Backers in Tango Therapeutics Inc.’s $60 million series B round represent “a group of really smart crossovers who normally don’t come in quite this early” and “hung in there” during some especially hard times on Wall Street recently, CEO Barbara Weber told BioWorld. “We were about to sign the term sheet the first time the market crashed, which was a little nerve-wracking.” The oversubscribed financing led by Boxer Capital of the Tavistock Group includes new investors Cormorant Asset Management and Casdin Capital.

Cambridge, Mass.-based Tango pursues therapies based on synthetic lethality. Specifically, the firm leverages DNA sequencing and CRISPR-based target discovery to reach beyond cancer therapies that deploy a single agent to induce partial, non-sustained responses. Since multiple lesions exist in each tumor that play roles in making cancer cells deadly, they must be targeted in order to gain sustained, complete responses and cures. By way of genomic screening, Tango can identify genes that exist in a symbiotic partnership with the mutated gene. A drug that takes aim at one of those “synthetic lethal” partners will kill only cells with the mutated gene: cancer cells. Poly ADP ribose polymerase (PARP) inhibitors stand as the first clinical example of synthetic lethal targeting and are active in cancers with BRCA mutations.

With the new money, Tango can advance into IND-enabling studies its lead program, which came out of data from the Broad Institute’s Project Achilles. “The baseline genetic lesion is a gene deletion that’s very frequent in multiple different solid tumors,” Weber said – at least seven or eight types in which as much as 20% of tumors bear the deletion. “The drug target is the synthetic lethal pair to that,” she said.

Further back in the pipeline are four more programs. One involves a tumor suppressor gene synthetic lethal pair in BRCA1-mutant tumors, different from the PARP approach. Another is a combination target for lung cancer patients who have “any number of MAP kinase pathway mutations,” Weber said. Also in the works is Tango’s first tumor-intrinsic drug target that should reverse checkpoint inhibitor resistance. The fifth effort just finished high-throughput screening (HTS), and partner Gilead Sciences Inc., of Foster City, Calif., will be doing the drug discovery with the prospect, which is another tumor suppressor gene synthetic lethal pair.

“Why are we three years out and we’re still not to a development candidate? The reason is – and very few companies do this, because it does create a financing challenge – that we start with target discovery,” Weber said. Tango discovers, validates and identifies novel chemical matter to targets “outside the standard chemical classes we’re used to. In oncology, everything’s been a kinase or a methylase until very recent times. That process adds maybe a year or two onto the standard drug discovery timelines,” but the labor ultimately provides more benefit, she said. “It’s what builds long-term value for us. We have the ability [to discover] and have now discovered a lot of novel targets. We have more targets than we know what to do with.” In other respects, Tango’s approach is “subject to the same sort of ups and downs” as any small-molecule efforts, she said. “We had one target we worked on for a year or two and have not been able to drug it convincingly” because of HTS issues. “We had to mostly abandon that target. On the flip side, we identified a really interesting target that another company was developing for a non-oncology indication and we were able to jump in with an in-licensing deal.” That company is Stockholm-based Medivir AB, and the license agreement in mid-March 2020 involved one of its preclinical research programs. Medivir banked an undisclosed up-front payment and is eligible to receive more as development and commercial milestones are met, along with low single-digit royalties.

China ties ‘flexed easily’

The deal with Gilead was signed in late 2018. Under the terms, Tango handles target discovery and validation. Gilead gained options to worldwide rights on up to five targets. For two programs, Tango kept the option to co-develop and co-detail in the U.S., collecting an up-front payment of $50 million from Gilead with about $1.7 billion more possible. The initial contract goes for three years, with an option for Gilead to extend one or two years more.

“Gilead and we think the deal is going really well,” Weber said. “They’ve taken one target so far,” and the arrangement could represent “one of the pathways to expanding our business development [BD] efforts in the future,” as Tango will need to raise more money before starting clinical work. “We’re looking at some very interesting BD options over the next four to six months – stay tuned on that,” she said. “The ideal scenario is probably another deal or an expanded BD deal, and then [we could] talk about another financing,” either a small round or an IPO. The company had 40 people at the time of the Gilead agreement and is up to 63 now. “We’re continuing to expand on the drug discovery team side,” she said. “We still need a little bit more internal biology and chemistry, although a lot of what we do is external.”

Given the COVID-19 crisis, “not being in the clinic right now is a little bit of an advantage. We’ve also been fortunate, some of it by design and some of it by coincidence. We do a lot of work with contract research organizations in China,” so when the virus struck there in January and February, “we were able to shift some of the work back to Tango and keep it going for them, and put it back in China” when things worsened in the U.S. “The good relationship we had [with them] let us flex that pretty easily,” and the fact that China and the U.S. “went down at different times was fortuitous for us.”

Tango also disclosed personnel changes: the appointments of Daniella Beckman as chief financial officer (CFO), John Ross as vice president of human resources, and Samy Tadros as vice president of BD. Beckman joined the company in September as interim CFO. Tadros most recently worked with Summit, N.J.-based Celgene Corp., now part of Bristol Myers Squibb Co., of New York. He replaced Shakti Narayan, formerly Tango’s chief business officer, who left to become CEO of Lexington, Mass.-based Accent Therapeutics Inc.