Stapled Peptide oncology drug candidate exhibits robust efficacy in xenograft cancer models
Published on November 8, 2012 at 5:08 AM
Aileron Therapeutics, Inc. and its collaborator Roche today announced new results of a preclinical study of its Stapled Peptide oncology drug candidate ATSP-7041, which exhibited robust efficacy in MDM2 and MDMX xenograft cancer models. The study represents an important step towards establishing ATSP-7041 as the first highly potent and specific dual inhibitor of MDM2 and MDMX for p53-dependent cancers. ATSP-7041 was developed as part of Aileron's collaboration with Roche to discover, develop and commercialize Staple Peptide drugs. The data were presented today at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (abstract number 226).
“We are particularly excited to see the emergence of this important program as we prepare to enter the clinic with our first Stapled Peptide drug for endocrine disorders early next year.”
Stapled Peptides are a new class of drugs, one of the first in 20 years, with the potential to attack complex diseases, including cancer, endocrine/metabolic disorders and inflammation. ATSP-7041 is a novel, selective Stapled Peptide dual inhibitor of MDM2 and MDMX, crucial regulators for the p53 pathway. The well-studied p53 pathway has long been pursued by the pharmaceutical industry as it represents a first line of defense and one of the most important tumor suppressor proteins in virtually all cancer types. Inhibition of MDM2 and MDMX leads to reactivation of the p53 pathway, thereby driving tumor cells to apoptotic death.
"Our p53 program with Roche is providing an excellent example of our ability to develop novel and valuable therapeutics as well as important insights into Stapled Peptides more broadly," said Joseph A. Yanchik III, president and chief executive officer of Aileron Therapeutics. "We are particularly excited to see the emergence of this important program as we prepare to enter the clinic with our first Stapled Peptide drug for endocrine disorders early next year."
In this study, researchers measured the affinity binding of ATSP-7041 to both MDM2 and MDMX, as well as its ability to induce p53-dependent cell death. ATSP-7041 reactivated the p53-dependent pathway, induced p53-dependent apoptosis and inhibited cell proliferation in multiple cancer cell lines, both in vitro and in vivo. The study further showed that the pharmacokinetic and tissue distribution properties of ATSP-7041 are consistent with sustained anti-tumor activity on intermittent dosing. It possessed efficient cell penetration, specific high affinity binding to both MDM2 and MDMX and excellent stability, all important drug properties that have propelled the program towards IND-enabling studies.