innate response targets for therapy cde themed competition launch
DESCRIPTION
TRANSCRIPT
Centre Defence Enterprise
for
Themed Competition Briefings
CDE themed competition
Innate response targets for therapy
Themed competition
Requirements
Bounded
Specific
Innovation Network events
Advice
Opportunity
Networking
Innate response session scope
Programme Overview
Military context
Technical challenges
Military Context
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Scope
• Mission • Future Force 2020 • CBRN protection requirement
– Threat – Policy
• CBRN programme – Policy – CBR protection – Current capabilities and challenges
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Defence in a changing world
Defence’s mission:
To protect our country and guarantee its security and independence
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Source: Defence Transformation
FF 2020 • Significant Defence reform
– Post Afghanistan Contingency – ‘Carter’s circles’ – FF 2020 structure – Budget c.£36Bn pa – Manpower: c.175k
• Navy c.30k • Army c.82k + 30k • RAF c.33k
Homeland Defence
Force Projection
Defence Engagement
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Source: Defence Transformation
CBR(N) Protection requirement
Threat
Policy Finance ££££ SDSR15
Defence Strategic Direction13
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CBRN protection
plan
Source: BBC.co.uk
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CBR Protection Requirement (Threat)
State Threat
Lone Wolf Threat Industrial Threat
Terrorist Threat
Source: Open source
CBR Protection Requirement (Threat - 2)
Nervous system• Nerve agents• Toxins
Lung• Sulphur mustard• Phosgene• Toxic industrial
chemicals
Skin• Sulphur mustard• Nitrogen mustard• Toxic industrial
chemicals
Multiple targets• Ionising
radiation
• Biological
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• Hazard area • ‘Detect to treat’
CBR Protection Requirement (Threat - 3)
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Source: Open source
CBRN Protection Requirement (Policy)
Prevention of Supply
Protection Elimination
Arms Control Disablement
Deterrence
Cooperative Non-Cooperative UK CBRN Protection Policy: Armed Forces should be able to “Survive and
Operate” in all CBRN environments
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CBRN Protection Requirement (Capability)
Decision Makers
Inform
Medical CM
Environmental Sense
Medical Sense
Non-CBR Surveillance
Protective Measures
Physical Protection
Hazard Manage-
ment
Sense
Knowledge Manage-
ment
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CBRN Protection Requirement (Capability - 2)
Deposited Hazard
Vapour Aerosol
Airborne Hazard
Liquid/solid
Sense
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Knowledge Manage-
ment
Networked BRACIS (IOC Oct 13)
CBRN Protection Requirement (Capability - 3)
RFI
Advice
CBRN Reachback (IOC Jan 14)
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Medical CM
CBRN Protection Requirement (Capability - 4)
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Physical Protection
CBRN Protection Requirement (Capability - 5)
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Hazard Management
CBRN Protection Requirement (Capability - 6)
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• Way forward? – A variety of projects are underway to improve our capability – There is a plan – Some funding has been allocated
CBRN Protection Requirement (Capability - 7)
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Summary
• Defence Reform – FF 2020 • Evolving threat – State and non-state • Policy challenges
– Bio: ‘Detect to treat’ – ‘Survive and operate in all CBRN environments’ is difficult
• CBRN Protection capabilities are beginning to get the investment they need
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Medical Countermeasures to Biological Agents
Defence Science and Technology Laboratory
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Biological Agents
• Very low infectious dose – Highly toxic
• Infectious via the inhalational route • Cause endemic disease • Usually zoonotic diseases • Lethal or incapacitating • BTWC has no schedules and no verification regime
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Microbiology capabilities
• Containment of highly dangerous microbiological organisms
• Aerosolisation of dangerous pathogens
• Modelling of diseases in animal models
UNCLASSIFIED
Microbiology high containment
UNCLASSIFIED
UNCLASSIFIED
Regulations and Best Practise
• Dangerous Pathogens work conducted in accordance with Health and Safety Executive (ACDP/ACGM/COSHH) and DEFRA guidelines
• Animal studies conducted under licence by the Home Office
UNCLASSIFIED
Vaccination • Name derived from use of cowpox (Vaccinia) to protect against
smallpox – Jenner 1796 – Pasteur 1881
• Suspension of dead, attenuated or otherwise modified micro-organisms USED TO INDUCE IMMUNITY TO A DISEASE – Stimulates immune system (e.g. antibodies) – Induces memory – Eradicates disease
The most cost effect way to treat infectious disease
UNCLASSIFIED
Time (days)
Perc
ent s
urvi
val
0 7 14 21 280
20
40
60
80
100ConjugateLPSTetHc + LPSPBSTetHc
Bac
teria
(cfu
/ sp
leen
)
Conjugate LPS
TetHc + LPSPBS
TetHc
10
100
1000
10000
100000
1000000
P<0.001
Exp.
1Ex
p.2
Exp.
1Ex
p.2
Exp.
1Ex
p.2
Exp.
1Ex
p.2
Exp.
1Ex
p.2
ConjugateLPSTetHc + LPSPBSTetHc
Burkholderia and Francisella vaccines
UNCLASSIFIED
Antibiotics
• Not active against some bacteria – Natural resistance
• Different antibiotics required for different agents • Relapsing infection • Trigger to treat required • Compliance/Side effects
– 44% completed 60 day course during BA letter attacks BUT • Broad spectrum of activity • No predefined threat spectrum
UNCLASSIFIED
CFI is a broad spectrum antibiotic effective against multiple BW agents
• Treatment with encapsulated
ciprofloxacin effectively treats three BW agents: F. tularensis, Y. pestis and C. burnetii
• In collaboration with Health Protection Agency, Defence Research and Development Canada and Aradigm Corporation
UNCLASSIFIED
Humanised Antibody for the Treatment of Venezuelan Equine Encephalitis Virus (VEEV)
• No available licensed vaccines or antivirals for treatment of VEEV
• A mouse monoclonal antibody is effective for the treatment of VEEV in a mouse model of disease
• Humanised antibody produced to reduce potential adverse reactions in humans
– biologically active
– protects mice against lethal VEEV challenge
0 5 25 50 75 100 0
20
40
60
80
100
Antibody (μg) Administered
Perc
ent S
urvi
val
Survival of BALB/c mice pre-treated with humanised antibody before challenge with 100LD50 of VEEV
O'Brien LM et al, Virology. 2012, Goodchild SA, et al, Antiviral Res. 2011
UNCLASSIFIED
Summary
• A flexible response is essential
• Vaccines provide excellent protection for those immunised before exposure
• Post-exposure therapies provide a rapid response capability against some agents
• Following a BW attack, and for some agents, it will be necessary to use both post-exposure therapies and vaccines
Innate response targets for therapy
CDE themed competition March 25 - June 5 2014
31 March 2014
Key dates
• Competition launches today • Presentation to follow • Opportunity for Q&A • Webinar Tuesday 1 April • Deadline for applications Thursday 5 June 2014 at 17:00 hrs via Centre for Defence Enterprise Portal • Funding decisions to be made July 2014 • Notifications end July
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Background: biothreat agents
• Pathogenic for man or animals
• Very low infectious dose
• Infectious via the inhalational route
• Cause endemic disease around world
• Usually are zoonotic diseases
• Lethal or incapacitating
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Defence against biothreats
• Many potential biothreat agents • How to defend against them? • Impossible to make a vaccine/therapy for every potential agent • Require generic therapy
Generic approach to therapy • By influencing the host response
• Requires an understanding of the host response to pathogen & safe ways to influence it
• Requires identification of relevant targets or pathways in the host
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Innate (host) response targets for therapy
• Objective of this competition is to look broadly across research and development to identify host cell targets and pathways
• Using data derived from diverse infection models
• Respondents to competition do not need to work directly with biothreat agents
• Ultimate aim is to apply the most innovative approaches to biothreat agents
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CDE themed competition specifics • Seeking innovative proposals for short projects (<1year); £30-
80k guide; (£500k total budget)
• Show proof-of-concept for your proposal; there is funding allocated for follow-on work for successful projects
• Competition divided into 3 challenges
• Respondents need to address 1 of the challenges, may address >1, do not have to address all 3
• Challenges described fully in the competition document
• Bids must be ethical and compliant with UK government legislation
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Challenge 1
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Identification of new cellular or host pathway targets
Identification of new cellular or host pathway targets • In host-pathogen model of your choice
– Does not need to be a biodefence pathogen – Does not need to be in vivo
• Conditioning of cells ex vivo eg to profile responses or prior to adoptive transfer
• Targeting cells in situ eg – to refocus them – to activate them – to induce them to traffic – to redirect them
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Identification of new cellular or host pathway targets May involve the identification of eg • immuno stimulants • modulators • transfection factors • chemokines, cytokines or the induction (or blockade) of these • cytokine/chemokine/growth factor receptors and application of these to modulate host responses
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Identification of new cellular or host pathway targets
• Some of these may be
exogenous and some endogenous factors
• Some endogenous natural
regulators /regulatory pathways may be exploited
• to reduce inflammation and to restore homeostasis
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Normal
Overactive Underactive
Possible outcomes Proposals for
– identification of new cellular targets /pathways – new applications of manipulating known cellular targets/pathways – demonstration that targets may be influenced beneficially, for
example to: • prevent cytotoxicity • prevent/reduce microbial invasion • reduce microbial load • restore normal cell function
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Challenge 2
Identification of new candidate therapies
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Identification of new candidate therapies Exploit appropriate cellular targets and pathways to identify new therapies by, for example:
• enhancing cell-mediated immunity • investigating novel combinations • identification and manipulation of significant
transcription factors • micro RNA-directed therapies or antagonists
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Possible outcomes • Candidate therapies should be druggable and generic • Proposals should show proof-of-concept
• Does not exclude the re-purposing or augmentation of existing
therapies
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Challenge 3
Identification of new platform technologies
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Identification of new platform technologies
For assessing therapeutic benefit • Novel technologies such as:
• non-invasive methods of in-vivo/ex-vivo analysis eg bio-imaging or tracking
• Transcriptomics including micro RNA analysis
• In-silico modelling of host responses
• Novel assays to monitor the host immune response
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Possible outcomes
• New technologies which may facilitate the identification and development of candidate therapies
• Proposals should demonstrate the impact of the technology on therapeutic development
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What we want • Highly innovative approaches that are significantly different from
existing technologies
• Generally technology readiness level (TRL) ≤ 3
• Generic approaches (not pathogen specific)
• Approaches applicable to intracellular pathogens where
appropriate
• Approaches that will lead to a feasible clinical product
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What we don’t want Proposals that concern: • high technology readiness level (TRL) capability • serological targets only (rather than cellular) • antibody-based therapies (but antibodies as a targeting
mechanism are acceptable) • existing solutions or technology already tested and found to
have limited utility • a paper study or review or similar • pre-exposure therapies or therapeutics • topical therapies for wounds
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Successful proposals
• Each will be assigned a Technical Partner
– Provides interface between project and defence community
– If project successful, potential routes to exploitation developed
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Summary
• Competition launches today • Webinar Tuesday 1 April • Closes on Thursday 5 June 2014 at 17:00 hrs • Short proof-of-concept proposals • If successful, potential for follow-on funding • May include additional research to develop technology for MOD • Competition information available on CDE website
www.science.mod.uk
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31 March 2014