ALS Association Awards $2 Million to Fund Phase 1 Trials of Two Novel ALS Therapies
Key Insights
The ALS Association (search) has awarded $2 million through its Hoffman ALS (search) Clinical Trial Awards Program to support two phase 1 trials testing novel ALS therapies.
Mayo Clinic Jacksonville will test PAS-004, a MEK (search) enzyme inhibitor targeting inflammation and nerve damage, in 12 ALS (search) patients in partnership with Pasithea Therapeutics Corp (search).
Molefy Pharma SL (search) will conduct first-in-human testing of AP-2, which targets TDP-43 protein imbalances found in 97% of ALS (search) patients.
The ALS Association (search) has committed $2 million to advance two promising investigational therapies for amyotrophic lateral sclerosis (search) (ALS (search)) through its 2025 Hoffman ALS Clinical Trial Awards Program. The funding, distributed as grants worth up to $1 million each, will support early-phase clinical trials designed to generate critical safety, dosing, and biomarker data for novel therapeutic approaches.
"Funding for early-stage clinical testing acts like 'ignition fuel' for the R&D engine," said Kuldip Dave, Ph.D., senior vice president of research at the ALS Association (search). "The knowledge gained from these initial trials helps propel drug development forward by providing critical data that can be used to inform larger efficacy studies. It also helps make these next steps less risky and more attractive to potential investors and partners."
MEK Inhibitor Targets Neuroinflammation
Mayo Clinic Jacksonville will conduct a phase 1 trial of PAS-004, an investigational therapy developed in partnership with Pasithea Therapeutics Corp (search). The study, led by consultant Jaimin Shah, M.D., will recruit 12 people living with ALS (search) to evaluate the safety and tolerability of the MEK (search) enzyme inhibitor.
PAS-004 targets MEK (search), an enzyme involved in the inflammation, nerve damage, and nerve loss characteristic of ALS (search). The trial will determine optimal dosing for future studies while measuring biomarkers to identify early signs of potential disease-modifying effects.
"While early phase studies cannot really determine whether a drug significantly slows or stops ALS (search), they are critical to understanding many important questions to determine a drug's potential to become an effective therapy," Dr. Shah said. "We hope this trial will improve the field's understanding of the role MEK (search) inhibitors could play in the treatment of ALS."
TDP-43 Protein Targeting Approach
The second award recipient, Molefy Pharma SL (search), will advance AP-2 into first-in-human testing under the leadership of co-founder and scientific director Ana Martínez, Ph.D. The investigational therapy has demonstrated promise in preclinical studies by helping restore balance of TDP-43, a protein that becomes dysregulated in approximately 97% of people with ALS (search).
TDP-43 imbalances lead to the formation of abnormal, disease-causing protein aggregates that contribute to ALS (search) pathology. The phase 1 trial will determine the highest safe dose of AP-2, establish its therapeutic window, and identify potential side effects.
"This first-in-human trial represents a crucial initial step toward testing in ALS (search) patients and paves the way for the clinical development of a new TDP-43–modifying drug," Dr. Martínez said. "We will work for the success of this project with all our strength and energy."
Addressing Critical Unmet Need
The awards address a significant therapeutic gap in ALS (search) treatment. The progressive neurodegenerative disease affects nerve cells in the brain and spinal cord, causing patients to lose the ability to move, speak, and eventually breathe. ALS is invariably fatal, typically within five years of diagnosis, with few existing treatment options.
The 2025 awardees were selected from a competitive international applicant pool based on compelling biological rationale, robust preclinical data, integrated biomarker programs, and clear future clinical development plans. The Hoffman ALS (search) Clinical Trial Awards support early- to mid-stage biomarker-driven clinical trials of novel or repurposed therapeutics for ALS.
"People living with ALS (search) urgently need new treatments," said Dr. Dave. "By funding early-stage clinical trials like these, we are working to accelerate the development of promising therapeutic candidates so we can make ALS livable until we can cure it."
The awards are funded through the Hugh and Herbert Hoffman ALS (search) Fund, established by a historic $58 million gift from the late Hugh Hoffman, whose father Herbert died from ALS. This contribution represents the largest single philanthropic gift ever made to an ALS organization and supports advancing new treatments, strengthening clinic infrastructure, and reducing barriers to multidisciplinary care access.