A synthetic lethality player emerges in China, armed with lessons on undruggable oncogene from Nobel laureate's lab
As a longtime postdoc in the UCSF lab of Michael Bishop — the Nobel laureate known, among other things, for cloning the oncogene MYC — Dun Yang knew the cancer target like an archer knows the bullseye.
“I always talk about if we needed to nominate the most important oncogene […] that should be MYC,” he told Endpoints News. “The second one would be RAS. Because more than 50% of human cancer overexpress MYC oncogene.”
All those years of research also gave him intimate knowledge about the pitfalls of trying to develop cancer therapies around the MYC protein. The consensus had been that MYC, a transcription factor, is undruggable; even if you somehow manage to hit it, the potential benefit would likely be offset by the potential side effects that come with blocking its essential physiological functions.
So in 2010 — just as PARP inhibitors were gaining traction — he and several other scientists in the lab proposed something new.
“A lot of people have of course heard of (Bishop),” said Thaddeus Allen, whose tenure as a research scientist at UCSF overlapped with Yang’s. “But I think what people don’t realize is the last 10 to 15 years of research that went on in Mike Bishop’s lab was really focused on synthetic lethality and really Dun Yang was at the center of that research that was going on.”
Instead of targeting MYC directly, they tried going after a kinase that tumors overexpressing MYC tend to rely on, and showed in mice that the compound they tested could kill cancer cells while sparing normal ones.
Yang would eventually leave San Francisco to return to his hometown of Chengdu, China, to start a cancer research institute eponymous with Bishop and see if he can go bigger with that idea.
Now, more than a decade after publishing that paper, he’s secured a total of $21 million from private Chinese investors to build a company that doesn’t just stand shoulder to shoulder with US synthetic lethality players like Repare, Artios, Cyteir and Ideaya, but someday grow up to be the Genentech of China.
Anticancer Bioscience is the development and commercialization arm of the J. Michael Bishop Institute of Cancer Research, Yang said, and the 50 employees technically work for both entities. The team is spread across China, the US, the UK and India — where the CEO recruited his medicinal chemists.
With two drugs, one of them in MYC, poised to complete IND-enabling studies this year and enter the clinic in 2022, the biotech is busy juggling a total of five preclinical pipeline programs, which they say span the areas of tumor suppressor synthetic lethality, polyploid cell synthetic lethality, centrosome amplification/declustering therapy and restoration of contact inhibition.
Building novel screenings — led by VP Jing Zhang in the UK — that zero in on the right vulnerabilities that can be targeted are core to Anticancer’s expertise, said Allen, the company’s VP of translational biology. In addition to screening on synthetic libraries, Anticancer is also keen on finding compounds from nature libraries — collections of plant samples from a province that Yang said accounts for 60% of the plant diversity in the country.
“What’s new about our platform is we collected from novel places,” added Allen, who’s also one of only two staffers based in California. “The company is in Chengdu for a reason.”
“We have an unmatched natural products library,” Yang wrote, “composed of over 17,500 crude extracts, over 1,200 partially purified fractions and around 2,500 pure natural compounds. These samples are made from over 2,600 plants, representing more than 1,500 plant species used in traditional Chinese medicine.”