Synthetic lethal drugs vs. cancer

CHENGDU, China—Anticancer Bioscience (ACB), a company focused on synthetic lethal approaches to precision oncology, has closed a successful funding round, raising $10 million from a small syndicate of undisclosed, experienced Chinese angel investors. The total equity raised is $21 million.

ACB will use the financing to advance its synthetic lethal platform and preclinical oncology pipeline. It intends to expand proprietary small-molecule and natural product screening libraries and to progress at least two synthetic lethal programs toward IND-enabling studies. The company has already reported positive animal data in its proprietary small-molecule program targeting MYC overexpression. Since its founding in 2016, ACB has grown to almost 50 employees in Chengdu, China; Hyderabad, India; San Francisco; and St. Andrews, UK.

Commercializing discoveries coming from China’s J. Michael Bishop Institute of Cancer Research, ACB uses its screening libraries and discovery platforms in cancer biology to uncover novel mechanisms to induce cancer cell death, without harming healthy cells. Synthetic lethality works when the same genetic changes that allow for carcinogenesis also render the cancer cell overly dependent on specific pathways and proteins. According to ACB, attacking these dependencies with drugs produces “dramatic anticancer effects,” while leaving normal cells healthy. Synthetic lethality enables the targeting of drivers of carcinogenesis that are do not currently lend themselves to drug development.

ACB’s five distinct synthetic lethality programs in drug development are oncogene-enabled synthetic lethality (focused on MYC inhibition), tumor suppressor synthetic lethality, polyploid cell synthetic lethality, centrosome amplification/delustering therapy, and restoration of contact inhibition. The company has invested in proprietary small-molecule and natural product libraries that include novel scaffolds of drug-like molecules and natural medicinal botanicals, with more than 20,000 botanical samples already collected and curated. ACB’s small-molecule libraries are based on novel scaffolds. 

Further diversity can be assembled on the scaffolds. ACB’s general-utility new scaffold-drug fragment (GUNS-DF) libraries are expanding and evolving through iterative screening/optimization processes for multiple phenotypic screening projects. The company’s lead MYC inhibition program uses a novel chemical series in which low nM activity has been identified in model cell lines. Functional activity of ACB’s lead ‘HJ’ compound series has been demonstrated in vitro, mimicking inhibition of Aurora B kinase. Inhibition of Aurora B kinase is known to trigger synthetic lethality in cells that overexpress MYC. The synthetic lethal phenotype involves the induction of cell cycle arrest early in mitosis, followed by accumulation of polyploid cells. ACB is studying a second MYC inhibitory compound series.

According to Dr. Dun Yang, founder, president, and CEO of ACB, “With the additional financing, we are well placed to accelerate our synthetic lethal approach and to maximize the value of our libraries and pipeline. Already a provisional filing covering the novel library of HJ compounds has been completed, and this is the first GUNS-DF library for which ACB has filed for PCT patent protection, testifying to the utility of our library technology platform. We expect to follow this with additional composition of matter filings as we progress our MYC and other discovery programs.”

“We have access to world-leading cancer biology expertise and drug discovery platforms that enable us to identify novel compounds that can target both genetic and epigenetic vulnerabilities of cancer cells,” he added. “Our pipeline is focused on cancers with MYC overexpression, which occurs in over half of tumors, and is correlated with poorly differentiated, and aggressive cancer. In addition to a chemical compound library, we have invested in developing one of the world’s largest natural product libraries, providing a rich screening resource for potential cancer therapeutics.

“ACB’s goal is to generate first-in-class oncology drugs for a broad range of indications (targeting over 30 percent of cancer patients), with a focus on therapies disabling previously untargeted mitotic regulators. Overexpression of MYC engenders vulnerability in mitosis and many other cellular processes. It is the most commonly deregulated oncoprotein, making targeting it through synthetic lethality an attractive strategy for cancer therapy.” 

An article in the Journal of Cellular Immunology further explained, “Targeting MYC overexpressing tumors with synthetic lethal agents is a promising alternative to targeting MYC directly. Our goal is to advance novel drug candidates identified via this synthetic approach to the clinic. Through screening for modifiers of MYC-VX680 synthetic lethal interaction on our unique platforms, we can identify new targets to treat MYC tumors, leading to first-in-class drugs.”