Pasithea Therapeutics Corp. has announced the activation of four clinical trial sites in the United States for its Phase 1 clinical trial of PAS-004. This next-generation macrocyclic MEK inhibitor is being developed for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications driven by the MAPK pathway. The trial's initiation follows FDA approval of the Investigational New Drug (IND) application for PAS-004.
Trial Design and Objectives
The Phase 1 study is a multicenter, open-label trial designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PAS-004. It will also evaluate the preliminary anticancer activity (efficacy) of PAS-004 and define the preliminary recommended Phase 2 dose. The trial is enrolling patients with MAPK pathway-driven advanced solid tumors harboring RAS, NF1, or RAF mutations, or those who have failed prior BRAF/MEK inhibition.
PAS-004: A Novel MEK Inhibitor
PAS-004 is a small molecule allosteric inhibitor of MEK 1/2, dual-specificity protein kinases in the MAPK signaling pathway. The MAPK pathway is implicated in cell proliferation, differentiation, survival, and other cellular functions, and its abnormal activation is critical for tumor formation and progression. Unlike current FDA-approved MEK inhibitors, PAS-004 is macrocyclic, potentially leading to improved pharmacokinetic and safety profiles. Macrocycles are known for stronger binding, better solubility, longer half-life, and greater selectivity.
Clinical Development Plan
Following the Phase 1 study, Pasithea plans to initiate a Phase 2 clinical trial in NF1 pediatric and adult patients, contingent upon establishing safety and PK parameters. Novotech has been selected as the clinical research organization (CRO) for the Phase 1 trial. Pasithea is collaborating with NEXT Oncology in the U.S., with Dr. Anthony Tolcher M.D. and Dr. Ildefonso Rodriguez M.D. serving as principal investigators. Three additional clinical trial sites in Eastern Europe are expected to open in the coming months. Preliminary interim data from the Phase 1 trial is expected in the second half of 2024.
Management Commentary
"Activating our four clinical trial sites in the U.S. is a significant milestone in Pasithea’s mission towards developing PAS-004 as a potential best-in-class next-generation MEK inhibitor," said Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. "We recognize the significant unmet needs and limited treatment options for patients with MAPK pathway-driven advanced solid tumors as well as NF1. We are ready to screen and enroll subjects in the coming month and look forward to gaining insight into the safety, tolerability and initial efficacy of PAS-004."
