Chasing ‘Holy Grail’ STAT3 Target, Houston Startup Refuels with $74M to Zero in on Liver Cancer

Tvardi launched out of Houston with the promise of finally developing the right inhibitors for the Holy Grail target of STAT3 — under the guidance of serial entrepreneur Ron DePinho and his colleague David Tweardy, a leading expert in the field. Almost three years later, they say they have the proof of concept data to keep going.

It’s good enough for a $74 million Series B, a big jump from the $9 million they got in the last round and, CEO Imran Alibhai would add, a reflection of the rep his team has built.

In Phase I dose escalation studies involving patients with solid tumors who have failed all other treatments, the lead compound was shown to have downregulated the STAT3 activity of interest: blocking it from becoming phosphorylated by the receptors it typically interacts with.

“The topline news is that in over half of our patients, we’ve seen clinical benefit” in the form of tumor stabilization, shrinkage or even partial responses, he said. “That drove a lot of interest, but beyond that what’s been striking has been the safety.”

He believes the secret lies in focusing on preventing the activation of STAT3, which drives the nuclear function related to disease, but not trying to remove it from the system, degrade it, or break it too much. The small window, after all, is what makes targeting STAT3 so tricky despite it being a top 5 target for cancer.

By the first half of next year, Tvardi expects to wrap up the Phase I trial and zero in on hepatocellular carcinoma in Phase II trials — while also starting to study the drug for fibrosis.

“When you think about growth and differentiation in tumors, and metastases, there’s probably three or four legs to the stool, and STAT3 is definitely one of those. Right? It is a central node,” Alibhai said. “When it comes to fibrosis, there is one leg to the stool. And STAT3 modulates that pathway. And so if you could find a safe drug that actually targets STAT3, you can potentially see some really beautiful data.”

Others have arrived at the same conclusion, with a small band of startups heralding new approaches such as protein degradation to target STAT3, Sanofi-partnered Kymera and Medicxi’s Janpix (now part of Centessa) among them.

For his part, Alibhai said he welcomes more options for patients and hopes Tvardi’s oral dosing small molecule treatment can set itself apart. Besides, it is not trivial to make drugs that can even get into the clinic.

“What the true test is: Can you actually get in, be safe, and be very very very targeted in the case of STAT3?” he noted. “Because there are multiple roles for STAT3 in every cell, and so we need to make sure that we’re targeting appropriately for the role that we’re interested in.”

The small company is already working on a second-generation molecule that will be three to eight times more potent than the lead candidate, he said. And their new investors are in for the long game, giving them the option to either jump straight into an IPO next or raise another crossover round and, more importantly, “do something interesting.”

Slate Path Capital, Palkon Capital, ArrowMark Partners and 683 Capital joined the round, with significant support from Sporos Bioventures and other existing investors.

Source: Endpoints News, Amber Tong, Senior Editor

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