With $9 million in series A financing, Tvardi Therapeutics has enough runway to finish a phase 1 trial of its lead asset, an oral STAT3 inhibitor, in solid tumors and to start multiple proof-of-concept studies in additional cancer indications.
The Houston-based startup hopes to finish the phase 1 trial by mid-2019 and to start its phase 1b studies in a variety of different indications, such as hepatocellular carcinoma—the most common form of liver cancer—by the second half of 2019, said co-founder Ron DePinho, M.D., who was president at MD Anderson Cancer Center until last year. The capital will also enable Tvardi to begin IND-enabling studies for an intravenous formulation of the candidate, called TT-101, as well as for a second compound, TT-102.
Tvardi’s work is based on STAT3, a molecule that’s important in cancer, inflammation and fibrosis.
“It’s a molecule that’s been studied for more than 20 years and one of the most validated targets in medicine,” DePinho said. “However, it’s very challenging to develop a drug that blocks STAT3 activity directly.”
DePinho’s fellow co-founder, David Tweardy, M.D., president and head of internal medicine at MD Anderson, discovered a molecule that “docks into a pocket required for STAT 3 activity,” thereby preventing it from switching on genes important in cancer, fibrosis and inflammation. Specifically, it stops the phosphorylation and homodimerization of STAT3, two steps in its activation.
As for its preclinical assets, DePinho said the IV version of TT-101 could be useful in certain settings, such as for the treatment of cachexia, also known as wasting syndrome. Many patients with chronic kidney disease and end-stage renal disease have cachexia. It would be a neat solution to deliver an IV bolus of TT-101 to patients as they undergo dialysis, he said.
Tvardi is considering potential applications for TT-102 but hasn’t settled on any in particular.
“We’re still open-minded about exactly where we’re going to use it, for example, in fibrosis or inflammatory bowel disease. One of the really wonderful things about STAT3 is that it’s not a one-disease-trick pony. It’s involved in many different diseases, so we’re going to have to think carefully about what areas we will prioritize first," DePinho said.
Tvardi counts about half a dozen staffers, and DePinho doesn’t envision it growing to hundreds of employees.
“We’ve been able to do this with a group of half a dozen individuals, which has allowed us to really focus on the development of the drug,” he said. It’s a similar strategy he used when he co-founded Karyopharm, another cancer-focused biotech that had a “lean, mean team” that stayed that way all the way through IPO.
In the near term, he expects to build the team to about 12 people. Because its immediate work will be to develop its molecules for IND and phase 1, “there isn’t a need to build a very large organization.” But as the company progresses, this may change, DePinho said. Tvardi is, however, on the hunt for a full-time CEO. Neil Warma, who previously helmed Opexa Therapeutics and Viron Therapeutics, is currently acting CEO.