MEK2

– SRC recommended that the trial escalate to the next dose level of 30mg capsule – – No dose-limiting toxicities (DLT’s) or rash observed to date – MIAMI, April 10, 2025 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (NASDAQ: KTTA) (“Pasithea” or the “Company”), 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, 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. Rash is a common adverse event (AE) that is observed at low doses with competitor MEK inhibitors and may lead to the discontinuation rate in real world practice. “We are seeing substantial enrollment demand and have already identified Cohort 6 patients. In addition, we continue to observe substantial exposure levels of PAS-004, and remain excited about the possibility of delivering relevant pERK inhibition below the no observed adverse effect levels (NOAEL) as we modeled and observed during our previously conducted nine-month chronic toxicity studies. The on label rash rate for both approved MEKi for NF1 exceeds 80% which leads to patients discontinuing who otherwise should remain on treatment for longer periods of time”, stated Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. “We will provide additional safety, pharmacokinetic (PK) and pharmacodynamic (PD) data over the next several weeks.” The ongoing Phase 1 clinical trial is a multi-center, open-label, dose escalation 3+3 study design to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy 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 (NCT06299839). About Pasithea Therapeutics Corp. Pasithea is a biotechnology company focused on the discovery, research and development of innovative treatments for central nervous system (CNS) disorders and RASopathies. With an experienced team of experts in the fields of neuroscience, translational medicine, and drug development, Pasithea is developing new molecular entities for the treatment of neurological disorders, including Neurofibromatosis type 1 (NF1), Solid Tumors, and Amyotrophic Lateral Sclerosis (ALS). Forward Looking Statements This press release contains statements that constitute “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements regarding the Company’s ongoing Phase 1 clinical trial and the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD) and preliminary efficacy of PAS-004, as well as all other statements, other than statements of historical fact, regarding the Company’s current views and assumptions with respect to future events regarding its business, as well as other statements with respect to the Company’s plans, assumptions, expectations, beliefs and objectives, the success of the Company’s current and future business strategies, product development, preclinical studies, clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of the Company. While the Company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the Company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties, including risks that future clinical trial results may not match results observed to date, may be negative or ambiguous, or may not reach the level of statistical significance required for regulatory approval, as well as other factors set forth in the Company’s most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other filings made with the U.S. Securities and Exchange Commission (SEC). Thus, actual results could be materially different. The Company undertakes no obligation to update these statements whether as a result of new information, future events or otherwise, after the date of this release, except as required by law. Pasithea Therapeutics Contact Patrick Gaynes Corporate Communications pgaynes@pasithea.com Released April 10, 2025

A genetic disease that causes tumors to form on nerves has a new FDA-approved treatment, a SpringWorks Therapeutics drug that can address a wider range of patients than the AstraZeneca product that was first to treat this rare disorder. The disease, neurofibromatosis type 1 (NF1), is technically not cancer as the tumors that form are benign. But NF1 can lead to cancers. Even if a patient’s tumors aren’t cancerous, they are painful and disfiguring. The FDA approval announced Tuesday covers the treatment of NF1 tumors that cannot be surgically removed. The drug, known in development as mirdametinib, will be marketed under the brand name Gomekli. SpringWorks expects the new product will become available within two weeks. Stamford, Connecticut-based SpringWorks estimates that of the approximately 100,000 in the U.S. who have NF1, about 40,000 have tumors that infiltrate nerves. The disease stems from mutations in the NF1 gene, which codes for a protein key to suppressing MAPK, a pathway that, when hyperactivated, drives cancer growth. Tumors that result from the mutations are usually aggressive, growing rapidly during a patient’s childhood. Surgery is the first treatment option, but the location of tumors at or near vital structures or organs can make this choice risky. Off-label drug options include cancer medications, such as chemotherapy and immunotherapy. Exclusive Improving the Healthcare Financial Experience to Help Care Flow Zelis CEO Amanda Eisel shares her perspective on how the company is solving the problems of a fragmented health financial system to benefit all. By Stephanie Baum Gomekli is an oral small molecule designed to block MEK1 and MEK2, two proteins that play key roles in the MAPK pathway. MEK inhibitors have already been approved for treating certain cancers. Koselugo, the AstraZeneca drug that became the first FDA approved NF1 therapy in 2020, is a MEK inhibitor that was initially tested in various solid tumors. In NF1, Koselugo is approved only for treating pediatric patients age 2 and older. The SpringWorks drug has an advantage with an approval that covers the treatment of adults as well as children. The FDA decision for Gomekli was based on the results of a single-arm, Phase 2 study that enrolled 114 patients — 58 adults and 56 children — with symptomatic, inoperable NF1-associated tumors. The main goal was to measure for the disappearance or reduction of tumors. Results showed the overall response rate was 41% for adults and 52% for children. The most common adverse reactions included rash, diarrhea, nausea, and muscle pain. The study results were published this past November in the Journal of Clinical Oncology. Dr. Christopher Moertel, medical director pediatric neuro-oncology and neurofibromatosis programs at the University of Minnesota and the lead investigator of the ReNeu clinical trial, said NF1 patients face significant health challenges and have limited treatment options. “It was very encouraging in the ReNeu trial to see that Gomekli provided deep and durable responses, with a manageable safety profile that enabled patients to stay on therapy,” Moertel said in SpringWorks’ announcement. “This approval represents an important advance, especially for adults who previously did not have an approved treatment.” presented by Artificial Intelligence What Keeps Healthcare CIOs Up at Night: Balancing Technology Investments with Consumer Expectations When it comes to managing inbound phone calls, underperformance has devastating cost implications. By Stephanie Baum Gomekli is still under regulatory review in Europe. In the U.S., the drug will be available as a capsule as well as a tablet that may be swallowed or mixed in water. The twice-daily drug will come in two dosage strengths. Precise dosing is determined by a patient’s body surface area, taking into account both height and weight. SpringWorks set a wholesale price of $206.25 per mg, according to a Wednesday regulatory filing. The company estimates the average cost of treatment will be about $22,000 per month for pediatric patients and $30,000 per month for adults. The Gomekli approval comes as SpringWorks has emerged as a potential acquisition target for Merck KGaA. Following a Reuters report of negotiations for a deal, the German company issued a statement Monday confirming advanced discussions with SpringWorks. However, Merck KGaA said the companies have not entered a legally binding agreement, adding that “critical conditions have yet to be met.” If Merck KGaA can swing a deal for SpringWorks, it will get more than the new NF1 drug. In 2023, SpringWorks drug Ogsiveo received the FDA nod for treating desmoid tumors, a rare type of tumor affecting connective tissue. For the nine months ended Sept. 30, 2024, Ogsiveo accounted for $110 million in revenue, according to the biotech’s most recent financial report. Both Ogsiveo and Gomekli were initially developed by Pfizer, which spun them off into standalone company SpringWorks in 2017. Beyond NF1, SpringWorks is testing Gomekli in certain cancers. As a monotherapy, the drug has reached mid-stage clinical testing in pediatric low-grade gliomas. Under a partnership with BeiGene, Gomekli is also being tested in solid tumors driven by RAS and RAF mutations; a Phase 1 study is evaluating the SpringWorks drug in combination with BeiGene’s experimental lifirafenib, a small molecule inhibitor of RAF enzymes. Photo by SpringWorks Therapeutics

Taylor Tieden for BioSpace The rare disease space is awaiting two FDA verdicts in February, one for a genetic disease and another for a non-malignant tumor. The FDA is looking at five big deadlines in February, including one for a broad meningococcal vaccine that promises to provide potent protection against five of the most common serogroups in the U.S. Read below for more. Indivior Proposes Alternate Injection Sites for Opioid Use Disorder Therapy By February 7, the FDA is set to release its decision on Indivior’s Prior Approval Supplement (PAS) filing, which proposes alternative injection sites for its opioid use disorder treatment Sublocade (buprenorphine extended-release). Sublocade is a long-acting formulation of buprenorphine, an opioid agonist, that is indicated for patients with moderate to severe opioid use disorder who have already initiated treatment with another buprenorphine-containing product. Currently, the drug is administered through a subcutaneous injection in the abdomen. If approved, the PAS will allow sublocade to be delivered through the thigh, buttocks and back of the upper arm. The PAS also proposes a rapid induction protocol that would shorten induction time from the presently approved minimum of 7 days, down to a single dose of transmucosal buprenorphine followed by a 1-hour observation period. Indivior is backing its PAS with data showing the safety and efficacy of the proposed routes of administration and rapid induction protocol. “These updates are expected to enhance the patient experience and expand treatment access especially for those patients who … have long-term opioid use including fentanyl,” the biotech wrote in its October 2024 news release . GSK Looks to Expand Meningococcal Protection with New Shot GSK is advancing a 5-in-1 vaccine candidate designed to elicit broad protection against the five most common bacterial groups causing invasive meningococcal disease. The FDA is currently reviewing the pharma’s Biologics License Application (BLA), with a decision due on Feb. 14. The investigational shot, dubbed MenABCWY, combines two well-established meningococcal vaccines: Bexsero, which targets group B bacteria, and Menveo, which covers the A, C, W and Y serogroups. Both Bexsero and Menveo are owned by GSK. According to the pharma, combining these five bacterial groups in one protective shot “aims to reduce the number of injections, simplifying immunization” and improving adherence and completion rates for the vaccine. In turn, this can lead to better health outcomes and lower the overall incidence of invasive meningococcal disease, GSK said in a statement . To back MenABCWY, GSK provided Phase III data showing that the vaccine candidate induced non-inferior immune responses as compared with one dose of Menveo and with two doses of Bexsero. MenABCWY was also well-tolerated and its adverse events were consistent with the two comparator vaccines. Ono Sets Sights on Rare, Non-Malignant Tumor Osaka-based Ono Pharmaceutical is proposing vimseltinib, an investigational colony stimulating factor 1 receptor (CSF1R) inhibitor, for the treatment of tenosynovial giant cell tumor (TGCT). The FDA is expected to release its decision by Feb. 17. TGCT is a rare type of non-malignant tumor that develops in or around joints. The disease is caused by a mutation in the CSF1 gene that results in the overexpression of the protein, in turn recruiting an abundance of CSF1R-expressing inflammatory cells to the tumor site. TGCT is benign but can damage surrounding tissue once progressed. Patients often suffer from pain, swelling and limitations in joint movement. Currently, TGCT is managed primarily through surgery, though this option frequently leads to disease recurrence. In patients who cannot undergo surgery, systemic therapies are limited, according to Ono. If left unchecked or allowed to continuously recur, TGCT can lead to significant disability. Vimseltinib is an orally available switch-control tyrosine kinase inhibitor designed to strongly block CSF1R, targeting a key disease pathway in TGCT. Ono, through its subsidiary Deciphera, is backing vimseltinib’s application with data from the pivotal Phase III MOTION trial, which found that the candidate elicits significantly better objective response rate versus placebo, while also hitting its key secondary endpoints. SpringWorks Awaits Verdict for Rare Genetic Disease Therapy By Feb. 28, the FDA is expected to decide on SpringWorks Therapeutics’ investigational MEK inhibitor mirdametinib, which the Connecticut-based biotech is developing for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) in adults and children. NF1 is a highly heterogeneous rare and genetic disease with varied manifestations across different organ systems, including tumor formation and growth, neurological complications and skeletal deformities. The PN subtype of NF1 is characterized by tumors along the sheathes of peripheral nerves, in turn leading to severe disfigurement, functional impairment and pain, according to SpringWorks. NF1, including the PN subtype, is caused by loss-of-function mutations in the NF1 gene, which under healthy conditions encodes for the neurofibromin protein that suppresses the MAPK pathway. Mirdametinib addresses this by penetrating into the central nervous system to inhibit MEK1 and MEK2, two signaling molecules that play key roles in the MAPK pathway. To back its drug application, SpringWorks provided data from the Phase IIb ReNeu study, which focused on patients aged 2 years and older and found that mirdametinib elicited “robust” objective response rates, deep and durable responses and notable improvements in pain and health-related quality of life. The FDA has granted mirdametinib its Priority Review and Orphan Drug designations for NF1-PN. Eton Pharma’s New Oral Hydrocortisone Formulation Nears Approval Also by Feb. 28, the FDA is scheduled to release its verdict regarding Eton Pharmaceuticals’ novel oral formulation of hydrocortisone, dubbed ET-400, for adrenal insufficiency in infants. ET-400 is a new and proprietary formulation of oral hydrocortisone that is stable at room temperature. Eton recently won patent protection over this formulation that will last until 2043. The biotech also has other patent applications for ET-400 that are currently under review. Eton also owns Alkindi Sprinkle, an oral granule formulation of hydrocortisone that is likewise indicated for children with adrenocortical insufficiency. The drug, approved in 2020 , is an immediate-release glucocorticoid that can sufficiently replace cortisol in these patients. Alkindi Sprinkle is specifically formulated to allow parents to give lower doses to small children, instead of needing to cut higher-strength hydrocortisone tablets. If approved, ET-400 would allow Eton to “capture a greater percentage of the oral hydrocortisone market,” CEO Sean Brynjelsen said in the biotech’s press statement on the FDA’s acceptance of ET-400’s drug application. Together with Alkindi Sprinkle, ET-400 could hit peak sales of more than $50 million per year, Brynjelsen added.