Following oncology and autoimmune diseases, the rapidly emerging weight loss sector has become one of the most significant variables affecting the global pharmaceutical industry landscape for years to come. The arms race surrounding the weight loss track has become one of the highest priority R&D topics for many pharmaceutical giants, with related M&A and business development (BD) transactions showing extremely active momentum. Just this past September, Pfizer acquired the Biotech company Metsera, established just over 3 years ago, for an astounding $7.3 billion to obtain their weight loss drug pipeline. For Chinese innovative drug companies, over the past year, there have been multiple weight loss drug pipeline BD deals with upfront payments exceeding $100 million, with buyers including major multinational pharmaceutical companies like Novo Nordisk, Merck, and Regeneron. However, this may only be a prelude, as the glorious chapter belonging to Chinese innovative drug companies in the strategic weight loss drug sector is still brewing.

**ActRII Antibodies with Superior Safety Profile**

On September 29, 2025, LAE102, an ActRII antibody from Chinese Biotech company LAEKNA-B (02105), announced Phase I clinical MAD study data. This was a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneously administered LAE102 in overweight/obese subjects. The study results announced this time were quite encouraging for all those following this pipeline.

On one hand, the MAD trial observed LAE102's muscle-building and fat-reducing trends: at week 5, subjects in the LAE102 6mg/kg dose group showed an average lean body mass increase of 1.7% from baseline, while average fat mass decreased by 2.2%; after placebo-controlled adjustment, average lean body mass increase reached 4.6%, while average fat mass decreased by 3.6%.

On the other hand, LEA102 demonstrated enormous potential in the safety dimension. During this Phase I MAD study, no serious adverse events occurred, with most treatment-emergent adverse events being mild (Grade 1) laboratory abnormalities, and no cases of diarrhea, muscle spasms, or acne were reported throughout the entire process.

These safety results are consistent with previously disclosed LAE102 safety assessment data, with no new safety signals observed. Previously, as a star target in the weight loss sector, the fat-reducing and muscle-building efficacy of Activin Type II Receptor (ActRII) has been convincingly validated, but safety remains a noteworthy concern.

At the 2025 ADA conference, Eli Lilly first publicly disclosed the 2b clinical study results of their ActRII-targeting antibody drug Bimagrumab combined with semaglutide in overweight and obesity indications. From a weight loss perspective, the data was stunning: at 72 weeks of treatment, the Bimagrumab monotherapy group achieved 10.8% weight loss, with 100% from fat and 2.5% muscle gain; the semaglutide treatment group achieved 15.7% weight loss, but only 71.5% from fat with 7.4% muscle loss; the combination treatment group achieved 22.1% weight loss, with 92.9% from fat and only 2.9% muscle loss.

Tirzepatide, currently the most prominent weight loss drug globally, previously showed average weight loss data of 20.2% at 72 weeks in the SURMOUNT-5 global clinical study. This means the "ActIIR+GLP-1" target combination has the strength to compete head-to-head with tirzepatide in weight loss efficacy. Additionally, ActIIR-targeting drugs possess significant muscle-building capabilities that most GLP-1 class drugs lack. Bimagrumab monotherapy showed an average lean body mass increase of 2.5% from baseline after 72 weeks of dosing.

However, Bimagrumab appears to have flaws in safety and tolerability. Bimagrumab's main adverse reactions include diarrhea, muscle spasms, or acne cases. In monotherapy situations, diarrhea rates exceeded 40%, muscle spasms reached 46% in low-dose groups and over 73% in high-dose groups, with acne rates also around 30%-40%.

In contrast, LAEKNA-B's LAE102 clinical trials to date have not found cases of diarrhea, muscle spasms, or acne, showing significant differences from Bimagrumab. This indicates LAE102's enormous potential advantages in safety, very likely becoming "best in class" among ActRII-targeting similar drugs.

**Potential Buyers**

As one of only two ActRII-targeting drugs globally entering clinical trials for weight loss indications, LAE102's latest clinical study data readout significantly increases the probability of BD for this drug. Eli Lilly, which has made heavy bets on the ActRII target, has already reached clinical trial cooperation with LAEKNA-B regarding LAE102. In November 2024, LAEKNA-B signed a clinical cooperation agreement with Eli Lilly, where Lilly will be responsible for executing a Phase I clinical trial of LAE102 in the United States and bearing related costs, while LAEKNA-B retains global rights to LAE102.

Obviously, as a commercial company, Lilly's choice to fund LAE102's clinical trials indicates considerable interest in this pipeline, not ruling out possibilities for deeper cooperation in the future. Although Lilly already has Bimagrumab, this doesn't mean they'll go down one path to the end. Just in September, according to reports from multiple media outlets, Lilly terminated a clinical trial of Bimagrumab with tirzepatide alone or in combination for treating obese or overweight Type 2 diabetes patients. Lilly didn't provide detailed explanations for the termination, only stating it was "based on strategic business reasons."

Regardless of specific reasons, this event indicates Bimagrumab's position in Lilly's research pipeline isn't absolutely unshakeable, and Lilly's investment in this pipeline involves trade-offs. Besides safety factors, LAE102 has another huge advantage over Bimagrumab. Although a "rising star" in the weight loss sector, the Bimagrumab molecule has a long history. As early as 2013, Bimagrumab received FDA "breakthrough therapy" designation for treating sporadic inclusion body myositis. By 2030, Bimagrumab's patent will expire. So Lilly faces a rather awkward prospect: potentially facing patent cliffs 2-3 years after Bimagrumab's official market approval.

In contrast, LAEKNA-B's LAE102 is still very "young," with patent expiration in 2042, providing ample time for commercialization after drug approval. Therefore, LAE102 possesses superior safety potential, better lean body mass increase capabilities, and longer patent validity. The probability of ultimately reaching a BD transaction with Lilly always exists.

Of course, Lilly isn't the only potential buyer. Take Novo Nordisk, for example - this company's flagship drug semaglutide is gradually falling behind in competition with tirzepatide, seriously affecting the company's stock price. But Novo Nordisk doesn't have better cards in the short term. Given the convincing clinical data validation of semaglutide and Bimagrumab combination effects, introducing a ready-made ActRII-targeting drug with potentially better safety to form combination therapy with semaglutide is obviously an option worth serious consideration for Novo Nordisk.

In fact, with "fat reduction + muscle building" becoming a new clinical paradigm in weight management, almost all multinational pharmaceutical companies with weight loss drug layouts have reasons to quickly build supporting muscle-building drug pipelines, or they may be disadvantaged in future market competition.

**BD Expectations**

In September 2025, LAEKNA-B successfully completed Hong Kong stock placement, raising net proceeds of HK$578 million, with nearly 90% allocated to R&D. Previously, the market once rumored that LAEKNA-B's financing was due to poor clinical data performance. The announcement of this MAD clinical study data also proves such rumors are pure nonsense. In fact, for any unprofitable Biotech, fundraising is as important as R&D before developing significant cash-generating capabilities. The ability to continuously raise massive funds needed for R&D is not only a reflection of a Biotech company's core capabilities but also a sign that its differentiated value is highly recognized by capital markets.

After completing this placement, LAEKNA-B has over HK$1.2 billion in cash, further enriching R&D funding. This is undoubtedly major good news, not only providing sufficient funds for R&D advancement but also giving more confidence in BD negotiations, maintaining selectivity when evaluating potential cooperation structures, ensuring aligned interests among all parties, thereby maximizing global commercial value of related pipelines.

Regarding LAE102's external cooperation, LAEKNA-B maintains an open and pragmatic attitude. The company states it's actively consulting with multiple potential partners, planning to seek partners with serious commitments and financial strength who are willing to prioritize this project, to accelerate LAE102's clinical development and commercialization process.

Besides ActRIIA-targeting LAE102, LAEKNA-B also owns ActRIIB-targeting antibody LAE103 and dual-target antibody LAE123 that completely benchmarks Bimagrumab while targeting both ActRIIA/IIB. With ActRII targets showing extremely high drug development probability for overweight/obesity indications, it wouldn't be surprising if LAE103 and LAE123 attract multinational pharmaceutical companies. Bundling all three pipelines for BD is also a possibility.

Considering Eli Lilly acquired Bimagrumab for $1.9 billion, there's every reason to expect that at some future moment, LAEKNA-B will contribute a major BD deal to China's innovative drug industry.

Beyond ActRII-class pipelines, LAEKNA-B also has LAE002, which is quite noteworthy. LAE002 is a potent AKT inhibitor that can inhibit all three AKT subtypes (AKT1, AKT2, and AKT3). According to public data, compared to other AKT inhibitors, LAE002 has multiple advantages including higher efficacy, better pharmacological effects, more significant tumor suppression exposure, and better safety. In the first half of 2026, LAE002 is expected to submit marketing applications. As one of only two anti-tumor AKT inhibitors globally at or completing pivotal clinical development stages, this pipeline also has BD expectations.