Pasithea Therapeutics (KTTA) Chardan's 10th Annual Healthcare Conference summary

NF1 disease burden and unmet need

• NF1 affects ~1 in 3,000 newborns and ~150,000 people in the U.S.; neurofibromin mutations overactivate the MAPK pathway and drive tumor growth.

• Cutaneous neurofibromas affect >99% of patients, often cause pain, itching, stigma and quality-of-life impact, and accumulate with age; >80% of cohort participants had >100 lesions by age 50.

• No FDA-approved systemic treatment exists for cutaneous neurofibromas; lesions can be removed individually by biopsy or laser, leaving small scars.

PAS-004 design and rationale

• PAS-004 is an oral macrocyclic MEK inhibitor designed for chronic, non-oncology use; its rigid structure supports a 60-hour half-life, while removal of primary alcohols is intended to avoid active metabolites.

• Existing MEK inhibitors used in NF1 are associated with rash in >90% of patients, grade 3 rash and ocular or cardiac toxicity in ~20%, GI toxicity in >50%, and 15%–20% discontinuations.

• Longer half-life may reduce peak-and-trough pathway inhibition; the development aim is partial pathway blockade to preserve efficacy while reducing safety burden.

Phase Ib trial and efficacy assessment

• Dose escalation is ongoing across six cohorts from 4–24 mg; plexiform neurofibromas are assessed by MRI and cutaneous lesions by digital calipers.

• Initial NF1 data covering 18 patients and >70 lesions are expected at the European Neurofibromatosis Conference next month; cutaneous success would mean significant lesion-volume and size reductions.

• For plexiform neurofibromas, the readout will emphasize tumor-volume trajectory; approved MEK inhibitors have an average response time of 7–8 months, and trial participants have varied treatment durations by dose cohort.

• Safety assessment will include adverse-event frequency and severity, dose reductions, interruptions and discontinuations, plus cardiac and ocular toxicity.