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Broad-Spectrum Antivirals: An Essential Tool for Biosecurity

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A presentation by Jassi Pannu of Stanford University's School of Medicine on "Broad-Spectrum Antivirals: An Essential Tool for Biosecurity."

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Broad-Spectrum Antivirals: An Essential Tool for Biosecurity

  1. 1. Broad-spectrum antiviral drugs: Tool for biosecurity Jassi Pannu
  2. 2. BACTERIA VIRUSESFUNGHI PARASITES PRIONS
  3. 3. Why are viruses particularly concerning? ● Airbourne, droplet or contact transmission between humans and/or animals ● Ability to harm hosts (virulence/pathogenicity) ● Small genomes, relatively easy to synthesize & manipulate, potentially weaponize ● Lack of medical countermeasures
  4. 4. Narrow- spectrum antivirals Broad- spectrum antivirals
  5. 5. “ Broad-spectrum therapeutics should be pursued given their potential value, even if the likelihood of identifying such medicines remains low. ” Source: Pandemic Pathogens. Johns Hopkins Center for Health Security
  6. 6. The promise of broad-spectrum antivirals ● Treat entirely new or engineered virus ● Treat before detailed diagnosis ● More cost-effective to develop versus “one bug-one drug” approach ● Treat only those infected, versus vaccinating all ● Efficient stockpiling in case of catastrophic event or attack
  7. 7. Main Roadblocks to Development Scientific Commercial Regulatory
  8. 8. Scientific Target shared mRNA secondary structures or shared host targets Repurpose existing host-targeting drugs (e.g. kinase inhibitors, chloroquine, nitazoxanide) Boost existing immune system function (e.g. novel interferons) Viruses are genetically and mechanistically divergent
  9. 9. Scientific Viruses are genetically and mechanistically divergent Target shared mRNA secondary structures or shared packaging mechanisms Repurpose existing host-targeting drugs (e.g. kinase inhibitors) Boost immune system function (novel interferons)
  10. 10. NIH-funded labs working on BSAVs Over $250M provided to fund this research: Paul Malone Allen Washington University - $32.7M, 2014-2018 Autophagy modulators as novel broad-spectrum anti-infective agents Jeffrey Glen Stanford University - $28.6M, 2014-2019 Advancing broad spectrum host-targeting antiviral strategies to the clinic Ulrich H Von Andrian Harvard Medical School - $9.751 M, 2014-2018 Mechanisms and immunological consequences of host-virus interactions Ralph Baric UNC Chapel Hill - $3.79M, 2017-2019 Broad-spectrum antiviral GS-5734 to treat MERS-COV and related emerging COV Anne Moscona Columbia University - $3.7M, 2015-2019 Engineering protease-resistant alpha-beta peptides for broad spectrum antivirals Beth C Levine (2) UT Southwestern - $2.0M, 2018 Autophagy-inducing peptides and target identification for treatment of viruses UT Southwestern - $1.5M, 2019 RP1: Targeting Beclin 1 complexes for broad-spectrum anti-infective therapeutics John Huibregtse UT Austin - $3.1M, 2011-2019 Mechanism and function of ISG15 Herbert W Virgin (2) Washington University - $1.6M, 2018 Genes/pathways for ATG gene-dependent inhibition of viruses & parasite infection
  11. 11. Commercial Little incentive to develop drugs for rare events in advance Low reimbursement for anti-infective drugs by government and insurance payers in absence of active epidemic Options market to distribute risk from pharmaceutical companies to more risk-tolerant investors Subscription model that provides health systems with access to latest antivirals after paying upfront
  12. 12. Commercial Advance market commitments from non-market actors such as governments, NGOs, philanthropists Little incentive to develop drugs for rare events in advance Low reimbursement for anti-infective drugs by government and insurance payers in absence of active epidemic
  13. 13. Regulatory New approval pathways for broad-spectrum drugs Increase patent length for antivirals to incentivize development Lobby for greater flexibility in BARDA funding Lobby for government “pull” mechanisms, i.e. rewards to companies for developing certain drugs FDA drug approval process for broad-spectrum drugs The Biological Advanced Research and Development Authority is reliant on Congressional vote for certain types of funding
  14. 14. BARDA, detail ● BARDA (2006) is the “biological DARPA” Source: BARDA FY 2017
  15. 15. Regulatory New approval pathways for broad-spectrum drugs Government patent buyouts Lobby for greater flexibility and consistency in BARDA funding Global prioritization of epidemic preparedness R&D FDA drug approval process for broad-spectrum drugs The Biological Advanced Research and Development Authority is reliant on Congressional vote for certain types of funding

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