XinThera, Inc.

Dive Brief:Gilead Sciences is teaming up with a Dutch biotechnology company to discover and develop a kind of cancer therapy known as trispecific antibodies.As the name suggests, these antibodies are designed to bind to three targets, including antigens associated with tumors. Bispecific antibody drugs have proven effective hemophilia, certain eye conditions and a range of cancers, from blood to lung to skin.Per deal terms, Gilead will make a $25 million equity investment in its new partner, Merus, and provide an upfront payment of $56 million. The partnership will cover two to three drug programs. Across those programs, Merus is also eligible to receive as much as $1.5 billion in additional payments.Dive Insight:Over the past decade, Gilead, which became one of the worlds wealthiest biotechs by developing highly effective treatments for viruses like hepatitis and HIV, has been trying to find similar success in oncology.In 2020, the company spent a warchest of more than $27 billion on a string of acquisitions meant to bolster its place in cancer drug development. But aside from its buyout of Immunomedics, those deals have yet to yield marketed products.There have also been more setbacks than some investors expected. For example, multiple studies testing the central medicine in Gileads $5 billion acquisition of Forty Seven either failed or were cut short. Gilead is now reviewing that drug, putting its future in doubt.Gileads oncology division generated $2.9 billion in product sales last year, with about 60% coming from cell therapies.Despite the problems, Gilead has continued cancer dealmaking. The company recently expanded a collaboration with cell therapy developer Arcellx, upped its equity stake in Arcus Biosciences, and bought the private biotechs XinThera and Tmunity Therapeutics.The Merus agreement gives Gilead the right to license programs after select research activities are completed. Should Gilead exercise the licensing option, it would become responsible for additional research, development and commercialization activities.The companies didnt specify what cancers or targets theyll focus on. But they did say Merus will lead early-stage research activities for two programs and have an option to pursue a third.Merus can receive tiered royalties from the mid-single to low-double digits on any products stemming from the collaboration. And if a third program materializes, the company may choose to evenly split net profits and losses with Gilead instead of collecting milestone and royalty payments. '

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.

MBrace Therapeutics said Tuesday that it bagged $85 million in an oversubscribed Series B round, bringing its total raise so far to $110 million. Funds will be used to support clinical development programmes for antibody-drug conjugates (ADCs) against difficult-to-treat cancers, including a first-in-human trial of its lead investigational ADC candidate MBRC-101.The company, which was founded in 2020, said preclinical data for MBRC-101 will be presented early next month at the San Antonio Breast Cancer Symposium (SABCS). The drug targets the EphA5 receptor tyrosine kinase, which is present in multiple cancers, including non-small-cell lung (NSCLC), colorectal, gastric and pancreatic cancers.Aside from pushing ahead with development of MBRC-101, MBrace is working on advancing its proprietary SPARTA antibody discovery approach. The platform combines an in vitro screening step of a naïve human antibody library against tumour targets, with in vivo selections based on tumour-homing capabilities of a pre-enriched antibody pool. "This unique approach overcomes several rate-limiting challenges for rapid translation into clinical applications," the company says on its website.TPG led the Series B round, which also saw contributions from new investors Avidity Partners and Cowen Healthcare Investments, as well as existing Series A investors, Venrock and Alta Partners.Meanwhile, Christopher LeMasters, chief executive at Gilead Sciences' subsidiary XinThera, will join MBrace's board as an independent director. XinThera is focused on small-molecule discovery and development of oncology and immunology therapeutics. Carolyn Ng, business unit partner with TPG Life Sciences Innovations, and Monal Mehta of Avidity Partners will also join the board in conjunction with the financing.