Pasithea Therapeutics Announces Positive Phase 1 Data Including Partial Response, Demonstrating Monotherapy Clinical Activity and Favorable Safety Profile for PAS-004 in Advanced Cancer Study

Rhea-AI Summary

Pasithea Therapeutics (Nasdaq: KTTA) reported positive interim Phase 1 data for oral MEK inhibitor PAS-004 in MAPK-driven advanced solid tumors, disclosed through a data cutoff of Nov 10, 2025. Key findings include an unconfirmed monotherapy partial response (–31.9%) in a BRAF V600E melanoma patient on Cohort 4A (15mg) who remains on study >11 months, and a second BRAF V600E patient with durable stable disease >6 months (Cohort 6, 30mg).

Other highlights: initial Disease Control Rate of 71.4% in BRAF-mutated tumors (5 of 7), overall 42.8% DCR in 21 evaluable patients, favorable safety with no DLTs or discontinuations, and pharmacokinetics showing dose-proportionality and AUC ~5,480 ng·h/mL at 30mg.

Positive

• Partial response –31.9% in Cohort 4A (15mg)
• DCR 71.4% in BRAF-mutated tumors (5 of 7)
• AUC ~5,480 ng·h/mL at 30mg (Cohort 6)
• No DLTs and no discontinuations through DLT period

Negative

• Partial response is unconfirmed
• Efficacy-evaluable population is small (n=21)
• BRAF-mutated subgroup size is small (n=7)

Insights

Clinical Oncology Analyst

Interim Phase 1 data show early monotherapy activity and a clean tolerability profile for PAS-004, warranting cautious optimism.

PAS-004 demonstrates measurable single‑agent anti‑tumor activity including an unconfirmed partial response in a BRAF V600E melanoma patient and a disease control signal among BRAF‑mutated tumors (5 of 7; 71.4%). Pharmacokinetics at the 30mg capsule (Cohort 6) show dose‑proportional, near‑flat exposure with AUC ~5,480 ng·h/mL and a long half‑life (~60 hours), consistent with sustained target engagement described.

Safety through the Day 28 DLT window across 27 dosed patients is favourable: no DLTs, no discontinuations, and all treatment‑related adverse events Grade 1–2 with limited rash (7.4%), nausea (18.5%), vomiting (14.8%), and no ocular or cardiovascular toxicity. These findings support further evaluation in NF1‑PN given the programmatic rationale stated.

Key dependencies and near‑term readouts to watch are confirmation of the reported partial response (durability beyond the current >11 months), expanded efficacy data across the efficacy evaluable set (21 patients reported, with overall stable disease/PR in 42.8%), and continued safety follow‑up beyond the DLT window; the cutoff for the reported safety/PK snapshot is November 10, 2025. Additional cohort PK/safety data and confirmed responses will materially affect interpretation over the coming months.

-- Evidence of Monotherapy Activity: Partial response observed in a MEK-rechallenge 3rd-line melanoma patient with BRAF V600E mutation who remains on trial for more than 11 months --

-- A second MEK-rechallenge 3rd-line melanoma patient with BRAF V600E mutation has achieved stable disease and remains on trial for more than 6 months --

-- Initial Disease Control Rate in efficacy evaluable patients of 71.4% with BRAF-mutated tumors: 5 of 7 patients achieved stable disease --

-- Favorable Safety Profile: PAS-004 has been well-tolerated with all treatment-related adverse events Grade 1 or 2, no ocular or cardio toxicity, and limited rash, nausea, diarrhea, and vomiting to date --

-- Favorable Pharmacokinetic (PK) Profile: PAS-004 demonstrates dose-proportional PK with Cmax/Cmin ratio <2. AUC >5,400 ng·h/mL at the 30mg capsule dose (Cohort 6) --

-- Potential Best-in-Class MEK Inhibitor Profile Emerging for NF1: Interim PK and safety data at pharmacologically active doses support PAS-004 as a differentiated candidate for NF1 treatment --

MIAMI, Nov. 20, 2025 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (Nasdaq: KTTA) (“Pasithea” or the “Company”), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic oral MEK inhibitor for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN), today announced positive interim Phase 1 data from its ongoing first-in-human trial evaluating PAS-004 in patients with MAPK pathway-driven advanced solid tumors with a documented RAS, NF1 or RAF mutation, or in patients who have failed prior BRAF/MEK inhibition.

Dr. Tiago Reis Marques, CEO of Pasithea said, “Today’s updated interim results from our advanced cancer trial demonstrate the safety, PK and anti-tumor activity of PAS-004, and support its potential to be a best-in-class MEK inhibitor for the treatment of NF1-PN. Achieving a monotherapy partial response in an advanced cancer patient who had previously received a MEK + BRAF inhibitor combination therapy, and whose prior best response had been stable disease, is very promising. At our highest reported cohort (30mg capsule), we are seeing significant drug exposures (Area Under the Curve (AUC) greater than 5,400 ng·h/mL), with a relatively flat PK curve, suggesting sustained pathway inhibition. We believe this profile is well aligned with what is needed to drive meaningful clinical responses in NF1-PN patients. Published clinical data has shown that tumor response in NF1-PN is positively correlated with drug exposure (AUC), reinforcing the relevance of these findings.”

Dr. Rebecca Brown, Director of the Neurofibromatosis (NF) and Schwannomatosis (SWN) Program at University of Alabama Birmingham (UAB) and Scientific Advisory Board member of Pasithea, stated: “I find it very encouraging that even when used as a monotherapy in advanced recurrent cancer patients, PAS-004 has demonstrated early signals of efficacy, but more importantly exhibited such a favorable safety profile that no dose interruptions or modifications were required. Maintaining NF1-PN patients on treatment for extended periods of time is paramount to achieving maximum tumor control. I believe that PAS-004’s early efficacy signals combined with the low rate of adverse side effects may translate into better tolerability and longer time-on-treatment for plexiform neurofibromas associated with NF1, compared with current FDA-approved therapies discontinuation rates estimated as high as 40-50% before year two.”

Interim Phase 1 Results for PAS-004:

Initial Signals of Clinical Activity

Among 21 efficacy evaluable patients (as per RECIST1.1):

• Partial Response:
  
  • A BRAF V600E melanoma patient in Cohort 4A (15mg capsule) achieved an unconfirmed partial response with a –31.9% tumor reduction and remains on trial for >11 months; prior best response when treated with a MEK + BRAF combination therapy was stable disease
• Disease Control Rate (DCR):
  
  • 71.4% (5 of 7) of patients identified with BRAF-mutated tumors achieved stable disease or partial response

• 42.8% (9 of 21) of patients achieved stable disease or partial response
  

• Durable Stable Disease:
  
  • A second BRAF V600E melanoma patient previously treated with MEK + BRAF combination therapy in Cohort 6 (30mg capsule) remains on trial for >6 months with a stable disease and tumor shrinkage of -1.6%
    

Safety and Tolerability

Among 27 dosed patients through the Dose Limiting Toxicity (DLT) period (Day 28) through the cutoff date of November 10, 2025:

• PAS-004, dosed once daily (QD), has been well-tolerated across all dose levels
  
• No dose-limiting toxicities (DLTs), and no discontinuations have been reported.
  
• All treatment-related adverse events (TRAEs) at least possible related to PAS-004 were Grade 1 or 2, with limited rash (7.4%), nausea (18.5%), vomiting (14.8%), diarrhea (7.4%), and no ocular retinal abnormalities or cardiovascular toxicities observed.
  

Pharmacokinetics (PK)

PAS-004 has demonstrated through Cohort 6:

• Linear PK and dose-proportionality
• PK curve with Cmax/Cmin ratio <2, with Cmax and Cmin above the IC50 (half-maximal inhibitory concentration) from our cellular assay.
  
• Long half-life (~60 hours)
  
• Cohort 6 (30mg capsule) has demonstrated:
  
  • AUC: ~5,480 ng·h/mL
    
  • Cmax: 249 ng/mL
    
  • Cmin: 215 ng/mL
    

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 ongoing 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 and financing 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 Reports on Form 10-Q and other filings made with the U.S. Securities and Exchange Commission. 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 interim Phase 1 results did Pasithea (KTTA) announce on November 20, 2025?

Pasithea announced interim data showing an unconfirmed –31.9% partial response in a BRAF V600E melanoma patient, a 71.4% DCR in BRAF-mutated tumors, no DLTs, and PK AUC ~5,480 ng·h/mL at 30mg.

How many patients were efficacy evaluable in the PAS-004 Phase 1 trial (KTTA)?

There were 21 efficacy evaluable patients reported per RECIST 1.1 in the interim dataset.

What safety findings were reported for PAS-004 in Pasithea’s Nov 2025 update (KTTA)?

Through the DLT period, PAS-004 had no dose-limiting toxicities, no discontinuations, and all treatment-related events were Grade 1–2 with no ocular or cardiovascular toxicity observed.

What pharmacokinetic profile did PAS-004 show at the 30mg dose (KTTA)?

Cohort 6 (30mg) showed linear, dose-proportional PK with AUC ~5,480 ng·h/mL, Cmax 249 ng/mL, Cmin 215 ng/mL, and a Cmax/Cmin ratio <2.

Which patients showed clinical activity on PAS-004 in the Phase 1 study for KTTA?

A BRAF V600E melanoma patient in Cohort 4A had an unconfirmed partial response and another BRAF V600E patient in Cohort 6 achieved durable stable disease (>6 months).

Does the Nov 2025 PAS-004 update include a data cutoff date for Pasithea (KTTA)?

Yes, the interim results are reported through a data cutoff of November 10, 2025.