[Edaily Reporter NA EUN-KYUNG ] Lose fat while preserving muscle. As Roche has discontinued emugrovat—a candidate it was developing to counteract muscle loss during obesity treatment—the role of “HM17321,” a technology licensed by HanmiPharm(128940)to Roche subsidiary Genentech, is coming to the fore. HM17321 goes a step further than simply preserving and increasing muscle mass; it aims to improve both strength and blood sugar control.

To this end, HanmiPharm has considered combination therapy with existing weight-loss drugs from the development stage. The plan is to combine HM17321 with drugs that reduce appetite to promote weight loss, thereby reducing fat while simultaneously improving muscle mass and function. Choi In-young, Head of the Future Growth Division (Vice President) at HanmiPharm, emphasized in an interview with E-Daily on the 30th, “One of the advantages of HM17321 is that it can be used in combination not only with simple glucagon-like peptide-1 (GLP-1) agents but also with dual- and triple-action agents, as well as other obesity treatments beyond incretins.”

Roche also highlighted the potential for combining HM17321 with existing obesity drugs. However, the discontinuation of Emugrovat does not necessarily prove the superiority of HM17321. Roche explained that the decision to discontinue Emugrovat was not due to the introduction of HM17321, but rather because the clinical data for that candidate failed to meet development criteria.

Beyond Weight Loss to Body Composition… The Role of HM17321 Highlighted

At “Roche PharmaDay 2026,” held in London, UK, on the 28th (local time), Roche highlighted the potential for combining HM17321 with incretin-based obesity treatments. Incretins are gut hormones secreted in response to food intake that play a role in insulin secretion and blood glucose regulation. Existing obesity treatments utilize the action of these hormones to suppress appetite and reduce body weight.

Roche’s obesity treatment portfolio includes “eniseptide,” a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, and “CT-996,” an oral GLP-1 receptor agonist. In addition, the company is developing “petrelinotide,” which utilizes amylin, a hormone distinct from incretins.

Even if the number on the scale remains the same, the significance of weight loss varies depending on what is lost. Incretin-based drugs reduce food intake by regulating appetite and satiety, but this weight loss process may be accompanied by a loss of lean body mass. Lean body mass is the portion of body weight excluding fat and includes muscle, body water, and organs. While not all loss of lean body mass can be attributed to muscle loss, excessive reduction in muscle mass can lead to problems such as decreased muscle strength and impaired physical function.

In contrast, HM17321 is a non-incretin-class urocortin-2 (UCN2) analog that distinguishes itself from these drugs. It selectively acts on the corticotropin-releasing factor 2 (CRF2) receptor to simultaneously target fat reduction and muscle preservation and growth. The combination strategy described by Roche is designed with the intention that, while incretin-class drugs reduce body weight, HM17321 complements this by improving body composition.

Regarding this announcement, Executive Vice President Choi explained, “This is proof that Roche also considers the quality of weight loss to be important,” adding, “Although this is preclinical, it can be seen as recognition of sufficient data. Furthermore, HM17321 has a unique advantage in that it can produce weight loss that is more specifically targeted at fat.”

Of course, an increase in muscle mass does not necessarily mean functional improvement. Even with a high muscle mass, insulin resistance can impair the body’s ability to process blood glucose. Vice President Choi noted, “Muscle is important not only for its mechanical function—generating force—but also for its metabolic functions, such as blood glucose regulation. In preclinical studies, HM17321 demonstrated both the mechanical and metabolic functions of muscle.” This means the company did not stop at simply increasing muscle mass but also examined whether the increased muscle functioned properly.

In animal studies presented by Roche, the additional weight loss observed with the combination of HM17321 and semaglutide resulted primarily from a reduction in fat mass, while lean body mass increased slightly. Manu Chakravarti, Vice President of Global Product Development for Cardiovascular, Renal, and Metabolic Diseases at Roche, commented, “If these results are replicated in humans, they could change the therapeutic paradigm.”

The ‘Brake’ and ‘Accelerator’ of Muscle Growth… A Different Approach

At the same event, Roche also announced the discontinuation of development for Emugrovat (GYM329), an obesity antibody candidate that targeted muscle tissue and had been considered an internal competitor to HM17321. Chugai Pharmaceutical, the original developer of Emugrovat, also announced Roche’s decision to return the rights on the same day. With Emugrovat’s removal, the role HM17321 will play in Roche’s body composition improvement strategy has become even more prominent.

Although both Emugrovat and HM17321 target muscle, they have different mechanisms of action. Emugrovat is an antibody that blocks myostatin, a protein that inhibits muscle growth. It works by releasing the “brakes” on muscle growth. In contrast, HM17321 is a candidate drug that mimics the action of UCN2, an endogenous peptide hormone that regulates muscle energy use and glucose metabolism. It aims to improve both muscle mass and metabolic function by selectively activating the CRF2 receptor, which is involved in muscle growth and energy metabolism.

However, the discontinuation of Emugrovat does not appear to negate the myostatin inhibition mechanism as a whole. Vice President Chakravarti also explained at the event that day, “The decision to discontinue Emugrovat was not due to the introduction of HM17321, but because the clinical data failed to meet the company’s development criteria.”

Consequently, analysts suggest it is difficult to directly apply this discontinuation to HM500197, another obesity drug candidate from HanmiPharm that utilizes the same myostatin inhibition mechanism. In particular, HM500197 is peptide-based, differing from the antibody-based Emugrovat in the form and size of its constituent molecules. While further verification is needed to determine whether these differences will translate into superior clinical efficacy in the future, HanmiPharm is currently presenting this as a favorable factor for the development of combination formulations with existing obesity treatments.

While the withdrawal of competing candidates may present an opportunity, it does not guarantee success for the remaining candidates. Roche, too, has been balancing the introduction of new candidates with the phasing out of existing ones, having faced market disappointment over gastrointestinal side effects associated with its oral obesity drug CT-996 and the weight-reduction efficacy of petrelintide. For HM17321, the challenge moving forward is to replicate in humans the fat reduction and muscle preservation effects observed in preclinical studies.

HanmiPharm plans to conduct Phase 1 clinical trials for HM17321 on its own through March 2027, after which Genentech will take over and lead development starting with Phase 2. However, Executive Vice President Choi emphasized that even if Phase 1 results are released in the future, one should be cautious about hastily judging the success or failure of HM17321 based solely on the extent of weight loss. He explained that significant weight loss over a short period does not necessarily indicate that a candidate obesity drug is highly competitive.

“Safety is the top priority in Phase 1 trials, and the dosing period is short,” he said. “If too much weight is lost in just four weeks, it could actually be due to severe side effects.” He went on to add, regarding the gastrointestinal side effects associated with existing weight-loss drugs, “We expect HM17321 to have advantages in that regard as well.”