Pasithea Therapeutics’ PAS-004 MEK inhibitor earns FDA Rare Pediatric Disease Designation for neurofibromatosis type 1

Pasithea Therapeutics (Nasdaq: KTTA), a clinical-stage biotech headquartered in Miami, announced that the US FDA has granted Rare Pediatric Disease Designation (RPDD) to PAS-004, a macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1). The designation is the third expedited regulatory status awarded to PAS-004, which previously received Orphan Drug Designation and Fast Track Designation from the FDA.

RPDD applies to serious or life-threatening conditions that primarily affect individuals aged birth to 18 years and affect fewer than 200,000 people in the US. Approximately 115,000 individuals in the US live with NF1. The designation is commercially material because it makes Pasithea eligible, upon NDA or BLA approval, for a Priority Review Voucher (PRV) that can be sold or transferred; disclosed PRV transactions over the preceding 12 months ranged from USD 150 million to USD 205 million.

PAS-004 is currently being evaluated in two Phase I trials. A dose-escalation study in adults with advanced solid tumors (NCT06299839) generated the most recent public efficacy and safety data, reported November 20, 2025. A separate Phase I/Ib multicenter, open-label trial in adult patients with symptomatic, inoperable, incompletely resected, or recurrent NF1-associated plexiform neurofibromas (NF1-PN) is also enrolling (NCT06961565).

The November 2025 data release, which supersedes an earlier ASCO 2025 presentation, covered 27 patients dosed through the Day 28 dose-limiting toxicity (DLT) assessment window across seven cohorts. One confirmed partial response was observed in a patient with BRAF V600E melanoma who had previously received MEK and BRAF inhibitor combination therapy. The disease control rate (DCR) among BRAF-mutated efficacy-evaluable patients was 71.4% (5 of 7 patients); across all 21 efficacy-evaluable patients, DCR was 42.8%. No DLTs were recorded, all treatment-related adverse events were Grade 1 or 2, and no ocular toxicity, cardiotoxicity, or treatment discontinuations were reported. Pharmacokinetics were dose-proportional across cohorts.

The current RPDD announcement contained no new clinical numeric readouts; the figures above are drawn from the November 2025 press release.

Research context

NF1 is caused by loss-of-function mutations in the NF1 tumor suppressor gene, leading to constitutive RAS-MAPK pathway activation. Plexiform neurofibromas affect 30–50% of NF1 patients and carry risk of malignant transformation; those compressing vital structures can be life-threatening.

The approved MEK inhibitor in this space is selumetinib (AstraZeneca’s Koselugo), which received FDA approval in 2020 for pediatric NF1-PN patients aged two and older. Mirdametinib (SpringWorks Therapeutics’ Gomekli) received FDA approval in 2025 for NF1-PN in adults and pediatric patients aged two and older, broadening the approved population. Both are allosteric MEK1/2 inhibitors.

PAS-004 is structurally differentiated as a macrocyclic MEK inhibitor. Macrocyclic scaffolds can confer selectivity advantages over non-macrocyclic allosteric inhibitors by constraining molecular conformation, potentially reducing off-target engagement. The Phase I advanced cancer data showing activity in a patient who had previously failed MEK and BRAF inhibitor combination therapy is relevant here: if the resistance-overcoming activity observed in that melanoma patient translates to NF1-PN, PAS-004 could address patients who have progressed on selumetinib or mirdametinib. The absence of ocular toxicity and cardiotoxicity in the Phase I safety data is also pertinent, as these are class-associated risks that have required monitoring protocols in pediatric MEK inhibitor programs. Whether the macrocyclic design is mechanistically responsible for this profile, or whether it reflects the dose levels evaluated to date, remains to be established in larger studies.