What You Need to Know About Tango Therapeutics

Tango Therapeutics officially launched in March 2017 with a significant Series A investment from Third Rock Ventures and hit the ground running as a cancer drug target discovery and drug development company based on CRISPR technology.

The company’s chief executive officer and founder, Barbara Weber, told BioSpace,"Tango was founded to be able to take advantage of CRISPR technology as a target discovery approach, but the company is constructed and functioning as a full discovery and development organization. We use CRISPR as a research tool; we’re not a CRISPR therapeutics company."

Weber is a venture partner at Third Rock Ventures, where she joined in 2015, and remains. "When I joined Third Rock," Weber says, "this company was in my head and I started working on it in the summer of 2015, working with Alexis Borisy, and later Cary Pfeffer, to build the company internally over that year and a half, and to publicly launch it in March 2017 this year. I came in, which is the Third Rock model, as an interim chief executive and my plan was to hire my replacement and return to Third Rock to work on another company. But I was so in love with Tango that I couldn’t do it, so I decided in September to accept their offer and stay on as permanent chief executive officer."

In addition to using CRISPR as a tool, Tango focuses on synthetic lethality, which is when a combination of deficiencies in two or more genes can lead to cell death. Weber describes it as being similar to a game of pickup sticks, or perhaps Jenga, where the removal of one piece—for example, an oncogene—doesn’t necessarily kill the cancer, but leads to other opportunities for drug targets. "What we can do now," she says, "is find those targets for a vulnerability or a second dependency. You can’t target a tumor suppressor, that’s gone, but the loss of a tumor suppressor creates new targets. That’s the concept behind what we’re doing and why we think we can discover and are discovering a wealth of new cancer targets and why we think we can move forward with those targets in combinations that will be truly transformational."

Company Leadership

Barbara Weber – chief executive officer. Weber remains a Venture Partner at Third Rock Ventures. She was a senior member of the team that launched Relay Therapeutics and was interim chief medical officer for Neon Therapeutics. Prior to joining Third Rock, Weber was senior vice president and global head of Oncology Translational Medicine at Novartis from 2009 to 2015. Before Novartis, she was vice president Oncology Discovery and Translational Medicine at GlaxoSmithKline.

Cary Pfeffer – interim chief business officer. A partner at Third Rock, Pfeffer heads Third Rock’s partner development efforts, and has been with the firm since 2007. He has been the interim chief business officer of Eleven Biotherapeutics, interim chief executive officer of Jounce Therapeutics and Neon Therapeutics, and currently serves on the boards of Albexis, Edimer, and Jounce.

Daniella Beckman – chief financial officer. Beckman serves as part-time CFO of Tango and for Neon Therapeutics. Prior to those positions, she was the chief financial officer of Idenix Pharmaceuticals until it was acquired by Merck in 2014.

Alexis Borisy – chairman. Borisy is a partner at Third Rock Ventures, which he joined in 2009. Before Third Rock, he founded CombinatoRx in 2000, serving as its chief executive officer and taking the company public.

Company Financing

Tango launched in March 2017 with a $55 million Series A investment from Third Rock Ventures. Weber says, "Third Rock is the sole investor. As you can see, a fairly significant investment. Third Rock has been moving more and more away from syndicates and more toward a company-building company rather than a traditional venture firm. Tango is an example of one of those companies where they felt strongly enough about it to make a sole investment."

Pipeline

Although a young company, Tango is moving toward the clinic with two full drug discovery programs. Weber says, "They are early, but we’re just starting a third and we have a fully operational discovery platform with about 10 fully validated targets that are ready to move forward."

She notes that Tango approaches target discovery in a way that might, by some, be viewed as backwards. They start thinking about the patient groups that currently have high medical needs, particularly cancer patients who are not responding currently to immuno-oncology approaches. "Patients that don’t have good targeted therapies available, essentially patients who only have palliative therapeutics as an option. There are many of them, most of the GI tumors, liver cancer, gastric cancer, colon cancer, brain cancer, sarcomas—a lot of patients who don’t have great options for therapy. We perform the genetics on the patients and conduct discovery in those models that select those subsets of patients."

One of the important focuses for Tango is context-specific targets. "We perform our drug discovery in a model system that mirrors those patients we ultimately want to treat. We discover the targets with the concept of synthetic lethality and then move ahead with the discovery program, and when we have our drugs, go right back into those same patient populations," she says.

Market Competition

Although many companies are in the oncology and immuno-oncology space, and many are using CRISPR, Weber thinks there are very few using CRISPR to get at synthetic lethality targets in cancer. She notes that Ideaya Biosciences and Repare Therapeutics are in the space, but all take a slightly different approach and focus. "It’s a big target space," she says, "and a lot of opportunities. I think the likelihood we’re going to be bumping up against those specific companies is relatively low, since we’re talking 50 targets or so in the next 10 years using this approach."

Dollars and Deals

Like most startups, there have been some pharma interests in partnerships, but it’s very early. Weber says, "Part of the Third Rock business model is to attempt a large pharma partnership deal. Interesting for us, unlike the situation in the past, we actually have a wealth of targets to choose from, so partnering with a big company that’s looking to expand their internal pipeline while we are still able to retain significant value and programs is a more straightforward path for us than it is for some companies. We’ve been talking to big pharma potential partners since before launch and are progressing with three or four, but it’s way too early to talk about at this time."

What to Look For

With two programs and a third on the way, Tango hopes that in a three-to-five year timeframe that it will have taken at least one drug into the clinic, and possibly more.