Erasca and MD Anderson Announce Strategic Research and Development Collaboration in RAS/MAPK-Driven Cancers

On August 23, 2022 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, and The University of Texas MD Anderson Cancer Center (MD Anderson), reported a strategic research and development collaboration to evaluate multiple agents from Erasca’s pipeline targeting the RAS/MAPK pathway as either single-agent or combination therapies (Press release, Erasca, AUG 23, 2022, View Source [SID1234639376]).

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The initial focus of the alliance will be Erasca’s potentially best-in-class ERK1/2 inhibitor ERAS-007 and its potentially best-in-class SHP2 inhibitor ERAS-601, which together comprise Erasca’s first MAPKlamp combination. ERAS-007 is being investigated in multiple ongoing trials, including in non-small cell lung cancer (NSCLC) as part of the HERKULES-2 master protocol and in gastrointestinal (GI) malignancies as part of the HERKULES-3 master protocol. ERAS-601 is being investigated in multiple ongoing trials, including the FLAGSHP-1 trial in triple wildtype (KRAS/NRAS/BRAF wildtype) colorectal cancer (CRC) and human papillomavirus (HPV)-negative advanced head and neck squamous cell carcinoma (HNSCC) and the HERKULES-2 NSCLC master protocol.

"Our strategic collaboration with MD Anderson broadens the evaluation of ERAS-007 and ERAS-601 and explores additional therapeutic opportunities across our pipeline," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "The RAS/MAPK pathway is one of cancer’s most frequently altered pathways, affecting more than 5 million new patients with cancer annually worldwide. We have designed our pipeline to comprehensively shut down this highly oncogenic pathway at multiple critical nodes, and we’re excited to work with MD Anderson to potentially address major unmet needs in the treatment of cancer."

The alliance will build on Erasca’s existing collaborations with MD Anderson investigators Scott Kopetz, M.D., Ph.D., professor of Gastrointestinal Medical Oncology, and David S. Hong, M.D., professor of Investigational Cancer Therapeutics. Kopetz is an investigator in HERKULES-3, which is evaluating ERAS-007 plus encorafenib and cetuximab in BRAF V600E-mutant metastatic CRC and ERAS-007 plus palbociclib in KRAS-mutant/NRAS-mutant CRC and KRAS-mutant pancreatic cancer. Hong is an investigator in FLAGSHP-1, which is evaluating ERAS-601 as monotherapy and in combination with cetuximab in triple wildtype CRC and HPV-negative advanced HNSCC.

"Durability and treatment resistance continue to present challenges in the treatment of lung cancers and GI malignancies, particularly stemming from reactivation of the RAS/MAPK pathway. Erasca’s pipeline of agents that target key nodes, including previously undruggable genetic drivers, has the potential to improve durability and minimize resistance," Kopetz said. "We look forward to collaborating with Erasca to further maximize the potential of promising treatment combinations across its pipeline."

The new strategic collaboration will enhance Erasca’s and MD Anderson’s evaluation of ERAS-007 and ERAS-601 in combination with investigational and standard-of-care agents, including with Erasca’s proprietary pipeline programs, such as the KRAS G12D inhibitor ERAS-4. Under the terms of the five-year agreement, collaborative preclinical and clinical studies will be conducted in NSCLC, GI malignancies and additional mutually agreed-upon indications.

About ERAS-007
ERAS-007 is a potential best-in-class oral ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. The broad therapeutic potential of ERAS-007 is being investigated initially across a series of HERKULES clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp combination) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with NSCLC. HERKULES-3 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with GI cancers.

About ERAS-601
ERAS-601 is a potential best-in-class oral, selective SHP2 inhibitor being investigated alone or in combination. SHP2 acts as a convergent node for receptor tyrosine kinase (RTK) signaling, relaying growth and survival signals from RTKs to intracellular signaling pathways. ERAS-601 is being investigated across a series of clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents. FLAGSHP-1 is a Phase 1/1b dose escalation trial evaluating ERAS-601 as a monotherapy in advanced solid tumors and in combination in triple wildtype CRC and HPV-negative advanced HNSCC. HERKULES-2 is a Phase 1b/2 master protocol clinical trial that includes evaluation of ERAS-601 in combination with various agents in patients with NSCLC.