? There may be two speculative reasons:
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Dose advantage: It can be seen that Bima is used at a relatively high dose (30mg/kg) in clinical use, and safety issues have been observed in studies targeting diabetic and obese patients, including a high incidence of gastrointestinal events and muscle cramps, which can be inferred from Eli Lilly's withdrawal of Bima from overseas Phase II diabetes clinical trials; in contrast, LAEKNA achieved excellent muscle gain effects at a lower dose (6mg/kg) in the MAD study, and in the SAD study, continuous pathway blockade was observed with 8mg/kg subcutaneous injection and 16mg/kg intravenous injection, which may be one of the secrets to LAEKNA's superior safety;
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Strong A weak B mechanism: Eli Lilly's Bima, as a dual receptor inhibitor, represents a strong B weak A, while LAEKNA represents a strong A; although the pathway mechanism is not definitively established, preclinical animal model data and recent studies indicate that ActRIIA inhibitors can provide more muscle gain effects compared to ActRIIB inhibitors, which may also explain the dose differences between Bima and LAEKNA in achieving similar muscle gain effects.
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Additionally, from the perspective of patient compliance, both LAEKNA and Eli Lilly's Bima are administered via subcutaneous injection; however, so far, Bima has not released data on subcutaneous injection, and due to dose differences, its development of a subcutaneous formulation requires more consideration of the balance between dose and safety; meanwhile, LAEKNA has already demonstrated preliminary excellent safety data in the MAD study, which alleviates some uncertainty regarding subsequent development and commercialization.
Safety is crucial for a drug to achieve blockbuster status in the chronic disease field, with the most typical example being IL-4Rα dupilumab, which, due to its excellent long-term safety, has outperformed JAK family inhibitors in the autoimmune skin disease market, becoming the king of the autoimmune field. Similarly, LAEKNA is also expected to leverage its robust safety data to cover a wide range of GLP-1 tolerant and intolerant populations, becoming the best companion for GLP-1 drugs in muscle gain and fat loss, with vast market potential
03 The Ultimate Weapon is the Combination with GLP-1
For ActRII pathway drugs, the biggest weapon is whether the combination with GLP-1 can maximize the preservation of muscle loss compared to monotherapy data, or even continue the increase in lean body mass.
Clearly, Bima has shown good completion in the phase 2b BELIEVE study. In the 72nd week, patients in the Bima 30mg/kg + Semaglutide 2.4mg combination group experienced a significant weight loss compared to the Semaglutide monotherapy group (-22.1% vs -15.7%), with a substantial reduction in fat-free mass loss (-2.9% vs -7.4%). Additionally, the proportion of patients with weight loss ≥20% and the proportion of patients with fat mass reduction ≥30% were significantly higher than those in the Semaglutide monotherapy group.
Moreover, in terms of metabolic indicators, the combination of Bima + Semaglutide significantly improved multiple cardiac metabolic indicators in patients, including the inflammatory protein hsCRP, triglycerides, HDL-C, etc.
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Based on the efficacy data of Bima + Semaglutide combination, there is reason to have greater expectations for the potential BIC of the future combination of Eli Lilly's Tirzepatide + LAE102.
Firstly, based on the data from the current phase 1 study of LAE102, which verifies the preclinical results, including the effect of inhibiting ActRIIA in promoting fat reduction being significantly better than the dose-optimized equivalent results brought by inhibiting ActRIIB. Additionally, compared to ActRIIB inhibitors combined with GLP-1, LAE102 can significantly reduce fat and prevent muscle loss when combined with GLP-1.
Secondly, there is information showing some blind data from Eli Lilly's overseas phase 1 studies, indicating that the PK/PD data shown in Western populations is consistent with the domestic SAD study data. This also means that overseas clinical trials are likely to replicate the excellent efficacy and safety data from domestic phase 1 studies. Furthermore, it is worth mentioning that Tirzepatide has previously outperformed Semaglutide in head-to-head trials. The combination of LAE102 + Tirzepatide, a &#34;double strong&#34; combination, will create more possibilities.
More importantly, the phase 1 clinical trial in collaboration with Eli Lilly and LAE102 was completed at the end of August and is currently in the follow-up stage. We look forward to seeing LAE102 continue to demonstrate excellent performance in Western populations while also observing some more positive signals for muscle gain and fat loss with the combination of LAE102 + Tirzepatide.
Conclusion: LAE102 from LAEKNA is gradually fulfilling its past commitments with solid and powerful efficacy and effectiveness data. The GLP-1 weight loss market is becoming increasingly competitive, while the muscle gain and fat loss track represented by ActRIIA/B is a rare blue ocean in the large weight loss market. A favorable competitive landscape represents a premium in asset prices. If LAE102 can truly realize its BIC potential in the future, achieving a grand transaction will be a natural outcome
This article is reprinted from the public account &#34;Dengling Society,&#34; edited by Chen Wenfang of Zhitong Finance

02105

LAEKNA-B has made significant progress in the field of fat reduction and muscle gain. Phase I clinical MAD studies show that patients in the 6mg/kg dosage group experienced an average lean body mass increase of 1.7% and a fat mass reduction of 2.2% by the fifth week. The drug has demonstrated excellent medication adherence and safety, with the potential to become best in class. The global weight loss market is active, and the success of LAE102 could bring surprises to the market

Muscle Gain BIC, Space Opens Up