On December 17, 2021 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, reported the United States Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for ERAS-801, an orally available small molecule epidermal growth factor receptor (EGFR) inhibitor specifically designed to have high central nervous system (CNS) penetration for the treatment of recurrent glioblastoma multiforme (rGBM) (Press release, Erasca, DEC 17, 2021, View Source [SID1234639381]). The company has also entered into a collaboration with the Global Coalition for Adaptive Research (GCAR) to determine the feasibility of the evaluation of ERAS-801 as part of the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) trial.

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"We are pleased with the pace at which our ERAS-801 program is advancing. Filing this IND a quarter ahead of schedule and receiving FDA clearance allows us to begin potentially helping patients sooner," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "GBM is a rapid and aggressive malignancy for which patients have limited treatment options and a median overall survival of 17 months after diagnosis. Aberrant EGFR signaling is implicated in approximately 125,000 patients with GBM worldwide annually. ERAS-801’s profile of strong CNS penetrance and broad activity against EGFR amplifications driven by both oncogenic EGFR variants and wildtype EGFR has the potential to address significant unmet need in this patient population. We look forward to initiating our THUNDERBBOLT-1 Phase 1 trial evaluating ERAS-801 in patients with recurrent GBM in the first quarter of 2022."

Dr. Lim continued, "We are honored to enter into an early collaboration with GCAR, a leading nonprofit sponsoring the innovative GBM AGILE trial, which uses a streamlined, patient-centric approach to identify and advance the most effective treatment options for GBM more rapidly. GBM AGILE, an adaptive clinical trial that evaluates multiple drugs against a common comparator, is a seamless, international Phase 2/3 trial that we believe supports a clear registrational path in the United States and other key markets. Our early involvement with GCAR and the GBM Knowledge Network made up of industry leaders further reinforces the therapeutic promise of ERAS-801. We look forward to working together with GCAR and the GBM AGILE team to explore the robust potential of ERAS-801 in patients with GBM who are in much need of better treatment options."

ERAS-801 was designed and developed by a renowned team of cancer researchers—David Nathanson, Ph.D., Michael Jung, Ph.D., and Timothy Cloughesy, M.D. ERAS-801 was licensed from Katmai Pharmaceuticals, Inc.

About GBM AGILE
GBM AGILE is an international, innovative, long-standing platform trial designed to identify and advance effective therapies more rapidly through response adaptive randomization, data connectivity, and a seamless Phase 2/3 design. Conducted under a master protocol, the trial design allows simultaneous evaluation of multiple candidates as monotherapy or in combination against common controls. The operational infrastructure enables a more efficient and expedited approach to testing new therapies for GBM with the intent of lowering the cost, time, and number of patients required to evaluate potentially effective therapies. Data from the GBM AGILE trial has the potential to be used as the foundation for a new drug application (NDA) with the FDA and/or any comparable submission with other health authorities.

About ERAS-801
ERAS-801 is a highly potent, selective, reversible, and orally available small molecule EGFR inhibitor with significantly enhanced CNS penetration. In animal models, ERAS-801 had a 3.7:1 brain-to-plasma ratio and a Kp,uu (partition coefficient that measures unbound drug concentration) that was up to four times higher than approved EGFR inhibitors, indicating a higher concentration of unbound drug in the brain compared to the blood. At clinically relevant exposures, ERAS-801 demonstrated a survival benefit in nine out of 10 (90%) EGFR amplified glioblastoma patient-derived models tested and had statistically significantly higher brain penetrance and prolonged survival compared to approved EGFR tyrosine kinase inhibitors.

About THUNDERBBOLT-1
THUNDERBBOLT-1 will evaluate the safety, tolerability, and preliminary efficacy of ERAS-801 as a monotherapy in patients with recurrent GBM. The dose escalation portion will determine the recommended dose, which will then be used during the dose expansion portion to further evaluate the efficacy and safety of ERAS-801. Future sub-studies of THUNDERBBOLT-1 will potentially explore ERAS-801 in combination with other agents and in broader patient types. Dosing of the first patient in THUNDERBBOLT-1 is anticipated in the first quarter of 2022.