- STI-1558, a novel oral Mpro inhibitor, effectively inhibits Omicron virus entry and replication in cells.
- STI-1558 is orally bioavailable with improved human liver microsomal stability to avoid using Ritonavir as a pharmacokinetic enhancer in humans.
The world is experiencing a huge wave of infection with the Omicron variant of SARS-CoV-2, and current vaccines and EUA-approved antibodies offer diminished protection against Omicron transmission and infection. STI-1558 is an oral Mpro inhibitor which has demonstrated in preclinical studies broad-spectrum anti-SARS-CoV-2 activity when tested for activity against the original SARS-CoV-2 strain and all previous predominant variants of concern (VOCs).
STI-1558’s antiviral activity against Omicron has also been tested in a cell-based neutralization assay. In VeroE6 cells challenged with Omicron variant, STI-1558 alone (without efflux inhibitor) showed significant antiviral activity with an EC50 value of 360 nM, equivalent activity to that seen against the Delta variant (EC50 value, 370 nM). Notably, in an Omicron S protein-mediated pseudovirus entry assay, STI-1558 effectively inhibited pseudovirus entry into cells, whereas EUA-approved nirmatrelvir showed no inhibition. Particularly, STI-1558 showed improved human liver metabolic stability as compared to nirmatrelvir, and its oral bioavailability does not depend on the ritonavir co-administration. Without the need to co-administer Ritonavir, STI-1558 potentially avoids significant adverse drug-drug interactions.
“With Omicron becoming a globally dominant variant of SARS-CoV-2 in such a short period of time, we are focused on developing an effective therapeutic strategy for fighting the Omicron variant and future variants of concern, and most importantly, for preventing or overcoming drug-resistance. Sorrento continues its commitment to develop and deliver effective anti-COVID therapies to save patient lives and end the pandemic,” stated Dr.
About
Sorrento is a clinical and commercial stage biopharmaceutical company developing new therapies to treat cancer, pain (non-opioid treatments), autoimmune disease and COVID-19. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as fully human antibodies (“G-MAB™ library”), immuno-cellular therapies (“DAR-T™”), antibody-drug conjugates (“ADCs”), and oncolytic virus (“Seprehvec™”). Sorrento is also developing potential antiviral therapies and vaccines against coronaviruses, including Abivertinib, COVI-AMG™, COVISHIELD™, COVI-MSC™ and COVIDROPS™; and diagnostic test solutions, including COVITRACK™ and COVISTIX™.
Sorrento's commitment to life-enhancing therapies for patients is also demonstrated by our effort to advance a first-in-class (TRPV1 agonist) non-opioid pain management small molecule, resiniferatoxin (“RTX”), and SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (SEMDEXA™), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, and to commercialize ZTlido® (lidocaine topical system) 1.8% for the treatment of post-herpetic neuralgia (PHN). RTX has cleared for Phase II trial for intractable pain associated with cancer and a Phase II trial in osteoarthritis patients. SEMDEXA announced highly statistically significant positive top-line results from its Phase III Pivotal Trial C.L.E.A.R Program for its novel, non-opioid product for the treatment of lumbosacral radicular pain (sciatica). ZTlido® was approved by the FDA on
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