NIH to Back First Phase II Trials for COVID-19 Therapy Targeting Viral Proteases

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Sound Pharmaceuticals announced the backing of the National Center for Advancing Translational Sciences (NCATS) for its planned Phase II trials of its oral anti-inflammatory SPI-1005 to treat patients with moderate or severe COVID-19, the first known trials for a therapy targeting main protease (Mpro) and papain-like protease (PLpro) on the SARS-CoV-2 virus. The $3.1 million NCATS grant will help the company test SPI-1005 in two trials, both OK’d by the U.S. Food and Drug Administration (FDA) last August.

Sound Pharmaceuticals’ co-founder and CEO Jonathan Kil said he expects the trials will begin dosing in the next two months.

The new trials will evaluate whether SPI-1005 can improve clinical outcomes and evaluate inflammatory and immune responses to the drug candidate. Patients in the trials will test SPI-1005 against placebo for seven or 14 days in 120 adults with moderate or severe COVID-19.

Ebselen, the active component of SPI-1005, has previously been shown to be immunomodulatory but not immunosuppressive. In vitro and preclinical testing has shown that ebselen can bind and inhibit mMpro and PLpro. Researchers from ShanghaiTech University showed that Mpro plays a role in viral transcription and replication, characterized it as a therapeutic target, and first ebselen as a possible therapy last year.

Ebselen is a selenium-based lab tool compound that has been tested for decades as a possible therapy in diseases ranging from brain ischemia to diabetes. Otologic disease company Sound Pharmaceuticals has SPI-100 in Phase III testing for patients with noise-induced hearing loss, and in Phase II testing for hearing loss in patients with the rare disease Meniere’s Disease (MD). It also has another formulation of ebselen, SPI-3005, in Phase II testing for patients with aminoglycoside-induced ototoxicity. The company says SPI-1005 has been tested in over 400 patients in six randomized controlled trials across disease areas.

According to Kil, these will likely be the first Phase II studies of an Mpro or PLpro inhibitor in moderate and severe COVID-19. At least nine other companies have developed potential therapies that target Mpro and PLpro, but it is unclear if any are in clinical development. Last week, Arbutus Biopharma, X-Chem and Proteros biostructures announced a partnership to discover Mpro inhibitors. And last month, Sunshine Biopharma announced over $2 million in new financing in part to develop potential COVID-19 therapeutics, including an PLpro inhibitor.