Trethera Corporation Partners With Massachusetts General Hospital To Study TRE-515 In Advanced ALS Under FDA Expanded Access

Trethera Corporation, a clinical-stage biopharmaceutical company developing first-in-class treatments for cancer, autoimmune, and neuroimmune disorders, announced a new clinical collaboration with Massachusetts General Hospital (MGH). Through this partnership, MGH will evaluate Trethera’s investigational therapy TRE-515 in up to six patients with advanced amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The study will be carried out under the FDA’s Expanded Access program. TRE-515 works by inhibiting deoxycytidine kinase (dCK), an enzyme involved in abnormal cell division and inflammatory signaling. Because growing evidence links inflammation to ALS progression, researchers believe TRE-515 may offer a new therapeutic approach.

Trethera’s Chairman and CEO, Dr. Keun Schultz, said that collaborating with MGH is an important next step toward broadening the company’s efforts to understand and treat ALS. He explained that this partnership follows encouraging findings Trethera reported in an ALS patient last year. He also noted that MGH was one of the first academic institutions to connect with the company, and Trethera hopes to bring additional medical centers into future studies once this trial concludes.

Dr. Merit Cudkowicz, Executive Director of the Massachusetts General Brigham Neuroscience Institute and the principal investigator for the trial, emphasized the continued need for new ALS treatment strategies. She explained that current therapeutic options for ALS remain limited, making it important to explore innovative approaches such as TRE-515. She added that MGH is pleased to work with Trethera on further evaluating the therapy.

MGH, the original and largest teaching hospital of Harvard Medical School, is internationally recognized for its leadership in ALS research and clinical care. Under Dr. Cudkowicz’s leadership, the institution has played a major role in advancing multiple ALS therapies and has become a leading center for testing new treatments.

As part of this collaboration, up to six advanced ALS patients will be enrolled in a clinical study run by MGH. The primary focus will be to assess the safety and tolerability of TRE-515 while also tracking how the disease progresses over time. Researchers will also collect pharmacodynamic biomarkers linked to the TRE-515 mechanism, as well as established ALS biomarkers such as neurofilament light chain. 

Patients will undergo monthly assessments, including evaluations using the ALS Functional Rating Scale-Revised and measurements of Slow Vital Capacity. By integrating clinical outcomes with biomarker data, the study aims to better understand how TRE-515 works in ALS patients, help refine patient selection for future trials, and lay the groundwork for larger studies.

Dr. Lawrence Steinman, a member of Trethera’s Scientific Advisory Board and a professor of neurology at Stanford University, said he is encouraged by TRE-515’s potential in ALS because of its selective effect on inflammatory pathways and its positive safety profile so far. He noted that although the upcoming study is small, it builds on early clinical observations, and strong results could support the transition into larger, more definitive clinical trials.

Trethera also shared information about its previously reported treatment of an 87-year-old patient with advanced ALS under the FDA Expanded Access program. This patient, treated in collaboration with Dr. Steinman, UCLA, Cedars-Sinai, and Saint John’s Health Center, had tried 11 therapies over 3.5 years with no meaningful improvement. During treatment with TRE-515, the decline in forced vital capacity slowed from about 1.2% per week before starting the therapy to 0.5% per week after three months, and further to 0.2% per week after 6.5 months. No side effects linked to TRE-515 were observed. 

According to the patient and his family, certain quality-of-life measures improved during treatment, including muscle strength and vocalization. Treatment ended after the patient experienced a fall at home, and he later passed away from pneumonia, which is consistent with the natural progression of advanced ALS. This new collaboration with MGH represents a significant next step as Trethera continues to explore TRE-515’s potential as a new treatment option for patients living with ALS.