ETS-001 / Etern Biopharma - LARVOL DELTA

TEAD upregulation promotes osimertinib resistance in NSCLC by recruiting YAP into the nucleus. (PubMed, Biochem Pharmacol) - "Additionally, since SHP2 is a critical signaling node in the EGFR pathway, the combination of SHP2 inhibitor ET0038 and ET825 exhibited significant synergistic anti-tumor effects in osimertinib-resistant NSCLC models in vitro and in vivo. This study elucidates a previously uncharacterized osimertinib-induced resistance mechanism mediated by TEAD upregulation and YAP-TEAD activation, and provides a translationally promising therapeutic strategy to overcome osimertinib resistance."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

SHP2 Inhibitors Undergo Exploration in Combinations (Targeted Oncology) - "Melissa Johnson, MD, discussed SHP2 inhibitors with Targeted Therapies in Oncology....Overall, the safety profiles of the SHP2 inhibitors undergoing development are comparable, according to Johnson. 'In my opinion, [the SHP2 inhibitors] have very similar mechanisms of action, with similar [adverse] effect profiles that include peripheral and pulmonary edema, decreases in ejection fraction, and some cytopenias,' Johnson said."

Media quote

FIRST: SHP2 Inhibitor ET0038 Monotherapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Etern BioPharma (Shanghai) Co., Ltd

Monotherapy • New P1 trial • Oncology • Solid Tumor

SHP2 Inhibitor ET0038 Monotherapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=37 | Recruiting | Sponsor: Etern BioPharma (Shanghai) Co., Ltd

Monotherapy • New P1 trial • Oncology • Solid Tumor

Synergistic effects of the combination of Kras (G12C) with SHP2, ERK 1/2, mTORC1/2 or XPO1 inhibition for the treatment of Kras (G12C) mutated cancer (AACR 2022) - "This study tested the antitumor effects induced by the combination of ATG-012, a KRAS G12C inhibitor, with SHP2 inhibitor (ET0038), ERK 1/2 kinase inhibitor (ATG-017), mTORC1/2 kinase inhibitor (ATG-008) or XPO1 inhibitor (selinexor), in preclinical tumor models. The in vivo combinations of the drugs were tested in NCI-H358 (non-small cell lung cancer) and Mia-Paca-2 (pancreatic cancer) CDX mouse model. Strong in vivo synergism has been observed for the combination of a Kras (G12C) inhibitor (ATG-012) with a SHP2 inhibitor, ERK 1/2 inhibitor, mTORC1/2 inhibitor or XPO1 inhibitor, suggesting promising clinical therapeutic strategies for cancer patients carrying the KRAS G12C mutation."

IO biomarker • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

ETERN Therapeutics Announces Completion of Series B Financing to Advance the Protein Liquid-Liquid Phase Separation Technology Platform and Accelerate the Development of Novel Drugs to Target “Undruggable” Proteins (PRNewswire) - “ETERN Therapeutics…announced the completion of a Series B financing round…Proceeds from this financing are anticipated to be used to enhance the Protein Liquid-Liquid Phase Separation (LLPS) technology platform and advance multiple pipelines through discovery and clinical development…IND application for another key product will be submitted in the second half of the year.”

Financing • IND • Oncology

[VIRTUAL] Discovery of ETS-001, a highly potent allosteric SHP2 inhibitor to treat RTK/RAS-driven cancers (AACR 2021) - "Here we show that ETS-001 exhibited strong synergistic effect with EGFR-TKI (osimertinib), KRASG12Ci (AMG510) or CDK4/6i (ribociclib) in appropriate cancer models in vitro and in vivo. In addition, combinational benefit of ETS-001 and ribociclib was observed in esophageal cancer models, which exhibited high frequency of concurrent oncogenic alterations in RTKs and cell cycle pathway. Taken together, our findings provide preclinical evidence that ETS-001 as a potent SHP2 inhibitor, alone or in combination with other targeted-therapy agents, can effectively inhibit MAPK activation and treat cancers with diverse oncogenic mutations in the RAS/MAPK pathway."

Esophageal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CDK4 • EGFR • KRAS • PTPN11 • PTPRT