Pasithea Therapeutics (KTTA) Oppenheimer 36th Annual Healthcare Life Sciences Conference summary

Program highlights and clinical development

• Lead program PAZ004 is the first macrocyclic MEK inhibitor advanced into clinical trials, targeting neurofibromatosis type 1 (NF1) and associated neurofibromas.

• Two ongoing clinical trials: a dose-escalation trial in advanced cancer and a phase I-B study in NF1, with data updates expected at ASCO and in the second half of the year.

• Focus on both plexiform and cutaneous neurofibromas, with cutaneous neurofibroma representing a large unmet need as no approved treatments exist.

• Plans to expand into pediatric populations and initiate registrational trials by 2028.

• Additional programs include a schizophrenia candidate (PAZ001) and investigator-led trials in ALS.

Differentiation and pharmacokinetics

• PAS-004 features a macrocyclic structure, offering high selectivity, reduced off-target effects, and improved oral bioavailability.

• Demonstrates a long half-life and flat PK profile, maintaining therapeutic levels with a Cmax/Cmin ratio below 2.

• Achieves high drug exposure (AUC), which correlates with treatment response in NF1.

• Less potent than mirdametinib but more potent than selumetinib, with exposures comparable to approved drugs.

• No active metabolites, reducing potential safety concerns seen with other MEK inhibitors.

Safety and efficacy data

• Early clinical data show a favorable safety profile: GI toxicity in less than 20% of patients, single-digit rates for rash, fatigue, and CK increase.

• No grade 3 adverse events, dose discontinuations, or DLTs observed so far; all patients remain on trial.

• Disease control rate of 70% in advanced cancer patients with BRAF mutations, with multiple patients achieving stable disease.

• Safety profile compares favorably to existing MEK inhibitors, which show higher rates of adverse events even at lower doses.

• Once-daily dosing and potential for further safety improvements with food effect studies.