Pasithea Therapeutics Presents Positive Initial Phase 1/1b Data for PAS-004, Showing Substantial Reductions in Cutaneous Neurofibroma Size and Early Activity in Plexiform Neurofibromas at the 2026 European Neurofibromatosis Conference

PAS-004 shows strong early efficacy and safety in NF1 neurofibroma patients, Phase 2 cleared.

What the company is saying

Pasithea Therapeutics Corp. is highlighting positive interim results from its ongoing Phase 1/1b study of PAS-004, an oral MEK inhibitor, in adults with NF1-associated cutaneous and plexiform neurofibromas. The company emphasizes substantial reductions in cNF size across all dose levels, with reductions deepening over time and notable activity even at the lowest doses. CEO Dr. Tiago Reis Marques frames the data as a significant clinical signal in a disease with no FDA-approved systemic treatments, while CMO Dr. Kartik Krishnan points to systemic, broad improvements and early activity in plexiform neurofibromas. The announcement stresses the favorable safety profile, dose-proportional pharmacokinetics, and the FDA’s clearance of the IND for a Phase 2 trial. The tone is confident and data-driven, focusing on both efficacy and tolerability, and positions PAS-004 as a potential once-daily oral therapy for long-term management of NF1-associated neurofibromas.

What the data suggests

The disclosed data show that all 15 evaluable participants experienced reductions in summed target cNF surface area, with a median best reduction of 41%. Among eight participants at 4, 8, and 12mg, the median best reduction was 46%, and all six at 4mg and 8mg achieved reductions greater than 40%. Reductions in cNF surface area deepened with continued treatment, rising from 12% at Cycle 1 to 38% at Cycle 4, 49% at Cycle 12, and reaching 71% at Cycle 15 in the 4mg cohort. At the 4, 8, and 12mg doses, 73% of target cNFs were reduced by at least 25% in longest diameter, and among non-resected cNFs, 83% met this criterion, with a median best reduction of 39%. All 18 evaluable participants showed reductions in plexiform neurofibroma volume, with two meeting the REiNS partial-response threshold, including a 22.5% reduction at first MRI in one participant. Safety data are favorable: 97.6% of treatment-related adverse events were Grade 1 or 2, with two Grade 3 events resolving after a one-week dose interruption. At the 4 to 12mg doses, dermatitis acneiform and diarrhea occurred in 33% and 11% of participants, respectively. Pharmacokinetics support once-daily dosing, with a 40–60 hour half-life and limited peak-to-trough fluctuation. The FDA has cleared the IND for a randomized, double-blind, placebo-controlled Phase 2 trial in approximately 200 adults. The evidence is robust for a Phase 1/1b study, but sample sizes remain small and longer-term outcomes are pending.

Analysis

The announcement presents detailed and specific clinical data from an ongoing Phase 1/1b trial, including response rates, adverse event profiles, and pharmacokinetic data, which are all realised and well-supported by the disclosed numbers. The tone is positive and highlights the potential of PAS-004, but most claims about future benefit (e.g., broad, visible improvements, long-term treatment potential) are forward-looking and not yet realised. The next steps, including a Phase 2 trial and pharmacodynamic analyses in 2027, indicate that any commercial or patient benefit is still several years away, placing the execution distance in the long-term category. There is no mention of a large capital outlay or immediate financial impact, and the company is at an appropriate stage for a biotech in early clinical development. The language is somewhat promotional, especially in projecting future impact and confidence, but the core clinical claims are substantiated. The gap between narrative and evidence is moderate, with most overstatement in the interpretation of early results rather than in the data itself.

Risk flags

• ●The clinical data are from a small sample size (19 enrolled, 15–18 evaluable), which limits statistical power and generalizability. Results may not replicate in larger, more diverse populations.
• ●The transition from Phase 1/1b to Phase 2 introduces risk that efficacy or safety signals may weaken or new adverse events may emerge in a broader trial setting. Early-phase success does not guarantee late-phase or regulatory success.
• ●No financial data, cash runway, or funding plan for Phase 2 and beyond is disclosed. The company’s ability to finance larger trials and eventual commercialization remains unaddressed in this release.
• ●The timeline to value realization is long, with key milestones (e.g., pharmacodynamic analyses, Phase 2 results) not expected until 2027 or later. Delays or setbacks in trial execution could materially impact the investment case.
• ●While no serious treatment-related adverse events have been reported, the long-term safety of PAS-004 remains unproven, especially with chronic administration in a larger patient population.

Bottom line

Pasithea’s Phase 1/1b data for PAS-004 in NF1-associated neurofibromas are strong for this stage, with all evaluable patients showing tumor reductions and a favorable safety profile. The FDA’s clearance for a 200-patient Phase 2 trial is a key regulatory milestone, but commercial or late-stage clinical value is still at least one to two years away. The absence of financial disclosure leaves open questions about funding for upcoming trials and operational runway. While the clinical results are promising and support continued development, the small sample size and early-stage status mean that efficacy and safety must be confirmed in larger, controlled studies. Investors should focus on Phase 2 trial initiation, enrollment progress, and interim data as the next critical catalysts. The most important takeaway is that PAS-004 has cleared early clinical and regulatory hurdles, but the path to approval and commercial impact remains long and uncertain.

Announcement summary

(NASDAQ:KTTA) Pasithea Therapeutics Corp. announced positive clinical data from its ongoing Phase 1/1b study (PAS-004-103, NCT06961565) of PAS-004, a next-generation macrocyclic oral MEK inhibitor, in adults with neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas (PN) and cutaneous neurofibromas (cNF), presented at the 2026 European Neurofibromatosis Conference in Vienna, Austria. Dr. Tiago Reis Marques, Chief Executive Officer, stated that the substantial reductions in cNF size represent an encouraging clinical signal in a condition with no FDA-approved systemic treatments, and that these reductions have deepened with longer treatment, including at the lowest doses tested. Dr. Kartik Krishnan, Chief Medical Officer, highlighted the potential of PAS-004 to provide broad, visible improvements for patients through a systemic treatment approach and noted early activity in plexiform neurofibromas, with reductions in tumor volume across all dose levels and two participants meeting the REiNS threshold for partial response. Study PAS-004-103 is an ongoing multicenter, open-label Phase 1/1b trial at five sites in the United States, Australia, and South Korea, enrolling adults with NF1 and symptomatic, inoperable, incompletely resected, or recurrent PN, and evaluating up to 7 cNFs per participant. As of September 15, 2026, 19 participants have been enrolled across six cohorts (4, 8, 12, 15, 18, and 24mg), with 15 evaluable for cNF and 18 for PN response. Median treatment duration ranged from 14.4 months at 4mg to approximately 4 months at 15mg and 24mg. All 15 evaluable participants showed reductions in summed target cNF surface area at best response, with a median best reduction of 41%. Among eight evaluable participants at 4, 8, and 12mg, the median best reduction was 46%, and all six participants at 4mg and 8mg achieved reductions greater than 40%. Among participants followed through 12 treatment cycles, the median reduction in summed target cNF surface area increased from 12% at Cycle 1 to 38% at Cycle 4 and 49% at Cycle 12, with the 4mg cohort reaching a median reduction of 71% at Cycle 15. At the 4, 8, and 12mg doses, 27 of 37 target cNFs (73%) were reduced by at least 25% in longest diameter, meeting the REiNS shrinkage criterion, and among the 29 cNFs not resected, 24 (83%) met the REiNS criterion, with a median best reduction in longest diameter of 39%. All 18 evaluable participants showed reductions in target PN volume by blinded independent central review, including two who met the REiNS partial-response threshold at 12mg and 15mg, with the 15mg participant achieving a 22.5% reduction at the first on-treatment MRI. No treatment-related serious adverse events, discontinuations, adverse events of decreased LVEF, or cases of retinopathy have been reported. Most treatment-related adverse events were Grade 1 or 2 (97.6% of events), with two Grade 3 events (asymptomatic increases in blood creatine phosphokinase) resolving after a one-week dose interruption. At the 4 to 12mg doses, dermatitis acneiform (rash) and diarrhea occurred in 33% and 11% of participants, respectively. PAS-004 showed approximately dose-proportional exposure across the 4 to 24mg range, a terminal half-life of 40 to 60 hours, and limited peak-to-trough fluctuations (Cmax/Cmin of 1.5 to 2.0), supporting once-daily dosing. The FDA’s Division of Dermatology and Dentistry has cleared the IND for Study PAS-004-201, a randomized, double-blind, placebo-controlled Phase 2 trial evaluating three once-daily doses of PAS-004 in approximately 200 adults with NF1-associated cNF. The ongoing Phase 1/1b study will continue participant follow-up and advance toward Part B, a randomized two-dose expansion phase. The company expects to complete pharmacodynamic analyses of resected cNFs in 2027 and present additional clinical data at future scientific meetings.

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