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
UNCLASSIFIED© Crown copyright 2014 Dstl
31 March 2014
Scope
• Mission
• Future Force 2020
• CBRN protection requirement
– Threat
– Policy
• CBRN programme
– Policy
– CBR protec...
Defence in a changing world
Defence’s mission:
To protect our country and
guarantee its security and independence
UNCLASSI...
FF 2020
• Significant Defence reform
– Post Afghanistan  Contingency
– ‘Carter’s circles’
– FF 2020 structure
– Budget c....
CBR(N) Protection requirement
Threat
Policy Finance
££££
SDSR15
Defence Strategic
Direction13
UNCLASSIFIED© Crown copyrigh...
UNCLASSIFIED© Crown copyright 2014 Dstl
31 March 2014
CBR Protection Requirement
(Threat)
State Threat
Lone Wolf Threat In...
CBR Protection Requirement
(Threat - 2)
Nervous system
• Nerve agents
• Toxins
Lung
• Sulphur mustard
• Phosgene
• Toxic i...
• Hazard area
• ‘Detect to treat’
CBR Protection Requirement
(Threat - 3)
UNCLASSIFIED© Crown copyright 2014 Dstl
31 March...
CBRN Protection Requirement
(Policy)
Prevention of
Supply
ProtectionElimination
Arms
Control
Disablement
Deterrence
Cooper...
CBRN Protection Requirement
(Capability)
Decision
Makers
Inform
Medical
CM
Environmental
Sense
Medical Sense
Non-CBR
Surve...
CBRN Protection Requirement
(Capability - 2)
Deposited
Hazard
Vapour Aerosol
Airborne
Hazard
Liquid/solid
Sense
UNCLASSIFI...
Knowledge
Manage-
ment
Networked BRACIS (IOC Oct 13)
CBRN Protection Requirement
(Capability - 3)
RFI
Advice
CBRN Reachbac...
Medical
CM
CBRN Protection Requirement
(Capability - 4)
UNCLASSIFIED© Crown copyright 2014 Dstl
31 March 2014
Physical
Protection
CBRN Protection Requirement
(Capability - 5)
UNCLASSIFIED© Crown copyright 2014 Dstl
31 March 2014
Hazard
Management
CBRN Protection Requirement
(Capability - 6)
UNCLASSIFIED© Crown copyright 2014 Dstl
31 March 2014
• Way forward?
– A variety of projects are underway to improve our capability
– There is a plan
– Some funding has been al...
Summary
• Defence Reform – FF 2020
• Evolving threat – State and non-state
• Policy challenges
– Bio: ‘Detect to treat’
– ...
Medical Countermeasures to
Biological Agents
Defence Science and Technology Laboratory
UNCLASSIFIED
Biological Agents
• Very low infectious dose
– Highly toxic
• Infectious via the inhalational route
• Cause e...
UNCLASSIFIED
Microbiology capabilities
• Containment of highly
dangerous
microbiological
organisms
• Aerosolisation of
dan...
UNCLASSIFIED
Microbiology high containment
UNCLASSIFIED
UNCLASSIFIED
Regulations and Best Practise
• Dangerous Pathogens work conducted in accordance
with Health and Safety Execu...
UNCLASSIFIED
Vaccination
• Name derived from use of cowpox (Vaccinia) to protect against
smallpox
– Jenner 1796
– Pasteur ...
UNCLASSIFIED
Time (days)
Percentsurvival
0 7 14 21 28
0
20
40
60
80
100
Conjugate
LPS
TetHc + LPS
PBS
TetHc
Bacteria(cfu/s...
UNCLASSIFIED
Antibiotics
• Not active against some bacteria
– Natural resistance
• Different antibiotics required for diff...
UNCLASSIFIED
CFI is a broad spectrum antibiotic effective
against multiple BW agents
• Treatment with encapsulated
ciprofl...
UNCLASSIFIED
Humanised Antibody for the Treatment of Venezuelan
Equine Encephalitis Virus (VEEV)
• No available licensed v...
UNCLASSIFIED
Summary
• A flexible response is essential
• Vaccines provide excellent protection for those
immunised before...
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...
Background: biothreat agents
• Pathogenic for man or animals
• Very low infectious dose
• Infectious via the inhalational ...
© Crown copyright 2014 Dstl
31 March 2014
Defence against biothreats
• Many potential biothreat agents
• How to defend aga...
Generic approach to therapy
• By influencing the host response
• Requires an understanding of the host response to pathoge...
Innate (host) response targets for therapy
• Objective of this competition is to look broadly across research and
developm...
CDE themed competition specifics
• Seeking innovative proposals for short projects (<1year); £30-
80k guide; (£500k total ...
Challenge 1
© Crown copyright 2014 Dstl
31 March 2014
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 bio...
Identification of new cellular or host pathway
targets
May involve the identification of eg
• immuno stimulants
• modulato...
Identification of new cellular or host pathway
targets
• Some of these may be
exogenous and some
endogenous factors
• Some...
Possible outcomes
Proposals for
– identification of new cellular targets /pathways
– new applications of manipulating know...
Challenge 2
Identification of new candidate therapies
© Crown copyright 2014 Dstl
31 March 2014
Identification of new candidate therapies
Exploit appropriate cellular targets and pathways to
identify new therapies by, ...
Possible outcomes
• Candidate therapies should be druggable and generic
• Proposals should show proof-of-concept
• Does no...
Challenge 3
Identification of new platform technologies
© Crown copyright 2014 Dstl
31 March 2014
Identification of new platform technologies
For assessing therapeutic benefit
• Novel technologies such as:
• non-invasive...
Possible outcomes
• New technologies which may facilitate the identification and
development of candidate therapies
• Prop...
What we want
• Highly innovative approaches that are significantly different from
existing technologies
• Generally techno...
What we don’t want
Proposals that concern:
• high technology readiness level (TRL) capability
• serological targets only (...
Successful proposals
• Each will be assigned a Technical Partner
– Provides interface between project and defence communit...
Summary
• Competition launches today
• Webinar Tuesday 1 April
• Closes on Thursday 5 June 2014 at 17:00 hrs
• Short proof...
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Innate response targets for therapy CDE themed competition launch

  1. 1. Centre Defence Enterprise for Themed Competition Briefings
  2. 2. CDE themed competition Innate response targets for therapy
  3. 3. Themed competition Requirements Bounded Specific
  4. 4. Innovation Network events Advice Opportunity Networking
  5. 5. Innate response session scope Programme Overview Military context Technical challenges
  6. 6. Military Context UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  7. 7. Scope • Mission • Future Force 2020 • CBRN protection requirement – Threat – Policy • CBRN programme – Policy – CBR protection – Current capabilities and challenges UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  8. 8. Defence in a changing world Defence’s mission: To protect our country and guarantee its security and independence UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014 Source: Defence Transformation
  9. 9. 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 UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014 Source: Defence Transformation
  10. 10. CBR(N) Protection requirement Threat Policy Finance ££££ SDSR15 Defence Strategic Direction13 UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014 CBRN protection plan Source: BBC.co.uk
  11. 11. UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014 CBR Protection Requirement (Threat) State Threat Lone Wolf Threat Industrial Threat Terrorist Threat Source: Open source
  12. 12. 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 UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  13. 13. • Hazard area • ‘Detect to treat’ CBR Protection Requirement (Threat - 3) UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014 Source: Open source
  14. 14. CBRN Protection Requirement (Policy) Prevention of Supply ProtectionElimination Arms Control Disablement Deterrence Cooperative Non-Cooperative UK CBRN Protection Policy: Armed Forces should be able to “Survive and Operate” in all CBRN environments UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  15. 15. 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 UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  16. 16. CBRN Protection Requirement (Capability - 2) Deposited Hazard Vapour Aerosol Airborne Hazard Liquid/solid Sense UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  17. 17. Knowledge Manage- ment Networked BRACIS (IOC Oct 13) CBRN Protection Requirement (Capability - 3) RFI Advice CBRN Reachback (IOC Jan 14) UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  18. 18. Medical CM CBRN Protection Requirement (Capability - 4) UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  19. 19. Physical Protection CBRN Protection Requirement (Capability - 5) UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  20. 20. Hazard Management CBRN Protection Requirement (Capability - 6) UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  21. 21. • 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) UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  22. 22. 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 UNCLASSIFIED© Crown copyright 2014 Dstl 31 March 2014
  23. 23. Medical Countermeasures to Biological Agents Defence Science and Technology Laboratory
  24. 24. UNCLASSIFIED 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
  25. 25. UNCLASSIFIED Microbiology capabilities • Containment of highly dangerous microbiological organisms • Aerosolisation of dangerous pathogens • Modelling of diseases in animal models
  26. 26. UNCLASSIFIED Microbiology high containment
  27. 27. UNCLASSIFIED
  28. 28. 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
  29. 29. 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
  30. 30. UNCLASSIFIED Time (days) Percentsurvival 0 7 14 21 28 0 20 40 60 80 100 Conjugate LPS TetHc + LPS PBS TetHc Bacteria(cfu/spleen) Conjugate LPS TetHc + LPS PBS TetHc 10 100 1000 10000 100000 1000000 P<0.001 Exp.1 Exp.2 Exp.1 Exp.2 Exp.1 Exp.2 Exp.1 Exp.2 Exp.1 Exp.2 Conjugate LPS TetHc + LPS PBS TetHc Burkholderia and Francisella vaccines
  31. 31. 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
  32. 32. 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
  33. 33. 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 PercentSurvival 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
  34. 34. 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
  35. 35. Innate response targets for therapy CDE themed competition March 25 - June 5 2014 31 March 2014
  36. 36. 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 © Crown copyright 2014 Dstl 31 March 2014
  37. 37. 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 © Crown copyright 2014 Dstl 31 March 2014
  38. 38. © Crown copyright 2014 Dstl 31 March 2014 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
  39. 39. 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 31 March 2014 © Crown copyright 2014 Dstl
  40. 40. 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 31 March 2014 © Crown copyright 2014 Dstl
  41. 41. 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 31 March 2014 © Crown copyright 2014 Dstl
  42. 42. Challenge 1 © Crown copyright 2014 Dstl 31 March 2014 Identification of new cellular or host pathway targets
  43. 43. 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 © Crown copyright 2014 Dstl 31 March 2014
  44. 44. 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 © Crown copyright 2014 Dstl 31 March 2014
  45. 45. 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 © Crown copyright 2014 Dstl 31 March 2014 Normal OveractiveUnderactive
  46. 46. 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 © Crown copyright 2014 Dstl 31 March 2014
  47. 47. Challenge 2 Identification of new candidate therapies © Crown copyright 2014 Dstl 31 March 2014
  48. 48. 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 © Crown copyright 2014 Dstl 31 March 2014
  49. 49. 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 © Crown copyright 2014 Dstl 31 March 2014
  50. 50. Challenge 3 Identification of new platform technologies © Crown copyright 2014 Dstl 31 March 2014
  51. 51. 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 © Crown copyright 2014 Dstl 31 March 2014
  52. 52. 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 © Crown copyright 2014 Dstl 31 March 2014
  53. 53. 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 © Crown copyright 2014 Dstl 31 March 2014
  54. 54. 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 © Crown copyright 2014 Dstl 31 March 2014
  55. 55. Successful proposals • Each will be assigned a Technical Partner – Provides interface between project and defence community – If project successful, potential routes to exploitation developed © Crown copyright 2014 Dstl 31 March 2014
  56. 56. 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 © Crown copyright 2014 Dstl 31 March 2014
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