Virus World

July 23, 2021 – SOUTH SAN FRANCISCO, Calif. – Cortexyme, Inc. (Nasdaq: CRTX), a company advancing a pivotal trial in Alzheimer’s disease with top-line data expected in the fourth quarter of 2021 and a growing pipeline of therapeutics for degenerative diseases, announced the selection of a lead 3CLpro inhibitor (COR803) for treatment of coronavirus infections, including COVID-19 disease, caused by SARS-CoV-2 infection. “There continues to be a large unmet need for coronavirus treatment. The target of COR803 is highly conserved across variants and among coronaviruses in general, therefore it is expected to address both current and future coronavirus strains, including the delta variant of SARS-CoV-2,” said Casey Lynch, Cortexyme’s chief executive officer, co-founder, and chair. “We have selected COR803 based on compelling data to support its development as a potential therapy that could be prescribed at the first sign of infection or after known exposures without requiring patients to be hospitalized, as well as for those in critical care. The novel characteristics of COR803 reflect the breadth and capabilities of our proprietary research and development as Cortexyme continues to apply our innovative science to areas of high clinical need.” COR803 is a novel patent-pending small molecule 3CLpro inhibitor discovered and developed by Cortexyme based on its expertise in cysteine protease inhibition. 3CLpro, or Mpro, is a validated antiviral drug target shown to be essential in viral replication of SARS-CoV-2. COR803 has beneficial properties over other COVID-19 therapeutics and 3CLpro inhibitors in development including:

• Covalent irreversible binding of the viral 3CLpro enzyme;
• High potency: Antiviral EC90 of 30 nM in human lung cell viral replication assays;
• Highly selective for 3CLpro versus other cellular proteases including Cathepsin L; and
• Excellent systemic exposure utilizing intranasal or subcutaneous administration, allowing for clinical use in multiple settings such as outpatient and inpatient.

About Cortexyme

Cortexyme, Inc. (Nasdaq: CRTX) is a clinical stage biopharmaceutical company pioneering upstream therapeutic approaches designed to improve the lives of patients diagnosed with Alzheimer’s and other degenerative diseases. The company is advancing its disease-modifying pivotal GAIN Trial in mild to moderate Alzheimer’s disease with top-line data expected in the fourth quarter of 2021, in addition to growing a proprietary pipeline of first-in-class small molecule therapeutics for Parkinson’s disease, periodontitis, and other diseases with high unmet clinical need. Cortexyme’s lead program targets a specific, infectious pathogen called P. gingivalis found in the brain and other organs and tied to degeneration and inflammation in humans and animal models. The company’s causation evidence for Alzheimer’s disease and the mechanism of its novel therapeutic has been independently replicated and confirmed by multiple laboratories around the world, as well as published in peer-reviewed scientific journals. To learn more about Cortexyme, visit www.cortexyme.com or follow @Cortexyme on Twitter.

The study will now assess the tolerability and safety of multiple ascending doses of PF-07321332, an oral antiviral agent against SARS-CoV-2. The study will now assess the tolerability and safety of multiple ascending doses of PF-07321332, Pfizer’s investigational oral antiviral agent against SARS-CoV-2. Pfizer is progressing its novel oral antiviral candidate against SARS-CoV-2 into multiple ascending doses after completing the dosing of single ascending doses in a Phase I study in healthy adults. The trial is evaluating the safety and tolerability of PF-07321332, a SARS-CoV2-3CL protease inhibitor, which demonstrated potent in vitro antiviral activity against SARS-CoV-2 and other coronaviruses. SARS-CoV-2 is the virus that causes COVID-19. 

“Tackling the COVID-19 pandemic requires both prevention via vaccine and targeted treatment for those who contract the virus. Given the way that SARS-CoV-2 is mutating and the continued global impact of COVID-19, it appears likely that it will be critical to have access to therapeutic options both now and beyond the pandemic,” stated Dr Mikael Dolsten, Chief Scientific Officer and President, Worldwide Research, Development and Medical of Pfizer. “We have designed PF-07321332 as a potential oral therapy that could be prescribed at the first sign of infection, without requiring that patients are hospitalised or in critical care. At the same time, Pfizer’s intravenous antiviral candidate is a potential novel treatment option for hospitalised patients. Together, the two have the potential to create an end-to-end treatment paradigm that complements vaccination in cases where disease still occurs.”

Protease inhibitors such as PF-07321332 bind to a viral enzyme, called a protease, which is vital for the virus to successfully replicate in human cells. Through their interaction with the enzyme, this class of medicines prevent the virus from replicating. Protease inhibitors have been used to treat various other viral pathogens, including HIV and hepatitis C virus, both alone and in combination with other antivirals. Currently marketed protease inhibitors are not generally associated with toxicity and as such, this class of molecules may potentially provide well-tolerated treatments against COVID-19.  The Phase I trial is a randomised, double-blind, sponsor-open, placebo-controlled, single- and multiple-dose escalation study in healthy adults evaluating the safety, tolerability and pharmacokinetics of PF-07321332. Pfizer is also investigating an intravenously administered investigational protease inhibitor, PF-07304814, in a Phase Ib multi-dose trial in hospitalised patients with COVID-19.

Pfizer Press Release (March 23, 2021):

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-initiates-phase-1-study-novel-oral-antiviral