Rift Valley Fever

Plus, Olema and Novartis update an agreement for a breast cancer trial, and Roche shares long-term data for Vabysmo in macular edema. CEPI puts $25M into vaccine for Rift Valley fever: The Coalition for Epidemic Preparedness Innovation is giving $25.9 million to Wageningen Bioveterinary Research to advance a live-attenuated vaccine for Rift Valley fever into a Phase I/IIa trial. CEPI said Tuesday that heavy rain and flooding are linked to outbreaks of the virus, which is primarily spread by mosquitoes in sub-Saharan Africa. “A RVF vaccine will contribute to preparedness for potential virus emergence in yet unaffected regions like Europe,” WBVR’s Paul Wichgers Schreur said in a statement. — Jaimy Lee

Antiviral therapies are notoriously difficult to develop, as viruses can quickly mutate to become resistant to drugs. But what if a new generation of antivirals ignores the fast-mutating proteins on the surface of viruses and instead disrupts their protective layers? Antiviral therapies are notoriously difficult to develop, as viruses can quickly mutate to become resistant to drugs. But what if a new generation of antivirals ignores the fast-mutating proteins on the surface of viruses and instead disrupts their protective layers? "We found an Achilles heel of many viruses: their bubble-like membranes. Exploiting this vulnerability and disrupting the membrane is a promising mechanism of action for developing new antivirals," said Kent Kirshenbaum, professor of chemistry at NYU and the study's senior author. In a new study published Aug. 2 in the journal ACS Infectious Diseases, the researchers show how a group of novel molecules inspired by our own immune system inactivates several viruses, including Zika and chikungunya. Their approach may not only lead to drugs that can be used against many viruses, but could also help overcome antiviral resistance. The urgent need for new antivirals Viruses have different proteins on their surfaces that are often the targets of therapeutics like monoclonal antibodies and vaccines. But targeting these proteins has limitations, as viruses can quickly evolve, changing the properties of the proteins and making treatments less effective. These limitations were on display when new SARS-CoV-2 variants emerged that evaded both the drugs and the vaccines developed against the original virus. "There is an urgent need for antiviral agents that act in new ways to inactivate viruses," said Kirshenbaum. "Ideally, new antivirals won't be specific to one virus or protein, so they will be ready to treat new viruses that emerge without delay and will be able to overcome the development of resistance." "We need to develop this next generation of drugs now and have them on the shelves in order to be ready for the next pandemic threat -- and there will be another one, for sure," added Kirshenbaum. Drawing inspiration from our immune systems Our innate immune system combats pathogens by producing antimicrobial peptides, the body's first line of defense against bacteria, fungi, and viruses. Most viruses that cause disease are encapsulated in membranes made of lipids, and antimicrobial peptides work by disrupting or even bursting these membranes. While antimicrobial peptides can be synthesized in the lab, they are rarely used to treat infectious diseases in humans because they break down easily and can be toxic to healthy cells. Instead, scientists have developed synthetic materials called peptoids, which have similar chemical backbones to peptides but are better able to break through virus membranes and are less likely to degrade. "We began to think about how to mimic natural peptides and create molecules with many of the same structural and functional features as peptides, but are composed of something that our bodies won't be able to rapidly degrade," said Kirshenbaum. The researchers investigated seven peptoids, many originally discovered in the lab of Annelise Barron at Stanford, a co-author of the study. The NYU team studied the antiviral effects of the peptoids against four viruses: three enveloped in membranes (Zika, Rift Valley fever, and chikungunya) and one without (coxsackievirus B3). "We were particularly interested in studying these viruses as they have no available treatment options," said Patrick Tate, a chemistry PhD student at NYU and the study's first author. How peptoids disrupt viral membranes and avoid other cells The membranes surrounding viruses are made of different molecules than the virus itself, as lipids are acquired from the host to form membranes. One such lipid, phosphatidylserine, is present in the membrane on the outside of viruses, but is sequestered towards the interior of human cells under normal conditions. "Because phosphatidylserine is found on the exterior of viruses, it can be a specific target for peptoids to recognize viruses, but not recognize -- and therefore spare -- our own cells," said Tate. "Moreover, because viruses acquire lipids from the host rather than encoding from their own genomes, they have better potential to avoid antiviral resistance." The researchers tested seven peptoids against the four viruses. They found that the peptoids inactivated all three enveloped viruses -- Zika, Rift Valley fever, and chikungunya -- by disrupting the virus membrane, but did not disrupt coxsackievirus B3, the only virus without a membrane. Moreover, chikungunya virus containing higher levels of phosphatidylserine in its membrane was more susceptible to the peptoids. In contrast, a membrane formed exclusively with a different lipid named phosphatidylcholine was not disrupted by the peptoids, suggesting that phosphatidylserine is crucial in order for peptoids to reduce viral activity. "We're now starting to understand how peptoids actually exert their antiviral effect -- specifically, through the recognition of phosphatidylserine," said Tate. The researchers are continuing pre-clinical studies to evaluate the potential of these molecules in fighting viruses and to understand if they can overcome the development of resistance. Their peptoid-focused approach may hold promise for treating a wide range of viruses with membranes that can be difficult to treat, including Ebola, SARS-CoV-2, and herpes. In addition to Kirshenbaum, Tate, and Barron, study authors include Vincent Mastrodomenico, Christina Cunha, and Bryan C. Mounce of Loyola University Chicago Medical Center; Joshua McClure of Maxwell Biosciences; and Gill Diamond of the University of Louisville School of Dentistry. The research was supported in part by the National Science Foundation (CHE-2002890 and NSF GRFP) and the National Institutes of Health (R35GM138199 and 1DP1 OD029517-01). Kirshenbaum is the Chief Scientific Officer for Maxwell Biosciences, a biotech company that has licensed patents originating from his lab at NYU. The company is seeking to commercialize these compounds and bring them to the clinic to advance human health.

ST. LOUIS, July 31, 2023 (GLOBE NEWSWIRE) -- Defender Pharmaceuticals, Inc. (the “Company” or “Defender”), a privately held life sciences company based in St. Louis, today announced that it had entered into an exclusive license agreement with the U.S. Army Medical Materiel Development Activity (USAMMDA), a subordinate laboratory of the U.S. Army. Medical Research and Development Command (USAMRDC), to develop and commercialize a total of eight products for use against the following tropical diseases: tularemia (rabbit virus); Venezuelan Equine Encephalitis (two formulations); Eastern Equine Encephalitis; Western Equine Encephalitis; Rift Valley Fever; chikungunya and Q Fever. The agreement was entered into on July 25th, 2023 and covers eight investigational vaccines that have been part of the Army’s Special Immunization Program. Under the agreement, USAMMDA will transfer the Investigational New Drug applications for each of the eight products, related data, and biological materials to Defender. Development work on these products will commence once this transfer is complete. Defender plans to work collaboratively with USAMMDA during the term of the agreement, with ongoing support from USAMRDC’s Office of Regulated Activities to advance product development, licensure, and commercialization of the licensed technology. “Entering into this license agreement with the U.S. Army is a significant step forward for Defender as a company and reinforces the strong and highly collaborative relationship we have established with the U.S. military and other government agencies,” said Barry I. Feinberg, M.D. and President & CEO of Defender Pharmaceuticals. “We are excited to begin work on these important and potentially life-saving products to protect not only our nation’s warfighters but everyone throughout the world exposed to these disease threats.” About the Tropical Diseases Information about Q Fever can be found at: Q Fever: Epidemiology and Statistics,” U.S. Centers for Disease Control and Prevention, available: https://www.cdc.gov/qfever/stats/index.html Information about Chikungunya Virus can be found at: Chikungunya Virus,” U.S. Centers for Disease Control and Prevention, June 2, 2022, available: https://www.cdc.gov/chikungunya/index.html Information about Rift Valley Fever can be found at: Rift Valley Fever, U.S. Centers for Disease Control and Prevention, Feb. 25, 2020, available: https://www.cdc.gov/vhf/rvf/index.html#:~:text=Rift%20Valley%20fever%20(RVF)%20is,through%20bites%20from%20infected%20mosquitoes Information about Lassa Fever can be found at: Lassa Fever: Signs and Symptoms,” U.S. Center for Disease Control and Prevention, March 25, 2014, available: https://www.cdc.gov/vhf/lassa/symptoms/index.html Information about Western Equine Encephalitis Virus can be found at: Western Equine Encephalitis,” Army Public Health Center, Entomological Sciences Division, FACT SHEET 18-045-0317, available:https://phc.amedd.army.mil/PHC%20Resource%20Library/WesternEquineEncephalitis_FS_18-045-0317.pdf Information about Eastern Equine Encephalitis Virus can be found at: Eastern Equine Encephalitis Virus: Statistics and Maps”, Oct. 31, 2022, Centers for Disease Control and Prevention, available: https://www.cdc.gov/easternequineencephalitis/statistics-maps/index.html Information about Venezuelan Equine Encephalitis can be found at: Venezuelan Equine Encephalomyelitis Standard Operating Procedures: 1. Overview of Etiology and Ecology,” U.S. Department of Agriculture, August 2013, available: https://www.aphis.usda.gov/animal_health/emergency_management/downloads/sop/sop_vee_e-e.pdf Information about Tularemia can be found at: Frequently Asked Questions (FAQ) About Tularemia,” U.S. Centers for Disease Control and Prevention, available: https://emergency.cdc.gov/agent/tularemia/faq.asp#:~:text=Tularemia%2C%20also%20known%20as%20%E2%80%9Crabbit,all%20U.S.%20states%20except%20Hawaii About Defender Pharmaceuticals, Inc. Defender Pharmaceuticals, Inc., located in St. Louis, MO, is a privately held life sciences company focused on discovering, developing and commercializing medicines to help safeguard health across civilian and military populations. Our work with the Department of Defense, NASA, the Department of Veterans Affairs, and other institutions advance our mission to improve the health of patients and help make the world a more secure place. Cautionary Note on Forward-Looking Statements Various statements in this press release, including but not limited to statements regarding Defender’s plans to co-develop products to treat various tropical diseases and pursue FDA approval, are forward-looking statements under securities law. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Examples of forward-looking statements include, among others, statements we make regarding our product candidates and the development thereof, such as the Company’s tropical disease co-development program; the therapeutic potential of our tropical disease product candidates; the Company’s regulatory plans and timelines for the tropical disease product candidates, including our planned submission of a New Drug Application for each of these product candidates. The process by which investigational therapies, such as these tropical disease product candidates, could potentially lead to an approved product is long and subject to highly significant risks. Other risk factors relevant to Defender include our reliance on third-party contract research organizations; the reliance of Defender on contract manufacturers to supply its products for research, development and commercialization and the risk of supply interruption from such contract manufacturers; the timing, plans and reviews by regulatory authorities of marketing applications such as NDAs for the tropical disease product candidates; alignment with the FDA on the regulatory pathway to approval for the tropical disease product candidates; market acceptance for approved product; competition; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated during development and following commercialization; and general business, financial, and accounting risks and litigation. The forward-looking statements contained in this press release reflect Defender’s current views with respect to future events as of the date of this press release, and Defender does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law. For media inquiries, please contact info@defenderpharma.com. For more information about Defender Pharmaceuticals, please visit www.defenderpharma.com. Source: Defender Pharmaceuticals, Inc.