Core Insights - Pasithea Therapeutics Corp. has completed enrollment and initial dosing of three subjects in Cohort 1 of its Phase 1/1b clinical trial for PAS-004, a next-generation macrocyclic MEK inhibitor targeting neurofibromatosis type 1 (NF1) [1][2] Group 1: Clinical Trial Details - The Phase 1/1b study aims to evaluate the safety and tolerability of PAS-004 in adult NF1 patients with symptomatic and inoperable plexiform neurofibromas [3] - 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] - The study will be conducted at five clinical trial sites across Australia, South Korea, and the U.S. [5] Group 2: Drug Profile and Advantages - PAS-004 is designed as a once-daily dosed MEK inhibitor, potentially improving patient compliance compared to current FDA-approved therapies that require twice-daily dosing [2] - The primary objective of the trial includes evaluating the preliminary efficacy of PAS-004 on target neurofibroma volume and associated symptoms [3] - Initial safety data from ongoing trials in advanced cancer patients have been encouraging, leading to optimism about PAS-004's potential for NF1 patients [2][6]

Core Viewpoint - Pasithea Therapeutics Corp. has appointed Dr. James Lee to its scientific advisory board to guide the development of PAS-004, a next-generation macrocyclic MEK inhibitor, for treating ETS2 pathway inflammatory diseases such as inflammatory bowel disease (IBD) [1][3] Company Overview - Pasithea Therapeutics is a clinical-stage biotechnology company focused on developing PAS-004, which targets RASopathies, MAPK pathway-driven tumors, and other diseases [5] - The company is currently conducting a Phase 1 clinical trial of PAS-004 in advanced cancer patients and a Phase 1/1b trial in adult patients with neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas [5] Dr. James Lee's Expertise - Dr. Lee is recognized for his research on the ETS2 pathway in inflammatory diseases and has published significant findings in prestigious journals like Nature [2][4] - His clinical research has the potential to lead to transformative therapies for patients with IBD, and his guidance is expected to expand PAS-004's development to additional indications beyond NF1 [3] Research and Development Focus - The company aims to fund the development of PAS-004 through non-dilutive financing, including grants and strategic collaborations [3]

Core Insights - Pasithea Therapeutics Corp. announced promising interim results for PAS-004, a next-generation macrocyclic MEK inhibitor, in a Phase 1 clinical trial targeting advanced cancer patients with MAPK pathway-driven tumors [1][6] Group 1: Clinical Trial Overview - The ongoing Phase 1 study employs a multi-center, open-label, dose escalation design to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of PAS-004 [1] - As of April 2, 2025, 21 patients have been enrolled across six cohorts, with pancreatic cancer (28.6%), colorectal cancer (28.6%), and melanoma (23.8%) being the most common diagnoses [2] Group 2: Efficacy and Safety - PAS-004 demonstrated a dose-dependent PK profile and preliminary clinical activity, with 10 out of 16 efficacy evaluable patients achieving stable disease at some point during the trial [5] - One patient with stage 4 BRAF-mutated melanoma showed a tumor volume reduction of -14.9% and has maintained stable disease for over 5 months [1][5] - All treatment-related adverse events were grade 1 or 2, with no known MEK inhibitor class-related adverse events observed [3] Group 3: Pharmacokinetics - Preliminary PK analysis indicates a linear PK profile with an estimated half-life exceeding 60 hours, and sufficient exposures for target engagement were achieved [4] - The peak to trough ratio was below 2 at steady state across all dose levels, supporting the potential for effective treatment [4] Group 4: Future Outlook - The CEO of Pasithea highlighted the potential of PAS-004 as a best-in-class MEK inhibitor, emphasizing its high selectivity and sustained pathway suppression, which may benefit both monotherapy and combination therapy [6] - The company is also conducting a Phase 1/1b clinical trial for PAS-004 in adult patients with neurofibromatosis type 1-associated plexiform neurofibromas [7]

Core Insights - Pasithea Therapeutics Corp. has announced new preclinical data indicating that PAS-004, a next-generation macrocyclic MEK inhibitor, demonstrates superior inhibition of ETS2-driven inflammatory responses compared to the FDA-approved MEK inhibitor selumetinib in a human macrophage model of chronic inflammation [1][3] Group 1: Study Findings - The study conducted at the Francis Crick Institute shows that PAS-004 consistently outperforms selumetinib across all tested doses (0.01 μM, 0.1 μM, and 1 μM), indicating more robust and durable MEK inhibition under inflammatory conditions [2][3] - PAS-004 exhibits superior suppression of ETS2 signaling, with greater downregulation of ETS2-regulated genes than selumetinib at all doses tested [3][4] - PAS-004 significantly reduces ETS2-dependent macrophage functions such as cytokine production, phagocytosis, and reactive oxygen species (ROS) generation, which are central to chronic inflammation [4] Group 2: Mechanistic Insights - Gene Set Enrichment Analysis reveals that PAS-004's effects closely mirror ETS2 knockout profiles, showing a higher normalized enrichment score (-3.96 vs -3.56) and greater statistical significance (1.2 x 10⁻²⁵⁰ vs 3.7 x 10⁻⁷⁴) compared to selumetinib [4] - The ability of PAS-004 to block ETS2 signaling suggests it may target multiple cytokines, including TNFα, IL-23, and IL-1β, which are critical in chronic inflammatory diseases [4] Group 3: Future Potential - The company believes that PAS-004 has the potential to be a new oral treatment option for inflammatory diseases such as inflammatory bowel disease (IBD), based on low adverse events and tolerable safety data observed in Phase 1 clinical trials [4][5] - The preclinical results suggest that PAS-004's ability to block ETS2 signaling and target multiple cytokines opens the potential for testing in large market inflammatory indications [5]

Financial Performance - The net loss for the three months ended March 31, 2025, was $3,563,238, a decrease of $297,602, or 7.7%, compared to the net loss of $3,860,840 for the same period in 2024[121] - Net loss for the three months ended March 31, 2025, was $3,563,238, an improvement from a net loss of $3,860,840 for the same period in 2024[130] - Other income, net decreased by approximately $63,000, or 35%, for the three months ended March 31, 2025, primarily due to a decrease in interest and dividends[128] Expenses - For the three months ended March 31, 2025, general and administrative expenses decreased by approximately $341,000, or 15%, compared to the same period in 2024[121] - Research and development expenses decreased by approximately $19,000, or 1%, for the three months ended March 31, 2025, primarily due to decreases in preclinical research and consulting expenses[126] - The company anticipates an increase in research and development expenses in fiscal year 2025 due to ongoing clinical trials for PAS-004[127] - The primary use of cash is to fund operating expenses, primarily general and administrative and research and development expenditures[134] Cash Flow and Working Capital - Working capital decreased by approximately $1.7 million from $6,248,444 as of December 31, 2024, to $4,530,046 as of March 31, 2025, primarily due to cash used to fund operations[129] - Cash and cash equivalents decreased by approximately $1.6 million for the three months ended March 31, 2025, compared to a decrease of approximately $4.3 million for the same period in 2024[130] - As of March 31, 2025, the company had approximately $5.3 million in operating bank accounts and money market funds, with a working capital of approximately $4.5 million[132] - The company is dependent on obtaining additional working capital funding from the sale of equity and/or debt securities to continue operations and execute development plans[132] - Future funding requirements will depend on various factors, including the costs of clinical trials and business development activities, with no committed sources of capital currently available[135] Regulatory and Development Updates - The company received FDA clearance for the Investigational New Drug application for PAS-004 in December 2023[114] - The ongoing FIH Phase 1 Dose Escalation Study of PAS-004 is being conducted at four clinical sites in the United States and three additional sites in Eastern Europe[114] - The company plans to seek marketing approval for PAS-004 in specific patient populations, including adults and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas[114] Public Offering and Capital Restrictions - The company completed a public offering on May 7, 2025, raising total gross proceeds of approximately $6.3 million[119] - The calculated public float as of March 31, 2025, is below $75 million, restricting the company from raising more than one-third of its public float through primary public offerings in any twelve-month period[133] Accounting Policies - There were no material changes to the company's critical accounting policies and estimates during the three months ended March 31, 2025[139] - The company has no off-balance sheet arrangements during the periods presented[138]

Core Insights - Pasithea Therapeutics Corp. has initiated a Phase 1/1b clinical trial for PAS-004, a macrocyclic MEK inhibitor, targeting adult patients with neurofibromatosis type 1 (NF1) and symptomatic plexiform neurofibromas, with the first patient expected to be dosed in Q2 2025 [1][4] Group 1: Clinical Trial Details - The trial aims to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of PAS-004 in adult NF1 patients [1][5] - The first clinical trial site is located at the Royal North Shore Hospital in Sydney, Australia, with additional sites planned in Australia, South Korea, and the United States [2][6] - The study will be conducted in two parts, with Part A focusing on dose exploration and Part B on determining the recommended phase 2 dose (RP2D) [8][9] Group 2: Financial and Operational Aspects - Pasithea has selected Novotech (Australia) Pty Limited as its clinical research organization (CRO) for the trial and anticipates eligibility for an Australian R&D Tax Incentive, which could provide a cash refund of up to 48.5% of eligible trial costs [3][6] - The company is funded to produce initial interim patient data in NF1 following recent financing activities, including the exercise of certain warrants [4] Group 3: Expert Commentary - Dr. Rebecca Brown, a member of Pasithea's Scientific Advisory Board, expressed optimism about the safety profile of PAS-004 based on previous data from advanced cancer patients and highlighted the importance of patient compliance due to the once-daily dosing regimen [4] - Dr. Tiago Reis Marques, CEO of Pasithea, emphasized the significance of this trial as a milestone for both the company and patients with NF1-related plexiform neurofibromas [4]

Core Viewpoint - Pasithea Therapeutics has successfully closed a public offering, raising a total of approximately $6.3 million, which will be utilized for various corporate purposes including ongoing research and clinical trials [1][4]. Group 1: Offering Details - The company closed a public offering of 3,571,428 shares of common stock at a price of $1.40 per share, along with Series C and Series D warrants [1][2]. - The Series C warrants have an exercise price of $1.40 and expire in five years, while the Series D warrants also have an exercise price of $1.40 and expire in 18 months [2]. - The total gross proceeds from the offering were $5.0 million, with additional proceeds of approximately $1.3 million from the exercise of Series D warrants [4]. Group 2: Use of Proceeds - The net proceeds from the offering will be allocated for general corporate purposes, including ongoing research, clinical trials, and the development of new technologies [4]. - The company plans to invest in or acquire synergistic companies and engage in licensing activities related to its current and future product candidates [4]. Group 3: Company Overview - Pasithea Therapeutics is a clinical-stage biotechnology company focused on developing innovative treatments for central nervous system disorders and RASopathies [7].

Core Viewpoint - Pasithea Therapeutics, a clinical-stage biotechnology company, has announced a public offering of shares and warrants to raise approximately $5.0 million for various corporate purposes, including ongoing research and clinical trials [1][4]. Group 1: Offering Details - The company is offering 3,571,428 shares of common stock at a price of $1.40 per share, along with Series C and Series D warrants [1][2]. - The Series C warrants will have an exercise price of $1.40 and will expire five years after issuance, while the Series D warrants will also have an exercise price of $1.40 but will expire 18 months after issuance [2]. - The closing of the offering is expected to occur on or about May 7, 2025, pending customary closing conditions [2]. Group 2: Use of Proceeds - The net proceeds from the offering will be used for general corporate purposes, including ongoing research, pre-clinical studies, clinical trials, and the development of new technologies [4]. - The company may also invest in or acquire synergistic companies and engage in licensing activities related to its current and future product candidates [4]. Group 3: Company Overview - Pasithea Therapeutics focuses on the discovery and development of innovative treatments for central nervous system disorders, RASopathies, and MAPK pathway-driven tumors [7].

Core Viewpoint - Pasithea Therapeutics Corp. has released promising interim pharmacodynamic data from its ongoing Phase 1 trial of PAS-004 in advanced cancer patients, leading to a significant increase in stock price during premarket trading [1][7]. Group 1: Clinical Trial Data - The Phase 1 trial evaluated different dosages of PAS-004, including 8mg, 15mg capsules, and 4mg tablets, with a focus on pharmacodynamic (PD) activity [1][4]. - Strong target engagement was demonstrated, with pERK levels showing reductions of up to 91% at the 8mg dose, indicating substantial target engagement in patients [2][4]. - Encouraging preliminary clinical observations were noted, with several patients achieving stable disease and tumor shrinkage while on PAS-004 treatment [4]. Group 2: Patient Outcomes - A notable case involved a patient with stage 4 KRAS G12R-mutated pancreatic cancer who experienced a tumor volume reduction of -9.8% over 5 months of treatment with the 15mg capsule [5]. - The external Safety Review Committee recommended proceeding to Cohort 6 (30mg capsule) based on safety data from previous cohorts, with no dose-limiting toxicities reported [6]. Group 3: Market Reaction - Following the release of the trial data, KTTA stock rose by 62.7%, reaching $2.33 during the premarket session [7].

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]