ERAS-801's CNS penetration: four times higher than approved EGFR inhibitors
Comprehensive inhibition against oncogenic EGFR vIII and wildtype alterations
Improved outcomes in over 90% of EGFR-driven patient-derived glioblastoma models
IND submission in refractory glioblastoma planned for Q1 2022
SAN DIEGO, Oct. 25, 2021 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced the presentation of preclinical data for ERAS-801, a small molecule epidermal growth factor receptor (EGFR) inhibitor specifically designed to have high central nervous system (CNS) penetration for the treatment of glioblastoma multiforme (GBM), at the American Association for Cancer Research (AACR) Special Virtual Conference on Brain Cancer.
“While mutations in EGFR are common oncogenic drivers in glioblastoma, approved EGFR inhibitors lack both sufficient CNS penetration for primary brain tumors and clinical activity against oncogenic EGFR alterations that are prevalent in GBM,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “ERAS-801 is an EGFR inhibitor with four times the CNS penetrance of approved EGFR inhibitors, resulting in robust CNS enrichment while limiting systemic exposure. In more than 30 GBM patient-derived preclinical models, ERAS-801 demonstrated potent activity across mutant and wildtype oncogenic EGFR alterations, and we are highly encouraged by the extensive therapeutic potential of ERAS-801 for patients with this aggressive malignancy.”
David A. Nathanson, Ph.D., Associate Professor of Molecular and Medical Pharmacology at the University of California, Los Angeles (UCLA), added, “About 60% of glioblastomas are driven by oncogenic alterations in EGFR that include amplifications and mutations such as the highly prevalent vIII deletion. Wildtype EGFR has a pathogenic role in glioblastoma and can drive disease following amplification or through heterodimerization with mutant EGFR. Effective disease control of glioblastoma ultimately requires comprehensive inhibition of both mutated and wildtype forms of EGFR, which approved EGFR inhibitors do not currently achieve. Our work demonstrates that ERAS-801 can improve outcomes in over 90% of diverse EGFR-driven patient-derived tumor models, highlighting a comprehensive inhibitory profile that has robust potential to effectively treat patients with CNS cancers with poor prognosis.”
ERAS-801 is a highly potent, selective, and reversible small molecule EGFR inhibitor with significantly enhanced CNS penetration. ERAS-801 has a 3.7:1 brain-to-plasma ratio and a Kp,uu (partition coefficient that measures unbound drug concentration) that is up to four times higher than approved EGFR inhibitors, indicating a higher concentration of unbound drug in the brain compared to the blood. Utilizing fluorodeoxyglucose-positron emission tomography (FDG-PET), a pharmacodynamic marker of metabolically active tumors, the Nathanson lab evaluated inhibition of tumor metabolism in over 30 patient-derived preclinical glioblastoma models following treatment with different FDA-approved EGFR inhibitors. At clinically relevant exposures, ERAS-801 demonstrated a survival benefit in over 90% of EGFR mutant and/or amplified glioblastoma patient-derived models tested to date and had statistically significantly higher brain penetrance and prolonged survival compared to approved EGFR tyrosine kinase inhibitors. ERAS-801 was designed and developed by a renowned team of UCLA cancer researchers—David Nathanson, Ph.D., Michael Jung, Ph.D., and Timothy Cloughesy, M.D. Erasca plans to submit an IND filing for development in refractory GBM in the first quarter of 2022.
At Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled what we believe to be the deepest RAS/MAPK pathway-focused pipeline in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer.
Cautionary Note Regarding Forward-Looking Statements
Erasca cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: our expectations regarding the potential therapeutic benefits of our product candidates and the potential patient populations for our product candidates, including ERAS-801; and the planned advancement of our development pipeline, including the development plan and planned IND filing date for ERAS-801. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our approach to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; delays in our preclinical and clinical development programs; our dependence on third parties to conduct manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization, or may result in recalls or product liability claims; unfavorable results from preclinical studies or clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates and maintain our rights under intellectual property licenses; our ability to fund our operating plans with our current cash, cash equivalents, and investments; our ability to maintain undisrupted business operations due to the COVID-19 pandemic; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our most recent quarterly report on Form 10-Q and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
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