Entering the Era of Weight Loss Drugs 2.0: From Weight Loss to Muscle Gain, Is the Catalyst Here?

Should the market expect a new wave of large BD transactions at the ADA (American Diabetes Association Annual Meeting) in late June?

On June 2, 2025, HANSOH PHARMA and Regeneron jointly announced a significant licensing collaboration: Regeneron obtained global exclusive development and commercialization rights for HANSOH's investigational GLP-1/GIP dual receptor agonist HS-20094 outside of Greater China for an upfront payment of $80 million and up to $1.93 billion in milestone payments.

HS-20094 is a weekly subcutaneous injection candidate that has shown significant weight loss and safety data comparable to Eli Lilly's tirzepatide (the only approved GLP-1/GIP dual agonist) in a Phase II trial involving over a thousand subjects. It is currently undergoing Phase III trials for obesity and Phase IIb trials for diabetes in China.

Notably, although this deal still involves GLP-1/GIP, the purpose for the buyer, Regeneron, is very clear: to combine its muscle-preserving products and enter the era of weight loss drugs 2.0 focused on fat reduction and muscle gain.

Regeneron and HANSOH: The Starting Point of Weight Loss Drugs 2.0 Era?

In the Q1 2025 earnings call, Regeneron's management clearly conveyed a new attitude towards obesity treatment: the company is "committed to advancing better obesity treatment by improving weight loss quality," focusing not only on the number on the scale but also emphasizing "high-quality, sustained weight loss."

Dr. George Yancopoulos, co-founder and Chief Scientific Officer of Regeneron, pointed out that while current popular weight loss therapies lead to transformative weight loss, "there remains a significant unmet need, including how to maintain weight loss effects over time and the ability to preserve muscle mass." This statement marks Regeneron's shift towards the "high-quality weight loss track," which emphasizes improving body composition and long-term health benefits while achieving weight loss.

Why did Regeneron choose HS-20094? On one hand, GLP-1 receptor agonists (such as Novo Nordisk's Wegovy and Eli Lilly's Zepbound) have been shown to help patients lose 15%-20% of their weight, but a significant proportion of this weight loss comes from lean mass (i.e., muscle and other non-fat tissues). Research shows that during the use of Wegovy, up to 40% of the weight lost comes from lean mass rather than fat.

After announcing the deal with HANSOH, Regeneron further revealed its ongoing research into a novel combination therapy for obesity involving semaglutide (GLP-1 receptor agonist) with trevogrumab (anti-GDF8/anti-myostatin) combined or not combined with garetosmab (anti-activin A).

This interim analysis showed that 34.5% of the weight loss in the semaglutide group came from lean mass loss, while all combination treatment groups retained more lean mass compared to the monotherapy group, achieving greater fat reduction.

Therefore, Regeneron sees HS-20094 as an advanced dual-target agonist that can be combined with its muscle-preserving drugs to achieve better weight loss quality Dr. Boaz Hirshberg, Senior Vice President of Regeneron, stated that the introduction of HS-20094 will enable the company to "explore combination therapies with Regeneron's proprietary drugs to comprehensively address obesity-related muscle loss and complications such as cardiovascular disease, diabetes, and liver disease." In other words, Regeneron aims to combine the GLP-1/GIP metabolic weight loss mechanism with its own muscle protection mechanism under development, paving a new path for "high-quality weight loss."

Giant Layout: Muscle Disease Pipeline Integrated into Weight Loss Track

The weight loss drug industry is undergoing a paradigm shift from the 1.0 era to the 2.0 era: in the past, the industry focused on "the decrease in weight numbers," while now it emphasizes "losing fat without losing muscle," and even explores "increasing muscle while losing fat."

Currently available GLP-1 drugs often lead to significant weight loss but are accompanied by a decrease in lean body mass, a concern that has drawn attention from the medical community. An American endocrinologist pointed out that new drugs must demonstrate not only an increase in muscle mass numbers but also functional improvements—"Clinicians want to see not just changes in muscle content but also improvements in strength or metabolic function."

To address the issue of muscle loss, major pharmaceutical companies are competing to develop "muscle-protecting" new weight loss drugs, striving to achieve "fat loss without muscle loss."

These candidate therapies often target muscle growth pathways, such as antibodies that inhibit myostatin or activin.

For example, as mentioned earlier, Regeneron is conducting the COURAGE Phase II trial to explore the combination of its anti-GDF8 (myostatin) antibody trevogrumab with Wegovy, along with the addition of the anti-activin A antibody garetosmab in a triple therapy scheme. The interim clinical data clearly confirmed that blocking GDF8 (±activin A) can maintain muscle and further increase fat loss in patients treated with GLP-1, thereby improving the quality of weight loss.

Similar concept validations have also emerged in other companies: in January of this year, small pharmaceutical company Veru announced data from a trial involving 168 participants, showing that its selective androgen receptor modulator (SARM) enobosarm combined with Wegovy reduced muscle loss in elderly obese patients by 71%. This result became a hot topic in the industry, further proving the feasibility of "retaining muscle" in the weight loss 2.0 era.

Moreover, ActRII pathway inhibitors can not only prevent muscle breakdown but also promote muscle synthesis. Bimagrumab, developed by Versanis, a company acquired by Eli Lilly in 2023, falls into this category. Previously published results from the bimagrumab Phase II trial showed that this antibody blocked the muscle growth inhibition pathway, significantly reducing fat mass while increasing lean body mass in overweight patients with type 2 diabetes, and improving metabolic function.

Before the acquisition, Eli Lilly had already collaborated with Versanis to conduct mid-stage clinical trials of bimagrumab combined with GLP-1 drugs, with the primary endpoint being weight change over 48 weeks, while also focusing on waist circumference, fat mass, muscle mass, and other indicators After the acquisition is completed, Eli Lilly intends to combine bimagrumab with its popular GIP/GLP-1 dual agonist Tirzepatide to verify whether the combination can achieve "weight loss without muscle loss," enhancing weight loss efficacy and safety margins. It is noteworthy that this clinical trial will disclose relevant data at the ADA (American Diabetes Association Annual Meeting) in June.

In addition to acquiring Versanis, Eli Lilly is also laying out collaborations on other similar products. By the end of 2024, Eli Lilly reached a cooperation agreement with the Chinese biotech company LaiKai Pharmaceutical to invest resources to accelerate the development of the latter's early-stage muscle-targeting obesity drug LAE102.

LAE102 has shown effects in animals of increasing lean body mass and reducing fat by affecting key pathways in muscle regeneration and fat metabolism, and it is expected to be used in combination with GLP-1 drugs to help obese patients "regrow" the muscle lost during weight loss.

According to the agreement, LaiKai Pharmaceutical retains global rights, while Eli Lilly provides funding and professional support to advance clinical trials in the United States.

Other multinational pharmaceutical companies are also not falling behind, incorporating "muscle protection/enhancement" modules into their obesity pipelines: Roche launched clinical trials of RG6237 (an anti-myostatin antibody) in high BMI populations in 2023, planning to advance the Phase II trial of RG6237 in combination with its own GLP-1 candidate drug CT-388 this year.

At the same time, biotechnology companies focused on muscle diseases are also joining the fray—such as Scholar Rock, which is repurposing its myostatin antibody apitegromab, originally for treating spinal muscular atrophy, for obesity trials.

Statistics show that there are currently about 12 such "muscle-friendly" weight loss drugs in development.

More importantly, this new track meets the urgent needs of specific patient groups, such as elderly obese patients and sarcopenic obesity patients. In these populations, merely pursuing weight loss is not the only goal; increasing muscle strength and improving metabolic health are equally important.

High-quality weight loss drugs are expected to provide a medical means to help patients reduce their burden while maintaining or even enhancing their physical fitness. This also extends the application scenarios of weight loss drugs from traditional clinical treatment to a broader field that includes preventive healthcare and aesthetic medicine. Under the premise of regulatory scrutiny to evaluate safety, weight loss drugs 2.0 have the potential to expand to a broader population base than ever before.

Medical Conferences Catalyze Transaction Fever: Insights from ADA 2025 and ASCO

The upcoming American Diabetes Association Annual Meeting (ADA 2025) in late June 2025 is receiving significant attention from the industry. It is expected that several important research results in the field of weight management will be announced, including preclinical or clinical data for the next generation of weight loss drugs.

Large medical conferences often serve as barometers for industry collaboration and transactions: once breakthrough data is announced, the stock prices of related companies and market expectations change accordingly, accelerating business development (BD) negotiations. For example, the positive results of the Phase II trial of HANSOH HS-20094 (significantly reducing blood sugar and weight in diabetic subjects with good tolerance) at the 2024 ADA Annual Meeting sparked widespread interest It can be considered that this has laid the groundwork for Regeneron to invest in HS-20094 next year.

This "meeting is trading" model is common in the innovative drug field.

For example, this year at the world's largest oncology conference ASCO, the clinical breakthroughs of PD-(L) 1/VEGF triggered a surge of capital, with Pfizer and 3SBio, BMS and BioNtech's transactions reaching the level of tens of billions of dollars, which excited pharmaceutical investors.

For the weight loss drug 2.0 track, the ADA annual meeting in 2025 may play a similar catalytic role, which is worth looking forward to for innovative drug investors