AZD9574

Armed with medical chemistry expertise, the biotech has worked to create better molecules against validated targets. A group of familiar faces to Incyte watchers has broken off to start their own biotech, pulling in $102 million to develop competitors to approved cancer drugs from AstraZeneca, GSK, Novartis and Pfizer. The biotech, Synnovation Therapeutics, was founded by Wenqing Yao, Ph.D., and Liangxing Wu, Ph.D. Yao spent 19 years at Incyte, rising to the post of head of discovery chemistry, before leaving and setting up Synnovation in 2021. Wu worked alongside Yao at Incyte, where he spent almost a decade to end up with the title executive director, medicinal chemistry. Armed with medical chemistry expertise that contributed to Incyte products such as Olumiant, Pemazyre and Tabrecta, the pair have worked to create better molecules against validated targets, namely PARP and PI3K. It is now almost 10 years since the first drugs against the targets were approved, with AstraZeneca and Merck & Co.’s PARP inhibitor Lynparza and Gilead’s PI3K inhibitor Zydelig both winning authorizations in 2014. Other companies have since secured approval for competitors to those first-in-class products but work to address the limitations of Lynparza and Zydelig is yet to yield a flawless therapy. Synnovation, which officially launched today, has identified hematologic toxicity as a weakness of first-generation PARP inhibitors. Like other companies, the biotech has fingered inhibition of PARP2 as the cause of the toxicity and bet that it can expand the therapeutic index by selectively targeting PARP1.  That isn’t a new idea. AstraZeneca has taken one selective PARP1 inhibitor, AZD5305, into phase 3 and moved its brain-penetrating sibling AZD9574 into the clinic. Gilead joined the race last year by acquiring XinThera and Merck KGaA has placed two PARP1 bets, one on Nerviano Medical Sciences and another on Jiangsu Hengrui Pharmaceuticals. Synnovation plans to start dosing patients in a phase 1 clinical trial of its brain-penetrating challenger, SNV1521, in the coming weeks. In preclinical tests, the biotech showed the molecule has greater than 500-fold selectivity against PARP2 and is more effective at inhibiting tumor growth than Lynparza. The biotech’s second candidate, SNV4818, is aimed at a target that has proven particularly troublesome. Zydelig and three other Gilead drugs that are too small to warrant their own line in the earnings collectively brought in $171 million over the first nine months of the year. Potential rivals have fled the space amid concerns PI3K inhibitors may shorten life expectancy and a resulting regulatory pushback.  Synnovation’s attempt to crack the PI3K puzzle has resulted in a molecule that targets the alpha form of the kinase and, according to the biotech, “is differentiated from competitor molecules by virtue of its excellent selectivity for H1047X and moderate selectivity over relevant E545/542X mutants.” The design reflects the belief that a lack of selectivity against wild type PI3K-alpha has held the class back to date.    Wu and Yao respectively work as CEO and senior vice president, drug discovery at Synnovation. The pair have been joined at the new biotech by two other leaders with lengthy stays at Incyte on their résumés. Phillip Liu, Ph.D., came on board as SVP, head of biology, while Kevin O’Hayer, M.D., Ph.D., took up the SVP, head of clinical development position last year.