Pasithea Therapeutics Amends Phase 1/1b NF1 Protocol to Add Dose Levels and Extend Treatment Duration

Protocol amendments filed mid-escalation signal that Pasithea Therapeutics is actively shaping the data package for PAS-004 ahead of a registrational submission, with changes that will directly influence dose selection, CMC planning, and the scope of the Q4 2026 interim readout. The company amended the Phase 1/1b study protocol (NCT06961565) for its macrocyclic MEK inhibitor in neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma, expanding both the breadth and depth of the dose-escalation arm.

The amended Part A now accommodates two additional higher dose cohorts at 24 mg and 32 mg, backfill enrollment of up to two participants per completed cohort (4 mg, 8 mg, 12 mg, and 18 mg), and evaluation of intermediate dose levels. Pasithea has already enrolled the 24 mg cohort and an intermediate 15 mg cohort, bringing total Part A enrollment to 18 patients across six dose levels. The treatment window in Part A has been extended to 18 months, and the imaging and measurement battery now includes additional MRI scans alongside more granular cutaneous neurofibroma assessments covering tumor height and volume.

For clinical operations and data management teams, the backfill provision is the operationally consequential element: it allows statistical strengthening of completed cohorts without reopening a new escalation sequence, a design choice consistent with adaptive frameworks under ICH E11A and current FDA guidance on rare disease dose optimization. The extended treatment period also expands the pharmacokinetic and pharmacodynamic dataset, which will bear directly on the exposure-response arguments required in any future 21 CFR Part 312 IND amendment or NDA submission.

Manufacturing and CMC leads should note that the addition of 32 mg as a ceiling dose, combined with the 18-month treatment horizon, materially alters projected API consumption and stability testing timelines relative to the original protocol. Scale-up assumptions built around the initial four-cohort design will need revision before Part B expansion cohort enrollment begins.

Pasithea's Chief Medical Officer, Dr. Kartik Krishnan, stated that the amendments are intended to inform dose selection for Part B and future registrational studies, and that six additional patients were rapidly enrolled and dosed following the protocol change.

The interim NF1 data update remains on schedule for Q4 2026, at which point the amended protocol's contribution to dose selection clarity will be measurable against the registrational design criteria Pasithea has yet to disclose.

Source: Pasithea Therapeutics Corp. via GlobeNewswire, June 16, 2026.