D&D Pharmatech Announces Positive 48-Week Histology Results for Zabopegdutide (DD01), Demonstrating Statistically Significant Fibrosis Improvement and MASH Resolution

• All key histological endpoints achieved with statistical significance
• 50.0% of patients achieved ≥1-stage fibrosis improvement with no worsening of MASH, compared to 15.8% for placebo
• 62.5% achieved MASH resolution with no worsening of fibrosis, versus 5.3% for placebo
• 37.5% achieved both fibrosis improvement and MASH resolution, compared to 5.3% for placebo
• Results support potential best-in-class profile for once-weekly GLP-1/glucagon dual agonist in MASH

GYEONGGI-DO, South Korea & GAITHERSBURG, Md.--(BUSINESS WIRE)--D&D Pharmatech, Inc. (D&D) (KOSDAQ: 347850), a clinical-stage biotechnology company developing breakthrough treatments for liver and metabolic diseases, today announced positive top-line 48-week histology results from its Phase 2 trial (DD01-DN-02) evaluating zabopegdutide (DD01) in patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH).

Following the rapid and robust liver fat reduction observed at the Week 12 primary analysis (businesswire), the final 48-week biopsy data demonstrated that zabopegdutide produced significant histological improvements in patients with biopsy-confirmed MASH and fibrosis stage F1-F3. The study met all three key histological endpoints, demonstrating the potential of zabopegdutide to both resolve steatohepatitis and reverse liver fibrosis.

Key Histological Findings at Week 48

Note: Percentages represent responder rates in the Per Protocol population. P-values were calculated using the prespecified Cochran-Mantel-Haenszel (CMH) test as outlined in the study’s Statistical Analysis Plan.

The DD01-DN-02 study was a randomized, double-blind, placebo-controlled Phase 2 trial conducted at 12 centers in the United States. The study enrolled 67 overweight/obese subjects with MASH and significant liver fat who received a 2-week titration at 20 mg followed by a 40 mg once-weekly maintenance dose of zabopegdutide or placebo. The Week 48 Per Protocol population included 35 subjects with biopsy-confirmed MASH and fibrosis (F1-F3) who completed paired baseline and the Week 48 liver biopsies and demonstrated high adherence to the treatment regimen and study protocol.

The placebo-adjusted effect size for fibrosis improvement with no worsening of MASH was 34.2% (p=0.0323), while the placebo-adjusted effect size for MASH resolution with no worsening of fibrosis was 57.2% (p=0.0003). Notably, the placebo-adjusted effect size for achieving both fibrosis improvement and MASH resolution was 32.2% (p=0.0192). These histological improvements were accompanied by significant reductions in liver fat measured by MRI-PDFF, liver stiffness measured by MRE, and multiple fibrosis biomarkers.

"These 48-week results represent a major milestone for zabopegdutide and for patients living with MASH," said Seulki Lee, Ph.D., President and CEO of D&D Pharmatech. "While we were encouraged by the rapid fat reduction and early improvements in liver stiffness at Week 12, seeing these effects translate into statistically significant fibrosis improvement at Week 48 is particularly compelling. Achieving significance across MASH resolution, fibrosis improvement, and the composite endpoint further supports the differentiated potential of zabopegdutide as a next-generation therapy for MASH."

A Differentiated Mechanism for Disease Reversal

Zabopegdutide is a long-acting, once-weekly dual agonist targeting both GLP-1 and glucagon receptors. While GLP-1 receptor agonism provides powerful metabolic benefits and weight loss, the addition of glucagon receptor agonism directly enhances hepatic lipid metabolism and contributes to anti-fibrotic activity within the liver.

The Week 48 data further support the differentiated profile of dual GLP-1/glucagon agonism, demonstrating that rapid and profound reductions in liver fat and liver stiffness observed early in treatment are durable and can translate into meaningful histological improvements following long-term therapy. In addition to biopsy endpoints, zabopegdutide treatment demonstrated continued improvements in non-invasive markers of liver health, body weight, and glycemic control, including HbA1c.

“For clinicians managing progressive MASH, the absolute priority is to stop or reverse fibrosis before it leads to irreversible cirrhosis or hepatic decompensation. The fact that 50% of patients treated with zabopegdutide experience a ≥ 1-stage improvement in fibrosis in less than a year is highly encouraging for the hepatology community. Coupled with a well-tolerated safety profile and low discontinuation rates, zabopegdutide is positioning itself as an incredibly robust and viable next-generation therapeutic option for individuals living with advanced metabolic liver disease,” commented Mazen Noureddin, MD, MHSc, Professor of Medicine at Houston Methodist Hospital; Co-Chairman of the Board, Summit & Pinnacle Clinical Research; Director, Houston Research Institutes.

The results from this study are presented at the EASL Congress 2026 in Barcelona, Spain, and are expected to be featured at additional upcoming scientific meetings.

Safety and Tolerability

Zabopegdutide remained well-tolerated from the initial 2-week dose-escalation phase through 48 weeks of treatment. The most common adverse events were gastrointestinal, which were generally mild-to-moderate and transient. Discontinuation rates were consistent with those observed for other incretin-based therapies in this patient population.

About Zabopegdutide (DD01)

Zabopegdutide is a proprietary, long-acting GLP-1/glucagon receptor dual agonist. By targeting both receptors, zabopegdutide aims to reduce liver fat, resolve inflammation, and reverse fibrosis more effectively than GLP-1 monotherapies.

In Phase 1 studies, zabopegdutide reduced liver fat by up to 50% in only 4 weeks in obese subjects with MASLD, accompanied by improvements in glucose tolerance and modest weight loss.

In earlier Phase 2 analysis, more than 70% of subjects treated with zabopegdutide achieved greater than 50% reduction in liver fat after 12 weeks of treatment, while approximately 50% achieved normalization of liver fat (<5%). These effects were accompanied by significant reductions in liver stiffness (MRE) and fibrosis biomarkers, including pro-C3 and ELF.

The pharmacokinetic profile of zabopegdutide, characterized by slow absorption (Tmax, ~6 days) and prolonged half-life, supports gradual systemic exposure and contributes to its favorable tolerability at clinically active doses. The GLP-1:glucagon potency ratio (11:1) is designed to balance metabolic efficacy, weight loss, and glycemic control, while glucagon receptor activity is believed to drive the rapid reduction in hepatic steatosis.

Zabopegdutide’s differentiated profile, combining rapid liver fat reduction, significant histological improvement, potential weight-independent liver benefits, and convenient once-weekly dosing, positions it as a next-generation therapy for MASH.

About D&D Pharmatech

D&D Pharmatech is a clinical-stage biopharmaceutical company focused on developing revolutionary medicines for patients with metabolic, fibrotic, and neurodegenerative diseases.

Its liver pipeline includes zabopegdutide and TLY012 for MASH and cirrhosis, with TLY012 demonstrating reversal of established fibrosis in multiple preclinical models, including liver cirrhosis, chronic pancreatitis, and systemic sclerosis. In neuroscience, pegsebrenatide (NLY01) and NLY02 target neuroinflammation and glial activation to slow neurodegeneration; pegsebrenatide has demonstrated clinical benefit in a Phase 2 Parkinson’s disease study, particularly in patients younger than 60, and is currently being evaluated in progressive multiple sclerosis.

Neuraly, Inc.
Ben Gibson
240-937-5876
bgibson@neuralymed.com