Cocrystal Pharma Provides Update on its COVID-19 Antiviral Discovery & Development Programs
Cocrystal Pharma, Inc. recently announced progress in developing broad-spectrum antiviral drug candidates that target coronaviruses including SARS-CoV-2, the coronavirus that causes COVID-19. Cocrystal initiated its COVID-19 program in March 2020 and has since expanded the program with additional development and licensing.
“We are aggressively developing novel coronavirus protease inhibitors for COVID-19 prophylactic and therapeutic use,” said Sam Lee, PhD, President of Cocrystal. “These drug candidates bind to a highly conserved region of the active site of SARS-CoV-2 protease that is required for SARS-CoV-2 viral replication. Our high-resolution x-ray cocrystal structures further confirmed the specific covalent interaction with this conserved region of the proteases of the coronaviruses SARS-CoV-2, SARS-CoV, and MERS-CoV viruses. We believe that, due to their novel mechanism of action, our protease inhibitors are likely to be effective against new variants of SARS-CoV-2. This may include the recent variants first identified in the United Kingdom, South Africa, Brazil, and India, which may be more contagious forms of the virus and may evade immunity produced by vaccines or previous infection.”
In December 2020 Cocrystal announced the selection of CDI-45205 as its lead coronavirus development candidate among a group of protease inhibitors obtained under an exclusive license agreement with Kansas State University Research Foundation (KSURF) announced in 2020.
CDI-45205 showed good bioavailability in mouse and rat pharmacokinetic studies via intraperitoneal injection, and also no cytotoxicity against a variety of human cell lines. The company recently demonstrated a strong synergistic effect with the FDA-approved COVID-19 medicine remdesivir. Additionally, a proof-of-concept animal study demonstrated that daily injection of CDI-45205 exhibited favorable in vivo efficacy in MERS-CoV-2 infected mice. Cocrystal has obtained promising preliminary pharmacokinetic results and is continuing to further evaluate CDI-45205.
“The immediate next steps in the process of advancing this candidate toward clinical development require scale-up synthesis and the subsequent manufacture of several kilograms of the active pharmaceutical ingredient (API) to support Investigational New Drug (IND)-enabling studies and Phase 1 trials,” said Dr. Lee. “Similar to our influenza CC-42344 program, we are exploring multiple routes of administration of preclinical lead molecules including oral, inhalation, and injection. We will also be examining in vitro activities of our compounds against the SARS-CoV-2 variants.”
Cocrystal has leveraged its antiviral development expertise by using its proprietary technology and drug discovery platform to launch a second COVID-19 program with additional antiviral compounds developed.
“While we are highly encouraged by preclinical progress with CDI-45205, we continue developing a new class of SARS-CoV inhibitors. We applied our proprietary drug discovery platform technology and high-throughput protein crystallography approach to design new chemical scaffolds to improve in vitro potency and pharmacokinetic properties,” explained Dr. Lee. “Lead discovery and optimization are ongoing. We anticipate identifying another SARS-CoV-2 preclinical lead for oral administration this year. In addition to these two SARS-CoV-2 protease programs, we are also developing novel SARS-CoV-2 inhibitors that block viral replication and transcription. Our goal is to rapidly advance multiple SARS-CoV-2 lead molecules to the clinical trial stage.”
“Public health officials are calling for the urgent development of potent antivirals that inhibit the replication cycle of SARS-CoV-2,” said Gary Wilcox, PhD, Chairman and Chief Executive Officer of Cocrystal. “Among the significant challenges scientists face is inhibiting viral replication without damaging the inner workings of healthy cells. Cocrystal’s approach to drug discovery could provide a solution for designing antivirals for use against a range of viruses, including coronaviruses, with limited off-target interaction. Our established, proprietary drug discovery platform is composed of computation, medicinal chemistry, and x-ray crystallography together with extensive knowledge of viruses and drug targets. This is a far different approach from traditional, empirical, medicinal chemistry approaches that often require iterative high-throughput compound screening and lengthy hit-to-lead processes.”
Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of coronaviruses (including SARS-CoV-2), influenza viruses, hepatitis C viruses and noroviruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For more information, visit www.cocrystalpharma.com.
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