PALO ALTO, Calif.—In September, Auransa Inc. presented new data on AU-409, the company’s novel lead drug candidate being developed for the treatment of hepatocellular carcinoma (HCC), at the 13th Annual Conference of the International Liver Cancer Association (ILCA) in Chicago.
The study results demonstrated promising antitumor activity for AU-409 in a preclinical orthotopic liver cancer model, as evidenced by statistically significant reductions in tumor burden. The anticancer activity of AU-409 was also demonstrated in culture using cells derived from patients’ tumors. The data were highlighted in an oral presentation at the 2019 ILCA conference by Dr. Andrew Protter, Auransa’s chief scientific officer.
According to Dr. Pek Lum, Auransa’s co-founder and CEO, “AU-409 is Auransa’s lead drug candidate and was generated leveraging the company’s proprietary AI-driven SMarTR Engine. The SMarTR Engine tackles disease heterogeneity and leverages gene expression profiles to predict responder patient populations, as well as compounds that might be effective against those patient populations. AU-409 combines three essential features: antitumor activity in-vitro and in-vivo, good oral bioavailability, and favorable tolerability.”
“To date, Auransa has strategically chosen to limit the amount of detail that it has disclosed publicly on the mechanism of action for AU-409. That said, the company believes that one of the key attributes of AU-409 is its ability to bind to DNA in a sequence specific manner,” Lum continues. “Auransa intends to continue to evaluate this activity as part of its ongoing development program for the compound. Studies conducted to date by Auransa suggest that the pharmacology is novel for an oncology drug.”
“The AU-409 program originated from a broader project in which Auransa leveraged its proprietary SMarTR Engine to evaluate data sets on a broad range of diseases (upwards of 30) in an effort to make clinically-relevant predictions. As part of this process, the SMarTR Engine predicted that AU-409 had promising therapeutic potential for various types of cancer, including HCC. Preclinical studies evaluating the anticancer activity of AU-409, along with assessments of the most pressing needs in cancer treatment, led the company to focus the initial development of AU-409 on hepatocellular carcinoma,” she adds. “However, Auransa continues to evaluate AU-409 in additional cancer types as well.”
As part of their work, researchers sought to evaluate the anticancer activity of AU-409 in cell culture. Data demonstrated that AU-409 reduced the viability of HCC cells from a number of patient-derived xenografts, as well as standard HCC stable cell lines.
Researchers conducted in-vivo studies to measure the antitumor activity of AU-409 in an orthotopic mouse model of HCC (Hep3B2.1-7-Luc cells that exhibit bioluminescence measured as total flux, a marker of tumor burden). Following tumor cell implantation into the liver, mice were treated orally with AU-409 (10 mg/kg or 20 mg/kg) or vehicle for four weeks. At day 28, treatment with AU-409 was associated with a dose-dependent, statistically significant decrease in tumor burden, as compared to vehicle. Tumor burden was reduced by 63 percent compared to vehicle in the AU-409 10 mg/kg treatment arm (p <0.001), and 76 percent compared to vehicle in the AU-409 20 mg/kg treatment arm (p <0.001).
“In our opinion, the most compelling aspect of the preclinical results is the broad anti-tumor activity demonstrated by AU-409 in both cell culture and an in-vivo mouse model,” Protter notes. “This consistent anticancer impact, combined with evidence of favorable tolerability for AU-409 in the orthotopic mouse model, provides us with confidence to advance the program into clinical trials. These preclinical data support the development of AU-409 for HCC, as predicted by Auransa’s proprietary AI-driven discovery and development technology platform. IND-enabling studies of AU-409 are currently ongoing and the company expects to submit its IND application to the FDA in the first half of 2020.”
Treatment with AU-409 in the orthotopic mouse model was well tolerated. There were no clinical observations associated with the treatment. Compared to vehicle, AU-409 treatment was associated with a statistically significant increase in body weight, as well as a decrease in liver enzymes that are indicative of liver toxicity.
“In addition to the excitement that these data provide for the AU-409 program, they also serve as an early, yet important, validation of the SMarTR Engine and the impact that this novel technology can have on significantly improving and accelerating the drug discovery and development process. Our unique approach to interrogating gene expression profiles in order to identify patient subpopulations offers a fundamentally disruptive approach to leveraging AI and machine learning. As such, we believe our platform—built upon the SMarTR Engine—has broad potential to transform drug discovery and development,” Lum concludes.