D&D Pharmatech Begins Phase 2 Trial Dosing for DD01 in Overweight/Obese MASLD/MASH Patients

D&D Pharmatech, Inc., a biotechnology firm based in Gyeonggi-do, South Korea and Gaithersburg, Maryland, has initiated dosing in a Phase 2 clinical trial to assess the efficacy and safety of DD01 in overweight and obese individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH). DD01 is a long-acting dual GLP-1/glucagon receptor agonist known to quickly resolve hepatic steatosis, improve glycemic control, and reduce body weight in patients with fatty liver disease.

The Phase 2 trial is structured as a randomized, double-blind, placebo-controlled, biopsy-driven study involving around 68 participants from approximately 12 sites across the United States. The participants, all overweight or obese (BMI ≥25kg/m^2) with biopsy-confirmed MASH or MASLD, will be randomly assigned in a 1:1 ratio to receive either 40 mg DD01 or a placebo once weekly over 48 weeks. The primary goal is to observe the proportion of participants achieving at least a 30% reduction in liver fat, as measured by MRI-PDFF, from baseline to Week 12. Secondary and exploratory endpoints include assessments of MASH resolution, fibrosis improvement, HbA1c levels, and overall body weight reduction over the 48-week period.

Previous Phase 1 trials of DD01 in overweight and obese patients with type 2 diabetes (T2D) and MASLD indicated that DD01 was generally safe and well-tolerated at doses up to 80 mg per week. Remarkably, within just four weeks of treatment, up to 100% of patients exhibited more than a 30% reduction in liver fat by MRI-PDFF, with an average relative reduction exceeding 50% in pooled analyses of 40 mg and 80 mg doses. These rapid improvements in liver steatosis were associated with decreased HbA1c in diabetic subjects and reductions in liver enzyme levels and serum lipids. Patients receiving 40 mg or 80 mg of DD01 also experienced modest weight loss, unlike those receiving a placebo.

The trial’s findings are supported by preclinical studies in obese mice and monkeys, which demonstrated that DD01 is more effective at reducing liver fat and promoting weight loss compared to diet or GLP-1 treatment alone. The dual-action mechanism preserves glucagon’s lipolytic effects while balancing them with GLP-1's anorectic and anti-diabetic properties, producing a comprehensive therapeutic effect. Preclinical models showed that DD01 treatment led to notable reductions in liver steatosis, lobular inflammation, hepatocyte ballooning, and fibrosis.

DD01 has been granted Fast Track designation by the US FDA for treating adults with MASLD/MASH. The company’s President and CEO, Seulki Lee, Ph.D., highlighted the study’s significance, noting that dual agonism of GLP-1 and liver-directed glucagon receptors could offer more effective treatment for MASH compared to GLP-1 analogs alone. Given DD01’s promising results in earlier studies, the Phase 2 trial aims to achieve clinically meaningful rates of MASH resolution and fibrosis improvement.

DD01 is notable for its dual receptor agonist mechanism, targeting both GLP-1 and glucagon receptors, leading to rapid and significant reductions in liver fat within just four weeks in MASLD patients. In preclinical models, DD01 induced substantial weight loss, reduced liver fat and fibrosis, and improved glucose tolerance.

D&D Pharmatech specializes in developing innovative treatments for metabolic, fibrotic, and neurodegenerative diseases. Their pipeline includes several promising candidates, such as NLY01 for Parkinson’s disease and TLY012 for fibrotic diseases, reflecting their focus on long-acting and orally active peptide drugs.