Binimetinib

-- PAS-004 inhibition of in vitro NRAS cell lines does not plateau in contrast to approved MEK inhibitors -- -- PAS-004 inhibition of in vitro NRAS cell lines is greater than selumetinib and binimetinib and similar to trametinib -- -- PAS-004 shows superior activity versus selumetinib and binimetinib in NRAS xenograft tumor models -- -- Poster presentation on Saturday, June 1, 2024 at the ASCO Annual Meeting -- SOUTH SAN FRANCISCO, Calif. and MIAMI, May 28, 2024 (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, announced today the publication of data showing PAS-004 strongly inhibiting NRAS mutant cancer cell lines with IC50 values ranging from 0.024 to 0.306 µM. Maximal growth inhibition of >50% was achieved by PAS-004 in more cell lines than binimetinib and selumetinib. In addition, PAS-004’s cell line inhibition was comparable to trametinib in 5 cell lines tested but, in contrast to trametinib, PAS-004 did not reach a plateau. The results will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting on June 1, 2024, in a poster session from 9:00 am - 12:00 pm CDT in Chicago, IL.​​ “We are excited to show new preclinical data showing enhanced potency of PAS-004 when compared to approved agents, with the potential for less frequent dosing which may lead to better tolerability and compliance.” said Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. “We believe this emerging pro the sweet spot balancing pharmacokinetics (PK), pharmacodynamics (PD) and tolerability and making PAS-004 an ideal candidate for the treatment of cutaneous and plexiform NF1 as well as a potential candidate for treatment of various cancers. We are looking forward to the initial readout of our Ph1 clinical trial.” PAS-004 is the first macrocyclic MEK inhibitor to enter human clinical trials, with an expected extended half-life which may provide better compliance rates, as well as improved efficacy in NF1. Macrocycles are known to exhibit stronger binding, better solubility and longer half-life with more selectivity and less off target effect as compared to acyclic small molecules. Presentation and poster details Title: PAS-004: A novel macrocyclic MEK inhibitor to inhibit cancer cell growth in vitro and tumor growth in mouse xenograft studies. Presenting author: Graeme Currie, PhD Session: Poster Session – Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology Date and Time: 6/1/2024, 9:00 AM – 12:00 PM CDT About PAS-004 PAS-004 is a small molecule allosteric inhibitor of MEK 1/2, which are dual-specificity protein kinases, in the MAPK signaling pathway. The MAPK pathway has been implicated in a variety of diseases, as it functions to drive cell proliferation, differentiation, survival and a variety of other cellular functions that, when abnormally activated, are critical for the formation and progression of tumors, fibrosis and other diseases. MEK inhibitors block phosphorylation (activation) of extracellular signal-regulated kinases (ERK). Blocking the phosphorylation of ERK can lead to cell death and inhibition of tumor growth. Existing FDA approved MEK inhibitors are marketed for a range of diseases, including certain cancers and neurofibromatosis type 1 (NF1). We believe these MEK inhibitors suffer from certain limitations, including known toxicities. Unlike current FDA approved MEK inhibitors, PAS-004 is macrocyclic, which we believe may lead to improved pharmacokinetic and safety (tolerability) pro Cyclization offers rigidity for stronger binding with drug target receptors. PAS-004 was designed to provide a longer half-life with what we believe is a better therapeutic window. Further, we believe the potency and safety pro PAS-004 has demonstrated in preclinical studies may also lead to stronger and more durable response rates and efficacy, as well as better dosing schedules. PAS-004 has been tested in a range of mouse models of various diseases and has completed preclinical testing and animal toxicology studies. Additionally, PAS-004 has received orphan-drug designation from the FDA for the treatment of NF1. 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 all 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 factors set forth in the Company’s most recent Form 10-K, Form 10-Q and 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

- Two clinical stage product candidates in development for the treatment of melanoma - - RAS mutant melanoma represents one of five arms in the company’s ongoing Phase 2a clinical study of IMM-1-104 - - Melanoma also being evaluated in ongoing Phase 1/2a clinical study of IMM-6-415 in patients with advanced solid tumors harboring RAF or RAS mutations - - Immuneering expects initial data from multiple IMM-1-104 Phase 2a arms in 2024 - CAMBRIDGE, Mass., May 06, 2024 (GLOBE NEWSWIRE) -- Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, recognizes the importance of early detection and treatment during Melanoma Awareness Month, and highlights RAS mutant melanoma as the focus of one of the five arms in its ongoing Phase 2a clinical study for its lead program IMM-1-104. RAF or RAS mutant melanoma is also being evaluated in its Phase 1/2a clinical study of IMM-6-415 in patients with advanced solid tumors. Melanoma Awareness Month is held each May to raise awareness, galvanize advocates and support research efforts toward new treatments and methods of detecting melanoma, the most serious type of skin cancer. “We encourage people diagnosed with melanoma to speak with their physicians about having their tumors tested for biomarkers which can help determine the most appropriate next steps in their treatment,” said Joan Levy, Ph.D., Chief Science Officer, Melanoma Research Alliance. “Several biomarkers are known to drive the growth and progression of melanoma and there are therapies being clinically evaluated with the potential to target these tumor biomarkers.” “Immuneering is proud to acknowledge Melanoma Awareness Month, especially since melanoma is a key area of focus in our development of IMM-1-104 and mutations in the RAS gene family are known to be present in approximately 20-25% of all melanomas,” said Brett Hall, Ph.D., Chief Scientific Officer, Immuneering Corporation. “We chose RAS mutant melanoma to be one of five arms in our Phase 2a trial of IMM-1-104, where we are investigating our lead development candidate as either monotherapy or in combination and are also evaluating RAF or RAS mutant melanoma in our Phase 1/2a clinical study with IMM-6-415. We are excited at the prospect of adding IMM-1-104 and IMM-6-415 to the melanoma treatment armamentarium and look forward to updating patients and physicians as we report data.” At the AACR-NCI-EORTC conference in October 2023, Immuneering presented preclinical data including expanded benchmarking of IMM-1-104 as a single agent across more than 190 patient-aligned models in humanized 3D-tumor growth assays, which demonstrated high sensitivity in a wide range of MAPK-driven tumor types, including models of RAS and RAF mutant melanoma, as well as pancreatic cancer, and lung cancer. Preclinical data the company has presented related to melanoma includes data showing that IMM-1-104 inhibits tumor growth in an animal model of NRAS mutant melanoma to a greater extent than binimetinib, and that IMM-6-415 in combination with encorafenib inhibits tumor growth in an animal model of BRAF mutant melanoma to a greater extent that binimetinib plus encorafenib. IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. In the Phase 2a portion of Immuneering’s ongoing IMM-1-104 Phase 1/2a clinical trial (NCT05585320), IMM-1-104 is being evaluated as both monotherapy and in select combinations with approved chemotherapeutic agents. The Phase 2a portion includes five arms, one of which focuses on RAS-mutant melanoma, another focused on RAS mutant non-small cell lung cancer (NSCLC), and three arms focused on patients with pancreatic cancer. The company expects initial data from multiple Phase 2a arms in 2024. IMM-6-415 is a Deep Cyclic Inhibitor of the MAPK pathway designed with unique drug-like properties including a shorter half-life for an accelerated cadence. IMM-6-415 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAF or RAS mutations. (NCT06208124). The Phase 1 portion of the Phase 1/2a clinical trial is an open-label study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of IMM-6-415 in patients with advanced RAF/RAS mutant solid tumors. The trial will include solid tumor patients with any mutation in RAF, KRAS, NRAS, or HRAS who meet the enrollment criteria. The company expects initial PK, PD and safety data for IMM-6-415 in 2024. About Immuneering Corporation Immuneering is a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients with an initial aim to develop a universal-RAS therapy. The Company aims to achieve universal activity through Deep Cyclic Inhibition of the MAPK pathway, impacting cancer cells while sparing healthy cells. Immuneering’s lead product candidate, IMM-1-104, is an oral, once-daily Deep Cyclic Inhibitor currently in a Phase 1/2a trial in patients with advanced solid tumors harboring RAS mutations. IMM-6-415 is an oral, twice-daily Deep Cyclic Inhibitor currently in a Phase 1/2a trial in patients with advanced solid tumors harboring RAS or RAF mutations. The company’s development pipeline also includes several early-stage programs. For more information, please visit www.immuneering.com. Forward-Looking Statements This press release contains forward-looking statements, including within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding: Immuneering’s plans to develop, manufacture and commercialize its product candidates; the treatment potential of IMM-1-104, alone or in combination with other agents, including chemotherapy; the design, enrollment criteria and conduct of the Phase 1/2a IMM-1-104 clinical trial; the translation of preclinical data into human clinical data; the potential advantages and effectiveness of Immuneering’s clinical and preclinical candidates; and the timing of results of the Phase 2a portion of the trial for IMM-1-104. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the risks inherent in oncology drug research and development, including target discovery, target validation, lead compound identification, and lead compound optimization; we have incurred significant losses, are not currently profitable and may never become profitable; our projected cash runway; our need for additional funding; our unproven approach to therapeutic intervention; our ability to address regulatory questions and the uncertainties relating to regulatory filings, reviews and approvals; the lengthy, expensive, and uncertain process of clinical drug development, including potential delays in or failure to obtain regulatory approvals; our reliance on third parties and collaborators to conduct our clinical trials, manufacture our product candidates, and develop and commercialize our product candidates, if approved; failure to compete successfully against other drug companies; protection of our proprietary technology and the confidentiality of our trade secrets; potential lawsuits for, or claims of, infringement of third-party intellectual property or challenges to the ownership of our intellectual property; our patents being found invalid or unenforceable; costs and resources of operating as a public company; and unfavorable or no analyst research or reports. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the annual period ended December 31, 2023, and our other reports filed with the U.S. Securities and Exchange Commission, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Media Contact:Gina Nugentgina@nugentcommunications.com Investor Contact:Laurence Watts619-916-7620laurence@newstreetir.com