NF1

-- Single patient in 2mg cohort with stage 3 colon cancer who received 4 prior lines of therapy achieves prolonged stable disease and remains on drug into 6th dosing cycle -- -- No treatment-related adverse events (TRAEs) or dose-limiting toxicities (DLTs) observed to date, including no rash or gastrointestinal (GI) AEs -- -- Systemic exposure at steady-state enables constant target inhibition while avoiding peak plasma toxicities -- -- Half-life of approximately 70 hours supports once-daily or less frequent oral dosing -- -- Distinctive MEK inhibitor profile for the treatment of both NF1-related plexiform and cutaneous neurofibromas, cancer, and other opportunities -- MIAMI, Sept. 26, 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, today announced safety, tolerability, pharmacokinetic (PK) and preliminary efficacy data from the first 2 cohorts of patients (n=6) in its Phase 1 clinical trial of PAS-004, being conducted at four clinical sites in the United States. The 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). “We are very pleased to share the PK, safety, and preliminary efficacy data from the 2 mg and 4 mg cohorts in our first-in-human Phase 1 clinical trial of PAS-004. We believe these data demonstrate a PK and safety profile that differentiates PAS-004 as a next-generation MEK inhibitor. We have already achieved significant PAS-004 exposures with a favorable safety profile and have not seen adverse side effects such as rash or GI toxicity, which are typical for MEK inhibitors even at low doses. The long half-life at approximately 70 hours, and the ability to achieve a flat PK curve at steady-state, aim to provide a constant target inhibition while avoiding peak plasma toxicities, which is a unique PK profile among MEK inhibitors used for the treatment of Neurofibromatosis type 1 (NF1),” stated Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. “In addition, we are encouraged to see early potential signs of efficacy, with a heavily pre-treated patient with colorectal cancer showing prolonged stable disease. Colorectal cancer is known to not provide a RECIST response when treated with single-agent MEK inhibitors. This patient has a BRAF K601E mutation, a mutational status with no approved therapies. We are encouraged that this patient has been treated continuously into the 6th 28-day dosing cycle with no toxicities or AEs observed. While still early in clinical development, we believe PAS-004 is showing early signs of differentiation, indicating PAS-004 has the potential to outperform current MEK inhibitors in terms of safety, reduced administration frequency, and potentially efficacy. Our goal is to provide a once-daily or less frequent dosing treatment with broader application, not only for NF1 but also for other indications.” Interim Phase 1 Results Pharmacokinetics (PK) Plasma exposure increased with an increase in dose and linear PK is observedLong half-life of approximately 70 hours will allow for once daily dosing or longer intervalsProlonged systemic exposure with minimal fluctuation in PAS-004 plasma concentration at steady state (Cmax/Cmin ratio of 1.2) indicates a potential to achieve constant target inhibition At steady-state, drug levels peaked at about 5 hours with a geometric mean maximum concentration (Cmax) of 16.2 and 61.3 ng/mL for the 2 mg and 4 mg dose groups, respectively. The mean elimination half-life was 67.9 hours supporting once-daily or less frequent oral dosing. “PAS-004 has demonstrated distinct properties that we believe are significant advantages for an oral MEK inhibitor. PAS-004 has a significantly longer half-life compared to early-generation MEK inhibitors, particularly those used for the treatment of NF1, which have half-lives of less than 8 hours. The ability to achieve prolonged plasma exposures, as reflected in stable plasma concentrations at steady state, may potentially allow PAS-004 to achieve efficacious doses with a favorable safety profile,” stated Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea. Safety & Tolerability No treatment-related adverse events (TRAEs) or dose limiting toxicities (DLTs) observed to date In the first 2 dosing cohorts (n=6), PAS-004 was shown to be well-tolerated with a favorable safety profile with no drug-related dose interruptions, reductions or discontinuations. There were no drug-related serious AEs (SAE) in any dose arm and no protocol-defined stopping criteria were met. Importantly, at the 2 and 4 mg dose levels no rash or skin toxicity, gastro-intestinal (GI) toxicity, or ocular toxicity have been observed to date. The study independent Safety Review Committee has completed its safety review of data from the second dose cohort of 4 mg and the Company has initiated cohort 3 dosing at an increased dose of 8 mg in capsules and has filed a protocol amendment to increase dosing schedule. PAS-004 Demonstrates a Differentiated MEK Inhibitor Profile Unlike first-generation MEK inhibitors for the treatment of NF1 that require twice-daily dosing (BID) and exhibit short half-lives (<8 hours), PAS-004 has the potential to achieve prolonged target inhibition due to its long half-life of approximately 70 hours with once-daily dosing (QD). The PK profile shows consistent plasma levels at steady-state, as reflected by a low Cmax to Cmin ratio, potentially reducing the risks for Cmax-related toxicity. These findings provide a compelling rationale for the advancement of PAS-004 into clinical trials for both the treatment of cutaneous and plexiform neurofibromas in NF1, cancer and other MAPK-driven opportunities. The company expects to provide additional trial updates on a periodic basis as the trial progresses. 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) 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 GaynesCorporate Communicationspgaynes@pasithea.com Photos accompanying this announcement are available at https://www.globenewswire.com/NewsRoom/AttachmentNg/4765238d-9961-438e-b459-509a5c917974 https://www.globenewswire.com/NewsRoom/AttachmentNg/0e484fc9-7068-4c8f-8060-f4109228d013

– PDUFA target action date of February 28, 2025 – – EU Marketing Authorization Application also validated by European Medicines Agency – Aug. 28, 2024 -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced today that the U.S. Food and Drug Administration (FDA) has accepted the Company’s New Drug Application (NDA) for mirdametinib, an investigational MEK inhibitor, for the treatment of adult and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of February 28, 2025. In addition, the FDA has stated that it is not currently planning to hold an advisory committee meeting to discuss the application. SpringWorks also announced today that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for mirdametinib for the treatment of adult and pediatric patients with NF1-PN. Mirdametinib has the potential to be the first approved therapy for the treatment of adult patients and a best-in-class therapy for children with NF1-PN. “These significant milestones bring us closer to our goal of delivering a transformative medicine to both adults and children with NF1-PN in the U.S. and Europe,” said Saqib Islam, Chief Executive Officer of SpringWorks. “People living with NF1-PN are in need of new advances and we look forward to working with the FDA and EMA during their review processes as we prepare to bring our second medicine to patients suffering from devastating diseases.” The FDA grants Priority Review to applications for medicines that offer, if approved, significant improvements over available options or that provide a treatment option where no adequate therapy currently exists. The FDA and the European Commission have previously granted Orphan Drug designation for mirdametinib for the treatment of NF1. The FDA has also granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity and Rare Pediatric Disease designation for the treatment of NF1. “Plexiform neurofibromas may sit next to or surround vital organs and can cause serious medical complications for patients. While progress has been made, there remains a pressing need for more treatment options, particularly for adults who currently have no approved therapy,” said Annette Bakker, Ph.D., Chief Executive Officer of the Children’s Tumor Foundation (CTF) and Board Chair of CTF Europe. “CTF is dedicated to deploying its time, talent and funding towards accelerating the development of new treatments. We congratulate our long-term partner SpringWorks on this important milestone and we are thrilled that patients in the United States and Europe could soon have a new therapy available to them. Both submissions include data from the pivotal Phase 2b ReNeu trial, which evaluated mirdametinib in patients ≥ 2 years of age with NF1-associated PN causing significant morbidity. Results were presented in an oral presentation at the 2024 American Society of Clinical Oncology Annual Meeting and demonstrated that mirdametinib treatment resulted in robust objective response rates confirmed by blinded independent central review, deep and durable responses, improvement in pain and health-related quality of life as well as a manageable safety profile across both the adult and pediatric cohorts.1 ReNeu (NCT03962543) is an ongoing, multi-center, open-label Phase 2b trial evaluating the efficacy, safety, and tolerability of mirdametinib in patients ≥ 2 years of age with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint is confirmed objective response rate assessed by proportion of patients with ≥ 20% reduction in target tumor volume on consecutive scans during the 24 cycle treatment phase, as measured by MRI and assessed by blinded independent central review. Secondary endpoints include safety and tolerability, duration of response, and changes in patient reported outcomes from baseline to Cycle 13. The treatment phase of the trial is complete and results were presented at the 2024 American Society of Clinical Oncology Annual Meeting. Patients who completed the treatment phase were eligible to continue receiving treatment in the optional long-term follow up portion of the study, which is ongoing. About NF1-PN Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from loss-of-function variants in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.2,3 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals, and approximately 100,000 patients living with NF1 in the United States.4,5 The clinical course of NF1 is heterogeneous and manifests as a variety of symptoms across numerous organ systems, including abnormal skin pigmentation, skeletal deformities, tumor growth, and neurological complications such as cognitive impairment.6 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.3 NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.7,8 NF1-PNs are most often diagnosed in the first two decades of life.7 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.9,10 Surgical removal of these tumors is challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.11 MEK inhibitors have emerged as a validated class of treatment for NF1-PN.12 Mirdametinib is a potent, oral, CNS-penetrant, allosteric small molecule MEK inhibitor in development as a monotherapy treatment for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) and low-grade glioma (LGG), and as a combination therapy for the treatment of several subsets of biomarker-defined metastatic solid tumors. Mirdametinib is an investigational drug for which safety and efficacy have not been established. Mirdametinib is designed to inhibit MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and survival and plays a central role in multiple cancers and rare diseases when genetically altered. The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1. The FDA has also granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity and Rare Pediatric Disease designation for the treatment of NF1. SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO® (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company’s first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need. References Moertel C, et al., ReNeu: A pivotal phase 2b trial of mirdametinib in children and adults with neurofibromatosis type 1 (NF1)-associated symptomatic inoperable plexiform neurofibroma (PN). Journal of Clinical Oncology 42, 3016-3016(2024). DOI:10.1200/JCO.2024.42.16_suppl.3016. The American Society of Clinical Oncology Abstract 3016. May 2024. Yap YS, McPherson JR, Ong CK, et al. The NF1 gene revisited - from bench to bedside. Oncotarget. 2014;5(15):5873-5892. doi:10.18632/oncotarget.2194. Rasmussen S, Friedman J. NF1 Gene and Neurofibromatosis 1. Am J Epidemiol. 2000;151(1):33-40. doi:10.1093/oxfordjournals.aje.a010118. CTF: Children’s Tumor Foundation. New and Improved: The way to talk about NF. Press release. May 9, 2023. Accessed February 2, 2024. Lee: Lee TJ, et al. Incidence and prevalence of neurofibromatosis type 1 and 2: a systematic review and meta-analysis. Orphanet J Rare Dis. 2023;18(1):292. Published 2023 Sep 14. doi:10.1186/s13023-023-02911-2. Weiss BD, Wolters PL, Plotkin SR, et al. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. Journal of Clinical Oncology. 2021;JCO.20.02220.doi.org/10. 1200/JCO.20.02220. Prada: Prada CE, Rangwala FA, Martin LJ, et al. Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1. J Pediatr. 2012;160(3):461-467. Miller: Miller DT, et al. Health Supervision for Children With Neurofibromatosis Type 1. Pediatrics. 2019;143(5):e20190660. Gross A, Singh G, Akshintala S, et al. Association of plexiform neurofibroma volume changes and development of clinical morbidities in neurofibromatosis 1. Neuro Oncol. 2018;20(12):1643-1651. doi:10.1093/neuonc/noy067. Nguyen R, Dombi E, Widemann B, et al. Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1. Orphanet J Rare Dis. 2012;7(1):75. doi:10.1186/1750-1172-7-75. Needle M, Cnaan A, Dattilo J, et al. Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr. 1997;131(5):678-682. doi:10.1016/s0022-3476(97)70092-1. Ferner R. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. The Lancet Neurology. 2007;6(4):340-351. doi:10.1016/s1474-4422(07)70075-3. The content above comes from the network. if any infringement, please contact us to modify.

CAMBRIDGE, U.K.--( BUSINESS WIRE )--Healx, an AI-enabled, clinical-stage biotech company specializing in rare diseases, announced it has raised $47 million in a Series C round. The Series C round was co-led by Silicon Valley-based R42 Group and Atomico, one of Europe’s largest venture capital firms, with participation from new and existing investors including Balderton, Jonathan Milner, Global Brain, btov, Ayana Capital, o2h and VU Venture Partners. Proceeds of the financing will be used to advance the company’s pipeline of medicines in rare oncology, renal and neurodevelopmental disorders, including advancing its lead program HLX-1502 through a Phase 2 clinical trial for the treatment of neurofibromatosis Type 1 (NF1). In conjunction with the financing, Stanford Medicine Adjunct Professor Ronjon Nag, Ph.D., founder of R42 Group and 2024 Silicon Valley Hall of Fame AI inductee, joins the board of Healx. “It is truly a pivotal time at Healx,” said Tim Guilliams, Ph.D., co-founder and CEO of Healx. “By December 2024, we will advance HLX-1502 into a Phase 2 clinical trial in patients with NF1 both for plexiform neurofibroma, a genetic condition with limited treatment options and for cutaneous neurofibroma, for which there are no FDA approved options. We are also generating important preclinical data for multiple additional compounds identified using our novel generative AI drug discovery engine. Those compounds target rare diseases with significant unmet needs, including additional nerve-related tumor disorders, autosomal dominant polycystic kidney disease and neurodevelopmental disorders such as Angelman syndrome. The Healx drug discovery pipeline is powered by Healnet, an AI-driven discovery platform designed to identify clinically de-risked therapeutic opportunities for rare diseases. Healnet incorporates recent advances in generative AI to find connections between biological and chemical entities that could be turned into new treatments. Healx was co-founded in Cambridge (UK) by its chairman and Viagra co-inventor David Brown, Ph.D ., and Tim Guilliams, Ph.D. , with a mission to apply emerging technologies to speed the discovery of rare disease treatments. U.S. FDA IND Clearance Healx also announced that it has received clearance from the U.S. Food and Drug Administration (FDA) to proceed with its Phase 2 clinical trial of HLX-1502. This trial will focus on treating adults with NF1 and inoperable plexiform neurofibroma. “This IND approval marks another significant milestone in our efforts to harness powerful AI to develop a new treatment for NF1-associated plexiform neurofibroma,” said Tim Guilliams, Ph.D., CEO of Healx. “We are committed to advancing this promising investigational treatment through clinical development and bringing it one step closer to patients in need." HLX-1502 is a tablet taken orally that works differently than other treatments and offers a new and differentiated investigational treatment option for patients with NF1. NF1 is a rare genetic disorder associated with predisposition to develop multiple benign and malignant tumors. It affects approximately 1 in 2,500 individuals. Two notable types of tumors associated with NF1 are plexiform neurofibromas and cutaneous neurofibromas. Plexiform neurofibromas are complex tumors growing aggressively along nerves, which often leads to significant morbidity and risk of malignant transformation. These tumors can affect various parts of the body, causing functional impairments, disfigurement and pain and requiring multidisciplinary management. Currently, there is only one treatment option available for some children with plexiform neurofibromas which is, however, associated with tolerability and safety concerns including gastrointestinal, heart, eye and skin toxicity. Cutaneous neurofibromas are benign tumors that often cause significant symptoms, leading to impairment in quality of life, and also result in considerable cosmetic concerns. There are no approved treatments for NF1-associated cutaneous neurofibromas, leaving a major unmet need for the estimated 3 million people with NF1 worldwide. HLX-1502 has received Orphan Drug and Rare Pediatric Disease designations from the FDA for treating NF1. These FDA designations provide several benefits to encourage the development of treatments for rare diseases and further highlight HLX-1502’s potential to significantly improve the lives of NF1 patients. “I could not be more excited to start this trial soon. Our treatment – with its novel mechanism of action and potential for a compelling and differentiated safety profile – represents a significant advancement in the NF1 field and a much needed hope for the NF1 community. It has the potential to greatly improve NF1 patients’ lives, which is by far what matters the most and what drives us,” said Simone Manso, Healx head of neurofibromatosis therapy development. Healx has an investment agreement with its long-term research partner, Children’s Tumor Foundation (CTF), whereby Healx will receive milestone-driven payments from CTF to support the advance of Healx’s NF programs including its lead candidate, HLX-1502. CTF has been a longtime partner of Healx and actively supports its mission to deliver much-needed therapies to this patient group. About Healnet Behind advances in our therapeutic pipeline lies Healnet, a unique AI-driven drug discovery engine that is tailored to discover treatments for rare diseases. The platform uses disease multi-omics signature reversal and AI to identify novel therapeutic hits. Using Healx lab-generated phenotypic and transcriptomics profiling data, novel disease biology, mechanisms and targets are identified, which enables the design of second-generation compounds using virtual screening, predictive modeling and phenomics. Healnet is now incorporating modern advances in generative AI, increasing the quantity and quality of its data sources, creating intelligent AI workflows and enabling natural language reasoning over its biological and chemical predictions. To better design optimized novel compounds for our programs, Healx will develop chemically-aware large language models (LLMs). Moving beyond general text-based large language models like ChatGPT from OpenAI, Healx is exploring how models trained on raw biological data that speak the language of the cell can identify and exploit targets and result in greater understanding of rare disease biology. These technological capabilities empower Healx’s scientists to operate with enhanced expertise, efficiency and accuracy in order to uncover previously undiscoverable treatments. About Healx Healx is a generative AI enabled, clinical-stage, rare disease biotech pioneering the next generation of drug discovery in order to bring novel, effective treatments to rare disease patients around the world. There are 10,000 known rare diseases that affect 400 million people across the globe, but only 5% of those conditions have an approved treatment. By combining generative AI technology with deep drug discovery and development expertise, Healx can accelerate the pace, increase the scale and improve the chance of success of rare disease treatment development in order to deliver global patient impact. Healx exists because every rare disease patient deserves a treatment. Healx was founded in Cambridge, UK, by Tim Guilliams, Ph.D., a biochemical engineer and tech entrepreneur, and David Brown, Ph.D., co-inventor of Viagra and former global head of drug discovery at Roche. Healx has raised approximately $110 million to date. For more information, visit www.healx.ai or follow us on LinkedIn or X .