PAS-004 / Pasithea - LARVOL DELTA

Pasithea Therapeutics Provides Outlook on PAS-004 Clinical Programs and Data Release Timelines (GlobeNewswire) - "(i) Ongoing Phase 1/1b clinical trial in adult patients with NF1-PN (NCT06961565): Pasithea has completed enrollment of 12 patients through the first 4 dose cohorts (4, 8, 12 and 18 mg tablets) in Part A of the study. The Company plans to present data in the second half of 2026, including available efficacy data through the six-month timepoint for both plexiform and cutaneous neurofibromas. The planned data release is also expected to include safety, tolerability and pharmacokinetic (PK) data; (ii) Ongoing Phase 1 clinical trial in advanced cancer patients (NCT06299839): Pasithea expects to present longer-term follow-up data from patients in Cohort 4 (15mg capsule) through Cohort 8 (45mg capsule) in the second quarter of 2026."

Enrollment status • P1 data • Neurofibromatosis • Solid Tumor

Pasithea Therapeutics Announces Positive PAS-004 Tablet Pharmacokinetic (PK) Data in Ongoing Phase 1/1b Trial in Adult NF1 Patients (GlobeNewswire) - "Dose normalized exposures following once daily administration of PAS-004 tablets were approximately 3-fold higher than those following administration with the capsule formulation, resulting in the 8mg tablet area under the curve (AUC) and Cmax being slightly greater than those of the 22mg capsule. The tablet formulation has demonstrated less patient variability and a similar Tmax range when compared to the capsule formulation."

P1 data • Neurofibromatosis

Pasithea Therapeutics…announced that the ALS Association has awarded a Hoffman ALS Clinical Trial Award grant worth ~$1 million to study PAS-004 in ALS patients (GlobeNewswire) - "The award was given to study the 'Efficacy, safety and tolerability of PAS-004 for the treatment of ALS'....This Phase 1 study, awarded to a leading ALS institution in the US, will evaluate PAS-004 in twelve patients with ALS enrolled across three sequential dose cohorts and followed for approximately 28 weeks."

Financing • New P1 trial • Amyotrophic Lateral Sclerosis

Pasithea Therapeutics…announced positive interim Phase 1 data from its ongoing first-in-human trial evaluating PAS-004 in patients with MAPK pathway-driven advanced solid tumors with a documented RAS, NF1 or RAF mutation, or in patients who have failed prior BRAF/MEK inhibition (GlobeNewswire) - "Evidence of Monotherapy Activity: Partial response observed in a MEK-rechallenge 3rd-line melanoma patient with BRAF V600E mutation who remains on trial for more than 11 months. A second MEK-rechallenge 3rd-line melanoma patient with BRAF V600E mutation has achieved stable disease and remains on trial for more than 6 months. Initial Disease Control Rate in efficacy evaluable patients of 71.4% with BRAF-mutated tumors: 5 of 7 patients achieved stable disease."

First-in-human • P1 data • Melanoma

Pasithea Therapeutics Announces Enrollment of Cohort 2 following Positive Safety Review Committee (SRC) Recommendation for its Ongoing Phase 1/1b Clinical Trial of PAS-004 in Adult NF1 Patients (GlobeNewswire) - "Recommendation that trial escalate to next dose level of 8mg tablet. Initial interim clinical data from first two cohorts expected in Q1 2026."

Enrollment status • P1 data • Neurofibromatosis • Oncology

Pasithea Therapeutics Completes Enrollment and Initial Dosing of First Cohort from its Phase 1/1b Clinical Trial of PAS-004 in Adult NF1 Patients (GlobeNewswire) - "Pasithea Therapeutics...announced the Company has completed enrollment and initial dosing of three subjects in Cohort 1 (4mg tablet) from its ongoing Phase 1/1b multicenter, open-label clinical trial evaluating PAS-004 in adult NF1 patients with symptomatic and inoperable, incompletely resected, or recurrent plexiform neurofibromas....Initial interim safety, tolerability, biomarker, and preliminary efficacy data expected in Q1 2026."

P1 data • Trial status • Neurofibromatosis

Phase I dose-escalation study of the safety and pharmacokinetics of PAS-004, a macrocyclic MEK inhibitor, for the treatment of patients with MAPK pathway–driven advanced solid tumors. (ASCO 2025) - P1 | "To date, PAS-004 is shown to be a safe and well-tolerated novel MEK inhibitor, with dose-dependent PK profile and preliminary clinical activity in monotherapy in patients with heavily pre-treated refractory solid tumors. PAS-004 has the potential to achieve prolonged target inhibition and once-daily dosing (QD) due to its long half-life and low Cmax to Cmin ratio. These findings provide a compelling rationale to continue to test PAS-004 into clinical trials for the treatment of MAPK-driven opportunities."

Clinical • Metastases • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Pain • Oncology • Solid Tumor • Urinary Incontinence • Urology • MAP2K1 • NF1

Pasithea Therapeutics Presents Updated Interim Data from Ongoing Phase 1 Study of PAS-004 at the ASCO Annual Meeting 2025 (GlobeNewswire) - P1 | N=48 | NCT06299839 | Sponsor: Pasithea Therapeutics Corp. | "PAS-004 demonstrates preliminary clinical activity as a monotherapy in patients with heavily pre-treated, refractory solid tumors; One patient in cohort 4A (15mg capsule) with stage 4 BRAF-mutated melanoma, who had progressed after two prior lines of therapy, including a prior MEK inhibitor + BRAF inhibitor combination therapy, achieves over 5 months of stable disease with tumor volume reduction of -14.9% and remains on treatment; PAS-004 pharmacokinetics profile potentially supports a prolonged target engagement at well-tolerated doses."

P1 data • Colorectal Cancer • Melanoma • Pancreatic Cancer

PAS-004 in Adults Who Have Neurofibromatosis Type 1 With Plexiform Neurofibromas (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Pasithea Therapeutics Corp. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Neurofibromatosis • Solid Tumor

Pasithea Therapeutics Announces Preclinical Data that Shows PAS-004 Inhibits ETS2 Signaling, a Key Driver of Inflammation in IBD and Other Large Addressable Market Diseases (Pasithea Press Release) - "In this new study RNA sequencing was used to measure gene expression, with PAS-004 consistently outperforming the FDA-approved MEK inhibitor selumetinib across all tested doses (0.01 μM, 0.1 μM, and 1 μM), showing greater downregulation of ETS2 target genes, as well as experimentally validated MEK1/2 pathway genes....Key findings of this study are: Superior and stronger suppression of ETS2 signaling: At all doses, PAS-004 showed greater downregulation of ETS2-regulated genes than selumetinib; - Suppression of core macrophage functions: PAS-004 significantly reduced ETS2-dependent functions such as cytokine production, phagocytosis, and reactive oxygen species (ROS) generation, all known to be central to chronic inflammation; Deeper mechanistic engagement: Gene Set Enrichment Analysis revealed that PAS-004’s effects more closely mirrored ETS2 knockout profiles, with a higher normalized enrichment score (-3.96 vs -3.56) and greater..."

Preclinical • Inflammation • Inflammatory Bowel Disease

Pasithea Therapeutics Announces Initiation of Phase 1/1B Study of PAS-004 in Adult NF1 Patients and Activation of First Clinical Trial Site (GlobeNewswire) - "Pasithea Therapeutics Corp....today announced initiation of its Phase 1/1b open label study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PAS-004, in adult participants with neurofibromatosis type 1 (NF1) with symptomatic and inoperable, incompletely resected, or recurrent plexiform neurofibromas....The first active clinical trial site is the Royal North Shore Hospital in Sydney, Australia, which is expected to begin patient enrollment in Q2 2025."

Trial status • Neurofibromatosis

PAS-004 in Adults With With Plexiform Neurofibromas (NF1) (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Pasithea Therapeutics Corp.

New P1 trial • Genetic Disorders • Neurofibromatosis • Solid Tumor

Pasithea Therapeutics Announces Completion of Enrollment and Initial Dosing of Patients in Cohort 6 from its Phase 1 Trial of PAS-004 in Advanced Cancer Patients (GlobeNewswire) - "Pasithea Therapeutics Corp...today announced the Company has completed enrollment and initial dosing of three subjects in Cohort 6 with 30 mg capsules of PAS-004....We are pleased to have recruited, enrolled and commenced dosing of the initial three subjects in Cohort 6 more rapidly than anticipated and we currently expect to complete enrollment of all patients in the trial by the end of 2025."

Trial status • Solid Tumor

Pasithea Therapeutics Reports Positive Pharmacodynamic Results Demonstrating Robust Target Engagement from its Ongoing Phase 1 Clinical Trial of PAS-004 (GlobeNewswire) - P1 | N=48 | NCT06299839 | Sponsor: Pasithea Therapeutics Corp | "Pasithea Therapeutics Corp...announced positive interim pharmacodynamic (PD) data from its ongoing Phase 1 trial of PAS-004 in advanced cancer patients. The data includes results from cohorts 3 and 4A, evaluating 8mg and 15mg capsules, as well as cohort 4B evaluating 4mg tablets, and demonstrates strong target engagement consistent with PAS-004’s favorable pharmacological profile...Preliminary results demonstrate robust pERK inhibition, with reductions in pERK levels of up to 91% even at the 8mg dose level, in line with a previous developed PK/PD model, confirming substantial target engagement in patients receiving PAS-004."

Preclinical • Neurofibromatosis • Solid Tumor

Pasithea Therapeutics to Present Updated Data from Ongoing Phase 1 Trial of PAS-004 in Advanced Cancer Patients at the 2025 ASCO Annual Meeting (GlobeNewswire) - "Pasithea Therapeutics Corp....today announced the acceptance of an abstract for a poster prenstation at the Annual Meeting of the American Society for Clinical Oncology (ASCO) taking place May 30 – June 3, 2025, in Chicago, Illinois....The Company will present updated interim clinical data from its onging Phase 1 clinical trial of PAS-004 in patients with MAPK pathway driven advanced solid tumors."

P1 data • Solid Tumor

Pasithea Therapeutics Announces Positive Safety Review Committee (SRC) Recommendation from its Ongoing Phase 1 Clinical Trial of PAS-004 in Advanced Cancer (GlobeNewswire) - "Pasithea Therapeutics Corp...today announced that the external Safety Review Committee recommended that the Company’s Phase 1 clinical trial of PAS-004 in advanced cancer should proceed to Cohort 6, 30mg capsule, without modification. This recommendation was based on the review of the safety data from three patients from Cohort 5 and the absence of any dose limiting toxicities (DLT’s). In addition, no rash has been observed to date during the DLT period in any of the first 19 patients in either capsule (15 patients) or tablet (four patients) formulation of PAS-004."

DSMB • Solid Tumor

Pasithea Therapeutics to Present at the 2025 CAGLA NeauxCancer Conference (GlobeNewswire) - "Mr. Lazarus’s presentation will provide an overview of Pasithea’s next generation macrocyclic MEK inihibitor, PAS-004, including interim safety, tolerability and pharmacokinetic (PK) data from the Company’s ongoing open-label dose escalation Phase 1 study in advanced cancer patients with MAPK pathway-driven advanced tumors."

P1 data • Solid Tumor

Pasithea Therapeutics Announces Positive Safety Review Committee (SRC) Recommendation from its ongoing Phase 1 Clinical Trial of PAS-004 in Advanced Cancer (GlobeNewswire) - P1 | N=48 | NCT06299839 | Sponsor: Pasithea Therapeutics Corp. | "Pasithea Therapeutics Corp...announced that the external Safety Review Committee recommended that the Company’s Phase 1 clinical trial of PAS-004 in advanced cancer should proceed to cohort 5, 22mg capsule, without modification. This recommendation was based on the review of the safety data from three patients in cohort 4A (15mg capsule) and the absence of any dose limiting toxicities (DLT’s). In addition, no rash has been observed to date in any of the first 14 patients who have been dosed with PAS-004 in either capsule (12 patients) or tablet (2 patients) formulation....'We are looking forward to presenting updated pharmakokinetic (PK) and pharmacodynamic (PD) data during Q1 2025'."

DSMB • P1 data • Neurofibromatosis

Pasithea Therapeutics Announces Opening of European Clinical Trial Sites and Completes Initial Dosing of Cohort 4 (GlobeNewswire) - "Pasithea Therapeutics Corp...announced it has opened three clinical trial sites in Eastern Europe. These sites in Romania and Bulgaria are actively recruiting patients along with the four open sites in the United States, for Pasithea’s PAS-004 Phase 1 trial....In addition, Pasithea has completed initial dosing of three patients in Cohort 4A (15mg capsule). Patient recruitment for Cohort 4B is ongoing (4mg tablet). The Company plans to present interim safety and pharmacokinetic (PK) data from Cohorts 4A and 4B in Q1 2025."

P1 data • Trial status • Neurofibromatosis • Solid Tumor

Pasithea Therapeutics Announces Positive Safety Review Committee (SRC) Recommendation from its ongoing Phase 1 Clinical Trial of PAS-004 in Advanced Cancer (GlobeNewswire) - "Pasithea Therapeutics Corp...announced that the external Safety Review Committee recommended proceeding to cohort 4, 15mg capsule, without modifications. This recommendation was based on the absence of any dose limiting toxicities (DLT’s). In addition, no rash was observed in any of the first 9 patients who received PAS-004. The Company has decided to add a cohort 4b to the trial, which will consist of 3 additional patients and introduce an alternate formulation which is intended for commercial use."

Trial status • Oncology • Solid Tumor

Pasithea Therapeutics Announces Positive Initial Safety, Tolerability, Pharmacokinetic (PK), and Preliminary Efficacy Data from its Phase 1 Clinical Trial of PAS-004 in Advanced Cancer (GlobeNewswire) - P1 | N=42 | NCT06299839 | Sponsor: Pasithea Therapeutics Corp. | "Single patient in 2mg cohort with stage 3 colon cancer who received 4 prior lines of therapy achieves prolonged stable disease and remains on drug into 6th dosing cycle; No treatment-related adverse events (TRAEs) or dose-limiting toxicities (DLTs) observed to date, including no rash or gastrointestinal (GI) AEs; Systemic exposure at steady-state enables constant target inhibition while avoiding peak plasma toxicities; Half-life of approximately 70 hours supports once-daily or less frequent oral dosing."

P1 data • Solid Tumor

Pasithea Therapeutics Announces Successful Completion of PAS-004 Chronic Toxicity Studies (GlobeNewswire) - "Pasithea Therapeutics Corp...announced the successful completion of long-term chronic toxicity studies in both rats and dogs with its lead candidate PAS-004, currently being investigated in a Phase 1 clinical trial in advanced cancer patients. Results show that once daily treatment with PAS-004 for 6-months in rats and 9-months in dogs at different dose levels confirms the observations of prior 28-day toxicity studies and indicates a similar safety profile following long-term dosing in both species. Further, the 9-month study in dogs established 0.5 mg/kg as the no adverse effect level (NOAEL) in dogs, the most sensitive species. PAS-004 demonstrated a consistent safety profile at doses that correlate with significant pathway engagement and will likely produce significant pERK reduction when dosed below the NOAEL."

Preclinical • Neurofibromatosis • Oncology • Solid Tumor

PAS-004: A novel macrocyclic MEK inhibitor to inhibit cancer cell growth in vitro and tumor growth in mouse xenograft studies. (ASCO 2024) - " Ten NRAS mutant cancer cell lines were cultured for 48 hrs in the presence of the MEK inhibitor PAS-004, trametinib, binimetinib (bini) and selumetinib (selu) and cell proliferation was assayed using a Cell Titer Glo luminescence assay. The novel macrocyclic MEK inhibitorPAS-004 inhibited NRAS mutant tumor growth in mouse xenograft studies with similar activity as the approved MEK inhibitors selu and bini. In vitro, PAS-004 provided greater maximal growth inhibition of NRAS lines than selu and bini. These results support investigating PAS-004 further and a clinical trial in patients with advanced solid tumors carrying RAS pathway mutations, including NRAS variants, is ongoing."

Preclinical • Gastrointestinal Cancer • Genetic Disorders • Hepatocellular Cancer • Lung Cancer • Melanoma • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • NF1 • NRAS

Pasithea Therapeutics Announces Completion of Enrollment and Initial Dosing of Cohort 2 following Positive Safety Review Committee (SRC) Recommendation for PAS-004 in Ongoing Phase 1 Clinical Trial (GlobeNewswire) - "Pasithea Therapeutics...announced today that an independent Safety Review Committee (SRC) has completed its safety review of data from the first dose cohort (2mg) treated in the ongoing Phase 1 clinical trial (NCT06299839) of PAS-004 in patients with MAPK pathway driven advanced solid tumors with a documented RAS, NF1 or RAF mutation or patients who have failed BRAF/MEK inhibition. Based on these findings, the SRC recommended that the trial escalate to the next dose level (4mg) without modifications. This recommendation was based on the absence of any dose limiting toxicities (DLT’s) or clinically relevant treatment-emergent adverse events in the initial cohort of 3 patients. The Company has now completed enrollment and initial dosing of 3 patients in the second cohort....We remain on track to present our initial safety and pharmacokinetic (PK) data in the third quarter of 2024."

DSMB • P1 data • Trial status • Solid Tumor

Pasithea Therapeutics to Present New Preclinical Data Showing PAS-004 Strongly Inhibits NRAS Cancer Cell Lines and Demonstrates Superior Activity in Xenograft Studies at 2024 ASCO Annual Meeting (GlobeNewswire) - "Pasithea Therapeutics Corp...announced today the publication of data showing PAS-004 strongly inhibiting NRAS mutant cancer cell lines with IC50 values ranging from 0.024 to 0.306 µM. Maximal growth inhibition of >50% was achieved by PAS-004 in more cell lines than binimetinib and selumetinib. In addition, PAS-004’s cell line inhibition was comparable to trametinib in 5 cell lines tested but, in contrast to trametinib, PAS-004 did not reach a plateau."

Preclinical • Oncology