D&D Pharmatech announced positive 12-week interim results from its Phase 2 trial of DD01, a once-weekly dual GLP-1/glucagon receptor agonist for metabolic dysfunction-associated steatohepatitis (MASH), demonstrating rapid and robust liver fat reduction that matches competitor results achieved over much longer treatment periods.
The DD01-DN-02 study, conducted across 12 U.S. centers in 67 overweight and obese patients with MASH, met its primary endpoint with 75.8% of DD01-treated subjects achieving at least a 30% reduction in liver fat at 12 weeks compared to 11.8% in the placebo group (p < 0.0001). The mean liver fat reduction was 62.3% in the DD01 group versus 8.3% with placebo.
Competitive Performance in Accelerated Timeline
The results position DD01 favorably against established competitors in the MASH space. Boehringer Ingelheim's servodutide recorded a 76.9% reduction in the proportion of patients with more than 30% liver fat reduction and an average reduction rate of 64.3% when administered at 6 mg for 48 weeks in completed Phase 2 trials.
"DD01 achieved similar levels of effectiveness in clinical trials over 48 weeks of Boehringer Ingelheim's competitive drug (Serbodutide) in just 12 weeks," said Lee Seul-ki, CEO of D&D Pharmatech. "As the administration continues until 48 weeks, we expect better results in the future."
The drug demonstrated even more pronounced effects at higher reduction thresholds, with 72.7% of patients achieving greater than 50% liver fat reduction and 57.6% achieving greater than 70% reduction. Notably, 48.5% of DD01-treated patients achieved normalization of liver fat levels (defined as less than 5% liver fat fraction), compared to no patients in the placebo group.
Superior Tolerability Profile
DD01 showed significant advantages in tolerability compared to competing GLP-1 based therapies. Only 9.09% of patients (3 out of 33) discontinued treatment due to gastrointestinal side effects, despite receiving the full 40 mg maintenance dose after just two weeks of titration at 20 mg.
"Despite the gradual increase in servodutide for 24 weeks, 20% of patients discontinued treatment due to side effects," Lee noted. "DD01 has the property of being slowly absorbed by the body, so it was possible to administer it stably with only a short increase of two weeks."
The favorable tolerability profile is attributed to DD01's unique pharmacokinetic properties, including very slow absorption (tmax = 6 days) and a long half-life (7-8 days), which create gradual exposure increases and avoid peaks associated with poor tolerability.
Non-Invasive Markers Show Disease Improvement
Beyond liver fat reduction, DD01 treatment was associated with statistically significant improvements in key non-invasive markers of MASH progression. Patients showed improvements in liver stiffness measured by magnetic resonance elastography (MRE), proC3 levels, and Enhanced Liver Fibrosis (ELF) scores at 12 weeks.
"The degree of liver fat reduction with DD01 is striking, with nearly three-quarters of patients achieving at least a 30% reduction and almost half reaching normalization within just 12 weeks," commented Mazen Noureddin, MD, MHSc, Professor of Medicine at Houston Methodist Hospital. "The observed improvement in liver stiffness by MRE, though early, adds further support to the biological activity of this dual GLP-1/glucagon approach, which is designed to act directly on the liver."
Metabolic Benefits Beyond Liver Health
The trial also demonstrated significant metabolic improvements. Despite the study population not being selected for diabetes, DD01 treatment resulted in statistically significant HbA1c reduction compared to placebo. Additionally, 42.4% of DD01-treated subjects achieved greater than 5% weight reduction at 12 weeks, while placebo-treated subjects showed no significant weight loss.
"The high proportion of GLP-1 action is effective not only in weight loss but also in blood sugar control, and blood sugar levels have decreased significantly compared to placebo in the patient group with actual diabetes," Lee explained.
Mechanism and Market Position
DD01's dual-agonist mechanism targets both GLP-1 and glucagon receptors with an 11:1 potency ratio. The glucagon component is designed to act directly on the liver, differentiating it from pure incretin approaches where liver benefits may be secondary to weight loss.
"Wigobi and Jebbound induce MASH improvement through indirect mechanisms, but DD01 is a structure that directly targets the liver to amplify the therapeutic effect," Lee added.
The MASH treatment landscape has been challenging, with the condition often called the "grave of new drug development" due to difficult clinical success rates. Madrigal's Rezdiffra received the first FDA approval for MASH in March 2023, renewing market interest in the space where global pharmaceutical companies including Boehringer Ingelheim, Merck, and Altimmune are competing in Phase 2 and 3 trials.
Future Development Plans
D&D Pharmatech plans to continue the 48-week trial to evaluate histological endpoints including MASH resolution and fibrosis improvement through liver tissue biopsy, which are required for FDA approval. Results from these major evaluation endpoints are expected in the first half of next year.
The company has received FDA Fast Track Designation for DD01 in MASH treatment and is seeking technology transfer partnerships with global pharmaceutical companies by the end of the year. "I think the results of phase 2 clinical trials are enough for global pharmaceutical companies to have confidence," Lee stated.
