Pasithea's ALS Drug Trial Gets $1M Boost, Targeting a New Pathway

MIAMI, FL – November 25, 2025 – In the relentless battle against amyotrophic lateral sclerosis (ALS), a glimmer of hope has emerged from a new and promising direction. Pasithea Therapeutics, a clinical-stage biotechnology firm, announced today it has received a grant of approximately $1 million from the ALS Association. The prestigious Hoffman ALS Clinical Trial Award will fund the first-ever clinical study of the company’s lead drug candidate, PAS-004, in patients living with the devastating neurodegenerative disease.

The award represents more than just crucial funding; it serves as a powerful validation for a novel therapeutic strategy in a field marked by high unmet need and recent setbacks. By targeting a fundamental cellular pathway involved in neuroinflammation, Pasithea aims to open a new front in a fight where progress has been painfully slow. For investors and healthcare leaders, this move signals a calculated expansion for Pasithea's pipeline, potentially unlocking value far beyond its initial focus.

A Novel Target in a Field of Need

ALS, a progressive disease that robs individuals of their ability to move, speak, and breathe, remains one of medicine's most formidable challenges. Current FDA-approved treatments, such as Riluzole and Edaravone, offer only modest benefits, typically extending survival by a matter of months without halting the disease's inexorable march. The landscape is littered with failed trials, and the recent voluntary market withdrawal of Relyvrio underscored the difficulty of finding effective therapies. This environment creates an urgent demand for innovative approaches that target the core biology of the disease.

Pasithea's PAS-004 steps into this void with a distinct mechanism of action. It is a next-generation macrocyclic MEK inhibitor. As the company's CEO, Dr. Tiago Reis Marques, explained, this approach targets enzymes that are central to the disease's progression. “Inflammation and the aggregation of a protein called TDP-43 are well-recognized contributors to the development and progression of ALS,” he commented. “Two enzymes, mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (MEK), have been shown to play a role in TDP-43–related neurodegeneration and neuroinflammation, suggesting they represent promising therapeutic targets.” By inhibiting MEK, PAS-004 aims to disrupt this destructive cascade at a critical junction, a strategy that has already shown significant promise in preclinical studies using the gold-standard SOD1 mouse model for ALS.

The Power of Strategic Validation

For a micro-cap biotech like Pasithea Therapeutics, the ~$1 million grant is a significant financial infusion. However, its strategic value far exceeds the dollar amount. The award comes from the ALS Association’s Hoffman Clinical Trial Awards Program, a highly competitive initiative designed specifically to "de-risk" and accelerate early-stage clinical programs with strong scientific rationale. By selecting PAS-004, the world's leading ALS research funder is placing a firm bet on the potential of MEK inhibition.

“We are pleased to support the first dosing of PAS-004 in people living with ALS,” said Dr. Kuldip Dave, Senior Vice President of Research at the ALS Association. “By funding programs at this critical stage, we are working to accelerate the development of therapeutic candidates that can help make ALS a livable disease until we can cure it.”

This endorsement from such a respected institution provides the kind of third-party validation that can catalyze further investment and partnerships. The market’s reaction was immediate and dramatic. Following the announcement, Pasithea’s stock (NASDAQ: KTTA) surged, demonstrating clear investor confidence in the de-risked clinical path and the expanded potential of PAS-004. For a company navigating the high-stakes world of drug development, this grant acts as a powerful signal that its science is sound and its strategy is on the right track.

Building a Multi-Indication Pipeline

The move into ALS is not an isolated venture but a key part of Pasithea’s broader corporate strategy. PAS-004 is being developed as a potential "pipeline in a product," with active clinical trials already underway in oncology and for a rare genetic disorder. The compound is currently being evaluated in a Phase 1 trial for advanced cancers driven by the MAPK pathway and a Phase 1/1b trial for patients with neurofibromatosis type 1 (NF1), a condition that causes tumors to grow on nerves.

This multi-pronged approach is strategically astute. Data from one trial can inform another, and success in one indication can attract the capital needed to fund development in others. Critically, the ongoing cancer and NF1 studies have already provided valuable human safety data. Dr. Lawrence Steinman, Chairman of Pasithea, noted that PAS-004 is “already in the clinic for neurofibromatosis and advanced cancers, is showing a promising safety profile and initial monotherapy efficacy signal.” This existing safety profile gives the company and regulators a higher degree of confidence as it enters a new and vulnerable patient population.

Dr. Steinman emphasized the broader vision: “Its support enables the initiation of the first clinical trial of PAS-004 in individuals living with ALS, which is a significant milestone for Pasithea as we look to provide proof-of-concept that PAS-004 may be the best-in-class MEK inhibitor for the treatment of many indications.” This ambition to establish a best-in-class compound across multiple diseases highlights a long-term strategy focused on maximizing the value of its core asset.

Charting the Path from Lab to Clinic

The newly funded study will be a Phase 1 trial designed to rigorously assess the safety, tolerability, and initial activity of PAS-004 in humans with ALS. The trial will enroll twelve patients across three sequential, dose-escalating cohorts, who will be followed for approximately 28 weeks. While the primary goal of any Phase 1 trial is to establish safety, the study’s design incorporates key exploratory endpoints that could provide early hints of efficacy.

Investigators will measure changes in the ALS Functional Rating Scale–Revised (ALSFRS-R), a standard clinical tool for tracking disease progression. Perhaps more importantly, they will also monitor levels of neurofilament light chain (NfL), a sensitive blood-based biomarker that reflects nerve cell damage. Rising NfL levels are correlated with faster disease progression, so a drug-induced stabilization or reduction could be a powerful early signal that the treatment is having a biological effect on the underlying neurodegenerative process.

The inclusion of a modern biomarker like NfL demonstrates a sophisticated trial design that aligns with the latest thinking in neurological drug development. It allows researchers to look for objective evidence of target engagement and therapeutic effect long before changes in clinical function might become apparent. This data will be crucial for making "go/no-go" decisions and for designing larger, more definitive Phase 2 and Phase 3 trials. As PAS-004 moves from promising preclinical models into human testing for ALS, the entire community—patients, clinicians, and investors—will be watching closely to see if this novel mechanism can finally change the trajectory of this relentless disease.