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 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 Insights - Pasithea Therapeutics Corp. has completed enrollment and initial dosing of three subjects in Cohort 6 with 30 mg capsules of PAS-004, a next-generation macrocyclic MEK inhibitor for treating neurofibromatosis type 1 (NF1) and other MAPK pathway driven cancers [1][2] Group 1: Clinical Trial Progress - The ongoing Phase 1 clinical trial is a multi-center, open-label, dose escalation 3+3 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 with documented RAS, NF1, or RAF mutations, or patients who have failed BRAF/MEK inhibition [3] - The company expects to complete enrollment of all patients in the trial by the end of 2025, having recruited and commenced dosing of the initial three subjects more rapidly than anticipated [2] Group 2: Company Overview - Pasithea Therapeutics is a clinical-stage biotechnology company focused on the discovery, research, and development of innovative treatments for central nervous system (CNS) disorders, RASopathies, and MAPK pathway driven tumors [4]

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].

Core Insights - Pasithea Therapeutics Corp. is advancing its Phase 1 clinical trial of PAS-004, a macrocyclic MEK inhibitor, for treating neurofibromatosis type 1 (NF1) and other cancer indications, with the external Safety Review Committee recommending progression to the next dose level of 30mg capsule without modifications [1][2] - The trial has shown no dose-limiting toxicities (DLTs) or rash in the initial 19 patients, which is significant as rash is a common adverse event associated with competitor MEK inhibitors [1][2] - The ongoing trial is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of PAS-004 in patients with advanced solid tumors driven by MAPK pathway mutations [2] Company Overview - Pasithea Therapeutics is focused on developing innovative treatments for central nervous system (CNS) disorders and RASopathies, with a team experienced in neuroscience, translational medicine, and drug development [3] - The company is working on new molecular entities for neurological disorders, including NF1, solid tumors, and amyotrophic lateral sclerosis (ALS) [3] Clinical Trial Details - The Phase 1 clinical trial is a multi-center, open-label, dose escalation study designed to assess PAS-004 in patients with documented RAS, NF1, or RAF mutations or those who have failed previous BRAF/MEK inhibition [2] - The trial has already identified patients for Cohort 6 and continues to observe substantial exposure levels of PAS-004, aiming to deliver relevant pERK inhibition below the no observed adverse effect levels (NOAEL) [2] - Additional safety, pharmacokinetic, and pharmacodynamic data are expected to be released in the coming weeks [2]

Financial Performance - The company incurred net losses of approximately $13.9 million and $16.0 million for the years ended December 31, 2024 and 2023, respectively, with an accumulated deficit of approximately $49.6 million as of December 31, 2024 [211]. - For the year ended December 31, 2024, the net loss was $13,904,584, a decrease of $2,057,074 or 12.9% compared to a net loss of $15,961,658 in 2023 [359]. - Working capital decreased by $7.8 million from December 31, 2023, to December 31, 2024, primarily due to cash used to fund operations [367]. - Cash and cash equivalents decreased by approximately $9.4 million for the year ended December 31, 2024, compared to a decrease of approximately $16.8 million for the year ended December 31, 2023 [369]. - Other income, net decreased by approximately $126,000, or 26.8%, for the year ended December 31, 2024, primarily due to an increase in the fair value of warrant liabilities [365]. Capital Requirements - As of December 31, 2024, the company had cash and cash equivalents of approximately $6.9 million, indicating a need for additional capital to fund operations [215]. - The company may need to raise additional funds sooner to pursue a more accelerated development of its product candidates [214]. - The company is dependent on obtaining additional working capital funding to continue executing its development plans and operations [370]. - The company entered into an At The Market Offering Agreement allowing it to issue and sell up to $2,076,000 of its Common Stock [217]. Product Development and Regulatory Challenges - The company is dependent on the successful development and commercialization of its lead product candidate, PAS-004, which is not yet approved [204]. - The regulatory approval processes for product candidates are lengthy and unpredictable, with no assurance of obtaining necessary approvals [243]. - The FDA or foreign regulatory bodies may delay or deny approval of product candidates, significantly harming the company's business prospects [247]. - The company may need to abandon or change the prioritization of product candidates based on various factors, including regulatory requirements and market conditions [238]. - Clinical trial delays may arise from various factors, including inability to generate sufficient preclinical data and delays in reaching agreements with contract research organizations [255]. Market and Economic Risks - The company faces risks from unfavorable global economic conditions, including extreme volatility in credit and financial markets, rising interest rates, and geopolitical events [228]. - Future adverse developments in the financial services industry may lead to market-wide liquidity shortages, impairing the company's ability to access working capital [230]. - Disruptions in the global economy and supply chains since 2020 have resulted in longer lead times and increased costs, impacting the company's financial condition and operations [281]. - Inflation may increase costs related to clinical trials and research and development, potentially leading to faster depletion of cash reserves [282]. Operational and Staffing Challenges - Increased labor costs and staffing challenges are expected, which could disrupt business operations and increase operating expenses [233]. - The company has incurred increased labor costs and may face challenges in attracting and retaining key leadership talent, impacting operational efficiency [232]. - The company has a limited operating history, making it difficult for investors to evaluate its current business and predict future success [205]. Internal Controls and Compliance - The company identified a material weakness in financial reporting related to certain tax disclosures, which has since been remediated [315]. - Management evaluated the effectiveness of internal control over financial reporting as of December 31, 2024, using the criteria from the Internal Control - Integrated Framework (2013) [392]. - Management concluded that internal control over financial reporting was effective at a reasonable assurance level as of December 31, 2024 [393]. - There were no changes in internal control over financial reporting during the fiscal quarter ended December 31, 2024, that materially affected internal control [398]. Stock and Market Conditions - The market price of the company's Common Stock ranged from $2.54 to $8.75 per share for the year ended December 31, 2024, indicating high volatility [305]. - The company has never declared or paid any cash dividends on its equity securities and does not anticipate doing so in the foreseeable future [326]. - The company’s stockholders may face significant fluctuations in the market price of its Common Stock and Warrants due to various market conditions [306]. Strategic Partnerships and Collaborations - The company may face significant competition in securing strategic partnerships, which could delay the development and commercialization of product candidates [275]. - Future collaborations may restrict the company's ability to independently pursue new product candidates, impacting strategic initiatives [304]. - The company faces risks related to potential conflicts with collaborators that could delay or terminate product development [300]. Research and Development Focus - The company is focused on developing PAS-004, a next-generation MEK inhibitor, with a Phase 1 multicenter trial currently underway at four U.S. sites and three in Eastern Europe [351]. - The FDA cleared the Investigational New Drug application for PAS-004 in December 2023, allowing the company to proceed with clinical trials [351]. - The company anticipates an increase in research and development expenses in fiscal year 2025 due to ongoing clinical research for PAS-004 [364].