$COCP reading dd & theory NEWS RELEASE 3-AUG-2020 New published study from K-State virologists identifies potential COVID-19 treatment
KANSAS STATE UNIVERSITY
MANHATTAN, KANSAS -- Yunjeong Kim and Kyeong-Ok "KC" Chang,
virologists in the College of Veterinary Medicine at Kansas State University,
have published a study showing a possible therapeutic
treatment for COVID-19.
Pathogenic coronaviruses are a major threat to global public health,
as shown by severe acute respiratory syndrome coronavirus, or SARS-CoV;
Middle East respiratory syndrome coronavirus, known as MERS-CoV;
and the newly emerged SARS-CoV-2, the virus that causes COVID-19 infection.
The study, "3C-like protease inhibitors block coronavirus replication
in vitro and improve survival in MERS-CoV-infected mice,"
appears in the Aug. 3 issue of the prestigious medical journal Science Translational Medicine.
It reveals how small molecule protease inhibitors show potency against human coronaviruses.
These coronavirus 3C-like proteases, known as 3CLpro, are strong therapeutic targets because they play vital roles in coronavirus replication.
"Vaccine developments and treatments are the biggest targets in
COVID-19 research, and treatment is really key,"
said Chang, professor of diagnostic medicine and pathobiology.
"This paper describes protease inhibitors targeting coronavirus 3CLpro, which is a well-known therapeutic target."
The study demonstrates that this series of optimized coronavirus
3CLpro inhibitors blocked replication of the human coronaviruses
MERS-CoV and SARS-CoV-2 in cultured cells and in a mouse model for MERS.
These findings suggest that this series of compounds should be investigated further as a potential therapeutic for human coronavirus infection.
Chang and Kim have been using National Institutes of Health grants
to develop antiviral drugs to treat MERS and human norovirus infections.
Their work extends to other human viruses such as rhinoviruses and SARS-CoV-2.
"The work that this group of collaborators has been doing on
antivirals and inhibitors for SARS and MERS at K-State for a number
of years has been vital to their ability to quickly pivot to emphasize research on SARS-CoV-2 virus and therapeutics,"
said Peter K. Dorhout, vice president for research at K-State.
Co-collaborators on the research include teams lead by Bill Groutas
at Wichita State University,
Stanley Perlman at the University of Iowa and Scott Lovell at the University of Kansas.
Lovell brought decades of experience to our research team,"
"We would not have been able to come this far without important collaborations with our colleagues at other institutions."
"Getting things published right now is very important for the scientific community," Kim said. "I think we are adding valuable information to the antiviral field."
The new compounds in the publication are exclusively licensed and being developed by Cocrystal Pharma for COVID-19. K-State Innovations Partners handles commercial technology licensing for the university.
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CONFERENCE , PRESENTATION
Cocrystal’s HCV Strategy , GILD , ABBV, Ongoing licensing discussions underway to secure development and commercialization partner
Lead program CC-31244, in ongoing Phase 2a study for the treatment of Hepatitis C
• Clinical limitations of existing long-term HCV therapies: • Longer period for viruses to replicate and mutate, creating significant drug resistance challenges
• Increased risk of adverse events
• Greater opportunity for missed doses
• Multiple opportunities in developing shorter combination therapy with approved HCV drugs
• Gilead EPCLUSA® + CC-31244 • AbbVie MavyretTM + CC-31244 • Other approved HCV drugs + CC-31244
Merck/Cocrystal Team Initiates Influenza Collaboration , MRK
• Exclusive license and collaboration agreement to discover and develop certain proprietary influenza A/B antiviral agents
• Merck will fund all: • Research and development • Clinical development • Worldwide commercialization of any products derived from the collaboration
• Dedicated joint research committee in place • First year of program completed and second year ongoing
• Collaboration is expected to advance the development of certain influenza A/B antivirals
$COCP, Upcoming Milestones Expected to Drive Value
Q1 2020 Hepatitis C Release Final Report on Phase 2a U.S. Trial
Q2 2020 Noro Preclinical Lead Molecule Selection
Q3 2020 Platform In-License New Lead Molecule
Complete Preclinical IND-Enabling Studies
Regulatory Submission (IND or European Counterpart)
Commence Phase 1a Study
Merck A/B Influenza A/B Lead Molecule Selection
H2 2020 Hepatitis C Commence Phase 2b Enabling Toxicology Study
Q3 2021 Noro Regulatory Submission (IND or European Counterpart)
Ongoing potential for licensing deals across the pipeline
Q2 2019 Influenza A Commence GLP Toxicology Studies ?
Q3 2019 Influenza Present Preclinical Data at ISIRV ?
Present at 26th International Symposium on Hepatitis C Virus and Related Viruses ?
Present Data at HCV 2019 and AASLD Scientific Conference
Ongoing potential for licensing deals across the pipeline
LINKS, https://www.cocrystalpharma.com/technology https://www.cocrystalpharma.com/development-pipeline/overview https://www.cocrystalpharma.com/development-pipeline/hepatitis-c https://www.cocrystalpharma.com/development-pipeline/influenza
.com/development-pipeline/norovirus https://www.cocrystalpharma.com/news/press-releases https://www.cocrystalpharma.com/news/presentations https://www.cocrystalpharma.com/news/fact-sheet https://www.cocrystalpharma.com/news/multimedia-videos https://ir.cocrystalpharma.com/analyst-coverage https://www.cocrystalpharma https://ir.cocrystalpharma.com/profile https://ir.stockpr.com/cocrystalpharma/quote
Drug Discovery Platform;
Protein Engineering Expression & Purification Crystal Screening Crystal Candidates Crystal Optimization X-ray Diffraction Test &
QC Crystal Production High Throughput X-ray Crystallography • Fully-optimized operations from expression through high resolution X-ray data
• Stringent quality oversight of procedures for crystal production • High throughput X-ray data collection and computational methods
• Large-scale crystal production capabilities Technology Platform D
Cocrystal Pharma, Inc. is a clinical stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication machinery of hepatitis viruses,
influenza viruses, and noroviruses.. We employ unique structure-based technologies and Nobel Prize winning expertise to create first- and best-in-class antiviral drugs.
The Company is developing CC-31244, an investigational, oral, broad-spectrum replication inhibitor called a non-nucleoside inhibitor (NNI). CC-31244 is currently being evaluated
in a Phase 2a study for the treatment of hepatitis C as part of a cocktail for ultra-short therapy of 4 to 6 weeks. Cocrystal recently entered into an exclusive worldwide license and
collaboration agreement with Merck & Co., Inc. to discover and develop certain proprietary influenza A/B antiviral agents. CC-42344, the Company’s molecule for the
treatment of influenza A, is currently being evaluated in preclinical IND-enabling studies. In addition, the Company has a pipeline of promising early discovery program
to identify and develop novel antivirals for the treatment of norovirus gastroenteritis.
A Structure-Based Drug Discovery Strategy for Viral Replication Inhibitors
Our proprietary structural biology, enzymology and medicinal chemistry expertise enable us to develop novel antiviral agents.
These technologies and our market-focused approach to drug discovery are designed to effectively create small molecule therapeutics
that are safe, effective and convenient to administer.
Advantages of our Technology
Our technology provides a 3-D structure of inhibitor complexes at near-atomic resolution and immediate insight to guide SAR.
This helps us identify novel binding sites and allows for a rapid turnaround of structural information through highly automated X-ray data processing and refinement.
Broad Spectrum Antiviral Activity
For any given viral disease, there are different subtypes of viruses that cause the disease. For example, there are six different subtypes of virus that cause hepatitis C.
In hepatitis C, these subtypes are termed "genotypes." Each hepatitis C genotype is common in some parts of the world and rare in others.
Our technology allows us to develop drug candidates that are effective against all subtypes of a given virus. The drug candidate is called broad spectrum.
High Barrier to Resistance
Viral resistance is a major obstacle to developing effective antiviral therapies that target viral molecules. Viruses reproduce rapidly and in enormous quantities.
During reproduction, random variations in viral molecules called mutations spontaneously develop. If such a mutation occurs in a viral molecule that is targeted
by an antiviral therapy that therapy may no longer be effective against the mutated virus. These mutated or "resistant viruses" can freely infect and multiply even
in individuals who have received treatment. In some cases, resistant virus strains may even predominate. For example, in the 2009 swine influenza pandemic,
the predominant strain was resistant to the best available therapies.
To overcome this obstacle, we identify and target critical components of viral replication enzymes that are crucial to the function of the enzyme and sensitive to change.
Any mutation in these critical enzyme components is likely to inactivate the enzyme and, in turn render the virus incapable of replicating. We test the effectiveness of
our compounds against potential viral mutations and select compounds with the highest barrier to resistance.
Market Driven Product Profiles
Patients at risk for suffering from many viral infections have few effective antiviral treatments from which to choose. Furthermore, some available treatment options have characteristics that limit their market potential. They are either priced too high, poorly tolerated, inconvenient to administer, ineffective against some viral subtypes or prone to emergence of resistance.
World Class Expertise
Our technology is based on the work of our Chief Scientist and Chairman of our Scientific Advisory Board, Dr. Roger Kornberg, and Dr. Raymond Schinazi.
Dr. Kornberg was awarded the 2006 Nobel Prize for Chemistry for his work to visualize a replication enzyme called RNA polymerase in action.
Using techniques called protein cocrystallization and X-ray crystallography, Dr. Kornberg and his colleagues generated three dimensional pictures
similar to the one on the left of RNA being transcribed by an RNA polymerase.
Dr. Schinazi is a world-class expert in discovering novel nucleoside therapeutics. He co-founded several successful antiviral companies including
Triangle Pharmaceuticals Inc., Idenix Pharmaceuticals Inc. and Pharmasset, Inc.
We are leveraging both Dr. Kornberg's and Dr. Schinazi's expertise in these methods to identify and develop new antiviral compounds.
Using these methods, our scientists are able to:
- Directly visualize how viral replication enzymes work
Identify key parts of these enzymes to target
Design compounds to block the function of these enzymes, thereby preventing viruses from replicating.
Discover novel nucleosides and other compounds, which inhibit viral replication
Influenza is a severe respiratory illness caused by either the influenza A or B virus that results in outbreaks of disease mainly during the winter months.
Currently approved antiviral treatments for influenza are partially effective and prone to viral resistance. Strains of flu virus that are resistant to approved treatments,
osteltamivir (Tamiflu™), zanamavir (Relenza™) and Xofluza have appeared and in some cases are predominant.
For example, the predominant strain of the 2009 swine influenza pandemic was resistant to Tamiflu™.
These drugs target one of two viral proteins, hemagglutinin or neuraminidase, neither of which is highly conserved between viral strains.
In fact, different influenza virus strains such as H1N1 and H5N1 are named by their respective differences in hemagglutinin (H) and neuraminidase (N) proteins.
The ability of the influenza virus to produce viable variants of these two proteins is the key to its ability to develop resistance.
To learn more about influenza, please visit the information page at the Center for Disease Control and Prevention (CDC).
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