Influenza in Birds

Patients are not islands, nor does medicine exist outside of society. Alliances of family, friends, community partners, caregivers, and clinicians accompany us through even the most acute health care experiences. Recognizing and building on these coalitions promotes people-centered care by activating relationships, supporting people through equity, and overcoming dehumanizing environments with solidarity — I am in this for you because I know that you are in it for me; we are in this together. How might such people-centered care impact health outcomes? Let’s reflect on this question through the story of Diego Naranjo. Diego’s story Diego Naranjo rose with great difficulty early on the morning of May 14, 2018, having tried to sleep off a combination cold and fever over the weekend, and drove to a client meeting in Medellín, Colombia, that he felt he could not miss. He exited the meeting unable to stop coughing and hardly able to breathe and called his wife Claudia to say that he needed to go to the emergency room and would pick her up on the way. Diego was quickly diagnosed with pneumonia and hospitalized, then taken to the intensive care unit (ICU) to be intubated as his condition deteriorated. The next thing he knew, he struggled to open his eyes, sensed Claudia’s presence, and told her that he loved her. She caressed his face and responded with great emotion that he was in the Clínica Cardio VID of Medellín, had been in a coma induced by the H1N1 influenza for 75 days, and should be careful not to move because he was connected to a machine (ECMO) that was keeping him alive. Diego had received exceptionally high-quality care throughout his coma, which continued through his recovery. A key ingredient, perhaps the key ingredient, was the bond established between his family and the team of health care providers and caregivers. Family and community members arrived from day one to support him and Claudia in any way possible, and they were permitted significant access. They established relationships with doctors, nurses, assistants, even the cafeteria staff, and their contagious love for Diego gelled with the positivity and warmth of his care team, even in the most difficult moments. The medical team communicated frequently and openly with Claudia and others, engaging them in important decisions, and took up Diego’s cause as their own, showing genuine enthusiasm for every glimmer of hope and sign of progress. This solidarity humanized Diego’s difficult treatment (one grandson counted 18 tubes and hoses coming in and out of his body) in the face of multiple near-death experiences, fostering trust that enabled the medical team and family to make effective and rapid decisions at critical moments, such as deciding to take him off the ECMO. “It was all or nothing!” Claudia wrote in her diary. “I told them yes, let’s go for it, and we jumped into the water.” The unity of support from loved ones, clinicians, and caregivers — when combined with his faith — kept Diego committed to life through the most difficult moments of his recovery. When he first opened his eyes, when he came off the ECMO, when he took his first steps, when he was finally cleared to go home weeks later, they all celebrated moments of mutual victory. Solidarity in people-centered care Since the groundbreaking 2001 Institute of Medicine report Crossing the Quality Chasm proposed the patient-centered care model, efforts to improve health care have emphasized health promotion as much as disease prevention. Many health and allied professionals in the United States now use the phrase person-centered care as they seek to address the “whole person.” Diego’s story indicates the potential in following the World Health Organization (WHO) and others in taking an additional step to speak of people-centered care. In a 2021 report by the National Academies of Sciences, Engineering, and Medicine on high-quality primary care, the authors write that “… relationships with the people, their families, and the communities being served; and equity, which acknowledges and empowers those people, families, and communities … represent an important transition in how primary care needs to move forward in the twenty-first century.” I would add solidarity as the critical galvanizing force necessary to overcome the institutional legacy of dehumanizing health care systems. Imbuing people-centered coalitions with solidarity for our health — the sense that we’re in it together — requires mutual trust and commitment and even, as Diego would say, love. How do we realize such solidarity? Whether in Colombia or the U.S. or elsewhere, this calls for strong social ties, equitable access to care, and providers enabled to bring their whole selves to work. Four modest system improvements in the U.S. are assisting with valuing and activating people’s families and support networks in health care today: What would it take for all patients’ supporters to feel as welcome as Diego’s did in the ICU, accompanying their loved ones and participating with medical teams in caregiving and decision-making? The adoption of flexible hospital visitation policies has shown progress in this regard, of course with dramatic setbacks during the Covid-19 pandemic. Medical respite, in which a professional “subs in” for an individual’s primary caregiver, usually a family member or close companion, for a meaningful number of days per year also supports family involvement. In California, 336 hours annually of medical respite are now a covered benefit offered through the state’s Medicaid program, enabling people to remain at home who otherwise might be institutionalized. A third positive development is the increasing adoption of policies and technology platforms that give trusted family and companions access to the medical record and empower them to collaborate with medical staff and other service providers as participants on the care team. In linguistically diverse environments, the uptake of AI and machine translation tools for communication between caregivers and families can address key gaps in translation services. Health care providers are just scratching the surface in learning how — and how not — to use such methods to establish solidarity with their patients and patients’ support networks. Conclusion Diego writes in his book that a much younger man was admitted around the same time as him to the same high-quality medical facility with the same condition, H1N1, and was also connected to an ECMO. This young man did not have any visitors, he was intolerant with the nurses and other staff, and could be heard shouting at them. Tragically, he died within a week. We don’t know anything about his circumstances except that he did not receive support from family or community in the ICU, as Diego did, nor did he feel solidarity with the medical team — and he suffered a dramatically different outcome. Dr. John Rowe, a professor of health policy and aging at Columbia University, tells his medical students, “One of the best indicators of how well an elderly patient will be faring in six months is to ask him ‘how many friends or family he’s seen in the last week.’” In reflecting on his own experience relative to that of others such as this man, Diego writes, “I am certain that science is fundamental… I simultaneously have the certainty and am a living witness that love and solidarity have an enormous curative effect beyond giving the patient an irreplaceable incentive to seek improvement.” Linking arms with individuals, their families, and their communities enables health care stakeholders to harness this power of love and solidarity, enriching today’s whole-person approaches with people-centered care at the heart of health.

The prospect of the worrisome triple threat of COVID, RSV and flu was assuaged last year by the effectiveness of flu vaccines. Two recent studies from the Centers for Disease Control and Prevention's VISION Network have found that flu vaccines were effective for all ages against both moderate and severe flu in the U.S. during the 2022-2023 flu season. The prospect of the worrisome triple threat of COVID, RSV and flu was assuaged last year by the effectiveness of flu vaccines. Two recent studies from the Centers for Disease Control and Prevention's VISION Network have found that flu vaccines were effective for all ages against both moderate and severe flu in the U.S. during the 2022-2023 flu season. Both the pediatric and adult VISION Network studies analyzed flu-associated emergency department (E.D.)/urgent care visits (indicative of moderate disease) and hospitalization (indicative of severe disease) from October 2022 through March 2023, a flu season in which far fewer individuals were social distancing or wearing masks than during the two previous flu seasons. Vaccination reduced the risk of flu-related E.D./urgent care visits and hospitalization for those 6 months to 17 years by almost half. For adults, regardless of age, vaccination reduced the risk of E.D. urgent care visits by almost half and reduced the risk of hospitalization by slightly more than a third. These results led the authors of both studies to conclude that flu vaccination is likely to substantially reduce illness, death and strain on healthcare resources. "We study the effectiveness of flu and other vaccines to ensure that our processes for forecasting the most effective vaccines are working well and therefore might potentially also be translatable to other diseases as well," said Shaun Grannis, M.D., M.S., a co-author of both the pediatric and adult VISION Network studies, Regenstrief Institute vice president for data and analytics and a family practice physician. "Given influenza's significant disease burden -- for example the H1N1 (swine) flu killed over a quarter of a million people worldwide in 2009-2010 -- we want to make sure that we understand virus trends as well as other factors and that we're continuing to do as well as and as much as we can to reduce the flu disease burden." Both the pediatric and adult studies evaluated electronic health record (EHR) data from sites across three healthcare systems in California, Utah, Minnesota and Wisconsin. Flu vaccine effectiveness: 2022-2023 flu season for ages 6 months to 17 years Vaccination reduced the risk of flu-related E.D./urgent care visits (moderate disease) by 48 percent and hospitalization (severe disease) by 40 percent overall across ages 6 months to 17 years. Broken down by age, risk reduction was greater for those age 6 months to 4 years than older children and adolescents. Ages 6 months to four years Ages 5 to 17 years Approximately 30 percent of E.D./critical care visits for acute respiratory illness in children and adolescents were positive for flu, as were 14 percent of hospitalizations. "Vaccine Effectiveness Against Pediatric Influenza-A-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2022-2023 Season, VISION Network" is published in Clinical Infectious Diseases. Flu vaccine effectiveness: 2022-2023 flu season for ages 18-64 Vaccine effectiveness was 45 percent against E.D./critical care visits(moderate disease) for adults under age 65. Effectiveness against hospitalization (severe disease) was 23 percent. Adults younger than 65 typically received standard-dose inactivated vaccines. Flu vaccine effectiveness: 2022-2023 flu season for ages 65 and older Vaccine effectiveness was 41 percent against both flu-associated E.D./urgent care visits (moderate disease) and hospitalization (serious disease) for this age group. Adults age 65 and older typically received enhanced vaccine products. "Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023" is published in the Journal of Infectious Diseases. "As with COVID, the dynamics of flu differs between children and adults. But we found that for both children and adults, vaccination significantly reduced the need for trips to the E.D, or critical care center and for hospitalization for flu-related illnesses last flu season and this is encouraging," said Dr. Grannis. "I'm hopeful that we will see similar or even better vaccine effectiveness during the current flu season. Even if they do experience symptoms, people who are vaccinated typically tend to have milder, shorter cases of the flu, a viral illness which can carry a severe disease burden. "The vaccine effectiveness we saw in last year's flu season is encouraging. As both a research scientist and a primary care physician, I urge everyone to be vaccinated for flu this year and every year -- it's good for each person's health and the health of your community." About Shaun Grannis, M.D., M.S. In addition to his role as the vice president for data and analytics at Regenstrief Institute, Shaun Grannis, M.D., M.S., holds the Regenstrief Chair in Medical Informatics and is a professor of family medicine at Indiana University School of Medicine.

SHELTON, CT / ACCESSWIRE / February 15, 2024 / NanoViricides, Inc. (NYSE American:NNVC) (the "Company"), a global leader in broad-spectrum antiviral nanomedicines, reports that it has filed its Quarterly Report on Form 10-Q for the fiscal second quarter ending December 31, 2023 with the Securities and Exchange Commission (SEC) on Wednesday, February 14, 2024. The report can be accessed at the SEC website at . Financial Status - Sufficient Funds to Conduct Clinical Trial We reported that, as of December 31, 2023, we had cash and cash equivalent current assets balance of approximately $5.31 Million. Additional agreements have resulted in a further approximately $2.5 Million available cash, that would be equivalent to a total of approximately $7.8 Million cash available to the Company with no further costs. In addition, we reported approximately $8.07 Million in Intangible Assets and Property and Equipment (P&E) assets, net of depreciation and amortization from $14.7 Million in P&E assets before depreciation. The strong P&E assets are comprised of our cGMP-capable manufacturing and R&D facility in Shelton, CT. The total current liabilities were approximately $0.95 Million. In comparison, as of June 30, 2023, we had cash and cash equivalent current assets balance of approximately $8.15 Million, and additional approximately $8.1 Million in Property and Equipment (P&E) assets, net of depreciation and amortization, while the total current liabilities were approximately $0.41 Million. The net cash utilized in the six months from July 1, 2023 was approximately $2.89 Million. As our clinical trials for NV-CoV-2, our lead drug candidate, progress further, our cash expenditure rate is expected to increase. NV-CoV-2 is a unique, ultra-broad-spectrum antiviral nanomedicine in that we believe it may be a single drug that is effective for the treatment of many viral infections. These include, SARS-CoV-2 infection that causes COVID, RSV infections as well as Poxvirus infections (including Smallpox, a bioterrorism threat, Mpox, a recurring epidemic causing virus, and Alaskapox, an emerging zoonotic infection that recently claimed one human life in the USA.) Several steps were taken to improve our cash flow and potential disbursements for the following one year budgeting period. The Company's Board requested TheraCour Pharma, Inc., our largest shareholder and licensor of our technology ("TheraCour"), to change the milestone payments clause of the COVID Licensing Agreement so that any forthcoming milestones would be acknowledged at achievement, but any cash award corresponding to the same would only be payable from a revenue stream generated from the product or product development operations, excluding capital or debt financings. The Coronavirus License Agreement between TheraCour, the Licensor, and NanoViricides, the Licensee was amended on February 12, 2023 to provide for the same. Additionally, the Company requested, and TheraCour agreed on February 12, 2023, that the required 2-month equivalent advance maintained by the Company, which at present is approximately $500,000, be applied to current bills and that no advance be required until the Company has sufficient funds to support the same. On October 27, 2023, TheraCour, our largest shareholder and licensor of our technology, exercised its right to convert the principal of the July 19, 2023 $1,500,000 convertible promissory note into 331,859 shares of the Company's Series A preferred stock and forgave and cancelled all of the accrued interest of $49,808 on the note. On November 8, 2023, the Company's President and CEO, Dr. Anil R. Diwan, agreed to provide a standby Line of Credit to the Company in the maximum amount of $2,000,000, with interest payable only on amounts drawn. On February 12, 2023, the maturity date of the Line of Credit was extended to December 31, 2025. The Company does not anticipate any borrowings under the Line of Credit during the current fiscal year. These actions have significantly improved the near-term liquidity outlook. NanoViricides Drug Pipeline Addresses Several Billion Dollars in Market Sizes for Many Unmet Medical Needs The market size for COVID drugs is expected to continue to be in the billions of dollars range. The market size of an RSV therapeutic is estimated to be several billions of dollars. Although smallpox therapeutics are limited to government stockpiling, the market size for an effective smallpox therapeutic is estimated to be in the order of several hundred million dollars per year. The nanoviricide drug NV-387 in Phase 1a/1b clinical trials itself alone addresses all of these markets. In addition the Company has previously developed the drug candidate NV-HHV-1 through IND-enabling safety/toxicology studies. NV-HHV-1 skin cream formulation is designed for the treatment of Shingles Rash, which is also effective against HSV-1 "cold sores" and HSV-2 "genital ulcers". The Company has a deep and wide pipeline of drug candidates with successful pre-clinical effectiveness against a large number of viruses including HIV, Influenza, and others. Drug Development Status Strong Safety and Tolerability of NV-CoV-2 Oral Syrup and Oral Gummies Established in Phase 1a/1b Human Clinical Trial On January 29, 2024, we reported that the Healthy Subjects Part of the Phase 1a/1b Human Clinical Trial of NV-CoV-2 (API NV-387), our broad-spectrum antiviral drug, were completed successfully. All subjects have been successfully discharged. There were no discontinuations. All dosage levels at all dosing instances were well tolerated. There were no adverse events. Thus the drug NV-387 was found to be safe for both single dosing and for repeat dosing even at amounts as high as 40 mg/Kg, including a first "loading" dose at 80mg/Kg. The data are undergoing internal audit. After this, the data will be provided for biostatistical analysis. The second part of the Phase 1a/1b clinical trial is the treatment of COVID patients suffering from mild to moderate disease. We believe that the recent COVID wave in India is providing an opportunity to conduct this part of treating COVID patients with our drug and we have undertaken efforts towards this goal. This part is designed to evaluate the safety and tolerability of NV-CoV-2 in COVID patients, and to obtain information on the effective dosing level(s) to select for the subsequent Phase II/III clinical trials. The clinical trial in India is managed by our licensee and collaborator, and Indian drug sponsor company, Karveer Meditech Pvt. Ltd., and is conducted by the clinical research organization (CRO) PristynCR. The strong safety and tolerability of NV-387 demonstrated in human clinical trial implies that it can be used: (i) across all ages from pediatrics to seniors; (ii) irrespective of co-morbidities such as diabetes, other pre-existing diseases, or immune compromised status of the individual; and (iii) at all levels of disease severity, from mild/moderate to severe to very severe (hospitalized patients)1. This capability of NV-387 is analogous to the highly successful antibiotics against bacteria. In contrast, currently available antiviral drugs have substantial limitations on the patient populations that they can be used in. For example, of the two remaining approved drugs for treatment of COVID, Paxlovid which is given orally, is not indicated for the treatment of COVID-19 in patients without a risk factor for progression to severe COVID-19, whereas Remdesivir can only be used in hospitalized cases. Ultra-Broad Antiviral Spectrum of NV-CoV-2 Oral Syrup and Oral Gummies Enables Phase II/III Clinical trials for Multiple Indications We believe that upon completion of the Phase 1a/1b human clinical trials of NV-CoV-2, the NV-387 oral formulations are expected to be eligible for Phase II/III clinical trials for RSV. There is no therapeutic available for RSV other than the last resort option of toxic drug Ribavirin. We anticipate that NV-387 formulations would be expected to be eligible for the development of Poxvirus therapeutics under the FDA "Animal Rule," if further studies are successful. We plan to seek non-dilutive government funding for this indication. NV-387 has such broad-spectrum activity because it is designed to mimic the attachment receptors to which over 90% of viruses bind before infecting a cell. We are currently engaged in expanding the spectrum of activity of NV-387. NV-387 is an example of NanoViricides Platform Modality #1 implementation. Escape of Viruses from NanoViricides Platform Drugs is Unlikely NanoViricides Platform Technology has an important advantage in that no matter how much a virus changes in the field, it is unlikely to escape the nanoviricide drug because it is designed to mimic the very features that the virus uses to bind to and enter cells. These specific molecular signature features on the cellular side do not change even as the virus mutates, and nanoviricides are designed to mimic these features. In contrast, viruses readily escape antibodies as drugs, as well as vaccine-induced immunity as they evolve in the field, as is well known from the COVID-19 pandemic as well as Influenza pandemics and the continuing HIV/AIDS pandemic. 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. Manufacturing Capacity Increase in Preparation of Drug Supply for Phase II Clinical Trials Importantly, in the reported quarter, we have approximately doubled our production batch size and capacity for NV-387 manufacture. We believe that this capacity will be sufficient for Phase II clinical trials for COVID or Phase II/III clinical trials for RSV. The production program for Phase II clinical supply is expected to be commissioned soon. Additional information regarding the NanoViricides Platform Technology, and the NanoViricides Drug Pipeline can be found in our Annual Report filed with the SEC filed with the SEC on October 13, 2023. [1] Statements regarding safety and effectiveness or NV-CoV-2 and NV-387 have not been evaluated by the US FDA. 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 COVID-19 disease caused by SARS-CoV-2 coronavirus. 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. 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". (1. Cagno V, Tseligka ED, Jones ST, Tapparel C. Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias? Viruses. 2019 Jul 1;11(7):596. doi: 10.3390/v11070596. PMID: 31266258; PMCID: PMC6669472.) 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