Upstart Tango stepped up to the dance floor today with a $55 million investment boost from VC Third Rock Ventures as it eyes a new way to help treat cancer.
The biotech, which has 10 staffers and is based in Cambridge, MA is set up to target cancer vulnerabilities beyond the older class of meds, which focus on mutated oncogenes, and will use CRISPR as a screening tool and cutting-edge DNA sequencing.
The idea is to find new paths to identify drug targets and combos that take advantage of weaknesses created by loss of tumor suppressor gene function, something biopharma has been unable to do effectively in the past.
It also wants to complement current immune-cell directed cancer therapies and Tango says it is working to “identify and target the genetic alterations in cancer cells responsible for helping them avoid immune destruction.”
Drugs against these targets could boost the efficacy of current immuno-oncology drugs, like checkpoint inhibitors from Roche, BMS, Merck and Pfizer/Merck KGaA, all without increasing immune damage to normal tissues.
What fuels each of Tango’s programs is the ability to use “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.
This leaves normal cells largely unaffected, with the potential to greatly boost anti-tumor efficacy and lower side effects.
The first FDA-approved example of this type of synthetic lethality in cancer are PARP inhibitors for BRCA-mutant ovarian cancer, which includes AstraZeneca’s Lynparza (olaparib), and more recently Tesaro’s Zejula (niraparib). The biotech, which is preclinical, did not tell FierceBiotech whether it would seek to test any of its future candidates alongside either a PARPi or checkpoint inhibitor.
Alan Ashworth, Ph.D., a scientific founder of Tango, in fact discovered that combining a BRCA1/2 mutation and PARP inhibition creates synthetic lethality.
The biotech tells me that it has: “Established the company with the right funding and approach to move multiple programs forward on its own. The commitment from Third Rock allows a long-term focus, building the core capabilities they will need in-house.
“That said, this is an area of great external interest and the company is working to open a huge swath of opportunities for drug discovery and development – likely more than one company can handle on its own. Tango is open to partnering discussion with companies interested in this approach and commitment to this area of development.”
The biotech says that using its approach, it will “upend the traditional paradigm” by doing target discovery in cancer subgroups with a pre-defined patient selection approach.
“Cancers are complex genetic diseases marked by multiple lesions in each tumor. These include genes that are turned on to drive cancer growth and those that are inactivated and thus unable to function as tumor suppressors,” said Barbara Weber, M.D., Tango’s interim CEO and a Venture Partner at Third Rock Ventures.
“Loss of tumor suppressor genes is a hallmark of cancer, but the genes themselves are not tractable targets for drug discovery. With the sophisticated genomics tools now available, the time is right for Tango to take on this challenge and focus on patients without effective treatment options.” As with most Third Rock companies, Weber will remain on board until a permanent CEO is found.
And as with all startups, the company is keeping mum on timelines. But it tells me: “The focus now is on building the company and team, and further developing the product engine. Lead programs are in early discovery. Tango believes, however, that the approach they are pursuing will ultimately lead to a more efficient and accelerated timeline in the clinic, based primarily on the benefits of placing patient selection at the fore.
While it has 10 staffers now, it said it “expects to grow substantially throughout the year.”
And what’s behind the name? “The fundamental understanding at the heart of Tango is the concept of synthetic lethality. In its simplest form, this means that certain cancer mutations create new vulnerabilities that are only present when these mutations occur. Tango is working to systematically uncover these vulnerabilities and develop drugs to target them. So, their treatments require two things; the mutation, and the right inhibitor to target this context-specific vulnerability. In other words, it takes two.”