RG7985 / Hanmi, Roche, Genentech - LARVOL DELTA

Daol Securities lifts Hanmi Pharma target as obesity pipeline gains value (Chosun Biz) - "Lee Ji-su, an analyst at Daol Investment & Securities, said, 'HM17321 (LA-UCN2) is a peptide therapy that targets fat reduction and muscle gain at the same time. 'Lee also saw expectations rising for the follow-up obesity treatment pipeline, the triple agonist HM15275 (LA-TRIA)....Lee said, 'HM15275 is expected to complete phase 2 in the first half of next year,' and analyzed, 'if the favorable tolerability and weight-loss effect confirmed in phase 1 are also demonstrated in phase 2, expectations for additional technology transfer will expand significantly.'"

Commercial • Trial completion date • Obesity

Hanmi Pharm announced today that it has entered into an exclusive licensing agreement with Genentech…for the development, manufacturing, and commercialization of Hanmi's novel metabolic treatment candidate, HM17321 (UCN2), for obesity and associated conditions such as type 2 diabetes and cardiovascular diseases, worldwide (PRNewswire) - "The agreement excludes South Korea....Under the terms of the agreement, Hanmi will receive an upfront payment of USD 190 million from Genentech. Including development, regulatory, and commercial milestone payments, the total deal value could reach approximately USD 2.3 billion. In addition, Hanmi will be eligible to receive tiered royalties on future product sales following commercialization."

Licensing / partnership • Cardiovascular • Obesity • Type 2 Diabetes Mellitus

Hanmi showcases AI platform behind clinical-stage obesity drug at ISMB (Korea Biomedical Review) - "Hanmi Pharmaceutical, the flagship affiliate of Hanmi Science, said Friday that it presented research demonstrating how its proprietary AI platform, HARP-pSAR, was used to generate a muscle-enhancing obesity drug pipeline at the International Conference on Intelligent Systems for Molecular Biology (ISMB), held in Washington, D.C., from July 12 to 16...HM17321 represents a new class of obesity therapy that goes beyond preventing muscle loss by simultaneously increasing muscle mass while selectively reducing body fat—a therapeutic profile long considered unattainable...Using only several dozen internally generated experimental datasets, Hanmi built predictive models capable of accurately estimating activity against both target and off-target receptors."

Clinical • Obesity

Research results related to HM17321, which is undergoing phase 1 clinical trials in the United States, have also been disclosed. (Maeil Business Newpaper) - "HM17321 is a candidate that aims to simultaneously reduce fat and increase muscle, improve motor and metabolic functions. At this conference, the results of research evaluating the effects of musculoskeletal, cardiovascular, and kidney protection as well as the possibility of using various mechanisms of drugs were published."

P1 data • Obesity

HM17321, a Novel UCN2 Analog, Improves Weight Loss Quality in Combination with Amylin Analogs in DIO Rats (ADA 2026) - "Here, we evaluated a novel combination potential of HM17321 and amylin analogs. Combination efficacy of HM17321 and amylin analogs (cagrilintide, petrelintide, and eloralintide) was evaluated in DIO rats. In DIO rats, combination treatment of HM17321 with amylin analogs enhanced FM reduction while promoting LM gain, leading to marked improvement in WLQ. These findings highlight the unique potential of HM17321 to improve body composition during weight loss and support its development both as a monotherapy and as a combination partner for amylin- or incretin-based therapies."

Combination therapy • Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity

Cardioprotective Effects of HM17321, a Novel UCN2 Analog, in Rodent Heart Failure Models and a Translational Nonhuman Primate Model (ADA 2026) - "HM17321 improved cardiac function and attenuated pathological cardiac remodeling in rodent HF models and a non-human primate model. These findings suggest that HM17321, developed as an anti-obesity therapy for improved WLQ, may also represent a novel therapeutic option for HF, supported by cardiovascular effects observed in primates."

Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity

Temporal Mechanistic Shifts Underlying Sustained Muscle Growth by HM17321 Revealed by Tissue Proteome Analysis (ADA 2026) - "HM17321 induces sustained muscle augmentation via early enrichment of sarcomere assembly and later-phase stabilized hypertrophic signaling. By maintaining the mTOR-mediated muscle growth, HM17321 ensures sustained weight loss while improving muscular mass and function, highlighting its potential to protect musculoskeletal health in obesity management."

Metabolic Disorders • Obesity

Cardiorenal Protective Effects of a CRFR2-Selective UCN2 Analog, HM17321, in Spontaneously Hypertensive Rats (SHR) (ADA 2026) - "HM17321 exerted integrated cardiovascular and renal protective effects in preclinical models of hypertension and kidney injury. Beyond its favorable impact on WLQ as a next-generation obesity therapy, HM17321 attenuated the progression of renal dysfunction, supporting its potential applicability as a therapeutic strategy for cardiorenal diseases."

Preclinical • Metabolic Disorders • Obesity

Body Composition and Functional Outcomes of HM17321, a CRFR2-Selective UCN2 Analog, Alone and in Combination with Myostatin/Activin Inhibition in DIO Mice (ADA 2026) - "Clinical studies combining incretin therapies with myostatin/activin pathway inhibition, such as bimagrumab (Bima), suggest benefits for WLQ. HM17321 induced fat-selective BWL with functional lean mass gain in both sexes, supporting its potential as a novel foundational WLQ therapy. These findings provide proof-of-concept for additional benefits of incorporating myostatin/activin pathway inhibition for body weight and body composition, warranting longer-term evaluation."

Combination therapy • Preclinical • Metabolic Disorders • Obesity

Protective Effects of HM17321, a Novel UCN2 Analog, on Obesity-Associated Musculoskeletal Diseases in Mouse Models (ADA 2026) - "HM17321 resulted in a significant fat reduction simultaneously increasing lean mass in obesity-associated OA and OP mice. These favorable changes in body composition, beyond simple weight loss, may contribute to more effectively improve obesity-associated OA and OP."

Preclinical • Metabolic Disorders • Obesity • Osteoporosis

HM17321, a CRFR2 Selective UCN2 Analog, Prevents Muscle Loss and Functional Decline in Sarcopenic Mice (ADA 2026) - "HM17321 attenuated sarcopenia across multiple etiologies by preserving muscle mass, function, and structural integrity. These findings support the potential of HM17321 as a therapeutic approach for sarcopenia."

Preclinical • Metabolic Disorders • CLSPN,

Body Composition and Functional Outcomes of HM17321, a CRFR2-Selective UCN2 Analog, Alone and in Combination with Myostatin/Activin Inhibition in DIO Mice (ADA 2026) - "Clinical studies combining incretin therapies with myostatin/activin pathway inhibition, such as bimagrumab (Bima), suggest benefits for WLQ. HM17321 induced fat-selective BWL with functional lean mass gain in both sexes, supporting its potential as a novel foundational WLQ therapy. These findings provide proof-of-concept for additional benefits of incorporating myostatin/activin pathway inhibition for body weight and body composition, warranting longer-term evaluation."

Combination therapy • Preclinical • Metabolic Disorders • Obesity

Results from eight studies on two new muscle-building obesity drugs to be presented at the ADA in June [Google translation] (Hanmi Press Release) - "The next-generation muscle-enhancing therapeutic 'LA-MSTN (HM500197),' being unveiled for the first time, is a new pipeline distinct from the existing innovative obesity drug 'LA-UCN2 (HM17321).' With this, Hanmi Pharmaceutical is assessed to have secured two pillars of next-generation drug pipelines in the field of muscle-enhancing obesity treatment. In particular, it is garnering significant anticipation as the development strategy, differentiation points, and preclinical research results of HM500197 are scheduled to be announced for the first time."

Preclinical • Obesity

A Single and Multiple Ascending Dose Study of HM17321 in Healthy and Obese Participants (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Apr 2026 ➔ Mar 2027 | Trial primary completion date: Apr 2026 ➔ Mar 2027 | N=40 ➔ 90

Enrollment change • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Hanmi Pharmaceutical is also pushing to license out HM17321, a first-in-class obesity drug designed to increase muscle mass. (Business Korea)

Licensing / partnership • Obesity

A SAD Study of HM17321 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

…Hanmi Pharmaceutical presented three preclinical studies on HM17321, a novel drug engineered to simultaneously promote muscle hypertrophy and lipolysis, thereby achieving what the company describes as 'high-quality weight loss.' (BioNews) - "In addition, Hanmi Pharmaceutical reported that administration of HM17321 in a diet-induced obese animal model promoted muscle growth through activation of the mechanistic target of rapamycin (mTOR) signaling pathway in skeletal muscle....Another study presented by the company demonstrated distinct differences in body composition outcomes between HM17321 and semaglutide in a high-fat diet-induced obese animal model."

Preclinical • Obesity

Discovery of HM17321: A Novel CRFR2 Selective and Biased UCN2 Analog for High-Quality Weight Loss (OBESITY WEEK 2025) - "HM17321, a novel long-acting, CRFR2-selective, and biased UCN2 analog, demonstrates significant potential as next-generation obesity and related metabolic disease medication. The synergy between the mechanistic goals for metabolic improvement and the structural insights into the involved molecules, coupled with the strategic application of AI technologies, led to the design of a promising therapeutic candidate. This seamless integration of computational tools and biological knowledge highlights the significant impact of collaborative approaches in driving progress in drug development."

Genetic Disorders • Metabolic Disorders • Obesity

HM17321 Promotes High-Quality Weight Loss and Improves Metabolic Health in Obesity Treatment (OBESITY WEEK 2025) - "Urocortin-2 (UCN2) has been proposed to promote muscle hypertrophy and lipolysis, which may contribute to improved weight loss quality (WLQ) and whole-body metabolism through the preservation of lean mass. HM17321 demonstrated a unique profile by achieving high-quality weight loss through favorable body re-composition, especially characterized by increased lean mass. In addition, HM17321 provided metabolic benefits such as enhanced energy expenditure and improved glycemic control, supporting the fact that HM17321 enhances not only muscle mass, but also its metabolic functionality. These findings position HM17321 as a promising next-generation therapeutic candidate for obesity and related metabolic disorders, with the potential to be used in combination with incretin-based therapies."

Genetic Disorders • Metabolic Disorders • Obesity

Blood and Muscle Proteomic Analysis Reveals Muscle-Preserving Effects of HM17321 in Mouse Model (OBESITY WEEK 2025) - "HM17321 is a novel corticotropin-releasing factor receptor 2 (CRFR2)-selective and biased urocortin-2 (UCN2) analog that has exhibited dual effects of fat mass loss and lean mass gain in diet-induced obesity (DIO) mouse model. Proteomic analysis in this study suggests that HM17321 directly acts on skeletal muscle to increase muscle mass and improve metabolism, irrelevant with its weight loss effect. These findings highlight its potential to improve the weight loss quality, supporting HM17321 as a next generation therapeutic option for obesity management."

Omic analysis • Preclinical • Genetic Disorders • Obesity

Korea’s Hanmi Pharmaceutical has begun a U.S. phase 1 study after the FDA cleared its investigational new drug application (NDA) for an obesity drug candidate the company says can reduce fat while increasing muscle (Korea Biomedical Review) - "Hanmi said HM17321 has shown preclinical efficacy in overweight and obese nonhuman primate models and is being advanced toward a 2031 launch target."

IND • Launch US • Obesity

A SAD Study of HM17321 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Hanmi Pharmaceutical Company Limited

New P1 trial • Genetic Disorders • Obesity

Hanmi Pharmaceutical said on the 1st that it has submitted a clinical trial plan for the obesity drug HM17321 to the U.S. Food and Drug Administration (FDA). (Chosun Biz) - "The company plans to evaluate safety and tolerability in a phase 1 clinical trial in healthy adults....The goal is commercialization in 2031."

IND • Launch • New P1 trial • Obesity

Efficacy of the novel UCN2 analogue HM17321 in weight loss without muscle wasting in obese non-human primates and its applications with incretins in obese mice (EASD 2025) - "The fat reducing efficacy of HM17321 without muscle wasting was confirmed in non-human obese primates, highlighting its potential as a monotherapy for obesity treatment with human relevance. Along with its human relevance, applications for the best quality in weight loss through various dosing regimens were also confirmed. These findings suggest that HM17321 could be a promising therapeutic option for treating obesity."

Preclinical • Metabolic Disorders • Obesity

A novel CRFR2 selective UCN2 analogue, HM17321, enhances favourable body recomposition, energy expenditure and metabolic health in DIO mice (EASD 2025) - "HM17321 monotherapy uniquely promoted favorable body recomposition by selectively reducing fat mass while increasing lean mass in DIO mice. The body recomposition could directly contribute to the increase in basal metabolic rate (BMR), as evidenced by elevated energy expenditure. Furthermore, HM17321 improved overall metabolic health, reinforcing its potential as a next-generation therapeutic for obesity and metabolic disorders."

Preclinical • Metabolic Disorders • Obesity