Baloxavir Marboxil

BOTHELL, Wash., June 20, 2024 (GLOBE NEWSWIRE) -- Cocrystal Pharma, Inc.’s (Nasdaq: COCP) novel, broad-spectrum antiviral CC-42344 inhibits activity in the highly pathogenic avian influenza A (H5N1) PB2 protein recently identified in infected dairy cattle, according to recently completed in vitro studies. CC-42344 is a new class of antiviral drugs designed to block essential steps in the replication and transcription of the influenza A virus. Cocrystal is conducting an influenza A Phase 2a clinical study with orally administered CC-42344 and expects to report topline results in the second half of 2024. This study is evaluating the safety, tolerability, antiviral and clinical benefits in influenza A infected subjects. In late 2022 Cocrystal reported favorable safety and tolerability results from a Phase 1 study in healthy volunteers. Cocrystal demonstrated the potential efficacy of CC-42344 against the new avian flu strain with the recently published genome sequence for H5N1. Using its proprietary structure-based platform, Cocrystal created a high-resolution crystal structure of this avian PB2 protein and confirmed that CC-42344 binds to its highly conserved PB2 region. The in vitro data were generated testing CC-42344 against the avian H5N1 PB2 protein and further support CC-42344’s activity similar to that of Cocrystal’s data with pandemic and seasonal influenza A. CC-42344 binds to the highly conserved region ofthe avian influenza A H5N1 PB2 protein “The findings validate our broad-spectrum approach to the treatment and prevention of pandemic flu. This is important as there are no specific FDA-approved vaccines to prevent infections by this virus in humans,” said Sam Lee, PhD, President and co-CEO of Cocrystal. “These findings support our previously reported preclinical data showing that CC-42344 is highly active against seasonal and pandemic influenza A strains, including emerging mutations. CC-42344 is an inhibitor compound providing a unique mechanism of action with a high barrier to resistance.” “Recent CDC reported avian flu outbreaks in the U.S., which include the first cases of humans exposed to infected dairy cows, are concerning,” said James Martin, CFO and co-CEO of Cocrystal. “The CDC reported three additional cases of avian influenza infection from exposure to dairy cows in early June and avian flu is now confirmed in more than 100 dairy herds in 12 U.S. states.” About Avian Influenza A H5N1Avian influenza A H5N1 was reported in 889 cases and caused 463 deaths in 23 countries between 2003 and April 2024, according to the World Health Organization (WHO). On April 1, 2024, the CDC reported a case of highly pathogenic avian influenza A H5N1 in a farmworker in Texas during a multistate outbreak of avian influenza in dairy cows. Two more cases were subsequently reported in farmworkers in Michigan. The CDC analyzed sera (blood) collected from people of all ages in all 10 Health & Human Services regions during the 2022-2023 and 2021-2022 flu seasons. These samples were challenged with H5N1 virus to see whether there was an antibody reaction. Data from this study suggest that there is extremely low to no population immunity to clade 2.3.4.4b A (H5N1) viruses in the U.S. Antibody levels remained low regardless of whether or not the participants received a seasonal flu vaccination, meaning that seasonal flu vaccination did not produce antibodies to H5N1 viruses. Cocrystal Pharma determined the high resolution X-ray crystal structure of the recent avian influenza A (H5N1) PB2 protein and confirmed activity of CC-42344 in vitro (NIH GeneBank ID:influenza A/Texas/37/2024(H5N1). The crystal structure of the avian influenza A (H5N1) PB2 protein showed new mutations located outside the PB2 active site. Subsequent studies showed that CC-42344 binds to the active site of the avian influenza A (H5N1) PB2 protein as previously demonstrated with the pandemic and seasonal influenza A PB2. Preliminary in vitro assays confirmed that CC-42344 exhibits high potency against the avian influenza A (H5N1) PB2 protein. About CC-42344CC-42344 is Cocrystal’s novel, broad-spectrum, antiviral investigational candidate for the treatment of pandemic and seasonal influenza A. CC-42344 inhibits the first step in influenza A’s viral replication by binding to a highly conserved PB2 site of the influenza polymerase complex that is essential to replication and was discovered using Cocrystal’s proprietary structure-based drug discovery platform technology. Cocrystal is conducting a Phase 2a human challenge study in the United Kingdom to evaluate safety, viral and clinical measures of oral CC-42344 in healthy volunteers who are challenged with influenza A. CC-42344 was advanced into Phase 2a testing following favorable safety and tolerability results reported in a Phase 1 study in healthy volunteers conducted in Australia. In vitro testing showed CC-42344’s excellent antiviral activity against influenza A strains, including pandemic and seasonal strains, as well as against strains resistant to Tamiflu® and Xofluza®, while also demonstrating favorable pharmacokinetic and safety profiles. About Cocrystal Pharma, Inc.Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), noroviruses and hepatitis C viruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For further information about Cocrystal, please visit www.cocrystalpharma.com. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the potential efficacy of CC-42344 against the avian influenza A H5N1 virus, the expected timing and results of the Phase 2a trial for CC-42344 for the oral treatment of influenza A in 2024, and the potential market for such product candidate. The words "believe," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "could," "target," "potential," "is likely," "will," "expect" and similar expressions, as they relate to us, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events. Some or all of the events anticipated by these forward-looking statements may not occur. Important factors that could cause actual results to differ from those in the forward-looking statements include, but are not limited to, risks relating to our ability to obtain regulatory authority for and proceed with clinical trials including recruiting volunteers and procuring materials for such studies by our clinical research organizations and vendors, the results of such studies, our and our collaboration partners’ technology and software performing as expected, general risks arising from clinical studies, receipt of regulatory approvals, regulatory changes, and potential development of effective treatments and/or vaccines by competitors, including as part of the programs financed by the U.S. government, potential mutations in a virus we are targeting that may result in variants that are resistant to a product candidate we develop. Further information on our risk factors is contained in our filings with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2023. Any forward-looking statement made by us herein speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law. Investor Contact:LHA Investor RelationsJody Cain310-691-7100jcain@lhai.com Media Contact:JQA PartnersJules Abraham917-885-7378Jabraham@jqapartners.com # # #

SHELTON, CT / ACCESSWIRE / June 20, 2024 / NanoViricides, Inc. (NYSE AmerIcan.:NNVC) (the "Company"), a clinical stage company and global leader in broad-spectrum antiviral nanomedicines, reports that the ultra-broad-spectrum antiviral NV-387, a clinical Phase II stage drug candidate, was found to be effective in protecting lungs from damage in a lethally infected Influenza A H3N2 mouse model. "We believe that the lung protection afforded by NV-387 is a very important result. The most severe cases that lead to hospitalization and fatalities in respiratory viral infections involve lung damage as an important factor," said Anil R. Diwan, PhD, President and Executive Chairman of the Company, adding, "This was starkly evidenced during COVID-19 pandemic wherein the Delta variant that caused severe lung damage also caused the largest number of hospitalizations and fatalities. Influenzas, RSV, COVID can all cause severe lung damage resulting in fatalities." 1. NV-387 Treatment Resulted in Significant Reduction in Lung Infiltration and Lung Cell Death Lungs of infected animals treated with NV-387, orally or intravenously, showed very limited presence of infiltrating cell-killing immune cells that are known to be an important cause of lung damage, in addition to the direct lung damage from infected cell death caused by the virus itself. Further, the overall lung damage was significantly reduced upon NV-387 treatment. On day 7 post-infection, NV-387 oral treatment resulted in only about 31% lung infiltration by immune system cells, and NV-387 intravenous treatment resulted in an even lower, about 22%, infiltration rate, whereas the lungs of infected untreated animals had a very high 68% infiltration rate (smaller is better), as determined by micro-histopathology of lung tissues using specific staining techniques. 2. NV-387 Treatment Resulted in Significant Reduction in Mucus Load in the Lungs Additionally, the extent of mucus in the lung tissue was substantially reduced in the case of oral as well as intravenous NV-387 treatment. The mucus index value in the case of NV-387 oral treatment was about 53, and for intravenous NV-387 treatment it was about 32, as compared to the infected untreated animals that had a mucus index value of 138 (smaller is better). Mucus is secreted by secretory cells in response to viral infection in an attempt to clear the virus, but it results in reduced lung capacity and eventually can lead to pneumonia. Thus reduction in mucus load is an important sign that the progress of the viral infection is arrested. NV-387 Treatment Significantly Protected Lungs of Balb-c Mice Lethally Infected with Influenza A/H3N2 Virus Treatment Lung Mucus Index % Immune Cell Infiltration NV-387, Intravenous 32 22% NV-387, Oral 53 31% Untreated Infected Control 138 68% These results indicate that NV-387 treatment led to a significant level of protection of lungs in Balb-c mice lethally infected with Influenza A H3N2 virus. 3. NV-387 Treatment Resulted in Significantly Greater Survival Improvement Compared to Three Approved Influenza Drugs Previously, we reported from this same animal study that NV-387 treatment led to substantially longer animal survival compared to the three approved influenza drugs, namely Oseltamivir (Tamiflu ®, Roche), Rapivab (Peramivir, BioCryst), and Baloxavir (Xofluza®, Shionogi, Roche). NV-387 treatment, both intravenous and oral, led to increase in survival of animals by a substantial 88% over the infected untreated controls, whereas the three approved drugs only increased survival marginally, by about 25% to 38%. These results indicate that NV-387 was substantially superior to the three approved influenza drugs in this animal study. The above results demonstrate that NV-387 possesses strong antiviral activity against Influenza viruses. 4. Viral Resistance to NV-387 is Unlikely as Opposed to Known Evolution of Viral Resistance Against Currently Approved Drugs Baloxavir resistant mutants were found to develop in as many as 10% of treated patients in its Phase III clinical trials. Oseltamivir resistant mutants are known and circulating, and they exhibit resistance to Peramivir as well. In contrast, even as influenza viruses mutate, they would be highly unlikely to escape NV-387. This is because NV-387 is an ultra broad-spectrum antiviral that is designed as a host-mimetic (See paragraph (a) below). 5. NV-387 Has Completed Phase I Human Clinical Trial There were no reported adverse events, and there were no dropouts in the Phase I human clinical trial of NV-387, indicative of excellent safety and tolerability of NV-387. This drug candidate is thus ready for further development in Phase II clinical trials. In summary, NV-387 is poised to become a very important drug in the fight against Influenza viruses, we believe. (a). Host-Mimetic Nanoviricide Drug Candidate NV-387 is Designed to Attack Many Viruses; with Escape of Virus Unlikely All influenza viruses bind to the host's sulfated proteoglycans ("S-PG") as primary attachment receptors and cellular sialic acids as cognate receptors; the latter enabling entry into cells. NV-387 is designed to copy the invariant or conserved features of S-PG and present itself like a human cell decoy to the virus. As the virus binds to the NV-387 metamorphic ("shape-shifter") micelle, the NV-387 polymer chains are expected to wrap onto the virus surface, via a well known process called "lipid-lipid fusion", merging the lipid chains of the NV-387 polymer with the lipid coat of the virus particle. This is expected to result in destabilization of the virus, uprooting the H and N proteins from the virus surface, thereby making the virus incapable of attacking human cells. A safe and effective antiviral drug that the virus would not escape by simple mutations or field evolution is the holy grail of antiviral drug development. We believe that the NanoViricides Platform technology meets this challenge. About NanoViricides NanoViricides, Inc. (the "Company") ( ) is a development stage company that is creating special purpose nanomaterials for antiviral therapy. The Company's novel nanoviricide® class of drug candidates are designed to specifically attack enveloped virus particles and to dismantle them. Our lead drug candidate is NV-CoV-2 for the treatment of RSV, COVID-19, Long COVID, and other respiratory viral infections. Our other advanced candidate is NV-HHV-1 for the treatment of Shingles (previously referred to as NV-HHV-101). The Company cannot project an exact date for filing an IND for any of its drugs because of dependence on a number of external collaborators and consultants. The Company is currently focused on advancing NV-CoV-2 into Phase I/II human clinical trials. NV-CoV-2 is our nanoviricide drug candidate for COVID-19 that does not encapsulate remdesivir. NV-CoV-2-R is our other drug candidate for COVID-19 that is made up of NV-CoV-2 with remdesivir encapsulated within its polymeric micelles. The Company believes that since remdesivir is already US FDA approved, our drug candidate encapsulating remdesivir is likely to be an approvable drug, if safety is comparable. Remdesivir is developed by Gilead. The Company has developed both of its own drug candidates NV-CoV-2 and NV-CoV-2-R independently. The Company is also developing drugs against a number of viral diseases including oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others. NanoViricides' platform technology and programs are based on the TheraCour® nanomedicine technology of TheraCour, which TheraCour licenses from AllExcel. NanoViricides holds a worldwide exclusive perpetual license to this technology for several drugs with specific targeting mechanisms in perpetuity for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Rabies, Herpes Simplex Virus (HSV-1 and HSV-2), Varicella-Zoster Virus (VZV), Influenza and Asian Bird Flu Virus, Dengue viruses, Japanese Encephalitis virus, West Nile Virus, Ebola/Marburg viruses, and certain Coronaviruses. The Company intends to obtain a license for poxviruses and/or enteroviruses if the initial research is successful. The Company's technology is based on broad, exclusive, sub-licensable, field licenses to drugs developed in these areas from TheraCour Pharma, Inc. The Company's business model is based on licensing technology from TheraCour Pharma Inc. for specific application verticals of specific viruses, as established at its foundation in 2005. As is customary, the Company must state the risk factor that the path to typical drug development of any pharmaceutical product is extremely lengthy and requires substantial capital. As with any drug development efforts by any company, there can be no assurance at this time that any of the Company's pharmaceutical candidates would show sufficient effectiveness and safety for human clinical development. Further, there can be no assurance at this time that successful results against coronavirus in our lab will lead to successful clinical trials or a successful pharmaceutical product. This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. Actual events could differ materially and substantially from those projected herein and depend on a number of factors. Certain statements in this release, and other written or oral statements made by NanoViricides, Inc. are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. Important factors that could cause actual results to differ materially from the company's expectations include, but are not limited to, those factors that are disclosed under the heading "Risk Factors" and elsewhere in documents filed by the company from time to time with the United States Securities and Exchange Commission and other regulatory authorities. Although it is not possible to predict or identify all such factors, they may include the following: demonstration and proof of principle in preclinical trials that a nanoviricide is safe and effective; successful development of our product candidates; our ability to seek and obtain regulatory approvals, including with respect to the indications we are seeking; the successful commercialization of our product candidates; and market acceptance of our products. The phrases "safety", "effectiveness" and equivalent phrases as used in this press release refer to research findings including clinical trials as the customary research usage and do not indicate evaluation of safety or effectiveness by the US FDA. FDA refers to US Food and Drug Administration. IND application refers to "Investigational New Drug" application. cGMP refers to current Good Manufacturing Practices. CMC refers to "Chemistry, Manufacture, and Controls". CHMP refers to the Committee for Medicinal Products for Human Use, which is the European Medicines Agency's (EMA) committee responsible for human medicines. API stands for "Active Pharmaceutical Ingredient". Contact: NanoViricides, Inc. info@nanoviricides.com Public Relations Contact: MJ Clyburn TraDigital IR clyburn@tradigitalir.com SOURCE: NanoViricides, Inc. View the original press release on accesswire.com