The obesity treatment market is rapidly evolving beyond simple weight loss, shifting toward competition centered on innovations in dosage forms, administration schedules, and mechanisms of action. As the market evolves from injection-based treatments to oral medications, long-acting formulations, and multi-action drugs, the treatment paradigm is also changing. Global pharmaceutical companies and domestic biotech firms are accelerating the development of next-generation obesity drugs. Accordingly, Edaily is shining a spotlight on the changes in obesity and diabetes treatment in the “post-GLP-1” era and the response strategies of K-Bio. This report was produced with the support of the Korea Science Journalists Association. [Editor’s Note]

[TIDE Reporter SHIN MIN JOON ] While glucagon-like peptide (GLP)-1-based obesity treatments have revolutionized the paradigm of obesity therapy, interest is surging in next-generation obesity treatments that go beyond simple weight loss to increase muscle mass.

Until now, the competition to develop obesity treatments has focused on how much weight could be lost. Novo Nordisk’s Wegovy and Eli Lilly’s Mounjaro have driven the growth of the global obesity treatment market by demonstrating outstanding weight-loss effects. As latecomers to the market, domestic pharmaceutical and biotech companies, such as HanmiPharm, have sought to differentiate themselves by focusing not only on weight loss but also on increasing muscle mass.

HanmiPharm, a Leader in Korea’s Next-Generation Obesity Treatments... Developing the World’s First Muscle-Building Treatment

According to the pharmaceutical and biotech industry on the 25th, domestic companies are accelerating the development of next-generation obesity treatments. HanmiPharm ( HanmiPharm(128940)) is recognized as the leader in the development of next-generation obesity treatments in Korea. HanmiPharm is developing HM17321, the world’s first muscle-building obesity treatment, and HM500197, a next-generation muscle-enhancing treatment. HM17321 is currently undergoing a Phase 1 clinical trial in the U.S., while HM500197 has completed preclinical trials.

HM17321 is being developed as a “first-in-class” innovative obesity drug that goes beyond simply compensating for muscle loss to simultaneously achieve muscle mass gain and selective fat loss—a feat previously considered impossible. HM17321 is a UCN2 analog that selectively targets the CRF2 receptor rather than incretin receptors such as GLP-1.

HM17321 was designed using HARP (HanmiPharm AI Driven Research Platform), a state-of-the-art artificial intelligence (AI) and structural modeling technology platform developed in-house by HanmiPharm based on the company’s proprietary drug design capabilities. CRF is a signaling molecule associated with stress responses and stress recovery; selectively targeting the CRF2 receptor can directly lead to fat reduction, muscle gain, and improved muscle function.

A HanmiPharm official stated, “HM17321 has presented a new paradigm for obesity treatment even as a monotherapy,” adding, “Furthermore, it is expanding its potential for innovation by demonstrating superior weight loss efficacy—both quantitatively and qualitatively—when used in combination with existing incretin-based obesity treatments.”

Most antibody-based muscle-preserving drugs offer poor convenience for obese patients due to their intravenous administration. When used in combination with existing subcutaneously administered obesity treatments, limitations arising from differences in administration methods have been pointed out. Significant side effects and the fact that these drugs are limited to preserving muscle mass rather than improving muscle function are also cited as constraints.

A HanmiPharm official said, “In contrast, HM17321 is designed as a peptide-based compound, offering high convenience of administration and cost competitiveness.” The official added, “In particular, if developed as a combination therapy, it can be administered simultaneously with existing incretin-class drugs—which are in the same peptide form—and is expected to significantly improve patient convenience.”

HM500197, designed as a peptide-based compound, is considered the fourth key new drug pipeline of the H.O.P. project, which was launched to overcome the limitations of the antibody-based approach. It was developed using HARP, HanmiPharm’s proprietary state-of-the-art artificial intelligence (AI) and structural modeling technology platform, built on the company’s unique drug design capabilities.

HM500197, the world’s first peptide-based compound, is designed to selectively inhibit myostatin, thereby increasing skeletal muscle-specific lean body mass. Unlike antibody-based drugs, it is expected to significantly improve patient convenience as it can be easily developed for use in combination with or as a fixed-dose combination with incretin-based therapies of the same modality.

HanmiPharm recently announced at the American Diabetes Association (ADA) Annual Scientific Session held in New Orleans that, in in vitro studies, HM500197 demonstrated myostatin inhibitory activity comparable to that of bimagrumab, an antibody-based muscle-preserving drug developed by global pharmaceutical giant Eli Lilly. HM500197 also demonstrated excellent myostatin selectivity, as no inhibitory activity against off-target cytokines was observed.

In in vivo studies, HM500197 was confirmed to have superior efficacy in increasing lean body mass selectively in skeletal muscle compared to bimagrumab. HM500197 also demonstrated differentiated results in terms of safety by minimizing off-target effects. In particular, in a high-fat diet-induced obese mouse model, HM500197 selectively increased skeletal muscle mass alongside a dose-dependent increase in lean body mass.

HM500197 has established a scientific basis supporting its potential as a healthy weight-loss treatment by effectively inhibiting muscle loss while inducing body weight loss primarily through the reduction of body fat when co-administered with GLP-1 agonists.

A HanmiPharm official stated, “While both HM17321 and HM500197 target muscle preservation or growth, their approaches differ,” adding, “
HM17321 is a long-acting UCN2 agonist designed to improve the quality of weight loss, and we are conducting a broad evaluation of its effects on muscle mass, metabolic function, and cardiovascular and renal outcomes.”

The spokesperson continued, “In contrast, HM500197 is a candidate compound designed with a peptide-based myostatin inhibition mechanism that induces an increase in lean body mass, primarily in skeletal muscle.”

He continued, “While both new drugs share the common potential to increase muscle mass, their mechanisms of action differ,” adding, “HM17321, a long-acting UCN2 analog, works by promoting muscle formation and remodeling. In contrast, HM500197, a selective myostatin inhibitor, works by inhibiting muscle breakdown.”

HK inno.N Corporation Develops Sarcopenia Treatment... Inhibits Muscle Loss by Regulating Chronic Inflammation

HK inno.N Corporation(195940)is developing IN-207907, a treatment for sarcopenia. HK inno.N Corporation has received approval for its Phase 2 clinical trial plan and has begun full-scale development. IN-207907 is based on KineScience’s peptide drug candidate, KINE-101. IN-207907 employs a differentiated approach that inhibits muscle loss by regulating chronic inflammation.

In particular, HK inno.N Corporation is focusing on the potential for combination therapy with IN-B00009, a GLP-1-based obesity treatment currently undergoing Phase 3 clinical trials in South Korea. Given that the sarcopenia treatment can counteract the loss of muscle mass that may occur during the use of obesity treatments, there is also speculation that obesity treatments and sarcopenia treatments could form a mutually complementary market in the future.

An official from the pharmaceutical and biotech industry stated, “As obesity treatments have established themselves as global blockbuster drugs, the focus is shifting from the amount of weight lost to how healthily weight can be reduced while preserving or increasing muscle mass,” adding, “Since domestic companies are developing differentiated obesity treatments to compete with global Big Pharma, all eyes are on whether they will succeed.”

Meanwhile, this article was supported by the Korea Science Journalists Association.