Huadong Medicine's First-in-Class Triple Agonist DR10624 Shows Up to 89.2% Reduction in Liver Fat in Phase 1b/2a Trial

China Finance and Economics Network, May 12th: This evening, Huadong Medicine (000963.SZ) announced that the Phase Ib/IIa clinical trial results of DR10624, a globally pioneering long-acting triple agonist independently developed by its holding subsidiary Zhejiang Doer Biologics Co., Ltd. ("Doer Biologics"), for the treatment of obesity combined with hypertriglyceridemia in New Zealand, were presented for the first time at the "EASL Congress 2025" (European Association for the Study of the Liver Annual Meeting).

The announcement showed that the research results were selected as the latest breakthrough (Late-Breaker) at the conference, demonstrating the key study data of DR10624 in obese subjects with hypertriglyceridemia, which is expected to provide comprehensive benefits for MASLD/MASH patients.

DR10624, as a long-acting triple-target agonist, is a globally first-in-class candidate innovative protein drug targeting FGFR1c/Klothoβ (FGF21R), GLP-1R, and GCGR. DR10624 consists of an N-terminal chimeric peptide segment targeting GLP-1R/GCGR fused with an engineered IgG1 Fc, and a recombinant FGF21 mutant fused to the C-terminus of the Fc.

The DR10624 1b/2a clinical trial, which has been selected for the EASL 2025 Late-Breaker, is a randomized, double-blind, placebo-controlled, multiple-ascending-dose study conducted in New Zealand, showcasing key research data of DR10624 in obese subjects with hypertriglyceridemia.

The most impressive result disclosed in the Phase 1b/2a study of DR10624 is its potent efficacy in reducing liver fat. After 12 weeks of treatment, the relative reductions in liver fat content (LFC) from baseline in the DR10624 dose groups (12.5 mg, 25 mg, 50 mg, and 75 mg dose titration groups) were 51.9%, 77.8%, 79.0%, and 75.8%, respectively, significantly higher than the 26.3% reduction observed in the placebo group.

Figure: Relative change in liver fat (%) from baseline to Day 85

In subjects with baseline liver fat content ≥8%, the relative reductions in LFC from baseline in the DR10624 dose groups (12.5 mg, 25 mg, 50 mg, and 75 mg dose titration groups) were 58.3%, 83%, 89.2%, and 87.2%, respectively, significantly higher than the 27.2% in the placebo group.

Table: Changes in LFC after 12 weeks of treatment in subjects with baseline >8% (assessed by MRI-PDFF)

A relative reduction of 50% in LFC is generally considered in clinical practice to likely achieve histological remission of fatty hepatitis, or MASH resolution. After 12 weeks of treatment, the proportion of subjects achieving a relative reduction in LFC of ≥50% in each dose group of DR10624 (12.5 mg, 25 mg, 50 mg, and 75 mg dose titration groups) was 66.7%, 88.9%, 100%, and 85.7%, respectively. DR10624 also demonstrated significant efficacy in lowering blood lipids, with minimal side effects and high safety, greatly alleviating insulin resistance in subjects.

Currently, the DR10624 injection is undergoing Phase II clinical trials in China for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) with a high risk of liver fibrosis, as well as metabolic dysfunction-associated steatohepatitis combined with alcohol-related fatty liver disease. The first patient is expected to be enrolled by April 2025. Meanwhile, another Phase II clinical trial of DR10624 in China for the treatment of severe hypertriglyceridemia has completed full patient enrollment, with top-line results expected to be announced in the third quarter of 2025 after unblinding. Additionally, the clinical trial applications for DR10624 for type 2 diabetes and weight management indications have been successively approved in China.

GLP-1 (Glucagon-like Peptide 1) is currently a major target and popular field in global new drug development. The mechanism of GLP-1 is diverse, with various drug forms such as peptides and small molecules, and it is widely used in multi-target differentiated drug design. Notably, most of the multi-target agonists currently under research globally are concentrated in the GLP-1/GIPR and GLP-1/GCGR fields, and most drug designs focus on dual targets. There is still no long-acting triple-target agonist targeting GLP-1R, GCGR, and FGF21R available on the market. Dongwu Securities pointed out that the clinical effects of triple-target drugs are significantly better than those of single-target and dual-target drugs. From a trend perspective, the number of new multi-target molecules under research is gradually increasing, and the superiority of multi-target over single-target is becoming a consensus.

Huadong Medicine stated that the company highly values innovation capabilities, with R&D efforts mainly focused on three areas: endocrinology, autoimmune diseases, and oncology. Currently, the innovative drug pipeline has exceeded 80 projects. Additionally, investment in R&D continues to increase.

According to the annual report, Huadong Medicine's industrial R&D investment (excluding equity investments) reached 2.678 billion yuan, increasing by 16.77% year-on-year. Of this, direct R&D expenditure amounted to 1.77 billion yuan, marking a year-on-year increase of 10.63%, with direct R&D expenditure accounting for 12.91% of pharmaceutical industrial revenue. Moreover, Huadong Medicine is actively deploying AI technology to enhance drug R&D and production efficiency.