Many cancer patients have benefited from targeted therapies that switch off cancer-driving oncogenes, but others, whose disease is driven by the loss of tumor-suppressing genes, have missed out on such treatments. Tango Therapeutics is working on a pipeline of drugs to change that, raising $60 million to fuel its efforts.
The series B financing, which comes from Boxer Capital, Cormorant Asset Management and Casdin Capital, will see Tango’s lead program into IND-enabling studies early next year and support earlier-stage work in target and drug discovery.
All of those programs are based on synthetic lethality, the interaction between two genes that causes cell death when both are inactivated. In cancer cells, one of these genes is inactivated by mutation; the other will be inactivated by a drug. The first FDA-approved example of this type of synthetic lethality in cancer are PARP inhibitors for BRCA-mutant ovarian cancer, which include AstraZeneca and Merck's Lynparza and Zejula from GlaxoSmithKline's Tesaro.
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Synthetic lethality is a way to get at lost tumor suppressor genes, which have long evaded drug developers.
“Tumor suppressor genes are lost. You can’t turn on something that is gone, as opposed to an oncogene, where you can turn someone off that is on,” Tango CEO Barbara Weber, M.D., told FierceBiotech.
To get at those genes, as well as tumor evasion genes—which keep the immune system from killing tumors—Tango is starting with patients, rather than with targets such as HER2 and BRAF. The company sequences the DNA of patients’ tumors and then uses CRISPR to find targets in those cancers and make small molecule drugs against them.
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“Our lead program is a drug target that is a synthetic lethal pair with a commonly lost gene in cancers,” Weber said. “We’re making great progress on that program and hope to have a clinical development candidate from that early next year.”
The company has four drug discovery programs following behind, targeting synthetic lethality in different patient groups. It believes that combining its synthetic lethality drugs with other cancer treatments can close the gap between partial responses and complete responses.
“[With] single agents you get significant responses, but the next step of really getting to complete responses and ultimately sort of long-term emissions or cures needs the next step," Weber said in a previous interview. "And many people, me included, feel that [synthetic lethality] is the next step."
Tango also added key players to its leadership team, including its new vice president of business development, Samy Tadros, who spent the last decade at Celgene working on deals ranging from early-stage research to late-stage development and commercial. The biotech inked an immuno-oncology pact with Gilead Sciences in 2018, under which the latter could pick up the worldwide rights to five targets discovered and validated by Tango. It will “absolutely” continue striking such deals, Weber said.
“The more targets we discover, the more targets we have, and we have a limited number we can prosecute at any given time,” she said. “We continue to see partnerships like that as a way to make sure that the novel targets we’re identifying and that we can’t develop ourselves in a smaller company … eventually make it to patients."