Merry Life Biomedical's investigational oral therapy TML-6 has moved into a global Phase 2 study in early Alzheimer's disease, the company said. The program involves 20 clinical sites: nine medical centers in Taiwan, seven sites in Sweden and four centers in the United States. It is expected to enroll about 210 participants with early Alzheimer's disease.
The study is randomized, double-blind and placebo-controlled. Participants will take either 100 mg of TML-6, 200 mg of TML-6 or a placebo once a day for 52 weeks. The main endpoint is the change from the start of the study on the Clinical Dementia Rating Sum of Boxes, a measure of cognition and daily function. Levels of the blood biomarkers p-Tau 217, Aβ, GFAP and NfL are secondary endpoints.
Alzheimer's disease involves the abnormal build-up of proteins in and around brain cells, including amyloid plaques and tau tangles. Recently approved therapies have shown that clearing amyloid can slow clinical decline in early Alzheimer's disease, but the disease continues to progress even with treatment. Research on TML-6 has increasingly centered on the autophagy–lysosomal pathway, which clears and recycles proteins and other cellular material; preclinical studies looked at its effects on autophagy and lysosomal function in neurons and microglia, along with amyloid-related pathology, oxidative stress and inflammation. Dr. Ih-Jen Su, the company's founder and chairman, said the next generation of Alzheimer's treatments must look past what accumulates in the brain and ask why neurons lose the ability to clear damaged proteins, and that the Phase 2 study will test whether targeting this biology delivers benefit to patients.
The Swedish sites work with Anne Börjesson-Hanson, MD, PhD, of Karolinska Institute and Karolinska University Hospital, who has served as primary investigator on more than 40 global clinical trials. On Oct. 4 she is scheduled to visit Taiwan for the Taiwan Dementia Society Annual Scientific Meeting, where she will give a plenary lecture and meet the nine Taiwanese principal investigators in the TML-6 study. Taiwan has the largest group of participating clinical sites in the program. Henrik Zetterberg, MD, PhD, will support blood biomarker analyses and Barbara B. Bendlin, PhD, will contribute expertise in amyloid PET and MRI analyses. Gary W. Small, MD, is a global medical consultant, and Jacobo Mintzer, MD, advises on clinical site execution.
The company said that with TML-6 in global Phase 2 development it is moving past early safety evaluation toward generating clinical efficacy, biomarker and imaging data. It said it will plan for Phase 3 and broader global development based on study progress and emerging data, and that it is exploring strategic investment, international venture capital, capital-market financing and partnerships with global pharmaceutical companies. Discussions with pharmaceutical companies and strategic partners will continue, and licensing, co-development and other partnership models will be evaluated subject to Phase 2 results and regulatory strategy.
