Insilico announces nomination of preclinical candidate targeting KAT6A for ER+/HER2- breast cancer therapy

Reviewed by Emily Henderson, B.Sc.Dec 27 2022

Insilico Medicine ("Insilico"), a clinical-stage end-to-end artificial intelligence (AI)-driven drug discovery company, today announced that the company's drug discovery team has nominated a preclinical candidate targeting KAT6A for ER+/HER2- breast cancer therapy utilizing its end-to-end Pharma.AI platform. The Company has now nominated eight preclinical candidates in 2022.

According to statistics released by the International Agency for Research on Cancer (IARC), breast cancer has exceeded lung cancer as the most commonly diagnosed cancer and the fifth cause of cancer deaths worldwide in 2020. ER+/HER2- breast cancer is the most common subtype and endocrine therapy in combo with CDK4/6 inhibitors is the standard treatment for this population with advanced or metastatic disease. However, the overall response rate reported is less than 50%, indicating a huge unmet medical need.

KAT6A is emerging as an attractive epigenetic target for ER+/HER2- breast cancer, and we are committed to rapidly progressing the PCC towards the clinical trial to evaluate its efficacy in the clinic."

Feng Ren, Ph.D., Co-CEO and Chief Scientific Officer, Insilico Medicine

KAT6A is a histone (lysine) acetyltransferase (HAT), playing an important role in cell cycle progression, neuron stem cell maintenance and hematopoietic development. In breast cancer, KAT6A is amplified as part of 8p11 amplicon in about 10-15% of the population and modulates the expression level of estrogen receptor (ER). Therefore, targeting oncogene KAT6A is expected to bring promising therapy for ER+/HER2- breast cancer patients.

The preclinical compound is a selective KAT6A inhibitor generated with the assistance of Insilico's AI drug design platform, Chemistry42. It demonstrates strong in vitro inhibitory activity and in vivo efficacy in ER+/HER2- breast cancer models and demonstrated significant efficacy on tumor models derived from patients who relapsed on multiple prior lines of therapy. It also has favorable in vitro ADME properties and in vivo pharmacokinetic profile. Insilico has initiated an Investigational New Drug (IND) enabling study of the compound to advance this internally developed program to the clinical stage.

"The nomination of the preclinical candidate for KAT6A target strengthens our growing oncology pipeline, further validating the strength of our proprietary AI platform," said Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine. "We are very happy to see how the Chemistry42 next-generation AI platform, which we provide to our partners, accelerates our own drug discovery efforts."

Powered by its end-to-end Pharma.AI platform, Insilico has delivered eight preclinical candidates with AI-discovered therapeutics of novel target with novel structure and AI-designed therapeutics of known targets with desired properties in the past 12 months, covering multiple disease areas, including immuno-oncology, inflammation, and COVID-19. It also entered Phase I clinical trials with its first internally developed program for fibrosis in New Zealand and China.