- Publication of 12-week Phase 2 data demonstrates rapid improvements in liver fat, liver stiffness, and fibrosis biomarkers that predicted the statistically significant histological improvements observed at 48 weeks
- Rapid, weight-independent liver improvements distinguish zabopegdutide from conventional incretin therapies and provide evidence of direct hepatic activity beyond the effects of weight loss
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 the publication of 12-week results from its Phase 2 DD01-DN-2 study evaluating zabopegdutide (DD01) in patients with MASLD/MASH in the Lancet Gastroenterology & Hepatology.
The publication follows D&D’s recent announcement of positive 48-week Phase 2 biopsy results, in which zabopegdutide achieved statistically significant improvements in both MASH resolution and fibrosis improvement in patients with biopsy-confirmed MASH and fibrosis stage F1-F3 (businesswire). The newly published analysis demonstrates that the robust histological benefits observed after 48 weeks were preceded by rapid, clinically meaningful improvements in liver fat, liver stiffness, and fibrosis biomarkers as early as 12 weeks, supporting the potential of these non-invasive markers to predict long-term histological benefit.
“Our recently announced 48-week biopsy results established that zabopegdutide produces clinically meaningful histological improvements in patients with MASH,” said Seulki Lee, Ph.D., President and CEO of D&D Pharmatech. “The publication in the Lancet Gastroenterology & Hepatology demonstrates that these outcomes were foreshadowed by rapid and substantial improvements in liver health within the first 12 weeks of treatment. Importantly, many of these benefits occurred before meaningful weight loss, suggesting that zabopegdutide provides direct therapeutic effects on the liver beyond weight reduction. Together, these findings highlight the differentiated profile of zabopegdutide and support its potential to become a best-in-class therapy for MASH.”
Early efficacy translated into durable histological benefit
DD01 is a long-acting, pegylated peptide designed to deliver balanced GLP-1 and glucagon receptor agonism. GLP-1 improves glycemic control and reduces body weight, while glucagon enhances lipid mobilization and reduces hepatic steatosis. This complementary mechanism is intended to drive rapid and robust reductions in liver fat, alongside gradual weight loss and improvements in metabolic parameters.
The randomized, double-blind, placebo-controlled Phase 2 DD01-DN-02 trial (NCT06410924) enrolled 67 overweight or obese patients with MASLD/MASH who received a 2-week titration at 20 mg followed by a 40 mg once-weekly maintenance dose.
Following a 1:1 randomization to 40 mg DD01 or placebo, the 12-week results showed that 75.8% of subjects treated with DD01 achieved at least a 30% reduction in liver fat, and moreover, 72.7% of subjects achieved greater than 50% reduction in liver fat, and 48.5% of treated subjects achieved normalization of liver fat (<5%). These effects were accompanied by significant reductions in liver stiffness (MRE) and fibrosis biomarkers (pro-C3 and ELF) at 12 weeks. DD01 also produced progressive weight loss (3.8% at 12 weeks; 6.4% at 24 weeks) and improved glycemic control and favorable effects on liver enzymes and lipid parameters.
Weight-loss-independent liver improvements highlight a differentiated mechanism
Although patients treated with zabopegdutide experienced meaningful weight loss, a key finding of the study was the demonstration of significant improvements in liver health that were not dependent on clinically meaningful weight reduction.
Among patients who achieved less than 5% of body weight loss by Week 12, zabopegdutide still produced significant reductions in liver fat (-37.4% by MRI-PDFF) and liver stiffness (-19.2% by MRE). Importantly, patients who achieved ≥5% weight loss experienced even greater reductions in liver fat (-81.1%), suggesting that zabopegdutide may exert both weight-independent and weight-dependent effects on liver disease.
These findings are particularly noteworthy because many incretin-based therapies are thought to improve liver outcomes primarily as a consequence of substantial weight loss, often requiring prolonged treatment before meaningful liver benefits become apparent. In contrast, zabopegdutide demonstrated robust improvements in liver-specific biomarkers early in treatment, before clinically meaningful weight loss had occurred.
Importantly, the recently completed 48-week biopsy analysis further demonstrated that patients with relatively modest weight loss also achieved statistically significant histological improvement, including fibrosis improvement and MASH resolution. These findings provide additional evidence that fibrosis improvement with zabopegdutide is not solely driven by weight reduction, supporting a differentiated mechanism of action.
Rapid onset with favorable tolerability
Zabopegdutide was generally well tolerated and required only a 2-week dose-escalation period to reach the target maintenance dose. The rapid onset of efficacy, demonstrated by reductions in liver fat, liver stiffness, fibrosis biomarkers, liver enzymes, and metabolic parameters like HbA1c and body weight within the first 12 weeks, was maintained throughout treatment and ultimately translated into statistically significant improvements in liver histology after 48 weeks.
“Our 48-week results demonstrated clinically meaningful fibrosis improvement and MASH resolution using the gold-standard biopsy endpoints,” added Dr. Lee. “This publication provides important mechanistic evidence showing that those long-term outcomes were preceded by rapid, objective improvements in non-invasive measures of liver disease. We believe these findings further differentiate zabopegdutide from existing therapies and strengthen its potential as a next-generation treatment for patients with MASH. We look forward to advancing the program into late-stage clinical development.”
About Zabopegdutide (DD01)
Zabopegdutide is D&D Pharmatech's investigational once-weekly dual GLP-1/glucagon receptor agonist being developed for MASH and other metabolic diseases. The program has demonstrated rapid reductions in liver fat and fibrosis biomarkers, favorable tolerability with only a two-week titration period, and statistically significant histological improvements after 48 weeks of treatment in patients with biopsy-confirmed 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.
Contacts
Neuraly, Inc.
Ben Gibson
240-937-5876
bgibson@neuralymed.com
