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].

Core Insights - Pasithea Therapeutics Corp. is set to present its next-generation macrocyclic MEK inhibitor, PAS-004, at the 2025 CAGLA NeauxCancer Conference, highlighting its potential in treating neurofibromatosis type 1 (NF1) and other cancer indications [1][2] - The presentation will include interim safety, tolerability, and pharmacokinetic data from an ongoing Phase 1 study involving advanced cancer patients with MAPK pathway-driven tumors [2] - The CAGLA NeauxCancer Conference is a significant event for oncology researchers and industry professionals, focusing on advancements in cancer treatment [3] Company Overview - Pasithea Therapeutics is a biotechnology firm dedicated to developing innovative treatments for central nervous system disorders and RASopathies, with a focus on conditions like NF1, solid tumors, and ALS [4] - The company boasts a team of experts in neuroscience, translational medicine, and drug development, aiming to create new molecular entities for various neurological disorders [4]

Clinical Trial Progress - Pasithea Therapeutics has opened three new clinical trial sites in Eastern Europe, specifically in Romania and Bulgaria, in addition to the four existing sites in the United States for the PAS-004 Phase 1 trial [1] - The company has completed initial dosing of three patients in Cohort 4A (15mg capsule) and is actively recruiting patients for Cohort 4B (4mg tablet) [3] - Interim safety and pharmacokinetic (PK) data from Cohorts 4A and 4B are expected to be presented in Q1 2025 [3] Partnerships and Collaborations - Pasithea is collaborating with Arensia Exploratory Medicine and several oncology institutes in Eastern Europe, including the Institute of Oncology Bucharest, Institute of Oncology Cluj-Napoca, and Multiprofile Hospital for Active Treatment Sveta Sofia- EOOD [2] Trial Design and Objectives - The ongoing Phase 1 clinical trial is a multi-center, open-label, dose-escalation 3+3 study designed to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of PAS-004 [4] - The trial focuses on patients with MAPK pathway-driven advanced solid tumors with documented RAS, NF1, or RAF mutations, or those who have failed BRAF/MEK inhibition [4] Company Overview - Pasithea Therapeutics is a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications [1] - The company is focused on the discovery, research, and development of innovative treatments for central nervous system (CNS) disorders and RASopathies, including NF1, solid tumors, and Amyotrophic Lateral Sclerosis (ALS) [5]

Core Viewpoint - Pasithea Therapeutics Corp. has successfully completed long-term chronic toxicity studies for its lead candidate PAS-004, a macrocyclic MEK inhibitor, which is currently in a Phase 1 clinical trial for advanced cancer patients [1][2]. Group 1: Study Results - The long-term studies showed that daily treatment with PAS-004 for 6 months in rats and 9 months in dogs confirmed previous 28-day toxicity study results, indicating a similar safety profile across both species [2]. - The 9-month study in dogs established 0.5 mg/kg as the no adverse effect level (NOAEL), which is significant for determining safe dosing in future studies [2]. - PAS-004 demonstrated a consistent safety profile at doses that correlate with significant pathway engagement, suggesting potential for significant pERK reduction when dosed below the NOAEL [2]. Group 2: Formulation and Administration - PAS-004 was administered in crystalline form during chronic toxicity studies, showing a similar adverse event profile and equivalent NOAEL in dogs compared to the original amorphous formulation [3]. - The company is utilizing the crystalline form of PAS-004 in its human clinical trials, which may enhance the drug's efficacy and safety [3]. Group 3: Future Outlook - The company believes that sustained MAPK pathway suppression over a prolonged period will lead to enhanced efficacy with a more manageable side effect profile compared to other MEK inhibitors [4]. - Additional data on PAS-004, including initial interim pharmacokinetic and pharmacodynamic data from the Phase 1 clinical study, is expected to be shared later this quarter [4]. Group 4: Company Overview - Pasithea Therapeutics is focused on developing innovative treatments for central nervous system disorders and RASopathies, with a team experienced in neuroscience, translational medicine, and drug development [5].

Core Insights - Pasithea Therapeutics Corp. has appointed Dr. Rebecca Brown to its Scientific Advisory Board to aid in the development of PAS-004, a next-generation macrocyclic MEK inhibitor targeting neurofibromatosis type 1 (NF1) and other indications [1][4] Company Overview - Pasithea is a clinical-stage biotechnology company focused on innovative treatments for central nervous system disorders and RASopathies, including NF1, solid tumors, and amyotrophic lateral sclerosis (ALS) [8] Dr. Rebecca Brown's Role - Dr. Brown is the Director of the Neurofibromatosis Clinic at The Mount Sinai Hospital and brings extensive experience in NF1 research, having participated in numerous studies related to cutaneous and plexiform neurofibromas [2][3] - Her expertise will provide valuable clinical insights as the company prepares to initiate its Phase 1/2a clinical trial for PAS-004 [4] PAS-004 Development - PAS-004 is designed as a small molecule allosteric inhibitor of MEK 1/2, targeting the MAPK signaling pathway, which is crucial for tumor growth and other cellular functions [6] - The drug aims to overcome limitations of existing MEK inhibitors by offering improved pharmacokinetic and safety profiles, a longer half-life, and potentially better therapeutic index [6][7] - PAS-004 has received orphan-drug designation from the FDA for NF1, which may grant seven years of marketing exclusivity upon NDA approval [7]

Financial Performance - For the three months ended June 30, 2024, general and administrative expenses were $1,587,060, a decrease of 11.9% from $1,800,536 in the same period of 2023[88]. - The net loss from continuing operations for the three months ended June 30, 2024, was $3,866,249, representing a 7.5% increase from $3,598,084 in the prior year[88]. - The net loss for the six months ended June 30, 2024, was $7,727,089, an increase of 5.8% from $7,300,909 in the same period of 2023[89]. - Net loss from continuing operations was $7,727,089 for the six months ended June 30, 2024, compared to $6,863,894 for the same period in 2023[104]. - Other income (expense), net decreased by approximately $152,000, or 66%, for the three months ended June 30, 2024, compared to the same period in 2023[100]. Research and Development - Research and development expenses increased by 16.3% to $2,357,974 for the three months ended June 30, 2024, compared to $2,028,165 in 2023[88]. - Research and development expenses increased by approximately $307,000, or 15%, for the three months ended June 30, 2024, primarily due to clinical trial costs related to PAS-004[96]. - Research and development expenses increased by approximately $982,000, or 31%, for the six months ended June 30, 2024, driven by clinical trial costs for PAS-004[97]. - The company expects research and development expenses to increase in fiscal year 2024 due to clinical development activities for PAS-004[98]. - The company has ceased further development of the PAS-002 program for multiple sclerosis due to high costs and the availability of effective treatments[82]. Operational Outlook - The company expects to incur significant operating losses for the foreseeable future as it advances its product candidates through development and clinical trials[84]. - The company anticipates ongoing inflationary pressures impacting costs throughout 2024, particularly in employee compensation and outside services[87]. - The company requires significant additional funds to meet operational needs and capital requirements for clinical trials and other research and development expenditures[106]. Clinical Trials and Developments - The FDA cleared the IND for PAS-004 in December 2023, allowing the company to proceed with a Phase 1 trial for patients with MAPK pathway-driven advanced tumors[81]. - The company plans to open three additional clinical trial sites in Eastern Europe in the third quarter of 2024[81]. Capital and Cash Flow - Working capital decreased by approximately $6.8 million from December 31, 2023, to June 30, 2024, primarily due to cash used to fund operations[103]. - Cash and cash equivalents decreased by approximately $8.4 million for the six months ended June 30, 2024, compared to a decrease of approximately $6.4 million for the same period in 2023[104]. - A one-for-20 reverse stock split was executed on January 2, 2024, reducing the number of authorized shares from 495 million to 100 million[85].

Core Viewpoint - 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 advanced solid tumors, following a positive safety review by an independent committee [1][2][3] Group 1: Clinical Trial Progress - The independent Safety Review Committee (SRC) has completed its safety review of the first dose cohort (2mg) and recommended escalating to the next dose level (4mg) due to the absence of dose limiting toxicities (DLTs) [2] - Enrollment and initial dosing of 3 patients in the second cohort at 4mg has been completed following the SRC's recommendation [2][3] - The Phase 1 trial is a multicenter, open-label, dose escalation study focusing on the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PAS-004 in patients with specific mutations or those who have failed previous treatments [3] Group 2: Company Overview - Pasithea Therapeutics is a biotechnology company dedicated to developing innovative treatments for central nervous system (CNS) disorders and RASopathies, with a focus on conditions like NF1, solid tumors, and amyotrophic lateral sclerosis (ALS) [9]

Financial Performance - For the three months ended March 31, 2024, general and administrative expenses increased by approximately $175,380, or 8.3%, compared to the same period in 2023[109]. - The net loss from continuing operations for the three months ended March 31, 2024 was $3,860,840, an increase of 18.2% compared to a net loss of $3,265,810 in the same period in 2023[109]. - Net loss for the three months ended March 31, 2024, was $3,860,840, compared to a net loss of $3,537,679 for the same period in 2023[119]. - Working capital decreased by approximately $3.3 million from December 31, 2023, to March 31, 2024, primarily due to cash used to fund operations[118]. - Cash and cash equivalents decreased by approximately $4.3 million for the three months ended March 31, 2024, compared to a decrease of approximately $3.2 million for the same period in 2023[119]. - The accumulated deficit as of March 31, 2024, was approximately $39.1 million, indicating significant operating losses and negative cash flows from operations[120]. Research and Development - Research and development expenses for the three months ended March 31, 2024 were $1,749,128, representing a significant increase of 59.6% from $1,096,286 in the same period in 2023[109]. - Research and development expenses increased by approximately $652,000, or 60%, for the three months ended March 31, 2024, compared to the same period in 2023[114]. - The company expects research and development expenses to increase in fiscal year 2024 compared to fiscal year 2023, primarily due to clinical development activities[115]. - The company has ceased further development of the PAS-002 program for multiple sclerosis due to high costs and the availability of effective treatment options[101]. - The FDA cleared the IND for PAS-004 in December 2023, allowing the company to proceed with a Phase 1 clinical trial for patients with MAPK pathway-driven advanced tumors[100]. - The company plans to open three additional clinical trial sites in Eastern Europe in the third quarter of 2024[100]. Operational Challenges - The company expects to incur significant operating losses for the foreseeable future as it advances its product candidates through development and clinical trials[102]. - The company anticipates that inflation will negatively impact its operations throughout 2024, particularly in employee compensation and outside services[106]. - The company requires significant additional funds to meet operational needs and capital requirements for clinical trials and other research and development expenditures[122]. Strategic Focus - The company aims to establish a sales, marketing, and distribution infrastructure to commercialize any approved product candidates[107]. - The company has discontinued support services to anti-depression clinics in the U.K. and related at-home services in New York, resulting in a focus on the Therapeutics segment[117]. Stock and Capital Structure - A one-for-20 reverse stock split was executed on January 2, 2024, reducing the number of authorized shares from 495 million to 100 million[104]. - Other income (expense), net increased by approximately $233,000 for the three months ended March 31, 2024, primarily due to dividend income of $153,000[116].

Corporate Structure and Control - As of March 23, 2024, officers, directors, and principal stockholders own approximately 30.4% of the outstanding Common Stock, potentially impacting corporate control [312]. - The company is classified as an emerging growth company until it exceeds $1.235 billion in annual revenue or meets other specific criteria [302]. Compliance and Regulatory Issues - The company received a Nasdaq compliance notice on January 19, 2023, for not maintaining a minimum bid price of $1.00 per share, with a compliance period extended to January 15, 2024 [316]. - On January 17, 2024, the company regained compliance with the Nasdaq minimum bid price requirement [318]. - The company may face increased legal and financial compliance costs due to changing laws and regulations affecting public companies [305]. - The company may be subject to securities litigation, which could divert management's attention and incur substantial costs [308]. Financial Performance and Strategy - The company does not currently intend to pay dividends on its Common Stock, focusing instead on retaining earnings for business development [309]. - Exchange rate fluctuations, particularly between the U.S. dollar, British pound, and Euro, may materially affect the company's financial results [315]. - The company has opted to delay adopting new accounting standards under the JOBS Act, which may impact financial reporting [303]. Operational Changes - As of December 31, 2023, the company has discontinued all operations of its Clinics segment [325].