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Yes to Flexus: The Science And Strategy Behind A Huge Biotech Return

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Flexus from its competitors. President and head of R&D Juan Jaen said Flexus has developed a once-a-day IDO inhibitor pill. It hasn’t been tested in humans yet, although under Bristol’s watch it should enter clinical trials this year. Jaen and other Flexus executives are optimistic about the safety of IDO-1 inhibitors based on the health of mice that lack the IDO-1 gene as well as early clinical data from two competitor drugs.

Juan Jaen, former head of R&D at Flexus Biosciences t

Jaen: Once a day.

Safety might not ultimately be a distinguishing factor between IDO programs, however. Other than cancer cells, the only cells known to express IDO—and therefore be susceptible to anti-IDO drugs—are the placenta and the lungs. It makes sense, Jaen said, not to give an IDO inhibitor to a pregnant woman. The biological relevance in the lungs is “far from understood,” he said, but there hasn’t been any indication that IDO inhibitors alone cause any lung problems.

Given the type of IDO/TDO dealmaking activity so far, it seems unlikely these drugs will be used on their own. So it bears watching what happens in the lungs of patients who receive them along with checkpoint inhibitors.

They could be used in combination with more conventional cancer treatments, too, said Rosen. That’s because pieces of dead tumor cells, killed by chemo or radiation, are like invaders and stimulate an immune response. Zap a tumor with radiation, some cells will die; the subsequent immune response might trigger the surviving cells to produce IDO as a counter-response.

Again, it’s not a new idea. (Here’s a 2005 paper discussing the marriage of IDO inhibition and chemotherapy.) But any advances in IDO/TDO development will now be in other hands. Flexus sold everything related to its program to Bristol. But as it announced Monday, it hasn’t sold everything.

Flexus can’t keep its name, but it has kept its underlying T cell research program that focuses on regulatory T cells, which are the peacekeepers that cool down other immune cells. And Flexus has kept a clinical program, licensed from Amgen (NASDAQ: AMGN), that aims to fight cancer by knocking out three targets at once: FLT-3, CDK4, and CDK6.

The same investor group, including Kleiner Perkins and The Column Group, will back the new company. (More on that from Xconomy next week.) There’s no name yet, but CEO Rosen promised it wouldn’t be named Reflexus; it is, after all, going after cancer, not upset stomachs.

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