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- NRG 1 Fusions
Claudin18.2 is a protein expressed across several types of solid tumors including many gastrointestinal cancers such as gastric, gastroesophageal junction (GEJ), and pancreatic cancer. EO-3021 is an ADC containing monomethyl auristatin E (MMAE) payload, a potent anti-mitotic agent. MMAE has been clinically validated as an effective anti-tumor payload and is the cytotoxic component of four U.S. Food and Drug Administration-approved ADCs.
Claudins are a family of proteins acting to maintain the tight junction that controls the interchange of molecules between cells. Claudin18.2 is a specific subtype that is expressed only in cancer cells of the gastric epithelia. When the gastric epithelial cells become malignant, the tight junctions become disrupted, exposing the Claudin18.2 epitopes and allowing them to be targeted by therapeutic antibodies and ADCs.
Currently being evaluated in a Phase 1, dose-escalation study in China, EO-3021 has been granted orphan drug designation and cleared to begin clinical trials in the U.S. by the FDA. The company anticipates initiating a Phase 1 clinical trial in 2023.
NRG 1 Fusions
Seribantumab is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3). HER3 is traditionally activated through binding of its primary ligand, neuregulin-1 (NRG1). The NRG1 gene fusion is a rare genomic alteration that combines NRG1 with another partner protein to create chimeric NRG1 “fusion proteins.” The NRG1 fusion protein is often also able to activate the HER3 pathway, leading to unregulated cell growth and proliferation. Importantly, NRG1 gene fusions are predominantly mutually exclusive with other known genomic driver mutations and are considered a unique oncogenic driver event associated with tumor cell survival.
NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, cholangiocarcinomas, and sarcomas. In preclinical experiments, seribantumab prevented the activation of HER3 signaling in cells that harbor an NRG1 gene fusion and destabilized the entire ERBB family signaling pathway including the activation of HER2, EGFR, and HER4. In addition to extensive nonclinical characterization and testing, seribantumab has been administered to more than 800 patients across twelve Phase 1 and 2 studies, both as a monotherapy and in combination with various anti-cancer therapies.
We are currently evaluating the safety and efficacy of seribantumab in patients with solid tumors of any origin that have an NRG1 fusion in the Phase 2 CRESTONE study (Clinical Study of Response to Seribantumab in Tumors with Neuregulin-1 (NRG1) Fusions; NCT04383210).Learn more about Crestone
Compassionate Use Statement
Expanded access, also referred to as compassionate use, is a pathway that allows the use of an investigational drug for treatment use prior to regulatory approval and outside of a clinical trial when no comparable alternative therapy options are available.
Elevation Oncology is committed to developing selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs. To make novel therapies more widely available to patients, Elevation Oncology conducts clinical trials to evaluate the safety and efficacy of investigational therapies to support regulatory approval. Patients are encouraged to speak with their treating physician about their potential treatment options and participation in clinical trials, if appropriate.
Currently, Elevation Oncology does not have an expanded access or compassionate use program for any of our investigational products outside of enrollment in our clinical trials anywhere in the world. We encourage you to stay informed regarding our development programs.