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 long-term treatment of chronic diseases including the neurocutaneous manifestations of neurofibromatosis type 1 (NF1), today announced updated interim safety and clinical activity 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, including patients who have failed prior BRAF/MEK inhibitor treatment (NCT06299839). The Company also announced details of its protocol amendment to extend dose escalation and initiate a pilot food effect assessment.

Dr. Kartik Krishnan, Chief Medical Officer of Pasithea, said, "The literature reports that patients with BRAF mutated cancer who progress on BRAF/MEK combination therapy have a median progression-free survival of approximately 5 months with rechallenge with BRAF/MEK combination therapy. We have observed that a number of these patients who previously progressed on prior BRAF/MEK inhibitor treatment have demonstrated stable disease on PAS-004 for greater than six months, including two patients for over one year. We believe that this demonstrates that PAS-004 is an active agent. Importantly, we continue to be encouraged by the observed adverse event (AE) profile and the ability to maintain dosing in patients over a long period of time without discontinuations. Given that we have not reached the maximum tolerated dose (MTD) and the tolerability of the doses we have evaluated to date, we have decided to continue dose escalation in the study with the introduction of our tablet formulation, while also exploring the effect of food on the PK of PAS-004 to enhance our understanding about how best to maximize the benefit of PAS-004 in long-term chronic dosing."

Interim Phase 1 Results for PAS-004 through May 22, 2026:

  • 34 patients have been enrolled and dosed
    • Heavily pre-treated population with a median of 3 prior lines of therapy (range 1 – 8)
    • Difficult to treat diagnoses (e.g., refractory pancreatic cancer and ovarian cancer), including 12 patients with BRAF V600E mutations, 10 of whom previously progressed on BRAFi and/or BRAFi/MEKi combinations



       
  • Well-tolerated safety profile with long-term, once daily dosing



    • No dose-limiting toxicities (DLTs), and no discontinuations due to TRAEs with 10 patients on study for >90 days, of which 6 patients >150 days, 4 patients >300 days, and 2 patients >365 days
    • All TRAEs were Grade 1 or Grade 2; Low cumulative rates of rash (12%) and diarrhea (6%) across all patients at all doses throughout the study, including no (0%) rash or diarrhea in the 4 patients on study >300 days and 2 patients >365 days
    • No events of retinal or cardiac toxicity
  • Disease stabilization in the refractory population (N=12)
    • Multiple patients demonstrating durable clinical benefit and tumor shrinkage, including several MEK/BRAF-pretreated patients who have remained on study for greater than six months and two patients on study for over one year – exceeding the approximately 5-month median PFS reported in the literature for BRAF/MEK rechallenge in this setting. The final PFS data will not be known until the end of the trial.
  • Pharmacokinetics support daily dosing and exploration of higher dose levels
    • Long half-life (approximately 60 hours)
    • Linear, dose proportional PK
    • Cmax/Cmin ratio <2, with both Cmax and Cmin above the IC50 (half-maximal inhibitory concentration) from our cellular assay at all dose cohorts

The Company plans to submit and present a more robust data set at a future scientific conference.