Aro Biotherapeutics Debuts Lead Centyrin Candidate at 2019 OTS Meeting
Preclinical in vitro data demonstrate ABX300’s anti-tumor activity vs various KRAS mutant epithelial tumors, which have been difficult to treat to date.
Aro Biotherapeutics Company announces that co-founder and Chief Scientific Officer Karyn O’Neil, PhD, debuted ABX300, the company’s lead Centyrin™-pan-KRAS siRNA program, during a presentation today at the 2019 Oligonucleotide Therapeutic Society (OTS) meeting in Munich, Germany.
In her presentation entitled, “Cell Specific Centyrin Targeting of Oligonucleotides for Cancer,” Dr. O’Neil highlighted preclinical data demonstrating ABX300’s efficacy in treating KRAS-driven epithelial tumors. ABX300 comprises the Company’s proprietary Centyrin protein scaffold technology, conjugated to a pan-KRAS small-interfering RNA (siRNA).
KRAS has been one of the most elusive and difficult to drug targets in cancer. Various point mutations can occur in the KRAS oncogene, resulting in persistent KRAS activation, which drives tumor growth. Recent reports on preclinical and clinical results with small molecule KRAS G12C mutant inhibitors have shown promise; however, this mutant represents only about 12 percent of all KRAS mutations. In contrast, ABX300 is designed to address all known KRAS mutations identified in human tumors.
“Tumor cells treated with ABX300 internalized the Centyrin-siRNA conjugate and exhibited potent, sustained knockdown of mutant KRAS RNA and protein that persisted for days, resulting in complete inhibition of proliferation,” said Dr. O’Neil. “This long-term intracellular activity reflects the unique stability and biochemical properties of Centyrins inside the cellular microenvironment.”
ABX300 contains two Centyrin-based binding domains that allow for selective targeting of the KRAS siRNA to epithelial-derived tumor cells. ABX300 was shown in preclinical studies to selectively reduce KRAS mRNA levels in cell lines with KRAS G12C, G12D, G12S and G12V mutations, providing proof of concept for broad KRAS inhibition with a single therapeutic.
Sue Dillon, PhD, co-founder and Chief Executive Officer of Aro, commented, “Dr. O’Neil’s presentation at the OTS Meeting is an important milestone for Aro Biotherapeutics. As demonstrated by ABX300 in our research to date, Centyrin-siRNA targeting is a powerful approach to addressing disease target genes in specific cell types, broadly expanding opportunities for RNA medicines.”
Building a Pipeline of Life Changing Therapies
Centyrins are small, structurally simple, ultra-stable, highly soluble proteins. These characteristics enable the discovery of medicines with new mechanisms of action for cancer and other devastating diseases. This first-of-its-kind combination of properties is designed to address unmet medical needs by targeting drug payloads in high concentration to the site of disease, while lowering the toxicity to non-target organs. The company holds an exclusive worldwide license for research, development, manufacturing and commercialization of Centyrin protein therapeutics.
