Pasithea Therapeutics Announces Positive Safety Review Committee (SRC) Recommendation from its Ongoing Phase 1 Clinical Trial of PAS-004 in Advanced Cancer

Rhea-AI Summary

Pasithea Therapeutics (NASDAQ: KTTA) announced positive progress in its Phase 1 clinical trial of PAS-004, a next-generation macrocyclic MEK inhibitor for treating neurofibromatosis type 1 (NF1) and other cancers. The Safety Review Committee recommended advancing to Cohort 6 with a 30mg capsule dose following review of Cohort 5 data.

Key highlights include:

• No dose-limiting toxicities (DLTs) observed across 19 patients
• Zero instances of rash reported during the DLT period
• Strong enrollment demand with Cohort 6 patients already identified

The trial (NCT06299839) is a multi-center, open-label, dose escalation study evaluating PAS-004's safety, tolerability, and preliminary efficacy in patients with MAPK pathway driven advanced solid tumors. The company plans to release additional safety, pharmacokinetic, and pharmacodynamic data in the coming weeks.

Positive

• No dose-limiting toxicities or rash observed in 19 patients, unlike competitor drugs
• Strong patient enrollment demand for the trial
• Trial successfully advancing to higher dose level (Cohort 6)
• Superior safety profile compared to existing MEK inhibitors that have 80%+ rash rates

Negative

• Preliminary Phase 1 data - efficacy results not yet available
• Multiple competing MEK inhibitors already approved in the market

Insights

Clinical Trial Specialist

Pasithea's Phase 1 trial progression to Cohort 6 (30mg) represents a significant positive safety milestone for their MEK inhibitor PAS-004. The absence of dose-limiting toxicities through the first five cohorts is encouraging, particularly given the trial's 3+3 dose escalation design which requires careful safety monitoring at each level.

Most notably, the complete absence of rash across 19 patients treated to date stands in stark contrast to the >80% rash rates reported with approved MEK inhibitors. Dermatological toxicity typically emerges early in treatment and represents one of the primary reasons patients discontinue MEK inhibitors, severely limiting their real-world effectiveness despite demonstrated efficacy.

The company's mention of "substantial exposure levels" suggests favorable pharmacokinetics, potentially achieving therapeutic levels without triggering the MAPK-pathway associated skin toxicities. If this safety profile holds through higher doses and larger patient populations, PAS-004 could potentially address a significant clinical limitation of current MEK inhibitors.

This positive safety review enables continued dose escalation, which is essential for establishing both the maximum tolerated dose and recommended Phase 2 dose. The strong enrollment demand mentioned indicates investigator interest, which often reflects perceived potential among clinicians familiar with the limitations of existing options for NF1 and other MAPK-driven cancers.

Biotech Investment Analyst

This safety milestone represents material progress for Pasithea's lead asset development program. For a micro-cap biotech with $3M market cap, advancement through Phase 1 safety cohorts without significant adverse events is particularly meaningful as it reduces one major risk factor in the development pathway.

The absence of rash through multiple dose levels creates a potentially compelling differentiation story versus established MEK inhibitors. The 80%+ rash rates for approved competitors represent a significant commercial limitation that impacts real-world use duration and effectiveness. If PAS-004's clean dermatological profile continues at higher doses, it could position the therapy favorably for both efficacy and compliance.

Importantly, the drug appears to be achieving "substantial exposure levels" below toxic thresholds - suggesting the potential for an improved therapeutic window. For MEK inhibitors, the ability to deliver sufficient target engagement without triggering pathway-related toxicities is the critical balance that determines clinical utility.

While still early-stage, this positive safety profile combined with strong enrollment demand suggests investigator interest in the program. For small biotechs, maintaining clinical momentum is essential for preserving capital runway. The company's ability to move efficiently through dose cohorts while generating potential differentiation data represents positive operational execution at this stage of development.

– SRC recommended that the trial escalate to the next dose level of 30mg capsule –

– No dose-limiting toxicities (DLT’s) or rash observed to date –

MIAMI, April 10, 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, for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications, today announced that the external Safety Review Committee recommended that the Company’s Phase 1 clinical trial of PAS-004 in advanced cancer should proceed to Cohort 6, 30mg capsule, without modification. This recommendation was based on the review of the safety data from three patients from Cohort 5 and the absence of any dose limiting toxicities (DLT’s). In addition, no rash has been observed to date during the DLT period in any of the first 19 patients in either capsule (15 patients) or tablet (four patients) formulation of PAS-004. Rash is a common adverse event (AE) that is observed at low doses with competitor MEK inhibitors and may lead to the discontinuation rate in real world practice.

“We are seeing substantial enrollment demand and have already identified Cohort 6 patients. In addition, we continue to observe substantial exposure levels of PAS-004, and remain excited about the possibility of delivering relevant pERK inhibition below the no observed adverse effect levels (NOAEL) as we modeled and observed during our previously conducted nine-month chronic toxicity studies. The on label rash rate for both approved MEKi for NF1 exceeds 80% which leads to patients discontinuing who otherwise should remain on treatment for longer periods of time”, stated Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. “We will provide additional safety, pharmacokinetic (PK) and pharmacodynamic (PD) data over the next several weeks.”

The ongoing Phase 1 clinical trial is a multi-center, open-label, dose escalation 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).

About Pasithea Therapeutics Corp.

Pasithea is a biotechnology company focused on the discovery, research and development of innovative treatments for central nervous system (CNS) disorders and RASopathies. With an experienced team of experts in the fields of neuroscience, translational medicine, and drug development, Pasithea is developing new molecular entities for the treatment of neurological disorders, including Neurofibromatosis type 1 (NF1), Solid Tumors, and Amyotrophic Lateral Sclerosis (ALS).

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 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, preclinical 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 no dose-limiting toxicities or rash in 19 patients, allowing progression to Cohort 6 with 30mg capsule dose. This is significant as competitor MEK inhibitors typically show rash as a common side effect.

How does PAS-004's safety profile compare to existing MEK inhibitors for NF1?

PAS-004 has shown no rash during trials, while approved MEK inhibitors have over 80% on-label rash rates that often lead to treatment discontinuation.

What is the current status of KTTA's Phase 1 PAS-004 trial enrollment?

The trial is experiencing substantial enrollment demand, with Cohort 6 patients already identified for the 30mg capsule dose level.

When will KTTA release more data from the PAS-004 Phase 1 trial?

Pasithea will provide additional safety, pharmacokinetic (PK), and pharmacodynamic (PD) data over the next several weeks.

What patient population is targeted in KTTA's PAS-004 Phase 1 trial?

The trial targets patients with MAPK pathway driven advanced solid tumors with RAS, NF1 or RAF mutations, or those who failed BRAF/MEK inhibition.