Pasithea Therapeutics to Present New Preclinical Data Showing PAS-004 Strongly Inhibits NRAS Cancer Cell Lines and Demonstrates Superior Activity in Xenograft Studies at 2024 ASCO Annual Meeting
Pasithea Therapeutics announced new preclinical data for PAS-004, revealing its strong inhibition of NRAS mutant cancer cell lines and superior activity in xenograft studies. PAS-004 demonstrated greater efficacy than selumetinib and binimetinib, comparable efficacy to trametinib without plateauing, and achieved over 50% maximal growth inhibition in more cell lines. The data will be presented at the ASCO Annual Meeting on June 1, 2024. PAS-004, a macrocyclic MEK inhibitor, is in clinical trials for neurofibromatosis type 1 (NF1) and other cancers, offering potential advantages in pharmacokinetics, pharmacodynamics, and tolerability.
- PAS-004 shows strong inhibition of NRAS mutant cancer cell lines with IC50 values from 0.024 to 0.306 µM.
- Maximal growth inhibition of >50% was achieved by PAS-004 in more cell lines compared to binimetinib and selumetinib.
- PAS-004 demonstrates comparable efficacy to trametinib without reaching a plateau.
- PAS-004 shows superior activity versus selumetinib and binimetinib in NRAS xenograft tumor models.
- PAS-004 is the first macrocyclic MEK inhibitor to enter human clinical trials, which may offer improved efficacy and compliance due to its extended half-life.
- None.
Insights
Given the emerging data on PAS-004, it's essential to contextualize the implications within the oncology field. MEK inhibitors are a class of medications designed to inhibit mitogen-activated protein kinase enzymes, which play a key role in the proliferation of cancer cells. PAS-004, being a macrocyclic MEK inhibitor, sets itself apart from other acyclic MEK inhibitors like selumetinib, binimetinib and trametinib. The reported data showing superior activity in inhibiting NRAS mutant cancer cell lines compared to its peers is promising.
NRAS mutations are prevalent in a variety of cancers, including melanoma, which often have limited treatment options. The fact that PAS-004 demonstrated superior activity in xenograft models suggests it could offer a more effective treatment option, potentially improving outcomes for patients who have few alternatives.
The unique property of PAS-004 not reaching a plateau in its inhibitory effect could suggest sustained efficacy over longer periods. This is significant in cancer treatment where drug resistance and diminishing efficacy are common challenges. Furthermore, the extended half-life and potential for less frequent dosing could improve patient compliance, a critical factor in long-term cancer therapies.
From a pharmacological perspective, the introduction of PAS-004 as a macrocyclic MEK inhibitor is noteworthy. Macrocycles tend to exhibit stronger binding affinity, better solubility and longer half-life compared to acyclic counterparts, which often translates to higher efficacy and reduced side effects. The IC50 values ranging from 0.024 to 0.306 µM indicate high potency, meaning lower concentrations of the drug are required to achieve effective cancer cell inhibition.
Additionally, the fact that PAS-004 shows superior activity over other MEK inhibitors like selumetinib and binimetinib in xenograft models highlights its potential for enhanced therapeutic outcomes. Xenograft studies, which involve transplanting human tissue into mice, are a critical step in preclinical trials as they provide insights into how the drug will perform in living organisms. While these results are promising, it’s important to remember that preclinical success does not always translate to clinical efficacy in humans.
If PAS-004 can maintain its promising profile in human trials, it could become a significant player in the oncology drug market. The focus on pharmacokinetics (PK) and pharmacodynamics (PD) will be important in the upcoming clinical trials to validate these preclinical findings.
-- 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 >
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 profile hits 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) profiles. 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 profile that 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
FAQ
What is PAS-004?
How does PAS-004 compare to other MEK inhibitors?
When will Pasithea Therapeutics present the new data on PAS-004?
What are the potential advantages of PAS-004?
What is the significance of PAS-004's performance in xenograft studies?
