Erasca Presents Compelling Preclinical Data Supporting Clinical Development of Potentially Best-In-Class Programs ERAS-007, ERAS-601, and ERAS-3490 at 2022 AACR Annual Meeting


April 12, 2022

ERAS-007 is a potent and selective small molecule ERK1/2 inhibitor with long target residence time, which promotes sustained RAS/MAPK pathway inhibition

ERAS-601 is a potent and selective small molecule SHP2 inhibitor with broad anti-tumor activity that blocks oncogenic signal transduction to multiple pathways to delay the onset of therapeutic resistance

ERAS-3490 is a CNS-penetrant KRAS G12C inhibitor with robust systemic and CNS activity in development for the treatment of KRAS G12C mutant lung adenocarcinoma

SAN DIEGO, April 12, 2022 (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 preclinical data from six poster presentations at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, Louisiana. The posters are available online at Erasca.com/science/#presentations.

“To shut down the highly oncogenic RAS/MAPK pathway, we are targeting multiple nodes and cooperative mechanisms using a data-driven clinical development effort that identifies single agent and combinations with potential to significantly prolong survival in patient populations with high unmet needs,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “This year, we were pleased to present six posters at the AACR annual meeting highlighting preclinical data supporting the clinical development of three of our best-in-class programs, including our ERK1/2 inhibitor ERAS-007, our SHP2 inhibitor ERAS-601, and one of our CNS-penetrant KRAS G12C inhibitors ERAS-3490, as well as our choice of combination partners for these product candidates.”

Poster Presentation Highlights
Abstract 2672: ERAS-007 is a selective ERK1/2 inhibitor with preclinical activity across RAS/MAPK pathway-driven CRC models
ERAS-007 demonstrates promising preclinical activity across a wide range of RAS/MAPK pathway-driven CRC models as a monotherapy and in combination. Over 50% of patients with colorectal cancer (CRC) have activating mutations in the RAS/MAPK signaling pathway, with available targeted therapies demonstrating limited overall response rates and duration of response.

Abstract 2671: ERAS-601, a potent allosteric inhibitor of SHP2, demonstrates compelling single agent anti-tumor activity in RAS/MAPK-driven tumor models
ERAS-601 blocks growth signals from multiple receptor tyrosine kinases (RTKs) to help prevent cancer growth. SHP2 acts as a convergent node for RTK signaling, relaying growth and survival signals from RTKs to intracellular signaling pathways. ERAS-601 inhibits SHP2, blocking oncogenic signal transduction through SHP2, which helps delay development of therapeutic resistance.

Abstract 2670: ERAS-601, a potent allosteric inhibitor of SHP2, synergistically enhances the efficacy of sotorasib/adagrasib and cetuximab in NSCLC, CRC, and HNSCC tumor models
ERAS-601 can serve as a backbone of combination therapy to enhance efficacy of other targeted therapies. Treatment durability with KRAS G12C inhibitors in non-small cell lung cancer (NSCLC) and with EGFR antibodies in CRC is limited due to RAS and RTK reactivation. ERAS-601 + sotorasib/adagrasib and ERAS-601 + cetuximab were evaluated for enhanced efficacy or prevention of resistance in advanced solid tumor models.

Abstract 3345: ERAS-601, a potent allosteric inhibitor of SHP2, synergistically enhances the activity of a FLT3 inhibitor, gilteritinib, in FLT3-mutated AML tumor models
ERAS-601 works synergistically with gilteritinib to inhibit RAS/MAPK signaling and cell viability of FLT3-mutated acute myeloid leukemia (AML), achieving more durable tumor inhibition than either agent alone. AML is dependent on RAS/MAPK pathway signaling, with prevalent mutations across multiple nodes of this pathway. Gilteritinib, a FLT3 inhibitor, has demonstrated clinical activity, but resistance limits the benefit of gilteritinib monotherapy. ERAS-601 + gilteritinib was evaluated non-clinically in FLT3-mutated AML models to assess potential for improvement with co-suppression of the RAS/MAPK pathway.

Abstract 2669: ERAS-007 (ERK1/2 inhibitor) + ERAS-601 (SHP2 inhibitor) exhibit nonclinical combination activity across KRAS mutated NSCLC, CRC, and PDAC tumor models
Erasca’s first MAPKlamp, ERAS-007 + ERAS-601, demonstrates combination activity in KRAS mutant tumor models by inhibiting both an upstream node of the RAS/MAPK pathway, SHP2, and the most distal node, ERK1/2. KRAS mutations occur in approximately 25% of all cancers and promote oncogenesis via constitutive activation of the RAS/MAPK pathway. Rapid emergence of resistance, often mediated by reactivation of RAS/MAPK signaling, limits monotherapy activity. Erasca’s first MAPKlamp (ERAS-007 + ERAS-601) was evaluated for the potential to prevent RAS/MAPK pathway reactivation more robustly than inhibition of a single node alone.

Abstract 2675: Discovery of potent CNS-penetrant covalent KRAS G12C inhibitors
Erasca has discovered multiple central nervous system (CNS)-penetrant KRAS G12C inhibitors (ERAS G12Ci’s) with robust systemic and CNS activity, highlighting these inhibitors’ potential to address systemic cancers with CNS involvement. The KRAS G12C mutation occurs in 14% of lung adenocarcinoma tumors, with brain metastases in up to 40% of patients. ERAS-3490, an ERAS G12Ci, is designed to address the high prevalence of CNS metastases in KRAS G12C mutant lung cancer.

About Erasca
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, including ERAS-007, ERAS-601, and ERAS-3490; the planned advancement of our development pipeline, including the anticipated timing of data readouts for our clinical trials, the expected timing of the IND filing for ERAS-3490, and other upcoming development milestones. 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; potential delays in the commencement, enrollment, and completion of clinical trials and preclinical studies; our dependence on third parties in connection with 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; the inability to realize any benefits from our current licenses and acquisitions and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; 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, including delaying or disrupting our clinical trials, manufacturing, and supply chain; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K for the year ending December 31, 2021, 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.

Contact:
Joyce Allaire
LifeSci Advisors, LLC
jallaire@lifesciadvisors.com

Source: Erasca, Inc.


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Source: Erasca, Inc.



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