New Competition in the GLP-1 Track: The Patent Layout and Clinical Journey of Hansoh's HS-10535

In recent years, GLP-1 receptor agonists have emerged as a key therapeutic category in the field of metabolic diseases due to their dual benefits of glycemic control and weight loss. Novo Nordisk’s semaglutide, available in both oral and injectable formulations, has rapidly positioned itself as a leading contender for the title of "global best-selling drug," propelling the company to the top of Europe's pharmaceutical market capitalization rankings. Meanwhile, small-molecule GLP-1 receptor agonists have garnered significant interest from multinational pharmaceutical companies due to their oral bioavailability and lower production costs. Industry giants such as Eli Lilly, Pfizer, Roche, and AstraZeneca have all entered the small-molecule GLP-1 receptor agonist market. Among them, Eli Lilly’s Orforglipron has advanced to Phase III clinical trials, establishing itself as a frontrunner in this sector.

Against this backdrop, on December 18, 2024, Hansoh Pharma entered into a strategic collaboration with Merck & Co. worth over $2 billion, granting Merck the exclusive global license for its investigational GLP-1 receptor agonist, HS-10535. Under the agreement, Hansoh will receive an upfront payment of $112 million, milestone payments of up to $1.9 billion, and royalties on future sales. This partnership not only accelerates the clinical development of HS-10535 but also leverages Merck’s global commercial infrastructure to expand into the U.S. and European markets.

HS-10535 is an orally administered small-molecule GLP-1 receptor agonist developed by Hansoh Pharma, with potential applications in obesity, type 2 diabetes, and other cardiovascular metabolic disorders. Currently, detailed information and structural data on the drug remain undisclosed. However, on February 6, 2025, Hansoh Pharma published an international PCT patent (Publication No. WO2025026270A1) related to small-molecule GLP-1 receptor agonists, suggesting that HS-10535 may originate from this patent.

A search using Patsnap Analytics reveals that this patent was filed on July 29, 2024, with a priority date of July 28, 2023, and was officially published on February 6, 2025. A thorough review of the patent documentation may allow for a reasonable structural inference of HS-10535.

The patent discloses a total of 514 specific compounds. Among them, Compound No. 143 exhibits the highest GLP-1 receptor agonist activity, with an EC50 (half-maximal effective concentration) as low as 0.013 nM, demonstrating exceptionally high receptor activation potency. In long-term administration studies, GLP-1 receptor-humanized mice fed a CDAHFD high-fat diet were used to evaluate the weight-loss effects of Compound No. 143. The results showed a significant reduction in body weight, with a weight loss rate of 19.43%, indicating substantial anti-obesity potential. Additionally, in oral pharmacokinetic studies conducted in mice, Compound No. 143 exhibited favorable metabolic properties, suggesting stable absorption and metabolism in vivo, further reinforcing its potential as a promising therapeutic candidate.

Additionally, Compound 282 is another key focus of this patent application. Its GLP-1 receptor agonist activity is measured at 0.074 nM, which is slightly lower than that of Compound 143. However, Compound 282 demonstrates exceptional pharmacokinetic properties. In pharmacokinetic studies across multiple animal models—including oral administration in mice and Sprague-Dawley (SD) rats, as well as oral and injectable administration in beagle dogs and cynomolgus monkeys—Compound 282 exhibited outstanding metabolic stability. These characteristics significantly enhance its likelihood of successfully advancing into clinical development.

Based on the experimental data provided in the patent application, it is highly probable that Compounds 143 and 282 are candidates for HS-10535. Further analysis of their chemical structures reveals a high degree of structural similarity to Eli Lilly’s Orforglipron, with the primary distinction being the substituent on the nitrogen atom of the indazole core. This suggests that if HS-10535’s structure indeed originates from patent WO2025026270A1, its design is likely based on an optimization and modification of Orforglipron’s structure.

From the drafting of the patent claims, the current Claim 1 encompasses a broad scope of protection, potentially even covering Eli Lilly’s Orforglipron (where R13 is a methyl group). The international search report lists eight X-category documents and three PX-category documents. Notably, the first X-category document is the original patent disclosing Orforglipron’s structure (WO2018056453A1, with the Chinese equivalent CN109790161A).

According to the examination opinion in the international search report, Claims 9 and 12 appear to have been recognized for their novelty and inventive step. Specifically, Claim 9 delineates a structural modification direction for the indazole substituents that differentiates it from Orforglipron. Notably, both Compound 143 and Compound 282 fall within the scope of Claim 9 (with 143 corresponding to A-1 and 282 to A-6). Therefore, as long as the patent undergoes appropriate claim scope adjustments during substantive examination in accordance with the examiner’s recommendations, its likelihood of being granted will significantly increase.

Through structural innovation and international collaboration, Hansoh Pharma’s HS-10535 demonstrates strong technological competitiveness in the small-molecule GLP-1 receptor agonist sector. The core compound data and claim strategies of patent WO2025026270A1 establish a preliminary technical barrier. However, with Eli Lilly’s Orforglipron already in Phase III clinical trials, prolonged preclinical studies for HS-10535 could result in a missed market opportunity. The success of HS-10535 will largely depend on the efficiency of its clinical advancement and the management of patent risks. If successfully commercialized, HS-10535 has the potential to secure a significant share of the oral GLP-1 receptor agonist market and drive Hansoh Pharma’s transition from a domestic pharmaceutical company to a globally recognized innovative drug developer.

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