Hanmi targets 'quality weight loss' with next-gen drugs beyond GLP-1

"We will focus on the qualitative aspect of weight loss with minimal muscle loss. In addition, we will focus on novel targets other than GLP-1 to develop new obesity drugs with novel mechanisms of action (MOAs)."

From commercializing GLP-1-based drugs to developing a pipeline of new mechanisms with new targets, Hanmi Pharmaceutical's obesity drug development strategy is organized under the HOP (Hanmi Obesity Pipeline) project. HM15275 and HM17321, the next-generation obesity drugs, as well as efpeglenatide, which was developed to improve access to GLP-1 drugs for Korean patients, have emerged from the HOP project.

At the center of these projects is Choi In-young, head of the R&D Center, along with 500 researchers at Hanmi Pharmaceutical.

Choi, who joined Hanmi Pharmaceutical in 1998, has played a central role in the development of several biopharmaceutical pipelines utilizing Hanmi Pharmaceutical's LABSCOVERY platform technology. In 2023, he was appointed head of the R&D center and reorganized it to focus on various diseases, including cancer, rare diseases, and metabolic disorders.

Obesity is also part of this disease-focused R&D.

Question: What is Hanmi Pharmaceutical's most focused strategy for developing obesity drugs?

Answer: Currently, the global obesity drug market is skewed toward competing weight loss numbers. However, the situation of each obese patient is very different. Some patients require losing more than 20 percent, but for most, achieving “high-quality weight loss” may be more important due to various factors, including age, race, comorbidities, and socioeconomic conditions.

Hanmi Pharmaceutical’s strategy was born out of the need for such patient-customized treatment. The HOP (Hanmi Obesity Pipeline) project, initiated in 2023, comprises six pipelines. The strategy goes beyond simple weight loss to include medication adherence, post-loss maintenance, and relapse prevention. The production infrastructure will also be built domestically to ensure price competitiveness.

Q: What are the pipelines being developed under the HOP project?

A: Efpeglenatide, a GLP-1, is in phase 3 clinical trials with the goal of launching in Korea next year. Considering the characteristics of Korean patients with low rates of severe obesity, it is expected to have sufficient weight loss effects by itself.

Another candidate to watch is HM15275. Phase 1 results, presented at the American Diabetes Association (ADA) 2025, showed an average reduction of 4.8 percent compared to the placebo after four weeks of treatment. The preservation of muscle mass was particularly notable, based on Hanmi's more than 10 years of experience in incretin research and triple active balancing technology. It is expected to enter phase 2 this year.

HM17321 is a CRF2 receptor agonist that induces weight loss while simultaneously increasing muscle mass. We have secured an optimized structure through HARP, an AI-based drug design platform, and expect to enter phase 1 this year. In particular, it will be differentiated from existing myostatin inhibitors in terms of improving muscle function.

Q: The pipeline being developed under the H.O.P project is:

A: First, 'Epeglenatide' is a GLP-1 and is in phase 3 clinical trials with the goal of launching in Korea next year. Considering the characteristics of Korean patients with low rates of severe obesity, it is expected to have sufficient weight loss effects alone.

Another candidate to watch is ‘HM15275’. Phase 1 results, presented at the American Diabetes Association (ADA) 2025, showed an average reduction of 4.8 percent compared to the placebo after four weeks of treatment. In particular, the muscle mass preservation effect was particularly prominent, which is based on Hanmi's 20+ years of experience in incretin research and triple active balancing technology. It is expected to enter phase 2 this year.

HM17321 is a CRF2 receptor agonist that induces weight loss while simultaneously increasing muscle mass. We have secured an optimized structure through HARP, an AI-based drug design platform, and expect to enter phase 1 this year. In particular, it will be differentiated from existing myostatin inhibitors in terms of improving muscle function.

Q: What do you mean by “qualitative weight loss,” which you claim as HM15275's advantage over existing therapies?

A: In the treatment of obesity, it's not just the number of kilograms that matters, but the change in body composition. HM15275 has the molecular physiology to selectively lose fat while maintaining muscle mass.

Transcriptomic analysis showed that it activates lipolytic genes while inhibiting muscle amino acid breakdown. These pharmacologic actions will be validated in subsequent clinical studies using quantitative metrics, such as DXA, MRI, and muscle function tests, to demonstrate functional muscle gain rather than just numerical muscle gain.

Q: It was interesting to hear that HM17321 also increases muscle. What are the specific mechanisms by which it does so?

A: Existing GLP-1 drugs are effective for weight loss, but have the limitation that they are accompanied by muscle loss. HM17321 is a UCN2 analog that selectively binds to the CRF2 receptor and exhibits a novel mechanism of action, which can reduce fat and increase muscle mass.

This resulted from optimizing pharmacological properties and receptor selectivity by actively utilizing Hanmi's AI-driven Research Platform (HARP), an internal artificial intelligence and structural modeling platform.

In particular, myostatin/activin pathway antibodies, which are being developed as drugs to increase or preserve muscle mass, have not yet demonstrated improved muscle function or enhanced motility. Existing pipelines in development may increase muscle mass, but there is still uncertainty about whether the muscle is metabolically and functionally intact.

Furthermore, safety-related adverse events, such as elevations in liver enzymes (ALT/AST) and lipid levels (LDL, TG), have been reported and require further confirmation of safety in long-term use. Additionally, the relatively high cost of antibody-based drugs compared to peptide-based drugs is also a significant burden.

In this regard, HM17321 is expected to have a significant differentiation in terms of pharmacology, efficacy, and cost.

Q: In addition to weight loss, what are the key metrics you want to demonstrate clinically?

A: Aside from weight loss, the key metrics we want to demonstrate clinically are body composition changes (fat vs lean mass), improved muscle function, and metabolic normalization. DXA can be used to first measure how much of the weight loss is due to fat and how much is due to lean tissue, and imaging modalities such as MRI can be used to more precisely measure changes in muscle mass (for example, intramuscular fat content).

For functional improvement, a less direct approach is to utilize physical function domain scores from clinical trial participant questionnaires, such as the IWQOL-CT or SF-36. The hand-grip test, six-minute walking test, and stair climb test are among the most widely recognized methods for assessing physical function in relation to weight loss and changes in muscle mass.

These metrics are key to demonstrating therapeutic value beyond simple weight numbers. Our products’ competitors, bimagrumab, developed by Eli Lilly, and trevogrumab/garetosmab, developed by Regeneron, are also in clinical trials using these metrics.

We are also considering a multidimensional clinical design that examines systemic metabolism and body function, rather than relying solely on a single weight measure, to reflect this global standard. We plan to demonstrate the differentiated value of both pipelines by this.

Q: What are your clinical development plans for both pipelines?

A: HM15275 is expected to enter phase 2 in the second half of next year. We plan to expand to the maximum dose of 8 mg and beyond, as well as clinical trials in patients with co-morbid diabetes. HM17321 is expected to enter phase 1 following IND submission later this year. After confirming safety, the study is designed to test muscle gain through repeated administration. In particular, we plan to utilize imaging techniques to demonstrate not only muscle mass improvement but also functional improvement.

Q: What is Hanmi Pharm's goal in the future obesity treatment market?

A: Currently, many patients still rely on surgical treatment for obesity due to high drug costs, muscle loss, and side effects. Hanmi Pharmaceutical aims to provide a “non-invasive and effective” alternative.

Through various mechanisms of action and pharmacological properties, we will build a lineup of treatments tailored to disease characteristics and present differentiated value in terms of cost, efficacy, and safety. We believe that this is not just about developing new drugs, but redefining the nature of obesity treatment.