Core Insights - Pasithea Therapeutics Corp. announced positive safety, pharmacokinetic (PK), and pharmacodynamic (PD) data from Cohort 7 (37mg capsules) in its ongoing first-in-human trial for PAS-004, a macrocyclic oral MEK inhibitor targeting MAPK pathway-driven advanced solid tumors [1][2][8] Safety and Tolerability Results - Zero treatment-related adverse events were observed during the dose-limiting toxicity (DLT) period in Cohort 7 [1][6] - The Safety Review Committee recommended proceeding to the next dose level, Cohort 8 (45mg capsules), without modifications [1][6] Pharmacodynamics (PD) Results - PD data supports continuous suppression of the MAPK pathway throughout the 24-hour dosing cycle [1][2] - PAS-004 demonstrated an ability to inhibit phosphorylated extracellular signal-regulated kinase (pERK) at levels of 80% near Cmax and above 60% at Cmin [6] Pharmacokinetics (PK) Results - The PK profile showed linearity and dose-proportionality with a Cmax/Cmin ratio of less than 2 [1][6] - Achieved AUC of 6,690 ng·h/mL, Cmax of 313 ng/mL, and Cmin of 260 ng/mL [1][6] Company Overview - Pasithea is focused on developing PAS-004 for treating RASopathies, MAPK pathway-driven tumors, and other diseases, currently in Phase 1 clinical trials for advanced cancer and neurofibromatosis type 1 [8]

Core Insights - Pasithea Therapeutics Corp. announced positive pharmacokinetic (PK) data for its oral MEK inhibitor PAS-004, indicating improved properties in tablet form compared to capsules [1][2] Pharmacokinetics (PK) - The tablet formulation of PAS-004 (4mg and 8mg cohorts) showed a Cmin of 37.6 ng/mL, with dose-normalized exposures approximately three times higher than the capsule formulation [2] - The 8mg tablet demonstrated an area under the curve (AUC) and Cmax slightly greater than the 22mg capsule, with less patient variability and a similar Tmax range [2] - Cohort 1 (4mg tablet) results: AUC of 1,120 ng·h/mL and Cmax of 58.1 ng/mL; Cohort 2 (8mg tablet) results: AUC of 2,290 ng·h/mL, Cmax of 118 ng/mL, and Cmin of 75.4 ng/mL [3] Company Overview - Pasithea Therapeutics is focused on developing PAS-004 for treating neurofibromatosis type 1-associated plexiform neurofibromas and other diseases, currently in Phase 1 clinical trials [6]

Core Insights - Pasithea Therapeutics Corp. announced positive interim Phase 1 data for PAS-004, a macrocyclic oral MEK inhibitor, targeting neurofibromatosis type 1-associated plexiform neurofibromas and advanced solid tumors with specific mutations [1][2]. Interim Phase 1 Results - Initial signals of clinical activity were observed, with a partial response in a melanoma patient previously treated with a MEK + BRAF inhibitor, remaining on trial for over 11 months [3][4]. - Among 21 efficacy evaluable patients, the disease control rate was 71.4%, with 5 out of 7 patients with BRAF-mutated tumors achieving stable disease [3][7]. - PAS-004 demonstrated a favorable safety profile, with all treatment-related adverse events classified as Grade 1 or 2, and no ocular or cardiovascular toxicities reported [3][7]. Pharmacokinetics and Drug Exposure - At the highest reported dose of 30mg, PAS-004 showed significant drug exposure with an Area Under the Curve (AUC) greater than 5,400 ng·h/mL, indicating sustained pathway inhibition [2][3]. - The pharmacokinetic profile was characterized by a Cmax/Cmin ratio of less than 2, with a long half-life of approximately 60 hours [7]. Safety and Tolerability - The drug was well-tolerated across all dose levels, with no dose-limiting toxicities or treatment discontinuations reported [7]. - Limited adverse effects included rash (7.4%), nausea (18.5%), vomiting (14.8%), and diarrhea (7.4%) [7]. Company Overview - Pasithea Therapeutics is focused on developing PAS-004 for RASopathies, MAPK pathway-driven tumors, and other diseases, currently conducting Phase 1 clinical trials in advanced cancer patients and NF1-associated plexiform neurofibromas [5].

As filed with the Securities and Exchange Commission on November 18, 2025 Registration No. 333- Delaware 001-40804 85-1591963 (I.R.S. Employer Identification No.) UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 PASITHEA THERAPEUTICS CORP. (Exact name of registrant as specified in its charter) | (State or other jurisdiction of | | --- | | incorporation or organization) | (Primary Standard Industrial Classification Code N ...

Financial Performance - The net loss for the three months ended September 30, 2025, was $3,037,420, representing a slight increase of 1.3% from the net loss of $2,999,834 in the same period in 2024 [135]. - Net loss for the nine months ended September 30, 2025, was $(10,316,815), a decrease of 3.8% compared to $(10,726,923) for the same period in 2024 [148]. - The loss from operations for the nine months ended September 30, 2025, was $10,601,133, a decrease of 3.5% from the loss of $10,990,412 in the same period in 2024 [135]. Expenses - For the three months ended September 30, 2025, general and administrative expenses increased by approximately $329,000, or 23.1%, compared to the same period in 2024, primarily due to higher legal and corporate expenses [136]. - For the nine months ended September 30, 2025, general and administrative expenses increased by approximately $62,879, or 1.2%, compared to the same period in 2024 [137]. - Research and development expenses for the three months ended September 30, 2025, decreased by approximately $223,583, or 14.1%, compared to the same period in 2024 [135]. - Research and development expenses decreased by approximately $224,000, or 14%, for the three months ended September 30, 2025, compared to the same period in 2024 [142]. - Research and development expenses decreased by approximately $452,000, or 8%, for the nine months ended September 30, 2025, compared to the same period in 2024 [143]. - The company expects research and development expenses to increase throughout fiscal year 2025 compared to fiscal year 2024 due to ongoing clinical trials for PAS-004 [144]. Cash and Working Capital - Working capital decreased by approximately $2.1 million from $6,248,444 as of December 31, 2024, to $4,152,115 as of September 30, 2025 [147]. - Cash, cash equivalents, and restricted cash decreased by approximately $2.7 million for the nine months ended September 30, 2025, compared to a decrease of approximately $7.0 million for the same period in 2024 [148]. - As of September 30, 2025, the company had approximately $4.1 million in operating bank accounts and money market funds, with working capital of approximately $4.2 million [149]. - The company is dependent on obtaining additional working capital funding from the sale of equity and/or debt securities to continue operations [149]. Regulatory and Development Updates - The FDA cleared the Investigational New Drug application for PAS-004 in December 2023, with a Phase 1 multicenter trial expected to complete in 2026 [125]. - The company initiated a Phase 1/1b trial for PAS-004 in adult patients with neurofibromatosis type 1 in May 2025, with a total of five sites involved [126]. - The company plans to seek FDA marketing approval for PAS-004 for the treatment of symptomatic plexiform neurofibromas in both adult and pediatric patients [127]. Economic Impact - The company anticipates inflation will continue to negatively impact its operations throughout 2025, affecting costs related to employee compensation and outside services [134]. - As of September 30, 2025, the calculated public float is below $75.0 million, restricting the company from selling more than one-third of its public float through primary public offerings in any twelve-month period [150]. Other Income - Other income, net increased by approximately $68,000, or 1,423%, for the three months ended September 30, 2025, compared to the same period in 2024 [145].

Core Insights - Pasithea Therapeutics Corp. has activated a new clinical trial site at the University of Alabama at Birmingham (UAB) for its Phase 1/1b study of PAS-004 in adult patients with neurofibromatosis type 1 (NF1) [1][2] - The company is also serving as a Platinum Sponsor for the 2025 NF Caregivers Symposium, emphasizing its commitment to the NF1 community [3] Clinical Trial Details - The Phase 1/1b study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PAS-004 in adult NF1 patients with symptomatic and inoperable plexiform neurofibromas [2][4] - The trial will be conducted in two parts: Part A will involve dose escalation with up to 24 participants receiving one of four planned dose levels (4mg, 8mg, 12mg, 18mg) [5] - Part B will enroll approximately 24 participants to receive doses at the recommended phase 2 dose (RP2D) for up to six continuous 28-day treatment cycles [5][6] Objectives of the Study - Primary objectives include evaluating the safety and tolerability of PAS-004, identifying the recommended Part B dose, and assessing preliminary efficacy on target neurofibromas and quality of life [4][5] - Secondary objectives focus on the impact of PAS-004 on cutaneous neurofibromas and associated symptoms, as well as pain and function related to plexiform neurofibromas [4][5] Company Overview - Pasithea Therapeutics is a clinical-stage biotechnology company focused on developing PAS-004, a next-generation macrocyclic MEK inhibitor for treating RASopathies and MAPK pathway-driven tumors [7] - The company is currently conducting multiple clinical trials, including a Phase 1 trial in advanced cancer patients [7]

Core Insights - Pasithea Therapeutics Corp. has initiated clinical trials for PAS-004, a next-generation macrocyclic MEK inhibitor, in South Korea targeting neurofibromatosis type 1 (NF1) patients with symptomatic plexiform neurofibromas [1][9] Clinical Trial Details - The Phase 1/1b study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PAS-004 in adult NF1 participants [5] - The trial will be conducted at two sites in South Korea: ASAN Medical Centre and Severance Hospital, which are now actively recruiting participants [2][3] - The study consists of two parts: Part A focuses on dose escalation to identify the recommended Part B dose (RPBD), while Part B will evaluate the recommended phase 2 dose (RP2D) [6] Institutional Background - ASAN Medical Centre is the largest hospital in South Korea with 2,432 beds and a significant NF1 caseload, providing a strong research background for the trial [3] - Severance Hospital, one of the oldest and largest university hospitals in South Korea, has 2,437 beds and treats millions of outpatients annually, enhancing the trial's recruitment potential [4] Objectives of the Study - Primary objectives include assessing the safety and tolerability of PAS-004 over a 28-day treatment cycle and evaluating its preliminary efficacy on target plexiform neurofibromas [5] - Secondary objectives involve identifying the RPBD, characterizing the PK and PD profile, and evaluating the impact on quality of life (QOL) and associated symptoms [5][6]

Core Viewpoint - Pasithea Therapeutics Corp. has received a recommendation from the external Safety Review Committee to proceed with the Phase 1/1b clinical trial of PAS-004 for neurofibromatosis type 1 (NF1) without modifications, indicating positive safety data from initial cohorts [1][8]. Group 1: Clinical Trial Details - The Phase 1/1b study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PAS-004 in adult participants with symptomatic and inoperable plexiform neurofibromas [3][4]. - The trial consists of two parts: Part A will identify the recommended Part B dose (RPBD) through a modified 3+3 design, while Part B will determine the recommended phase 2 dose (RP2D) [4][5]. - The study is being conducted at five clinical trial sites across Australia, South Korea, and the U.S. [5]. Group 2: Company Overview - Pasithea Therapeutics is a clinical-stage biotechnology company focused on developing PAS-004, a next-generation macrocyclic MEK inhibitor targeting RASopathies and MAPK pathway-driven tumors [6]. - The company is also conducting a Phase 1 clinical trial of PAS-004 in advanced cancer patients [6]. Group 3: Enrollment and Future Expectations - There is substantial enrollment demand for the trial, with the first three patients in Cohort 2 already enrolled [2]. - Initial interim clinical data from the first two cohorts is expected to be released in Q1 2026 [8].

Core Points - Pasithea Therapeutics Corp. is a clinical-stage biotechnology company focused on developing PAS-004, a next-generation macrocyclic MEK inhibitor for treating RASopathies and MAPK pathway-driven tumors [2] - The company will present at the H.C. Wainwright 27 Annual Global Investment Conference on September 8, 2025, at 5:00 PM ET [1][2] - PAS-004 is currently undergoing a Phase 1 clinical trial for advanced cancer patients and a Phase 1/1b clinical trial for adult patients with neurofibromatosis type 1-associated plexiform neurofibromas [2] Event Details - The presentation will take place at the Lotte New York Palace Hotel during the H.C. Wainwright 27 Annual Global Investment Conference [2] - Management will be available for one-on-one meetings throughout the event [2]

Core Insights - Pasithea Therapeutics Corp. is participating in the H.C. Wainwright 27 Annual Global Investment Conference scheduled for September 8-10, 2025, in New York City [1][2] - The CEO, Dr. Tiago Reis Marques, will present the company and is available for one-on-one meetings during the event [2] - Pasithea is focused on developing PAS-004, a next-generation macrocyclic MEK inhibitor, currently in Phase 1 clinical trials for advanced cancer and neurofibromatosis type 1 [2] Company Overview - Pasithea Therapeutics is a clinical-stage biotechnology company dedicated to researching and developing PAS-004 for treating RASopathies, MAPK pathway-driven tumors, and other diseases [2] - PAS-004 is being tested in two clinical trials: a Phase 1 trial for advanced cancer patients (NCT06299839) and a Phase 1/1b trial for adult patients with NF1-associated plexiform neurofibromas (NCT06961565) [2]