Ron DePinho raises seed cash for MD Anderson colleague’s work on a ‘Holy Grail molecule’ in cancer, inflammation

Ron DePinho has blazed a wide trail in cancer research. As founding director of the Belfer Institute for Applied Cancer Science at Dana-Farber and former president of MD Anderson Cancer Center in Houston — where he departed after a rocky tenure which he now fiercely defends — DePinho spearheaded translational programs and managed, among other things, to build a clinical trial engine that proved pivotal in a number of FDA approvals.

That’s why when he learned about his colleague David Tweardy’s work on STAT3 — a protein tied to a wide range of diseases — the serial entrepreneur went all in to co-found Tvardi Therapeutics.

“It’s been one of these Holy Grail molecules that folks have tried to develop inhibitors for,” he tells me.

Using a screen he designed 10 years ago, Tweardy, head of internal medicine at MD Anderson, had found a compound that prevents STAT3 from becoming phosphorylated by the receptors it typically interacts with, meaning it cannot then go on to turn on genes that are important in cancer, fibrosis and inflammation. Given that hyperactivated STAT3 is present in more than 50% of cancers — often turning up immunosuppression in the tumor microenvironment — he theorized that a potent inhibitor here that doesn’t trigger safety issues could have a big impact.

That seems to be the case throughout the preclinical testing done in his lab, which led Tweardy and DePinho to the Phase I that Tvardi is currently conducting. Now, with a fresh $9 million in Series A funding, the biotech expects to wrap up dose and safety studies in 3 to 4 cancer types for its lead oral drug, explore an IV formulation for use in non-cancer indications, and hustle a second program to the door of the clinic.

Somewhere in that timeline are trials involving checkpoint inhibitors, as Tvardi believes TTI-101 could be used in combo or as a follow-up to PD-1 agents.

And they hope to do all that by the end of 2019, with the help of a permanent CEO they are still searching for.

It’s not a ton of money in today’s mega-round studded world, but DePinho says staying flexible and capital efficient would be a key strategy for the company’s early days — a strategy that also involves seeking non-dilutive grant funding. Most of the investors in this round will remain unnamed, but he volunteered Monica Beam at Alexandria as an example of the “very sophisticated but private investors” he chose to work with.

“We don’t have a large bureaucratic organization, so we’re able to make decisions and be very flexible which is critically important here, because STAT3 has so many different opportunities […] that one needs to have a certain level of focus and prioritization,” he says.

At around a dozen employees, the small company is reminiscent of Karyopharm, another oncology company DePinho helped start before joining MD Anderson — where he is still faculty after stepping down from a six-year tenure as president. During that time, the center experienced reported operating losses of more than $460 million over 16 months and hundreds of staffers were laid off.

DePinho, however, sees it differently.

“It was an extraordinarily successful financial situation,” he tells me, citing “$3.7 billion in margin, the healthiest financial balance sheet in the United States for an academic medical center, record philanthropy and ranked No. 1 in corporate alliance revenues and IP revenues.”

He’s now moved on to new endeavors, including Tvardi. Once the Phase I data are in, DePinho expects to ramp up business development talks. He’s already thinking about the next round, which “would likely be our last one en route to either an IPO or other event.”

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