Pasithea Therapeutics Presents Updated Interim Data from Ongoing Phase 1 Study of PAS-004 at the ASCO Annual Meeting 2025

Rhea-AI Summary

Pasithea Therapeutics has presented updated interim data from its Phase 1 study of PAS-004, a next-generation macrocyclic MEK inhibitor, at ASCO 2025. The study enrolled 21 patients with MAPK pathway-driven advanced solid tumors across six dosing cohorts. Key findings show PAS-004 demonstrating preliminary clinical activity in heavily pre-treated patients, with notable results in cohort 4A (15mg capsule). A stage 4 BRAF-mutated melanoma patient achieved stable disease with -14.9% tumor reduction after 5+ months. The drug showed favorable pharmacokinetics with a half-life exceeding 60 hours and maintained good tolerability with only grade 1 or 2 adverse events. Of 16 evaluable patients, 10 achieved stable disease, with progression-free survival up to 159 days and overall survival up to 253 days. The results suggest PAS-004's potential as a best-in-class MEK inhibitor for various MAPK pathway-driven tumors.

Positive

• Demonstrated preliminary clinical activity with 10 out of 16 evaluable patients achieving stable disease
• Strong safety profile with only grade 1 or 2 adverse events and no dose-limiting toxicities
• Promising pharmacokinetics with half-life exceeding 60 hours and linear PK profile
• Notable tumor reduction in two patients: -14.9% in melanoma and -9.8% in pancreatic cancer patients
• Achieved up to 91% pERK inhibition in cohort 3 (8mg capsule)

Negative

• Study is still in early Phase 1 stage with limited patient data
• No complete or partial responses reported yet, only stable disease achieved
• Majority of patients eventually experienced disease progression

Insights

Oncology Clinical Researcher

Pasithea's MEK inhibitor PAS-004 shows promising safety profile with early efficacy signals in treatment-resistant tumors with manageable side effects.

The interim Phase 1 data for PAS-004 reveals several encouraging signals. The drug demonstrates a favorable safety profile with only grade 1-2 adverse events and notably absence of typical MEK inhibitor toxicities (ocular, cardiac, skin) during the dose-limiting toxicity observation period. This is particularly significant as toxicity often limits therapeutic window for this drug class.

The pharmacokinetic profile is especially promising, showing an estimated half-life exceeding 60 hours with a Cmax/Cmin ratio below 2 at steady state. This suggests sustained target engagement with minimal peak-trough fluctuations—a key advantage for continuous pathway inhibition. The linear PK and dose-dependent profile further support predictable drug behavior.

Efficacy signals are emerging despite the early-phase setting. Among 16 evaluable patients, 10 achieved stable disease, with two patients in the 15mg cohort showing tumor reductions of -9.8% and -14.9%, respectively. The melanoma patient's response is particularly noteworthy as they had previously progressed on MEK+BRAF inhibitor therapy, suggesting PAS-004 may overcome resistance mechanisms.

The drug's macrocyclic structure likely contributes to its improved selectivity profile. As context, recent approvals of mirdametinib and avutometinib underscore continued interest in MEK inhibitors despite previous generation limitations. If PAS-004 maintains this safety profile at higher doses while demonstrating consistent anti-tumor activity, it could potentially establish a differentiated position among MEK inhibitors, particularly for combination regimens where toxicity overlap often proves limiting.

-- PAS-004 demonstrates preliminary clinical activity as a monotherapy in patients with heavily pre-treated, refractory solid tumors --

-- One patient in cohort 4A (15mg capsule) with stage 4 BRAF-mutated melanoma, who had progressed after two prior lines of therapy, including a prior MEK inhibitor + BRAF inhibitor combination therapy, achieves over 5 months of stable disease with tumor volume reduction of -14.9% and remains on treatment --

-- PAS-004 pharmacokinetics profile potentially supports a prolonged target engagement at well-tolerated doses --

MIAMI, June 02, 2025 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (NASDAQ: KTTA) (“Pasithea” or the “Company”), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, today announced updated interim results from its ongoing dose escalation Phase 1 study evaluating PAS-004 in advanced cancer patients in a poster presentation at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting

The Phase 1 clinical trial is a multi-center, open-label, dose escalation, modified 3+3 study design to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of PAS-004 in patients with MAPK pathway-driven advanced solid tumors with a documented RAS, NF1 or RAF mutation, or patients who have failed BRAF/MEK inhibition (NCT06299839).

As of the cut-off date of April 2, 2025, a total of 21 patients had been enrolled and received at least one dose of PAS-004 in six cohorts (Capsules: 2mg, 4mg, 8mg, 15mg, 22mg / Tablets: 4mg). The most common cancer diagnosis was pancreatic cancer (28.6%), colorectal cancer (28.6%), and melanoma (23.8%).

All treatment-related adverse events (AEs) have been either grade 1 or grade 2. No known MEK inhibitor class-related AEs such as ocular toxicities, cardiotoxicities, and skin toxicities were observed during the DLT observation period. No DLTs were reported, and dose escalation is ongoing.

Preliminary PAS-004 PK analysis suggests linear PK with an estimated half-life in excess of 60 hours. The Cmax (peak) to Cmin (trough) ratio was below 2 at steady state in all dose levels and has achieved potentially sufficient exposures for target engagement. This is supported by previously reported preliminary pERK inhibition observed in cohort 3 (8mg capsule), with pERK inhibition of up to 91%.

PAS-004 has demonstrated a dose-dependent PK profile and preliminary clinical activity as a monotherapy in patients with heavily pre-treated, refractory solid tumors. In the efficacy evaluable population (n=16), early response evaluation reveals stable disease (SD) by RECIST 1.1 in 10 patients at some point during the trial, with progression free survival of up to 159 days and overall survival of up to 253 days. In Cohort 4A (15mg capsule), two out of three patients achieved stable disease and remain on therapy. One patient with stage 4 KRAS G12R-mutated pancreatic cancer, having progressive disease while on three prior lines of therapy, achieved a tumor diameter reduction of -9.8% and remains on study for over 5 months. The second patient with Stage 4 BRAF-mutated melanoma, having progressed on two prior lines of therapy, including a prior MEK inhibitor + BRAF inhibitor combination treatment, achieved tumor diameter reduction of -14.9% and remains on study for over 5 months.

“The interim results from our ongoing Phase 1 study are encouraging and we believe underscore the potential of PAS-004 as a best-in-class MEK inhibitor to serve patients with a broad range of MAPK pathway driven tumors,” said Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. “MEK inhibitors have been a transformative class of treatment therapies and we continue to witness groundbreaking advances and new approvals with this class of drug across tumor types and mutational profiles. At ASCO 2025, over 15 data sets featuring MEK inhibitors are being presented underscoring the growing momentum in this field. Additionally, we have recently seen approval of two novel MEK inhibitors, mirdametinib and avutometinib, highlighting the continued relevance of this drug class in the past several months alone. As a macrocyclic compound, PAS-004 potentially represents a significant advancement in the MEK inhibitor field by offering high selectivity and sustained pathway suppression while maintaining good tolerability. This profile may make it optimal for both monotherapy and combination therapy, including in patients who have failed prior MEK inhibitors.”

The poster presentation will be available on the Pasithea website on the date of the poster session.

About Pasithea Therapeutics Corp.

Pasithea is a clinical-stage biotechnology company primarily focused on the research and development of its lead drug candidate, PAS-004, a next-generation macrocyclic MEK inhibitor intended for the treatment of RASopathies, MAPK pathway-driven tumors, and other diseases. The Company is currently testing PAS-004 in a Phase 1 clinical trial in advanced cancer patients (NCT06299839), and a Phase 1/1b clinical trial in adult patients with neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas (NCT06961565).

Forward Looking Statements

This press release contains statements that constitute “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements regarding the Company’s ongoing Phase 1 clinical trial of PAS-004 in advanced cancer patients, the Company’s Phase 1/1b clinical trial of PAS-004 in adult NF1 patients, and the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD) and preliminary efficacy of PAS-004, as well as all other statements, other than statements of historical fact, regarding the Company’s current views and assumptions with respect to future events regarding its business, as well as other statements with respect to the Company’s plans, assumptions, expectations, beliefs and objectives, the success of the Company’s current and future business strategies, product development, pre-clinical studies, clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of the Company. While the Company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the Company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties, including risks that future clinical trial results may not match results observed to date, may be negative or ambiguous, or may not reach the level of statistical significance required for regulatory approval, as well as other factors set forth in the Company’s most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other filings made with the U.S. Securities and Exchange Commission (SEC). Thus, actual results could be materially different. The Company undertakes no obligation to update these statements whether as a result of new information, future events or otherwise, after the date of this release, except as required by law.

Pasithea Therapeutics Contact

Patrick Gaynes
Corporate Communications
pgaynes@pasithea.com

FAQ

What are the key findings from KTTA's Phase 1 trial of PAS-004?

The trial showed PAS-004 achieved stable disease in 10 of 16 evaluable patients, with tumor reductions up to 14.9%, good tolerability with only grade 1-2 adverse events, and favorable pharmacokinetics with 60+ hour half-life.

How does PAS-004's safety profile compare to other MEK inhibitors?

PAS-004 showed no known MEK inhibitor class-related adverse events such as ocular toxicities, cardiotoxicities, or skin toxicities, with only grade 1-2 adverse events reported.

What types of cancers were treated in KTTA's PAS-004 trial?

The most common cancers in the trial were pancreatic cancer (28.6%), colorectal cancer (28.6%), and melanoma (23.8%).

What was the duration of response in KTTA's Phase 1 trial?

The trial showed progression-free survival up to 159 days and overall survival up to 253 days, with some patients remaining on treatment for over 5 months.

How many patients were enrolled in KTTA's Phase 1 study of PAS-004?

A total of 21 patients were enrolled across six dosing cohorts, with 16 patients evaluable for efficacy as of the April 2, 2025 cut-off date.