ATSP-9172 exhibits on-target binding activity in human prostate cancer model

Aileron Therapeutics, Inc. today announced new preclinical data demonstrating that ATSP-9172, its Stapled Peptide inhibitor of HIF-1α-dependent transcription, exhibits on-target binding activity, favorable pharmacokinetic properties and potent in vivo efficacy in a human prostate cancer model. These data will be presented today in a late-breaking poster presentation titled, "ATSP-9172, a novel Stapled Peptide inhibitor of HIF-dependent transcriptional activity with in vivo antitumor efficacy in a preclinical model of prostate cancer," at the American Association for Cancer Research (AACR) Annual Meeting 2013, abstract number LB-304.

“We are pleased to share the first data supporting ATSP-9172 as a potent and specific oncology drug candidate targeting HIF-1α”

Expression of HIF-1α in a broad range of human cancers frequently correlates with poor patient prognosis, and there are currently no drugs that can directly and specifically inhibit HIF-1α-dependent transcription. ATSP-9172 is a Stapled Peptide drug candidate designed to mimic the structure and function of the CITED2 protein, a known negative regulator of HIF-1α. In this study, Aileron researchers showed that ATSP-9172 directly disrupts the HIF-1α /p300 interaction in cancer cells and specifically down-regulates the transcription of HIF-1α target genes without affecting off-target gene expression. The study further demonstrated favorable solubility and pharmacokinetic properties of high systemic exposure, low plasma clearance and long elimination half-life. Finally, dose-dependent inhibition of tumor growth in a human prostate cancer xenograft model was seen following intravenous administration of ATSP-9172 on an every other day schedule.

"We are pleased to share the first data supporting ATSP-9172 as a potent and specific oncology drug candidate targeting HIF-1α," said Joseph A. Yanchik III, president and chief executive officer of Aileron Therapeutics. "HIF-1α is a key driver of tumor growth for many cancers, including prostate, breast, non-small cell lung and colorectal cancers. Despite its appeal as a target, HIF-1α has been undruggable by small molecule and biologic therapeutics, and our results to date with ATSP-9172 show our Stapled Peptide platform is uniquely suited to target this well-understood transcription factor for cancer therapy."

Stapled Peptides are a new class of drugs with a unique set of properties that fully capitalize on 25 years of genetic research to attack drivers of complex diseases, including cancer, endocrine/metabolic disorders and inflammation. The Stapled Peptide platform locks peptides into their biologically active shape and imparts pharmaceutical stability within the body. Stapled Peptide drugs, like ATSP-9172, are derived from natural peptides and are designed to potently and specifically target protein-protein interactions both inside and outside the cell. This new class of drugs represents a fundamental scientific breakthrough as they offer the most advanced way to modulate signaling pathways to treat human disease.