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news.Ensem Therapeutics has received clearance from the US Food and Drug Administration (FDA) for its investigational new drug (IND) application for ETX-636.
The company utilises its Kinetic Ensemble platform to develop precision medicines for oncology. Credit: National Cancer Institute on Unsplash.
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This allosteric pan-mutant-selective phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitor and degrader is poised to enter first-in-human trials in the second quarter of this year.
According to the company, mutant PI3Kα is considered a prevalent oncogenic driver in various cancers, notably in up to 40% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancers.
Ensem co-founder and CEO Dr Shengfang Jin said that ETX-636 is the company’s second new compound to enter clinical development, following ETX-197, an oral selective cyclin-dependent kinase 2 (CDK2) inhibitor, now in Phase I trials as BG-68501 for advanced or metastatic solid tumours with CDK2 dependency. ETX-197 was licenced to BeOne.
Dr Jin said: “Targeting mutant PI3Kα within tumours while sparing wildtype PI3Kα in normal tissues represents a significant clinical challenge, which ETX-636 overcomes.
“The IND clearance is an important milestone for the company, and we are laser-focused on driving ETX-636 through clinical development.”
The Phase I/II trial will assess ETX-636’s tolerability, pharmacokinetics, safety, preliminary antitumor activity and pharmacodynamics in subjects with advanced solid tumours harbouring a mutation of PI3Kα.
It will explore ETX-636 as a monotherapy and in conjunction with fulvestrant, a therapy for advanced HR+/HER2- breast cancer.
ETX-636’s dual mechanism not only inhibits mutant PI3Kα catalytic activity but also triggers the degradation of the mutant protein, sparing the wildtype.
This mechanism of action is said to lead to durable inhibition of the pathway, inducing concordant tumour regression in helical and kinase domain PI3Kα-mutant breast cancer xenograft models as a single agent and with fulvestrant.
The company utilises its Kinetic Ensemble platform to develop precision medicines for oncology.
