innovation in drug development processes - cde themed call launch 25 june 2013

Innovation in Drug Development Processes

Centre for Defence Enterprise

Rapid technological change

© Crown Copyright MOD 2011

The aim of CDE


Prove the value of novel, high-risk, high-potential-benefit research


Cost-effective military capability advantage

25 June 2013

Five key operating principles underpin the CDE model

Engaging innovators

25 June 2013

Accessible opportunity

Sustaining incentives

Minimising participation costs

Compliance

Two routes to funding

Online bid submission

Intellectual property

Themed calls

CDE themed call programme

Countering insider threat attacks Call closes 27 Jun 2013

Secure communications Call closes 22 Aug 2013

Innovation in drug development processes

Call closes 29 Aug 2013

Enhancing military medical training and support for the medic

Call launch 16 July 2013 (Birmingham)

Novel solutions for emulating ship signatures (counter mine)

Call launch 23 July 2013 (Webinar)

Register and further details at www.science.mod.uk under ‘Events and Calls’

All call close at 17:00 hrs

Defence Open Call

Seeking the exceptional

Challenging conventions

4419 proposals received

17% proposals funded

£39M contracts awarded

Exemplar project

Fuel efficiency

‘Micro generators’


Effective proposals

Challenge, pace & exploitation

The future of CDE

Network and question


01235 438445

[email protected] www.science.mod.uk/enterprise

© Crown copyright 2013 Dstl

25 June 2013

An Introduction to CBR Science and Technology

UNCLASSIFIED © Crown copyright 2013

Dstl

25 June 2013

Chemical, Biological, Radiological

VISION Maximise the impact of science and technology (S&T) in

realising the UK policy aim of maintaining our political and

military freedom of action despite the presence, threat, or use

of chemical, biological or radiological weapons.

SDSR: NATIONAL SECURITY TASKS & PLANNING

GUIDELINES:

We will .. tackle those who threaten the UK & our interests,

including maintenance of underpinning technical expertise in key

areas. To deliver this we require …

Retention of our CBRN science and technology capabilities that

contribute to counter-proliferation and our response to the

potential use of such materials by terrorist or state actors.

NATIONAL SECURITY STRATEGY: RISKS

Tier 1 : International terrorism including the use of CBRN

materials

Tier 2 : Attack on the UK or its Territories by a state or proxy

using CBRN weapons.


Dstl

25 June 2013

• Strategic objectives

– SUPPORT 3 Model Block (MB)

acquisitions

• More tech watch type activity. Less

development activity in research

programme

– INCREASE the amount of speculative,

high-risk, high-reward research.

• Emphasis on scientific quality and

innovation.

• Pause mature research

25 June 2013

Context


F12/13 F13/14

Threat 6.4M 6.1M

Inform 7.9M 7.1M

Prot Measures 14.9M 14.2M

Strat Facilities 6.2M 6.4M

£35.4M £33.8M

CBR research programme funding

UNCLASSIFIED

Sense

Knowledge

Management Physical

Hazard

Management

Medical

Countermeasures

Hazard

Assessment

Operational

Analysis

Counter

Proliferation

Duty Of Care

CBR Inform

(MOD & Industry)

CBR Protective Measures

(International

Collaboration)

CBR Threat Reduction

(Cross Government)

CBR S&T

Programme

Prevention

of Supply

Protection Elimination

Arms

Control Disablement

Deterrence

Programme structure


Dstl

25 June 2013

Programme and Delivery Directorate

CBR programme Other programmes

Dstl Depts Industry Academia

S&T Requirements

Partners


Dstl

25 June 2013

Working across government

• Aim: programme coherency and mutual benefit from shared investments

• Number of other government departments with interest/requirement for CBRN S&T advice

• Different exploitation routes, similar fundamental requirements


Dstl

25 June 2013

http://www.motorboatsmonthly.co.uk/imageBank/d/defra-logo.jpg

http://www.chevronmultimedia.com/images/cabinet_office_logo.jpg

http://cmtconsultants.com/wp-content/uploads/2010/02/DFT-logo-CMYK.jpg

Impact of S&T


Dstl

25 June 2013

Exploitation of S&T and where industry is involved

Early Innovation

Proof of concept

Assessment

Tech transfer Into service


Dstl

25 June 2013

Alternative model

N2

Sample

Inlet to Detector

Capability

Research exploitation

Non-MOD markets

Rapid

Adaptation


Dstl

25 June 2013

CBRN PROTECTION RESEARCH GOAL 9 – Medical Countermeasures

• Explore technology options to upkeep, update and upgrade the CBRN medical countermeasures capability. • To prevent individuals from experiencing the physiological effects of exposure to CBRN agents by the use of medical countermeasures, in order to maintain operational effectiveness on operations. • To move towards a post-exposure treatment posture while maintaining the current pre-exposure capability.


Dstl

25 June 2013

Desired outcome: Strategic approach

• Where practicable all future medical

countermeasures (MedCM) should be

licensed (ie possess a Marketing

Authorisation in the UK).

• Broad-spectrum MedCM: provide protection

against more than one agent.

25 June 2013


Dstl

Programme aim

• MOD long-term aim: broad-spectrum

post-exposure therapies

• Allow a flexible response to current

and emerging threats


Dstl

25 June 2013

BW MedCM strategy

Pre-exposure therapies

• Devise vaccines against biological agents

Post-exposure therapies

• BW-specific post-exposure therapies

• Broad-spectrum therapies

Lessens the need to pre-define the threat

spectrum

Delivery is dependent on collaboration

Ris

k

30%

70%

UNCLASSIFIED 25 June 2013

© Crown copyright 2013

Dstl

A technical challenge

• The challenge of devising broad-spectrum MedCM is significant

– very challenging technical aspiration

• Incentivising industry to engage with MOD is difficult in this area

• Few incentives to develop broad-spectrum therapies

– Profit is in specific therapies for chronic diseases

• Low investment means there are very few broad-spectrum antibiotics in the pipeline


Dstl

25 June 2013

Summary • The CBR research programme is designed to maximise the

impact of science & technology in realising the UK policy aim of

maintaining our political and military freedom of action despite

the presence, threat, or use of chemical, biological or radiological

weapons.

• Broad-spectrum medical countermeasures are mechanism to

achieve this

• This CDE themed call is aimed to help identify future medical

countermeasures

25 June 2013


Dstl

CDE Themed Call:

Innovation in Drug Development

Processes


25 June 2013

UNCLASSIFIED

CDE call: Innovation in Drug Development Processes

Aims to stimulate the development of antibacterial drug

development processes…

• benefiting the antibacterial development industry

• supporting the UK’s defence and security needs


© Crown copyright 2013

Dstl

• Research proposals for this CDE themed call will also

be assessed by representatives from Dstl’s

collaborators in US Government, the Defence Threat

Reduction Agency (DTRA) and a selection of UK

based University academics.

• The US/academia will not be funding any of the

proposals resulting from this CDE call – funding will

only be from Dstl.


25 June 2013

CDE call: Innovation in Drug Development Processes

UNCLASSIFIED


25 June 2013

Innovations in Drug

Development Processes

25 June 2013

© Crown copyright 2013 Dstl UNCLASSIFIED

Overview

• Background: target identification at Dstl

• CDE call: improving target exploitation



25 June 2013


Broad-spectrum antibacterials

In order to support the development of novel antibiotics

by industry, MOD funds research to identify and validate

broad-spectrum antibacterial targets

Bacillus

anthracis

Burkholderia

pseudomallei /

mallei

Yersinia

pestis

Francisella

tularensis Coxiella

burnetii Brucella spp

UNCLASSIFIED

Dstl’s key capabilities

25 June 2013

Animal models

Genetic manipulation of pathogens

In vitro models of infection

Cytoplasmic

membrane

Cell

wall

Capsule


Dstl

http://www.google.co.uk/imgres?imgurl=http://www.rione.it/canarini/lancashire/img/alimentazione/afidi_camole/galleria mellonella 3.jpg&imgrefurl=http://www.rione.it/canarini/lancashire/afidi_it.htm&usg=__hqVkdP2hOw5-CwHX7zT_EsfVb2M=&h=472&w=447&sz=50&hl=en&start=4&zoom=1&tbnid=W1s032Ay5T_riM:&tbnh=129&tbnw=122&ei=5ig1T4S7A8en8gPsqtSvAg&prev=/images?q=galleria+mellonella+images&hl=en&sa=N&gbv=2&tbm=isch&itbs=1

http://www.google.co.uk/imgres?imgurl=http://www.aspexdesign.co.uk/drusillas-zoo-photos/drusillas-common-marmosets-019.jpg&imgrefurl=http://www.aspexdesign.co.uk/photos-of-common-marmosets.htm&usg=__ge768v8x-lgBFUMkc8CZlRgB3n8=&h=600&w=800&sz=187&hl=en&start=62&zoom=1&tbnid=HBTNpW5gK0yVnM:&tbnh=107&tbnw=143&ei=dic1T83IHYPg8APblZCcAw&prev=/images?q=marmoset+images&start=42&hl=en&sa=N&gbv=2&tbm=isch&itbs=1

http://www.google.co.uk/imgres?imgurl=http://trialx.com/curetalk/wp-content/blogs.dir/7/files/2011/05/diseases/Macrophage-3.jpg&imgrefurl=http://trialx.com/curebyte/2011/07/10/macrophage-photos-and-related-clinical-trials/&usg=__X2eNaKtLOu0FSPHLZjv0UWGfOzg=&h=394&w=500&sz=26&hl=en&start=2&zoom=1&tbnid=KO9q8FSX3w3IhM:&tbnh=102&tbnw=130&ei=ZSk1T6ejNcHZ8gO79eC0Ag&prev=/images?q=macrophage+images&hl=en&sa=N&gbv=2&tbm=isch&itbs=1

http://www.google.co.uk/imgres?imgurl=http://upload.wikimedia.org/wikipedia/commons/thumb/e/e8/Intercellular_connections_in_a549_cells.jpg/300px-Intercellular_connections_in_a549_cells.jpg&imgrefurl=http://en.wikipedia.org/wiki/A549_cell&usg=__ZpU3Ri2u5yB6BETm7TjZAWL-BGw=&h=224&w=300&sz=14&hl=en&start=4&zoom=1&tbnid=_VWnsFhZJIcnOM:&tbnh=87&tbnw=116&ei=jik1T_q6Mozb8gPW3fnMAg&prev=/images?q=A549+images&hl=en&sa=N&gbv=2&tbm=isch&itbs=1

25 June 2013

• Target selection Identification

• Biological evaluation of target

• Down-selection Characterisation and

validation

• Collaborations

• Evaluation of novel technologies for inhibitor selection

Exploitation

Approach to antibacterial targets


Dstl

Target identification

• Whole genome approaches – Using high-throughput sequencing

technology

• Bioinformatics – Database of Essential Genes

– Pathogen vs non-pathogens

• Computational systems

biology – Mathematical modelling

25 June 2013


Dstl

http://www.lce.hut.fi/publications/annual2003/fig21.jpg

Target characterisation and validation

• Genetic characterisation

– Development and construction of targeted mutants

– In vitro & in vivo evaluation

• Virulence

• Essential

• Biochemical characterisation – Protein engineering

– X-ray crystallography

25 June 2013


Dstl

http://christinaa14.files.wordpress.com/2010/12/mutation.jpg

Target exploitation

• Engagement with academia and/or industry

Currently:

– Target protein structures

– Assay development

– Inhibitor screening (proof-of-concept)

Future:

– Inhibitor screening & lead molecule

development

25 June 2013


Dstl

25 June 2013

Aspiration

– Enable development of broad-spectrum

antibacterials

– Engage with academic/industrial partners at an

early stage


Dstl

25 June 2013

CDE call Innovation in Drug Development Processes

Aims to stimulate the development of antibacterial drug

development processes…

• benefiting the antibacterial development industry

• supporting the UK’s defence and security needs


Dstl

Target-based antibacterial discovery

25 June 2013

Target identification

High throughput

screening or alternative

approach

Inhibitor identification

Lead inhibitor optimisation

(PK, distribution, toxicity, etc)

Structure-based drug

design


Dstl

25 June 2013

Challenge 1: Specific target inhibitor

identification

• eg

– decreasing propensity for resistance acquisition

– increasing hit rate

Technologies that improve the robustness of inhibitors identified for targets by HTS or other

approaches


Dstl

25 June 2013

Challenge 2: Improving structure-

based drug design

• eg

– reducing the time taken to produce high-resolution

target structures

– increasing robustness of in silico small molecule

design

Technologies that improve the process of structure-based drug design of antibacterials


Dstl

25 June 2013

Challenge 3: Potency for intracellular

pathogens

• eg

– altering physiochemical properties of inhibitors to

enhance uptake

– coupling inhibitors to other molecules to increase

intracellular retention

Technologies that improve the uptake of antibacterials into target cells and/or reduce efflux


Dstl

25 June 2013

What we WANT

• Proof-of-concept proposals

• Highly innovative approaches, tools, technologies

• Applicability to broad-spectrum targets

• Applicability to intracellular bacteria


Dstl

25 June 2013

What we DONT WANT

• Existing technologies

• Target identification

• Target-specific approaches


Dstl

25 June 2013

Proposals

• Proof of concept

• Value: no cap but likely £20-80K

• Duration: typically 3-9 months; to be completed by September

2014

• Call closes: 29 August 2013 at 1700 hrs

• Contract placement to be initiated from October 2013


Dstl

25 June 2013

Enquiries

• Technical enquiries: [email protected]

• General enquiries: [email protected]

+44 (0)1235 438445


Dstl


25 June 2013

Crown Copyright (c) 2012


www.science.mod.uk/enterprise [email protected]

UNCLASSIFIED / FOR PUBLIC RELEASE

Centre for Defence Enterprise Submitting a Successful Proposal

Centre for Defence Enterprise (CDE)

Maximising your chances

Dstl is part of the

Ministry of Defence

UNCLASSIFIED / For Public Release



Crown Copyright Dstl 2012

Know what is available

Dstl is part of the

Ministry of Defence





Read available

information

Start with –

Quick Start Guide

plus other CDE manuals –

Account Manual, User

Manual, Technology

Application Manual


Dstl is part of the

Ministry of Defence






Dstl is part of the

Ministry of Defence





Developing a CDE proposal

Dstl is part of the

Ministry of Defence

Value from technology

Innovative concept

Future capability

Proof of

concept Incremental development

The essentials

Description

mins

Assessment

Not an exam

MOD Performance Assessment Framework

Five criteria:

Operational relevance

Likelihood of exploitation

Builds critical S&T capability to meet UK needs

Scientific quality/innovation

Science, innovation and technology risk

Commercial tab

Dstl is part of the

Ministry of Defence





Government-furnished X

Health and safety

Ethics

Unclassified





Proposal health check

Claim of future benefit

Contribution to future benefit

Logical programme of work

Generation of evidence

Demonstration of progress





Based on a claim of future benefit

Contribution to realisation of future benefit

Logical programme of work

Evidential outcomes

Demonstration of progress towards goal

Health check

Early birds

Dstl is part of the

Ministry of Defence





This call closes:

17:00 hrs on

Thursday 29 August 2013

Deadline






[email protected]

www.science.mod.uk/enterprise

Call process queries

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Ministry of Defence





[email protected]

Call technical queries

Dstl is part of the

Ministry of Defence





www.science.mod.uk

Events and Calls > Current calls for proposals > Innovation in drug

development processes

Further information

innovation in drug development processes - cde themed call launch 25 june 2013

Technology

crown copyright mod

context crown copyright

aim of cde

cbrn science

mod longterm aim

government aim

cbrn agents

exploitation of st