©2006, all rights reserved, nanoviricides, inc., a publicly traded company (nnvc)...
TRANSCRIPT
©2006, All Rights Reserved, NanoViricides, Inc., A Publicly Traded Company (NNVC)
©2006, All Rights Reserved, NanoViricides, Inc., A Publicly Traded Company (NNVC)
Nanotechnology-Enabled Specifically Targeted Viricides
Anil R. Diwan, PhD President
Cell: [email protected]
Leo Ehrlich, Chief Financial Officer
Cell: [email protected]
Eugene Seymour, MD, MPHChief Executive Officer
Cell: [email protected]
135 Wood Street, Ste. 205, West Haven, CT 06516. T/F: (203) 927-6137.
Slide 2
Vaccines Therapeutics
Utility Prevention After Disease
Rabies vaccine is therapeutic. Further work for other diseases.
Current antiviral therapies have limited successes.
Logistics100% Compliance of
Billions NeededA few Patients
Polio, Influenza, HIV ... Epidemics - Large Numbers
Low Incidence Diseases
Unsuitable Well Suited
Ebola, Marburg, Hanta ...
Difficulties Antigen Variation - Mutations, Resortments, Recombinations
Efficacy & Safety
Influenza, HIV, EBV, many other...Many Partial Successes.
Few, if any, complete successes.
“Two Wheels of a Cart”
Prophylactics and Therapeutics
Slide 3
NanoViricides Pendantized Polymeric Micelles based,
Conformationally Flexible, Specifically Targeted Drugs
> Regulatory Implications for
(a) Normal IND-enabling Study, and
(b) a Novel "War-like" Bio-threat Response Mechanism
44Slide
NanoViricides Approach
Build a “Guided Missile”
‣ A “Homing Device” (Biochemical Ligand)
Target Specifically the Infectious Agent
Hide API in the “Belly” of the “Missile”• API = Active Pharmaceutical Ingredient
• OPTIONAL!
NanoMedicine Concept: 1959 Polymer Chemistry!
First Actualization: 2006 by NanoViricides
4
Slide 5
NanoViricides Nano-Machines
Bind to Specific Receptors on Viruses
Multiple Receptors at Once!
Multi-Point Docking (”Velcro Effect”)
Can Encapsulate or Attach Multiple APIs for -
‣ Viral Dis-Assembly
‣ Genetic Material Destruction
Non-Viral Nano-Machines
Patents PendingAPI = Active Pharmaceutical Ingredient
Slide 6
First Generation: Simple Products - No Encapsulation
Covalently Attached Ligands to a Single Molecular Chain
7Slide
Antiviral Spectrum is Specified by Ligand Set
H5N1:Strain-SpecificCurrent Threat
High Path Influenzas:Group-Specific
Common Influenzas - All: Broad Spectrum
33,000 deaths US, >250k World Per Year
Emerging Pandemic Threats
enables A Novel Treatment Methodology
ex: Influenzas
8Slide
Several Magnitudes Efficacy Improvement over Current Drugs with NanoViricidesEx: Influenzas, Comparative Efficacies
(Putative Estimates)
Based on our Current Work, Literature Data and using similarity projections
NanoViricide D = Broad Specificity FluCide-I NanoViricide J = H5N1 Specific AviFluCide-I
9Slide
It is of Interest toAccelerate the Development
of Highly Efficacious Antiviral Drugs
such as Nanoviricides Potentially Reduced Mutation Frequency
• Need to establish experimentally
• to what extent?
Likely Less Resistant Strains
• guidelines
©2006, All Rights Reserved, NanoViricides, Inc., A Publicly Traded Company (NNVC)
©2006, All Rights Reserved, NanoViricides, Inc., A Publicly Traded Company (NNVC)
Future of our Approach
Can be Extended to Many Viruses
Some other non-viral Infectious Diseases also
Difficulties Exist
11
Slide
NanoViricides Polymeric Micelles: Key Differences from Usual Drugs & Biologics:
I. Characteristics Conformationally FLEXIBLE Polymers
‣ “Well Defined” Non-Particulate Materials
Single Molecular Chains
‣ Heterogeneous Molecular Sizes
‣ MW Avg, MW Distributions
Ligands Attachment
‣ non-Quantitative Chemistries
‣ Average Substitution Levels
‣ Blocking “open sites” -Or Not!
12
Slide
NanoViricides Polymeric Micelles: Key Differences from Usual Drugs & Biologics:
II. Limitations in Chemical Characterization “Operational” Definition of the Species: MW
‣ Retained by NMWL xxx & Rejected by NMWL yyy
• Membrane Manufacturer QA Dependence
MW Distribution - Very Little Control
‣ Process Parameters: Not very viscous materials
Ligands Substitution Levels
‣ Averages Characterized over all species
• possibly via surrogate chemical characteristics
13
Slide
NanoViricides Polymeric Micelles: Key Differences from Usual Drugs & Biologics:
III. Limitations in Physical Characterization
Amphiphilic Materials - Complications
‣ self-assembly - MW, MW-Distr experiments
‣ mostly soluble in organic, aqueous as well as intermediate solvents - fractionation issues
Non-Particulate Materials
‣ SEM, TEM, AFM not very useful
• optical microscopy not useful
14
Slide
Polymeric Micelles: PrecedenceClosest Cases are Some Excipients
Some “Excipients” in common use are polymers with similar average-specified characteristics
However, there is no efficacy associated with them in theory
Slide 15
IndustryIndustry
As Much as Possible!!!
As Much as Possible!!!
FDAFDA
Minimum, Expedient,
Informative, & Critical
SAFETY, EFFICACY, CMCData and Studies
A Balanced Approach is Needed to
Speed up Development of
Extremely High Efficacy Drugs
such asNanoViricides
IndustryIndustry
16
Slide
Part II : “War-Like” Scenario- Unknown Agent - Bioterrorism or Natural -NanoViricides Enable Novel Public Health
Approach Food for Thought:
Minimize Stockpiling
Minimize Response Time Lag
Contain Epidemic before it Grows past small cluster
Avoid Pandemics Altogether
Minimize Drugs Against Scarce Pathogens
Respond to Unknown (incl. Engineered) Pathogens
Minimize Casualties and Morbidities
How?... next slide
17
Slide
Part II : “War-Like” Scenario- Unknown Agent - Bioterrorism or Natural -NanoViricides Enable Novel Public Health
Approach Small Initial Clusters: 5 to 100 patients
Immediately on Presentation - No Pathogen Id. Need
Use Patient Infectious Fluids
Raise Animal Antibodies - Polyclonal
Attach epitope to core nanoviricide material
Treat with resulting NaonoViricide drug agent
Within 3 Weeks - Eradicate Threat
Respond Before Epidemic is Created!
Only Core Nanoviricide Material is Stockpiled
18
Slide
Part II : “War-Like” Scenario- Unknown Agent - Bioterrorism or Natural -NanoViricides Enable Novel Public Health
Approach
Beyond Emergency Use Authorizations
FDA and Industry Must Start Thinking
Possibly Legislative Initiatives May be Necessary
Slide 19
Title: NanoViricides, Polymeric Micelle-based flexible Specifically Targeted Drugs, Regulatory Implications for (a) IND-enabling Study, and (b) a Novel "War-like" Bio-threat Response Mechanism
Brief Description:1. A nanoviricide is a polymeric single chemical chain with covalently attached ligands that specify the virus target. The antiviral spectrum of the drug is determined by the specificity of the set of ligands attached to the chain, in addition to other functionally
important aspects inherent in the chemistries.
2. The following aspects distinguish these materials from usual drugs and biological materials seen by the FDA: 2a. As a polymer, it is not possible to manufacture a single molecular weight species. It is possible to operationally
define a molecular weight distribution, such as "retained by membrane with NMWL xxx and passing through membrane with NMWL yyyy". The actual MW distribution can be characterized, but the result values are strongly dependent on the technique of
measurement. 2b. These are not hard particle species. Therefore, SEM/TEM/AFM characterization is not possible.
2c. These are amphiphilic materials, limiting the use of many standard procedures. 2d. The polymer chemistries only enable "substantially complete" attachment of ligands, and this is essentially true for
most of the chemistries used in the process. 2e. The material product can be defined operationally (i.e. in terms of processes used to make it), and further can be
characterized in terms of average result values of chemistries (e.g. average MW, and MWD, average number of ligands per chain, etc.).
3. The biological efficacy of nanoviricides drugs may be several orders of magnitude better than that of usual chemical drugs (test case- influenza - preliminary studies). This in itself may limit the potential for mutant generation. There are also other key aspects
of the design of nanoviricides that are expected to lead to minimizing mutant generation.
The above discussion relates to normal drug development of nanoviricides drugs. In addition:
4. "War-like" Bio-threat Response: 4a. In case of an unknown threat, it is possible to generate antibodies in the field, fragment them, and use well-
specified fragments as ligands, attach them, and build a specific nanoviricide drug against the unknown, uncharacterized threat agent. Such scenario can occur in bioterrorism as well as in natural outbreaks (e.g. SARS).
4b. This is a different level of "Emergency Response", relating to scenarios where stockpiling is not possible because pathogen itself is unknown.
4c. This new scenario enabled by the naoviricides systems solution to biothreats may require additional regulatory perspectives. Such as (a) standard or EUA approval for the core nanomaterial, enabling its stockpiling, and (b) very limited, life-threatening-use approval for the nanoviricide generated in-field using the approach outlined in (4a) or a variant thereof such as
using some small chemicals or peptides instead of antibody fragments. 4d. The purpose of such regulatory perspective would be to enable treatment within 2-3 weeks of threat event
notification - or shorter if feasible - in order to limit casualties and morbidity and contain the threat at its source thus limiting the potential that it can convert into an epidemic or a pandemic.