Hanmi Pharm, NeuroBo unveil next-gen obesity drugs at Bioplus-Interphex Korea 2024

GLP-1 drugs for diabetes and weight loss have emerged as the latest blockbuster pharmaceuticals with Novo Nordisk and Eli Lilly's GLP-1-based obesity drugs taking the lead since June 2021, when Novo Nordisk’s Wegovy (semaglutide), the company’s first GLP-1, was launched in the U.S. 

The GLP-1 market is currently worth over $10 billion and is expected to reach $100 billion by 2030, industry watchers say.  D&D Pharmatech CEO Lee Seul-ki says the GLP-1 drug is becoming the “most successful drug in the history of pharmaceuticals.” 

On Tuesday, major domestic GLP-1 obesity drug developers shared their pipeline strengths and related indication changes at the "GLP-1: Expansion from Diabetes to Obesity, Heart Disease and Parkinson’s" session at Bioplus-Interphex Korea 2024 in COEX, southern Seoul, on Tuesday. 

To date, Eli Lilly’s Zepbound (tirzepatide) and Mounjaro (tirzepatide) stand as the only FDA-approved GLP-1-GIP dual agonists for weight loss, and there is no commercialized triple agonist that also includes glucagon on the market. 

Hanmi Pharm, a pharmaceutical giant, is aiming to fill this gap and develop the first-in-class drug in this category.

While second-generation medications such as tirzepatide—a GLP-1 and GIP dual agonist—have made significant strides, the focus now shifts to third-generation treatments. These new therapies must not only promote weight loss but also address other critical aspects, such as increasing energy expenditure through glucagon and providing a lasting sense of fullness.

“We are currently competing with the absolute purpose of losing weight,” said Choi In-young, head of the R&D center of Hanmi Pharm. “While current treatments are judged primarily by number of pounds lost, the future focus will likely be on the quality of that weight loss.”

“In the end, weight loss should be centered on body fat reduction, not overall weight loss.”

Hanmi Pharm is developing a new drug candidate — HM15275 — a next-generation GLP-1, gastric inhibitory peptide (GIP), and glucagon (GCG) triple agonist obesity drug. HM15275 is Hanmi’s sixth incretin-based drug to enter clinical trials and recently entered U.S. phase 1 clinical trials.

The company said that with proven efficacy and safety, incretin-based drugs will continue to hold a dominant position in the rapidly growing obesity market.

While clinical trials show that approximately 40 percent of the weight loss with Wegovy comes from lean mass loss, including muscle, leading to significant rebound weight gain once the medication is stopped, Choi said the HM15275 triple agonist “not only reduces fat mass but also increases muscle mass, making it a unique candidate.”

In early-stage laboratory tests with animals, HM15275 demonstrated the ability to reduce body weight by 25 percent, exceeding the 22.5 percent weight loss achieved by Mounjaro. 

“This weight loss is primarily due to fat mass reduction rather than muscle loss,” Choi said. "HM15275 also showed less muscle mass loss and higher overall weight loss than Eli Lilly's tirzepatide.”

This distinguishes HM15275 by ensuring that the quality of weight loss is superior, focusing on fat loss while preserving muscle mass, according to Choi. 

Hanmi Pharm plans to disclose more information at the ObesityWeek 2024 conference in November in San Antonio, Texas, the U.S. 

"There is still an unmet demand for the weight loss effects of GLP-1 obesity drugs such as Zepbound and Wegovy,” Choi said. “The quality of weight loss and reduction of the yo-yo effect will eventually be the key indicators of competitiveness,” Choi said.

Dong-A ST also diagnosed that as second-generation obesity drugs like Mounjaro and Zepbound have demonstrated weight loss effects of more than 20 percent, the market is demanding a treatment that is safe and has additional benefits.

Dr. Kim Mi-kyung, vice president at Dong-A ST and chief scientific officer of NeuroBo Pharmaceuticals, said the third-generation obesity drug, which focuses on “healthy weight loss” beyond the second-generation drugs that target appetite suppression, will become mainstream. 

She added that a comprehensive metabolic disorder treatment that minimizes muscle loss and treats diabetes and cardiovascular diseases is expected to be a "game changer" in the obesity drug market.

“The weight loss achieved through tirzepatide and semaglutide includes reductions in both fat and muscle,” she said. "This dual reduction is not ideal for long-term health, as preserving muscle mass is crucial, with limitations such as losing both weight and muscle and the inability to prevent rapid weight gain when stopping the drug.

During Eli Lilly’s presentation at J.P. Morgan last year, Daniel Skovronsky, chief scientific officer of the company said that in the company’s clinical trials on the efficacy of tirzepatide, “about half of the patients probably didn’t achieve their ultimate BMI body goal and didn’t get to normal body weight.”

NeuroBo has focused on increasing energy expenditure, as the company believes that merely suppressing appetite does not sufficiently address the quality of weight loss.

DA-1726, NeuroBo’s long-acting oxyntomodulin peptide analog that binds and activates both GLP-1 and glucagon receptors, was selected for development. DA-1726 has completed preclinical studies and is in phase 1 of clinical trials.

Preclinical data show that DA-1726 not only suppresses appetite but also enhances peripheral energy metabolism, leading to weight loss without the muscle loss typically seen with other treatments. Unlike other drugs that merely reduce food intake, DA-1726 demonstrated sustained weight loss and improved energy expenditure in preclinical models.

"DA-1726, which focuses on active balance, is a mechanism that suppresses appetite while increasing metabolism, and we have confirmed the differentiation of reducing body fat mass and significantly increasing muscle mass in animal experiments," Dr. Kim said.

DA-1726 also demonstrated similar weight loss efficacy despite higher food intake compared to trizepatide, with less rebound after weight loss.

"The U.S. FDA standard for approval of an obesity drug is a weight loss effect of 5 percent or more, but the market's standard is higher," said Dr. Kim. "We are focusing on the quality of weight loss."