METiS Therapeutics Announces MTS-004 Meets Primary Endpoint in Phase III Trial, Poised to Fill Critical Gap in PBA Treatment in China

China Finance Network October 22nd — METiS TechBio announced today that the candidate drug MTS-004 from its self-developed artificial intelligence-driven small molecule formulation optimization platform AiTEM has successfully reached the primary endpoint of Phase III clinical research, becoming the first AI-empowered formulation new drug in China to complete Phase III clinical trials.

MTS-004 is also the first and currently the only drug in China to have completed Phase III clinical trials for PBA (Pseudobulbar Affect), with the potential to fill the gap in China where there are currently no approved drugs for PBA treatment.

MTS-004 is a novel PBA oral treatment candidate drug designed with METiS TechBio's proprietary AiTEM orally disintegrating tablet (ODT) formulation. This formulation addresses the common issue of swallowing difficulties in PBA patients, as it dissolves rapidly in the mouth without the need for water, significantly improving the medication experience and treatment adherence for patients.

PBA (Pseudobulbar Affect) Commonly known as "involuntary emotional expression disorder," is a neurological condition characterized by episodes of uncontrollable and inappropriate laughing or crying that do not align with the patient's actual emotional state. It is typically secondary to various central nervous system diseases or injuries, such as Amyotrophic Lateral Sclerosis (ALS, commonly known as Lou Gehrig's disease), Multiple Sclerosis (MS), stroke, Traumatic Brain Injury (TBI), or Parkinson’s Disease (PD).

AiTEM, Powered by METiS TechBio's Self-developed AI Nanodelivery Platform NanoForge, Serves as the Technical Engine for Drug Formulation Design and Optimization Through Proprietary Algorithms. The platform predicts interactions between drugs and excipients via quantum chemistry and molecular dynamics simulations, generating optimized nanoscale formulation solutions to enhance drug solubility and bioavailability, achieving ideal pharmacokinetic properties. In the MTS-004 project, AiTEM was responsible for modeling and predictive analysis in formulation development, reducing the preclinical formulation optimization cycle from the industry average of 1-2 years to within 3 months. MTS-004 progressed from initiation to completion of Phase III clinical trials in just 38 months, significantly improving drug development efficiency compared to industry averages.

The principal investigator of the MTS-004 Phase III clinical trial is Professor Fan Dongsheng, an authoritative expert in ALS and neurological diseases in China and the director of the Department of Neurology at Peking University Third Hospital. This study adopts a multicenter, double-blind, randomized, placebo-controlled design to evaluate the efficacy and safety of MTS-004 in PBA patients secondary to neurological diseases such as ALS, MS, stroke, TBI, and PD. The enrollment period lasted 9.5 months, with a total of 264 subjects enrolled. The clinical trial was led by Peking University Third Hospital and jointly participated by 48 clinical centers, including Xuanwu Hospital, Tiantan Hospital, West China Hospital, First Affiliated Hospital of China Medical University, Second Affiliated Hospital of Zhejiang University, Jiangsu Provincial People's Hospital, Shandong Qianfoshan Hospital, Guangdong Second Provincial General Hospital, First Affiliated Hospital of Zhengzhou University, Renji Hospital Shanghai, and Xiangya Hospital Central South University.

Currently, NUEDEXTA, approved in the United States, is the only drug available globally for the treatment of PBA. MTS-004 is a new modified drug under Category 2.2 with the same indication. Compared to the capsule form of NUEDEXTA, the orally disintegrating tablet form of MTS-004 offers enhanced convenience for PBA patients, effectively addressing the common issue of swallowing difficulties within this patient population.

The study results showed that MTS-004 demonstrated a favorable overall safety profile and exhibited clear efficacy and good tolerability in treating PBA secondary to neurological disorders. After 12 weeks of treatment, MTS-004 significantly reduced the average number of PBA episodes, with a statistically significant difference, which was consistently validated across multiple sensitivity and subgroup analyses. Therapeutic effects were observed starting from Week 2, with a significant increase in episode-free days during the treatment period, and the degree of improvement increased over time. In addition to the primary endpoint, MTS-004 significantly outperformed placebo in CNS-LS scores, CGI-C and PGI-C assessments, and the SF-36 mental health index, suggesting its ability to markedly improve patients' emotional control and quality of life. MTS-004 also significantly improved the total CNS-BFS score as well as swallowing and drooling symptoms.

MTS-004 is planned to submit a New Drug Application (NDA) to the National Medical Products Administration (NMPA) in 2026 for the PBA indication, and upon approval, initiate clinical research to evaluate its potential expanded indications for the treatment of dysphagia.

"Artificial intelligence is bringing revolutionary changes to new drug development. The clinical research of MTS-004 was extremely challenging at the start but was ultimately completed with high quality." Professor Fan Dongsheng stated that the significant value of this drug lies in its ability to improve patients' quality of life, particularly in alleviating swallowing difficulties, thereby reducing the occurrence of complications and having a very positive impact on patient survival. Although this study focused on ALS initially, its range of indications is expected to expand further, potentially benefiting an even broader population.

Dr. Lai Caida, co-founder and CEO of METiS TechBio, stated that the mission of AI is to empower clinical treatment, race against time in fighting diseases, and deeply understand the unmet needs of patients. "This is the original intention and driving force behind the initiation of MTS-004 development, reaching the endpoint of Phase III clinical research in 38 months, and it is also the goal of our self-developed AI nanodelivery platform, NanoForge. MTS-004 represents the first complete closed-loop process from research and development to clinical validation completed by METiS TechBio, and the experience gained from this process will accelerate the progress of subsequent pipelines."