Typhus, Endemic Flea-Borne

NV-387 Advancing to Phase II Clinical Trial for the Treatment of RSV Infection SHELTON, CT / ACCESSWIRE / May 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 March 31, 2024 with the Securities and Exchange Commission (SEC) on Tuesday, May 14, 2024. The report can be accessed at the SEC website by searching for the Company's filings. Financial Status We reported that, as of March 31, 2024, we had cash and cash equivalent current assets balance of approximately $3.51 Million. Additional agreements have resulted in a further approximately $2.5 Million available cash, that would be equivalent to a total of approximately $6 Million cash available to the Company with no further costs. In addition, we reported approximately $7.92 Million in Property and Equipment (P&E) and Intangible 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 $0.81 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 nine months from July 1, 2023 was approximately $4.84 Million. We anticipate certain additional costs from the Phase 1 clinical trial in India, which was completed recently, from the continuing work on statistical evaluations, and generation and submission of the Phase 1 final report. Management believes that the Company's existing resources, including availability under its $2 million line of credit will not be sufficient to fund the Company's planned operations and expenditures for at least 12 months from the date of the filing of this Form 10-Q. As a result substantial doubt exists about the Company's ability to continue as a going concern. Management plans to continue controlling its overall expenses and identifying and securing additional financing, as it has done in the past. We are seeking to mortgage our headquarters facility, estimated to be worth over $12-15 million, with a replacement cost exceeding $25 Million, in order to free up liquidity. There is currently no mortgage on this facility and it is fully owned by NanoViricides, Inc. To date, we have raised funds in the equity markets for the development of our assets. Additionally, we now have a clinical asset in NV-387 that is available for partnering. If partnered successfully, we can anticipate substantial initial payment, and milestone and royalty payments. NV-387, A Unique Drug Candidate with Broad-Spectrum Antiviral Activity Poised to Transform the Treatment of Viral Infections Reminiscent of the Broad-Spectrum Antibacterial Activity of Penicillin that Transformed Treatment of Bacterial Infections While NV-387 was developed in the context of the COVID-19 pandemic as a broad-spectrum pan-Coronavirus drug, we have found that it has strong antiviral activity against diverse types and families of viruses that include Coronaviruses, RSV, Influenza A, as well as Smallpox/Mpox in relevant animal models of these infections. Thus NV-387 could be the single drug that can combat all of the "tripledemic" viruses - Coronaviruses, RSV, and Influenza, an unmet medical need. We have found that the antiviral activity of NV-387 against RSV is strong enough to enable lethally infected animals to survive completely and not succumb to the infection. NV-387 thus could possibly be able to cure RSV infection. Therefore, having completed the Phase I successfully, we plan on advancing NV-387 towards Phase II clinical trial for the treatment of RSV infection under the US FDA. Our goal is to obtain regulatory approval for the use of NV-387 for the treatment of RSV infection in infants and children, where there is a critical unmet need. There is no drug approved for RSV treatment, except the last resort toxic drug ribavirin. Additionally, we plan on advancing NV-387 into Phase II studies for antiviral indications in India as well. We are in discussions with subject matter experts to determine how to harness the extremely broad-spectrum antiviral activity of NV-387 for rapid approval for the treatment of severe acute respiratory infections caused by viruses. Update on Further Development of NV-387 (NV-CoV-2) for COVID Indication The Phase 1 clinical trial for our lead drug candidate NV-CoV-2 (API NV-387) has completed successfully with no adverse events reported and clinical sites were closed in India. The COVID patient treatment part of the clinical trial could not be completed due to lack of patients eligible for recruitment as there were no COVID patients when our licensee and collaborator, Karveer Meditech Pvt Ltd and the CRO, PristynCR opened a second site in Salem, TamilNadu where a mini-COVID wave happened during February, 2024. However, by the time the second site was fully authorized with all regulatory approvals, the COVID wave had already passed and no COVID patients were found in a whole week of testing. Therefore, the CRO, the drug sponsor KMPL, in consultation with Principal Investigator, took the decision to close the clinical trial, having completed the Phase 1 clinical trial for the evaluation of safety and tolerability of NV-387 in healthy subjects in Single Ascending Dose and Multiple Ascending Dose studies, with no adverse events reported. The work on this clinical trial will continue and a final Phase 1 Clinical Trial Report will be generated and submitted. The weakening of the pandemic has worsened the difficulties in conducting clinical trials for COVID indication. We will continue to find non-dilutive funding for both COVID and Long COVID treatment, because we believe NV-387 has substantial chances of providing patient benefits in these cases. We plan on focusing our meager resources towards further development of NV-387 for the treatment of RSV, which is an endemic infection. 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 while drug development for this indication has become challenging. 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. 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, and is also effective against HSV-1 "cold sores" and HSV-2 "genital ulcers". Additionally the Company has a deep and wide pipeline of drug candidates with successful pre-clinical antiviral activity found against a large number of viruses including HIV, Influenza, and others. 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 host-side 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. Specifically, NV-387 is designed to mimic the host-side feature of Sulfated-Proteoglycans (S-PG) that is used by over 90% of human pathogenic viruses. This, we believe, is the key to its unprecedented, ultra-broad-spectrum antiviral activity crossing virus family and type boundaries. 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. 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. 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. Additionally, nanoviricides mimick the host-side features that the viruses continue to require in spite of mutations, and therefore the viruses would be highly unlikely to escape the nanvoricide drugs. Our lead drug candidate is NV-387 (drug product NV-CoV-2) for the treatment of RSV, COVID-19, Long COVID, Influenza, Bird Flu H5N1, and other respiratory viral infections. NV-387 has successfully completed a Phase 1a/1b human clinical trial in healthy subjects with no reported adverse events even at the highest and repeated dosages. The Company is currently focused on advancing NV-387 into Phase II human clinical trials for treatment of RSV infection. Our other advanced candidate is NV-HHV-1 for the treatment of Shingles rash, HSV-1 "cold sores" and HSV-2 "genital ulcers". 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 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". API means 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

A team of animal scientists is set to deliver a potential game changer for subsistence farmers in Tanzania: cows that produce up to 20 times the milk of indigenous breeds. A team of animal scientists from the University of Illinois Urbana-Champaign is set to deliver a potential game changer for subsistence farmers in Tanzania: cows that produce up to 20 times the milk of indigenous breeds. The effort, published in Animal Frontiers, marries the milk-producing prowess of Holsteins and Jerseys with the heat, drought, and disease-resistance of Gyrs, an indigenous cattle breed common in tropical countries. Five generations of crosses result in cattle capable of producing 10 liters of milk per day under typical Tanzanian management, blasting past the half-liter average yield of indigenous cattle. After breeding the first of these calves in the U.S., project leader Matt Wheeler, professor in the Department of Animal Sciences in the College of Agricultural, Consumer and Environmental Sciences (ACES) at Illinois, is ready to bring embryos to Tanzania. "High-yielding Girolandos -- Holstein-Gyr crosses -- are common in Brazil, but because of endemic diseases there, those cattle can't be exported to most other countries," Wheeler said. "We wanted to develop a high health-status herd in the U.S. so we could export their genetics anywhere in the world." Wheeler's team plans to implant 100 half-blood Holstein-Gyr or Jersey-Gyr embryos into indigenous cattle in two Tanzanian locations this March. The resulting calves will be inseminated through successive generations to create "pure synthetic" cattle with five-eighths Holstein or Jersey and three-eighths Gyr genetics. Unlike Girolandos, Jersey-Gyr pure synthetics do not yet have an official name. Pure synthetics are worth the time and effort; once the five-eighths/three-eighths genetics are established, they're locked in. In other words, calves from successive matings will maintain the same genetic ratio. "The whole idea is to keep the disease and pest resistance linked together with the milk production so that as you breed, those traits don't separate," Wheeler said. "That's going to be the challenge in developing countries; until you get to the pure synthetic generation, there will always be the temptation to breed to the bull down the road, losing the effect." Wheeler's team, including coauthor Moses Ole-Neselle of the Food and Agriculture Organization of the United Nations (FAO), cares about getting this effort right. Although developing the embryos took years of meticulous work, they're not stopping there. The team hosted its first online course on bovine assisted reproduction technology last summer, including 12 participants from Tanzania. And there's more to come. "It was important to start training the first group of veterinarians and graduate students to adopt the technology, so when we get there, it's not a foreign thing," Wheeler said. "The Tanzanian government wants this training and student exchanges. We're going to continue investing in this program for as long as it takes." Wheeler recognizes the best genetics and most comprehensive training won't amount to much if the plan doesn't account for the local culture. With advice from collaborators like the Tanzania Livestock Research Institute and Teresa Barnes, director of the Center for African Studies at Illinois, Wheeler has already adjusted his strategy to accommodate the preferences of local Maasai herdsmen. "We've learned some Maasai clans strongly prefer smaller, red cattle, so the Holstein crosses we made initially, which were large and black, weren't going to work," he said. "I had to start over with Jerseys, which set us back a bit. It will be worth it if they're better accepted." But some aspects of Tanzanian cattle management will have to change to realize the full potential of the improved genetics. For example, Wheeler said nomadic Maasai herders often graze cattle 25 miles from their enclosures each day, limiting the energy available for milk production. While the project is still in its early stages, it represents a step toward more climate-resilient animal agriculture, the topic of the special issue of Animal Frontiers in which Wheeler's article is published. While Wheeler's current priority is to bolster food security in the Global South where climate change is hitting hardest, he said the same technology could be used to protect cattle from changing climates here in the U.S. and around the world. In other words, tropical genetics could be inserted into our already high-yielding cattle to better withstand heat, drought, and disease. "These cattle would work very well in Mexico, Texas, New Mexico, and California. Maybe it's time to start thinking about that now," Wheeler said. "People don't usually think that far ahead, but my prediction is that people are going to look back and realize having tropical genetics earlier would have been a good thing."

FRIDAY, Aug. 4, 2023 -- Los Angeles county is seeing more cases of flea-borne typhus, with 171 cases and three deaths reported in 2022, health officials reported Thursday. That's a big rise, they noted: Since 2010, when only 31 cases of typhus were reported, fleas have been spreading the disease widely in the California city. While many people who become infected don't even know they're sick, those with serious medical conditions are at risk for severe illness or death, according to the U.S. Centers for Disease Control and Prevention. "We don't completely understand how typhus causes complications, but we do know that flea-borne typhus can cause complications in general, such as sepsis, fevers and issues with your liver," said report author Dr. Jemma Alarcon , a CDC epidemic intelligence service officer stationed in Los Angeles. The report was published Aug. 4 in the CDC's Morbidity and Mortality Weekly Report . "A majority of people are asymptomatic or have very mild disease. They might just get a headache and not even know that this is what they had," she explained. "In this instance, the flea-borne typhus, unfortunately, did affect the patients... one of them, her heart, and another one, his immune system was hyperactive, and the last one was related to sepsis and blood issues." Report co-author Dr. Umme-Aiman Halai , from the Los Angeles County Department of Public Health, said the number of infected fleas living on animals that people come into contact with has been increasing in Los Angeles. "There could be population expansion to suburban areas, increased contact with wildlife, lack of rodent control programs in urban centers and suburban areas," she noted. Global warming might also be leading to more infected fleas, but that's only speculation, Halai said. Regardless of the reason for the increase in cases, one expert said doctors need to take note. "This has been a rare and unusual condition, and to see reports that describe the increasing frequency of this tells me that in this world things are always changing," said Dr. Bruce Hirsch , an infectious disease specialist at North Shore University Hospital in Manhasset, N.Y. These three deaths are unusual, he noted. "Individuals who are dealing with other health conditions are more vulnerable to all kinds of complications, and all kinds of outcomes," Hirsch said. "We must add flea-borne typhus to that list." Alarcon is also concerned that doctors don't think of typhus when symptoms appear. "I am concerned that there could be cases where the patient does go to see the doctor, but the doctor might not know to test for this disease," she said. To protect yourself, the researchers suggested controlling fleas on your pets and avoiding contact with animals likely to carry fleas. In the first case detailed in the report, a 68-year-old Hispanic man suffering from lymph node disease, type 2 diabetes and obesity was hospitalized with typhus and treated with the antibiotic doxycycline. But he later died from a blood disorder and septic shock. The second patient, a 49-year-old Hispanic woman also treated with doxycycline, suffered several episodes of cardiac arrest and later died of multiple organ failure caused by typhus. The woman had feral cats living in her backyard. The third patient was a 71-year-old Hispanic man with a compromised immune system who also died of septic shock linked to typhus infection . This patient had been living in a homeless encampment, where he was most likely exposed to infected fleas. The fact that all the patients were Hispanic isn't relevant, Halai noted. It's merely a reflection of the population of Los Angeles, she explained. Flea-borne typhus is caused by a bacteria called Rickettsia typhi . It's spread by contact with fleas that are infected when they bite infected animals, such as rats, cats or opossums. Once bitten, the disease carried by flea poop can get into the wound and cause sickness. The infected poop can also be inhaled or rubbed into the eyes. This bacteria is not spread from person to person. Flea-borne typhus occurs in tropical and subtropical climates around the world, including Southern California, Texas and Hawaii, according to the CDC. Just last month, a Texas man lost his hands and part of his feet after contracting a severe case of typhus and going into septic shock. Symptoms begin within two weeks after contact with infected fleas or flea poop and may include: Fever and chills Body aches and muscle pain Loss of appetite Nausea Vomiting Stomach pain Cough Rash (typically occurs around day 5 of illness) Severe illness is rare and most people recover completely, sometimes without treatment. However, untreated disease can cause severe illness and damage to one or more organs, including the liver, kidneys, heart, lungs and brain, the CDC says. "The biggest concern here is that it's got to be under-diagnosed, because it's got a lot of symptoms that are easily mistaken for other symptoms, so it's got to be treated early," said infectious disease expert Dr. Marc Siegel , a professor of medicine at NYU Langone Medical Center in New York City. Siegel said typhus is easy to treat with doxycycline. But he's worried about the growing rodent and rat population in Los Angeles. "I'm concerned about more and more fleas carrying typhus and spreading it, but I don't know how to stop it," he said. Sources Jemma Alarcon, MD, epidemic intelligence service officer, U.S. Centers for Disease Control and Prevention Umme-Aiman Halai, MD, Los Angeles County Department of Public Health, Los Angeles Marc Siegel, MD, professor, medicine, NYU Langone Medical Center, New York City Bruce Hirsch, MD, infectious disease specialist, North Shore University Hospital, Manhasset, N.Y. Morbidity and Mortality Weekly Report , Aug. 4, 2023 Posted August 2023