Pasithea Therapeutics Reports Promising Phase 1 Data on PAS-004 in Advanced Cancer

Pasithea Therapeutics Corp. has released promising preliminary data from its Phase 1 clinical trial of PAS-004, a next-generation macrocyclic MEK inhibitor developed for treating neurofibromatosis type 1 (NF1) and other cancer indications. Conducted across four clinical sites in the United States, the trial focuses on patients with advanced solid tumors driven by MAPK pathway mutations, particularly those who have not responded to previous BRAF/MEK inhibition therapies.

The trial employs a multi-center, open-label, dose-escalation design to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of PAS-004. The study has thus far involved six patients in its initial 2 mg and 4 mg dosing cohorts. The findings indicate that PAS-004 has a favorable safety profile with no treatment-related adverse events (TRAEs) or dose-limiting toxicities (DLTs) reported. Moreover, no occurrences of rash, gastrointestinal toxicity, or other common MEK inhibitor side effects were observed.

One patient in the 2 mg cohort with stage 3 colon cancer and a history of four prior therapy lines achieved prolonged stable disease. This patient, harboring a BRAF K601E mutation, has continued on the drug into the sixth dosing cycle without experiencing any toxicities. This is particularly notable given that colorectal cancer typically does not respond to single-agent MEK inhibitors.

Dr. Tiago Reis Marques, Pasithea's Chief Executive Officer, emphasized that these early results highlight PAS-004's differentiating characteristics. The drug achieves significant systemic exposure at steady-state with minimal peak plasma toxicities, supported by its approximately 70-hour half-life. This extended half-life facilitates the potential for once-daily or even less frequent dosing schedules, offering a distinct advantage over first-generation MEK inhibitors that typically require twice-daily administration due to their shorter half-lives.

The pharmacokinetic data reveal that plasma exposure of PAS-004 increases proportionally with the dose. At steady-state, the drug maintains consistent plasma levels, peaking around five hours post-dose. The geometric mean maximum concentrations (Cmax) were reported as 16.2 ng/mL for the 2 mg dose and 61.3 ng/mL for the 4 mg dose. This steady-state consistency, with a Cmax/Cmin ratio of 1.2, underscores the potential for constant target inhibition without significant fluctuation.

Safety and tolerability have been strong points in the trial. The initial two dosing cohorts demonstrated that PAS-004 is well-tolerated. No drug-related dose interruptions, reductions, or discontinuations were required, and no serious adverse events (SAEs) linked to the drug were reported. Following a positive safety review by an independent Safety Review Committee, the trial has progressed to a third cohort with an increased 8 mg dose, accompanied by a protocol amendment to further adjust the dosing schedule.

PAS-004's distinctive profile positions it as a potentially superior option for treating NF1-related plexiform and cutaneous neurofibromas, as well as other MAPK-driven cancers. The drug's prolonged half-life and stable plasma concentrations at steady-state may offer significant advantages in efficacy and safety over existing MEK inhibitors.

Pasithea Therapeutics is dedicated to advancing this promising candidate through continued clinical trials, with the aim of providing an effective, less frequently administered treatment option for NF1 and other related conditions. The company plans to deliver ongoing updates as the trial progresses.