Leveraging synthetic lethality to find novel cancer drug targets and combinations.
CEO: Barbara Weber, M.D.
Based: Cambridge, Massachusetts
Clinical focus: Oncology
The scoop: Tango was launched by venture capital firm Third Rock Ventures with a $55 million series A boost in March, after some gestation time at the VC firm.
The team built up within the firm for about 18 months, around an idea that Tango's founding CEO and a partner at Third Rock, Barbara Weber, and other renowned scientific founders had been polishing—using synthetic lethality powered by CRISPR-enabled sequencing for novel cancer drug discovery. Weber has just transitioned to become the company's permanent CEO.
Still an early-stage discovery company, Tango doesn’t have a lead drug candidate yet, but “we already have more targets validated than a small, early company can manage on its own,” Weber said. “So, we are substantially discussing with a large number of potential pharma partners, who could take on some of that drug discovery and development effort, but retaining enough significant value that Tango—which is being built as a standalone company—can continue to retain the value and bring Tango itself to an IPO.”
What makes Tango Fierce: The idea of synthetic lethality, where two genes inactivated either by mutation or by a drug can collectively cause tumor cell death, has already been proven in AstraZeneca’s Lynparza and Tesaro’s Zejula.
“We all got to a point with targeted therapy where we hit a wall—there’s a finite number of mutated oncogenes that are druggable, and 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. "And many people, me included, feel that [synthetic lethality] is the next step."
But there were technical difficulties, until CRISPR.
“The technology that CRISPR brings to us has opened up a big target space that's really amenable to taking a number of different approaches, and I think it's going to be a big step forward for cancer drug discovery,” Weber said.
Tango will use data from DNA sequencing of patient-derived tumor samples to define genetic contexts, and deploy CRISPR-based target discovery techniques in those cancer subtypes to identify synthetic lethal interactions that lead to novel drug targets.
But to Weber, what really sets Tango apart from other companies using the same technology is its paradigm-shifting approach that puts patient selection before target identification. Tango's drug development process starts with patients' unmet medical needs, Weber explained. “Who are the patients that are currently not benefiting from standard targeted therapies against mutated oncogenes, who are not significantly benefiting from some of the new immuno-oncology advances, who mostly have palliative chemo therapies options? Let's start with those patients first of all.
“Then let's think about what are the genetics of those tumors," Weber said, "and what are the areas where targeting might actually make a significant difference. We then move forward with our proprietary druggable genome CRISPR library screens and identify novel targets that have very significant preclinical effects in that model, and then, when we go back into the clinic, we're going right back into the same patients that we used as the models to do the drug discovery.”
Weber said this model will help move drug development along far more quickly than the traditional approach of identifying targets in the biologic system first and then trying to figure out which cancer patients will benefit from them—and it could almost guarantee a strong signal from the very first clinical testing.
“In the end, if you start with patient need, you end up with a drug that makes a big difference to patients, that means big signals and rapid regulatory decisions, and it should hopefully mean reasonable pricing as well,” Weber said.
An academics-to-industry oncology R&D veteran, Weber was a senior member of the team that launched another Fierce 15 winner this year, Relay Therapeutics, in September 2016, and served as interim CMO for 2016 Fierce 15 winner Neon Therapeutics till December 2016. Tango’s scientific founders, who are still actively involved in the company, include Alan Ashworth, Ph.D., a pioneer in the synthetic lethality approach in cancer treatment who discovered the potential of inhibiting PARP in BRCA-mutant cancer.
The young biotech has now grown to a team of more than 20 people. Although discussions to partner programs with other larger companies are still early, the company’s unique discovery efforts, according to Weber, could open up a broad range of opportunities for different deal structures in the future.
Investor: Third Rock Ventures