Pasithea Therapeutics advances cancer trial after positive safety review of PAS-004

Pasithea Therapeutics Corp. (NASDAQ: KTTA) has reached a significant milestone in its Phase 1 clinical trial of PAS-004, an advanced macrocyclic MEK inhibitor developed to treat neurofibromatosis type 1 (NF1) and other MAPK pathway-driven cancers. Following a comprehensive safety review, the independent Safety Review Committee (SRC) has recommended escalating the trial to a higher dosage level without modifications.

This positive safety assessment comes after a thorough evaluation of data from three patients in cohort 4A, who received a 15mg capsule of PAS-004. With no dose-limiting toxicities (DLTs) observed, the committee has cleared the way for testing the 22mg capsule in the next phase. Additionally, none of the first 14 patients—whether treated with the capsule or tablet formulation—have experienced rashes, a common adverse reaction associated with existing MEK inhibitors. This development underscores PAS-004’s potential as a well-tolerated treatment option for patients with NF1 and other advanced cancers.

What Sets PAS-004 Apart From Other MEK Inhibitors?

MEK inhibitors play a crucial role in targeting the MAPK signaling pathway, a key driver of many cancers. However, traditional inhibitors often come with significant side effects, including skin rashes, which can lead to high discontinuation rates in real-world treatment scenarios. PAS-004, a next-generation macrocyclic MEK inhibitor, is engineered to provide a more targeted approach while reducing adverse effects.

Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea Therapeutics, expressed optimism about the drug’s performance. He highlighted that PAS-004’s prolonged half-life of over 60 hours and its specificity could position it as a breakthrough treatment for patients with NF1 and inoperable plexiform neurofibromas. By mitigating the side effects commonly seen with competitor MEK inhibitors, PAS-004 may offer a more viable long-term treatment option for patients with limited alternatives.

How Does the PAS-004 Phase 1 Clinical Trial Work?

Pasithea Therapeutics is conducting a multi-center, open-label Phase 1 clinical trial to evaluate PAS-004’s safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy. The trial follows a 3+3 dose-escalation study design, assessing the treatment in patients with advanced solid tumors linked to RAS, NF1, or RAF mutations.

Notably, the study also includes patients who have not responded to existing BRAF/MEK inhibitors, providing critical insights into PAS-004’s potential advantages over currently available treatments. With the SRC’s latest recommendation, the trial is moving forward to cohort 5, where participants will receive a 22mg capsule. Researchers will continue monitoring safety outcomes and assessing whether the higher dosage maintains PAS-004’s favorable risk-benefit profile.

Why Is the Absence of Rash a Key Finding in PAS-004’s Trial?

One of the most promising aspects of PAS-004’s clinical progress is the absence of rash among trial participants. Dermatologic side effects are a well-documented issue with existing MEK inhibitors such as trametinib, where up to 87% of patients experience skin-related adverse events, often leading to treatment discontinuation.

The fact that none of the first 14 patients treated with PAS-004 have developed a rash suggests a differentiated safety profile. If these findings hold at higher dose levels, PAS-004 could provide an improved treatment option for patients who cannot tolerate current MEK inhibitors due to severe side effects. This could also expand its potential use in broader oncological applications.

What Are the Implications of PAS-004’s Progress for Cancer Treatment?

As Pasithea Therapeutics advances its clinical program, PAS-004’s promising safety profile positions it as a strong candidate in the competitive MEK inhibitor market. If subsequent trial phases confirm its efficacy and tolerability, PAS-004 could become a preferred option for treating NF1-related tumors and other cancers driven by MAPK pathway mutations.

Pasithea’s ability to develop an effective, well-tolerated MEK inhibitor could offer new hope for patients facing aggressive cancers with limited treatment options. The ongoing Phase 1 study will provide further clarity on PAS-004’s clinical potential, particularly as higher dose cohorts are evaluated for both safety and therapeutic impact.

What’s Next for Pasithea Therapeutics and PAS-004?

Looking ahead, Pasithea Therapeutics plans to release updated pharmacokinetic and pharmacodynamic data in Q1 2025. These findings will help determine PAS-004’s effectiveness and long-term viability as a cancer treatment. Additionally, the company is expected to explore expanded indications, potentially broadening PAS-004’s application beyond NF1 and into other malignancies where the MAPK pathway plays a central role.

With PAS-004 showing early signs of being a safer and more tolerable alternative to existing MEK inhibitors, the biotech industry will be closely watching its clinical progress. Investors and healthcare professionals alike are eager to see whether PAS-004 can redefine the treatment landscape for NF1 and related cancers.

Pasithea Therapeutics remains committed to addressing unmet medical needs, and its advancements in the PAS-004 trial mark a significant step forward in oncology research.