Clinical Trial Results of Atebimetinib - Atebimetinib + mGnP in first-line pancreatic cancer (1L PDAC) showed a 6-month Overall Survival (OS) of 94% in a Phase 2a trial (N=34)[18, 21] - The same combination also demonstrated a 6-month Progression-Free Survival (PFS) of 72%[24, 27] - The Overall Response Rate (ORR) for Atebimetinib + mGnP in 1L PDAC was 39% (14/36), and the Disease Control Rate (DCR) was 81% (29/36)[30] - Grade ≥ 3 Neutropenia adverse event incidence was 15%, Fatigue was 3%, Diarrhea was 0%, Sensory Neuropathy was 0%, Leukopenia was 0%, Vomiting was 3%, Febrile Neutropenia was 0%, Thrombocytopenia was 0%, Anemia was 18%, Hypokalemia was 3%, Nausea was 0%[35] Patient Characteristics - The median age of patients in the Atebimetinib + mGnP Phase 2a trial was 69 years, with 65% of patients being 65 years or older[37] Mechanism and Rationale - Atebimetinib targets the MAPK pathway with Deep Cyclic Inhibition (DCI) to improve durability and tolerability[71, 81] - Approximately 97% of pancreatic cancers are driven by the MAPK pathway[70] Future Plans - The company plans to initiate a pivotal study in 2026 for atebimetinib in 1L pancreatic cancer[81]

Core Insights - Pasithea Therapeutics Corp. announced positive interim pharmacodynamic data from its Phase 1 trial of PAS-004, a macrocyclic MEK inhibitor targeting neurofibromatosis type 1 and other MAPK pathway-driven cancers [1][5] - The trial demonstrated up to 91% inhibition of pERK, confirming substantial target engagement and a favorable pharmacological profile [1][3] - One patient with stage 4 KRAS G12R mutated pancreatic cancer showed a tumor volume reduction of -9.8% over 5 months of treatment with PAS-004 [1][4] Pharmacodynamic Data - Inhibition of ERK phosphorylation (pERK) is a recognized biomarker for assessing MEK inhibitor activity, with measurements taken from patients at baseline and day 22 [2] - The results indicated robust pERK inhibition, with reductions of up to 91% at the 8mg dose level, aligning with previous PK/PD models [3] Clinical Observations - Preliminary clinical observations showed several patients achieving stable disease and tumor shrinkage while on PAS-004 treatment [4] - The ongoing Phase 1 trial is a multi-center, open-label, dose escalation study evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with MAPK pathway-driven advanced solid tumors [5] Company Overview - Pasithea Therapeutics is focused on developing innovative treatments for central nervous system disorders, RASopathies, and MAPK pathway-driven tumors [6]

Core Viewpoint - Pasithea Therapeutics Corp. announced the acceptance of an abstract for a poster presentation at the ASCO Annual Meeting, highlighting the ongoing Phase 1 clinical trial of PAS-004, a macrocyclic MEK inhibitor for treating neurofibromatosis type 1 and other MAPK pathway-driven conditions [1][2]. Group 1: Clinical Trial Details - The ongoing Phase 1 clinical trial is a multi-center, open-label, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of PAS-004 in patients with MAPK pathway-driven advanced solid tumors [5]. - Updated interim clinical data from cohorts 4A and 4B of the trial has shown clinical activity, target engagement, and a favorable safety profile [3]. Group 2: Presentation Information - The poster presentation will take place on June 2, 2025, from 1:30 PM to 4:30 PM CDT, under the title "Phase 1 dose-escalation study of the safety and pharmacokinetics of PAS-004" [4]. - The full abstract will be available on the ASCO website on May 22, 2025, at 5:00 PM ET [4]. Group 3: Company Overview - Pasithea Therapeutics is focused on the discovery, research, and development of innovative treatments for central nervous system disorders, RASopathies, and MAPK pathway-driven diseases [6].