Gedatolisib
Gedatolisib offers a new approach to inhibiting the PAM (PI3K/AKT/mTOR) pathway.
To address the challenges of targeting the PAM pathway, we are developing a potential first-in-class multi-target PAM inhibitor that:
- Targets all Class I PI3K isoforms and mTORC1 and mTORC2;
- Was designed to achieve pathway inhibition while being evaluated for its safety and efficacy in clinical studies.
Gedatolisib is a pan-class I isoform PI3K and mTOR inhibitor with low nanomolar potency for the p110α, p110β, p110γ, and p110δ PI3K isoforms, as well as mTORC1 and mTORC2, that induces comprehensive blockade of the PAM pathway. Its mechanism of action and pharmacokinetic properties are highly differentiated from other currently approved and investigational therapies that target PI3Kα, AKT, or mTORC1 alone. We believe this will enable gedatolisib to treat a broader patient population than these single-target inhibitors.
Gedatolisib targets all four Class I PI3K isoforms, α, β, δ and γ, and both mTOR complexes, mTORC1 and mTORC2.
Ex vivo studies found that gedatolisib inhibited higher levels of PI3K/AKT/mTOR involved signaling activity than approved single target PI3K, AKT, or mTOR therapies, regardless of PIK3CA mutational status. Synergistic activity with selected targeted therapies has been observed in nonclinical studies.
Our current clinical development program is focused on treatment of patients with HR+/HER2- advanced breast cancer and metastatic castration resistance prostate cancer. VIKTORIA-2 is an ongoing Phase 3 clinical trial incorporating two independent studies, Study 1 and Study 2, in two separate cohorts of patients with ABC who are treatment-naive in the advanced setting.
Study 1 is evaluating gedatolisib plus palbociclib plus fulvestrant as first-line treatment for patients with endocrine-resistant HR+/HER2- ABC. Study 2 is evaluating gedatolisib plus palbociclib plus letrozole as first-line treatment for patients with endocrine- sensitive HR+/HER2- ABC. A Phase 1/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration-resistant prostate cancer, is ongoing.
