WASHINGTON – A little more than a year after first reporting phase IIb results showing oral TORC1 inhibitor RTB-101 reduced the number of respiratory tract infections (RTIs) in older adults, Restorbio Inc. is illuminating what may be the mechanism behind its efficacy: the up-regulation of innate antiviral immunity. The data, presented at the Infectious Disease Society of America's IDWeek 2019, put the company on track to move into two phase III data readouts next year. (See BioWorld, July 26, 2018.)

From the top-line data, "we knew respiratory tract infections went down, but we didn't know the etiologies of that decrease," Restorbio's co-founder and chief medical officer, Joan Mannick, told Bioworld.

Now, following prespecified analyses it is discussing at IDWeek, the company can show that a 10-mg dose of RTB-101 given once daily up-regulates interferon-stimulated antiviral gene expression in whole blood (p=0.00001 vs. placebo) while decreasing the incidence of RTIs caused by multiple different viruses.

Describing innate antiviral immunity as an "endogenous defense system, that isn't specific for one virus, but fights them all," Mannick said it's "a whole new approach where you fight not just flu, but rhinovirus and respiratory syncytial virus and parainfluenza virus – all these different viruses, by up-regulating these genes."

"If we can confirm it in phase III, ours would be the first broad antiviral that inhibits multiple respiratory viruses," she said. And that's where the team's focus is now, with the first of two planned phase III trials, called Protector1, currently enrolling. If all goes as planned, top-line data are expected by early first quarter of 2020, followed by a readout of Protector2 in mid-2020.

In addition to its prespecified analysis, the company is presenting two post-hoc analyses of data generated by the phase IIb trial. One of them looked at time-to-alleviation of moderate to severe symptoms, the endpoint for which influenza drugs are approved, showing RTB-101 reduced that measure by an average of five days vs. placebo (p=0.025). The other analysis found that treatment with RTB-101 reduced the rate of all-cause hospitalization by 56% (p=0.047). Both findings will need to be confirmed in phase III studies, Mannick said.

Restorbio's shares (NASDAQ:TORC) fell 2.4% on Wednesday to $8.18.

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