New K-drugs for metabolic diseases make international debut

Offering diverse formulations and mechanisms of action

Hanmi, Ildong, Dong-A, Inventage Lab, and others announce results of new obesity drugs at the American Diabetes Association

Diverse products ranging from triple agonist drugs, oral drugs, long-acting injectable drugs, etc... developed drugs for MASH treatment

Major Korean pharmaceutical and biotechnology companies have signaled their full-scale entry into global clinical trials, presenting new drug development results at overseas conferences.

 

The companies presented their achievements in developing new drugs for various metabolic diseases, including obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH).

 

Although most of the data disclosed is focused on early clinical or preclinical trials, the companies are attempting to diversify their mechanisms of action with triple agonists and oral small molecule formulations.

 

Hanmi reveals triple agonist data...

 

Oral and long-acting injectable formulations are also under development

30According to industry sources, the American Diabetes Association Diabetes Conference was held in Chicago, USA, from the 21st to the 24th.

 

At the conference, various domestic companies, including Hanmi Pharmaceutical, Ildong Pharmaceutical, Dong-A ST, and Inventage Lab, revealed the clinical results of their novel drug candidates.

 

Obesity drugs are rapidly emerging as a global R&D trend.

 

With Novo Nordisk and Lilly's GLP-1-based obesity treatments becoming global blockbuster drugs, latecomers are also intent on developing their versions.

 

Major domestic companies are conducting clinical studies on GLP-1 agonists in various areas, including obesity and MASH with drugs that have different methods of administration or focus on the quality of weight loss effects.

 

Hanmi Pharmaceutical announced the results of its Phase I clinical trials and preclinical data for HM15275, a GLP-1 class triple agonist, and HM17321, a UCN2-based candidate substance, at the conference.

 

First, Hanmi Pharmaceutical announced the results of the Phase I clinical trial for HM15275.

 

HM15275 is a new obesity drug candidate that acts on glucagon-like peptide (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon (GCG).

 

No new drug with this mechanism targeting all three has been commercialized to date.

 

The Phase I clinical trial was conducted on 74 healthy and obese adults.

 

HM15275 was administered subcutaneously once a week for four weeks, followed by an evaluation of the candidate drug’s safety, tolerability, pharmacokinetics, and pharmacodynamics.

 

The results confirmed HM15275’s tolerability and safety.

 

Specifically, the average weight loss rate at day 29 in the highest dose group was 4.8%.

 

At day 43, the maximum weight loss rate was 10.6%.

 

Preclinical data for HM15275 demonstrated greater weight loss efficacy compared to semaglutide (brand name Wegovy) and tirzepatide (Zepbound), which are currently marketed as obesity treatments.

 

In animal models, switching from tirzepatide to HM15275 resulted in additional weight loss effects.

 

Hanmi Pharmaceutical also announced the results of preclinical studies on HM17321, a new drug candidate that simultaneously targets weight loss and muscle gain.

 

HM17321 is a UCN-2 analogue that selectively targets the CRF2 (corticotropin-releasing factor 2) receptor rather than GLP-1 or other incretin receptors.

 

It is being developed as an innovative first-in-class drug that selectively reduces fat while increasing muscle mass.

 

HM17321 demonstrated weight loss effects and improved body composition in both mouse models and non-human primate models.

 

Yunovia, a subsidiary of Ildong Pharmaceutical Group specializing in new drug research and development, is conducting Phase I clinical trials for ID110521156, a GLP-1 receptor agonist class new drug candidate targeting metabolic disorders such as diabetes and obesity.

 

ID110521156 is a low-molecular-weight compound-based drug, and the company aims to develop it as an oral synthetic new drug for diabetes and obesity with distinct advantages such as superior productivity and excellent ease of use over existing representative treatments like peptide injections.

 

Previously, Yunovia confirmed the efficacy of insulin secretion and blood glucose control through preclinical efficacy and toxicity evaluations.

 

It also demonstrated superior safety compared to competing drugs in the same class and confirmed the drug's characteristics in a recently completed Phase 1 single-ascending dose (SAD) trial.

 

According to the study poster presented at the conference, in the single-dose escalation trial, ID110521156 demonstrated good tolerability with fewer gastrointestinal side effects across the entire effective dose range, unlike existing GLP-1 class drugs.

 

Inventage Lab also introduced preclinical data for its 1-month long-acting injectable formulations ‘IVL3021’ and ‘IVL3024’ based on semaglutide and tirzepatide, as well as its oral semaglutide formulation ‘IVL3027.’ After GLP-1 class obesity treatments such as Saxenda, Wegovy, and Zepbound emerged as global blockbuster drugs, the pharmaceutical industry has been actively pursuing formulation changes.

 

The existing drug Saxenda requires a once-daily injection, while Wegovy and Zepbound require weekly injections.

 

Oral formulations or long-acting injectables are expected to gain a competitive edge in terms of convenience of administration if commercialized.

 

According to the company's preliminary preclinical results, IVL3021 showed stable drug release in the blood over a one-month period.

 

Also, the long-acting injectable suppressed initial over-release and maintained stable drug release.

 

IVL3027 demonstrated high bioavailability compared to existing oral formulations and sustained drug release over a one-week period.

 

Poster presentation by Inventage Lab (Source=Inventage Lab).

MASH clinical trial results also announced Dong-A ST and its subsidiary MetaVia announced the results of non-clinical studies on DA-1241, which is being developed as a treatment for MASH, and combination therapy that uses efruxifermin, a fibroblast growth factor (FGF21) analog.

 

Metabolic dysfunction-related fatty liver disease was previously referred to as non-alcoholic steatohepatitis (NASH), but overseas academic societies such as the American Association for the Study of Liver Diseases have decided to change the name to metabolic dysfunction-associated steatohepatitis (MASH).

 

To date, Madrigal's rezdiffra is the only new drug for MASH that has cleared regulatory hurdles.

 

The U.S.

 

Food and Drug Administration (FDA) approved rezdiffra in March last year for the treatment of adult patients with non-cirrhotic MASH in combination with diet and exercise.

 

Rezdiffra is a selective thyroid hormone receptor (THR)-β agonist designed to target the core pathophysiological mechanisms of MASH within the liver.

 

The pharmaceutical industry is also developing new drugs for MASH that target not only THR-β but also GLP-1 and FGF21, which influence lipid metabolism.

 

DA-1241 is a synthetic new drug that activates GPR119.

 

Preclinical results have confirmed that DA-1241 improves blood sugar and lipid levels and directly acts on the liver to improve inflammation and fibrosis, making it a promising candidate for MASH treatment.

 

A Phase 2a clinical trial targeting patients with estimated MASH was completed in December last year.

 

Efruxifermin is a recombinant protein designed based on FGF21 (Fibroblast Growth Factor 21), a hormone secreted by the liver.

 

FGF21 is involved in energy consumption and the regulation of glucose and lipid metabolism in the body and is used as a target for the development of treatments for MASH, obesity, diabetes, and other conditions.

 

According to the study results presented at the conference, in the DA-1241+efruxifermin combination therapy group, approximately 94% of subjects showed an improvement of 2 points or more in NAS (Non-Alcoholic Steatohepatitis Activity Score) compared to baseline.

 

Additionally, the DA-1241+efruxifermin group showed a significant reduction in liver fibrosis area compared to the MASH control group that did not receive combination therapy, and in some individuals, a decrease in fibrosis stage was observed compared to pre-treatment levels.

 

Dong-A ST is currently conducting clinical studies on the combination therapy of DA-1241 with semaglutide, a GLP-1 agonist, in addition to a Phase II clinical trial on DA-1241 as monotherapy.