ISCF Application of whole Genome Sequencing approaches to Cancer

Application of whole genome sequencing
approaches to cancer
Ian McKay
Innovation Lead - Advanced Therapies
Innovate UK
ian.mckay@innovateuk.ukri.org
1

2
Aims
• Explain the background to the current competition
• Provide detailed overview of the competition,
including:
– Eligibility
– Scope
– Data Sharing
– How to apply

Benefiting everyone
through knowledge,
talent and ideas.
3
UK Research and Innovation
brings together the 7 Research
Councils, Innovate UK and
Research England.
As part of UK Research and
Innovation, Innovate UK drives
productivity and economic
growth by supporting
businesses to develop and
realise the potential of new
ideas including those from the
UK’s world-class research base.
Arts and
Humanitie
s Research
Council
Biotechno
logy and
Biological
Sciences
Research
Council
Economic
and Social
Research
Council
Engineeri
ng
and
Physical
Sciences
Research
Council
Medical
Research
Council
Natural
Environm
ent
Research
Council
Science
and
Technolog
y Facilities
Council
Innovate
UK
Research
England

4
Jan-Mar
2017
Apr-Jun
2017
Jul-Sep
2017
Oct-Dec
2017
Jan-Mar
2018
Apr-Jun
2018
Jul-Sep
2018
Wave 1
ISCF announced
Wave 2
ISCF announced
Oct-Dec
2018
Industrial Strategy and Life Sciences Sector Deal

5
Industrial Strategy Challenge Fund
• Delivers the science that business needs to
transform existing industries and create new ones
• Accelerates commercial exploitation of the most
exciting technologies the UK has to offer the world
• Ensures that scientific investment truly delivers
economic impact, jobs and growth right across
the country
• Industry-led and powered by multi-disciplinary
research and business-academic collaboration

Wave 2 Challenges (up to £729.5m)
Early diagnosis & precision
med (up to £212m)
Healthy ageing
(up to £98m)
Next generation
services (up to £20m)
Audience of the future
(up to £33m)
Quantum technology
(up to £20m)
Transforming construction
(up to £170m)
Transforming food
production (up to £90m)
Energy revolution
(up to £102.5m)
6

7
• Up to £5.4 million funding from through the Industrial
Strategy Challenge Fund
• To encourage the development of new approaches to
targeted therapy based on the molecular signatures
of cancers
• Eligible projects include feasibility studies, industrial
research and experimental development

8
Feasibility studies
• total eligible costs between £50,000 and £100,000
• must be led by a micro, small or medium-sized enterprise (SME)
based on EU-definition
• single organisation or collaborative
Industrial research and/or experimental development projects:
• total eligible project costs between £100,000 and £1 million
• must be collaborative and include an SME

9
• Projects must start by 1 July 2020 and end by 31 March 2022. They
can last between 6 and 18 months.
• The lead and any partners must carry out their project work and
intend to exploit the results from or in the UK.
• If your project’s total eligible costs or duration fall outside of our
eligibility criteria, you must provide justification by email to
support@innovateuk.ukri.org at least 10 days before the competition
closes. We will decide whether to approve your request.

10
Project lead must be
• a UK registered SME for feasibility studies
• a UK registered business, of any size, or a research and technology
organisation (RTO) for collaborative research and development (R&D)
• involve at least one SME
• Academic institutions cannot lead or work alone.

11
Collaborative projects
The lead and at least one other organisation must claim funding.
Eligible organisations includes:
• a UK registered business
• an academic institution
• a public sector organisation or charity
• an RTO
Projects can involve organisations not claiming funding

12
Multiple applications
• Any one business or RTO can lead on one application and collaborate
in a further 2 applications.
• If a business is not leading an application, they can be a collaborator
in up to 3 applications.
If an RTO is a lead on an application they must have 2 business
collaborators (one SME, and one other business of any size)
Academic institutions can collaborate in any number of applications.

13
For feasibility studies and industrial research projects
• up to 70% if you are a micro or small business
• up to 60% if you are a medium-sized business
• up to 50% if you are a large business
For experimental development projects
• up to 45% if you are a micro or small business
• up to 35% if you are a medium-sized business
• up to 25% if you are a large business
Research organisations in your consortium can share up to 30% of the total
eligible project costs. If your consortium contains more than one research
organisation, this maximum will be shared between them.

14
Projects must work with whole genome sequence data. This can include:
• the manipulation of existing whole genome sequence data
• the collection of other whole genome sequences or through both
Possible approaches include but are not limited to:
• the development of new analytical or reporting tools
• the identification of molecular signatures
• supporting a personalised approach to patient management
• the comparative assessment of alternative assay methods in parallel
with whole genome sequencing

15
Specific themes might include:
• improving the diagnosis and prognosis of cancer and the selection of
therapies
• the analysis of complex molecular signatures, including copy number
variants, structural changes and tumour heterogeneity
• supporting the identification of tumours of unknown primary origin
• further analysis of existing whole genome sequence data held by
Genomics England

16
Data management
We expect projects that generate new whole genome sequence data to
make this data available within as part of the dataset held by Genomics
England at the end of the project:
• Subject to appropriate periods of preferential access
• Applicants are encouraged to take advice regarding appropriate
patient consent and sequence quality

17
We will not fund projects that:
• do not involve whole genome sequencing
• involve other forms of genetic analysis, unless as part of a
comparison with whole genome sequencing
• use other forms of genetic analysis, such as panel tests or arrays
in isolation

18
Key Dates
Competition opens 7 October
Competition closes noon 22 January 2020
Applicants notified 3 April 2020
Projects start 1 July 2020

Application of whole genome
sequencing approaches to cancer
Applicant briefing
30th October 2019

1 Welcome and introductions
Scope, eligibility criteria
2 Part 1
Scope, eligibility criteria
3 Part 2
The Innovation Funding Service, application finances,
academic partners
4 Part 3
Submitting your application, assessment, project setup for
successful applicants
Agenda

• Fiona Newbury – Portfolio Manager, Competitions Team
• Julie Brown – Portfolio Manager, Competitions Team
Welcome and Introductions

Resubmission Not a resubmission
A resubmission is:
an application Innovate UK judges as not materially
different from one you've submitted before (but it
can be updated based on the assessors' feedback)
A brand new application/project/idea that you have
not previously submitted into an Innovate UK
competition
OR
A previously unsuccessful or ineligible application:
 has been updated based on assessor feedback
 and is materially different from the application
submitted before
 and fits with the scope of this competition
Resubmissions
This competition does not allow resubmissions.

FEASIBILITY STUDIES
 Lead must be a UK registered SME
 Can be single or collaborative
Total eligible costs between £50,000 and £100,000
 Projects must start by 1 July 2020 and
end by 31 March 2022
 They can last between 6 and 18 months
 You must carry out your project in the
UK
 Exploit the results from / in the UK
COLLABORATIVE RESEARCH & DEVELOPMENT
 Lead must be a UK registered business of any size or an RTO
 At least one UK SME (if lead is not an SME)
 Must be collaborative
Total eligible costs between £100,000 and £1 million
Eligibility criteria

• Business – Small/Micro, Medium or Large (EU definition) registered in the UK
• Research Organisation (RO):
• Universities (HEIs)
• Non profit distributing Research & Technology Organisation (RTO) including Catapults
• Public Sector Research Establishments (PSRE)
• Research Council Institutes (RCI)
• Public sector organisations and charities doing research activity
• Check out the EU definition of a business (it may affect the grant you are able to claim)
http://ec.europa.eu/growth/smes/business-friendly-environment/sme-definition_en
• If you are 100% owned by a large parent company as a small subsidiary this means by EU rules you are classed as a
large company and will only be entitled to the relevant grant
Types of organisations we fund

Eligibility for State Aid
• Innovate UK is offering funding for this competition under the General Block Exemption Regulation. This is
available to eligible UK businesses.
• We are unable to grant funding to limited liability companies meeting the condition known as ‘undertakings in
difficulty’.
• This is where more than half of a company’s subscribed share capital has disappeared as a result of
accumulated losses.
• This test only applies to companies that are more than 3 years old.
• If you have a parent company the test can be performed on your parent or holding company.
• When submitting an application you must certify that you are eligible for state aid. If you are unsure, please
take legal advice before applying.
• Should you be successful, we will apply this test as part of our viability checks before confirming the grant
offer.
• Further information is available on our website in the general guidance under state aid

• The aim of our State Aid scheme is to:
• optimise the level of funding to business and
• recognise the importance of research base to project
• At least 70% of total eligible project costs must be incurred by business
• The maximum level (30% of project costs) is shared by all research organisations in the
project
Participation Rules

In all collaborative Research and Development projects there must be:
• at least two organisations claiming grant within the application (including the lead)
• a business or RTO-led consortium, which may involve both business and the research base
and
• evidence of effective collaboration
• we would expect to see the structure and rationale of the collaboration described in the
application.
What is collaboration?

Making more than one application
• Any one business may be involved in up to 3 applications to this competition, but can only be the lead
partner in one application
• Any one research and technology organisation may only be the lead partner in one application. There
must be at least two other UK businesses (at least 1 SME) claiming grant. If they are leading an
application they may be involved in up to 3 applications to this competition.
• If a research and technology organisation is not the lead on any application, they can be a partner in
any number of applications

Other Innovate UK projects
• If you have an outstanding final claim and/or Independent Accountant Report (IAR) on a live
Innovate UK project, you will not be eligible to apply for grant funding in this competition, as a lead
or a partner organisation.
• If you applied to a previous competition as the lead or sole company and were awarded funding
by Innovate UK, but did not make a substantial effort to exploit that award, we will award no more
funding to you.

Timeline Dates
Competition Opens 7th October 2019
Briefing Event 30th October 2019
Submission Deadline 22nd January 2020
Applicants informed 3rd April 2020
Key Dates

Innovation Funding
Service (IFS)

Search for a funding competition and
review criteria

Applicant: create an account
To create your account:
UK based businesses - Use Companies House
lookup as it speeds up our checks by providing your
company number and your are unable to enter it at a
later date
Research organisations, academics &
Universities - Enter your information manually so
you’re not listed as a business on IFS and ensure
you receive the correct funding

Project Details
• Application Team
- Collaborators: Invite organisations who you are working with on the project
- Contributors: Invite colleagues from your own organisation to help you complete your application
• Application Details
- Title, Timescales, Research Category
• Project Summary
- Short summary and objectives of the project including what is innovative about it
• Public Description
- Description of your project which will be published if you are successful
• Scope - How does your project align with the scope of this competition?
- If your project is not in scope, it will be ineligible for funding

Application form
Question 1 Need or challenge
Question 2 Approach and innovation
Question 3 Team and resources
Question 4 Market awareness
Question 5 Outcomes and route to market
Question 6 Wider impacts
Question 7 Project management
Question 8 Risks
Question 9 Added value
Question 10 Costs and value for money
Appendix Q3
Appendix Q7
Appendix Q8
Appendix Q2
Application Questions
Detailed Guidance
Available on IFS

To claim funding:
Your business does not have to be UK registered with Companies House when you apply but it must be
registered before you can receive funding.
You are unable to claim funding if:
• You are an overseas organisation so your company number begins with FC
• You organisation is setup as a branch so your company number begins with BR
• Your company is based in Jersey so your company number begins with JE

Ineligible:
• Dividends
• Bonuses
• Non productive time
Eligible:
• Staff working directly on
project
• Paid by PAYE
• NI, pension, non-
discretionary costs
Labour

Overheads
Innovate UK’s definition: additional costs and
operational expenses incurred directly as a result of
the project. These could include additional costs for
administrative staff, general IT, rent and utilities
Indirect (administration) overheads
• please ensure they are additional and
directly attributable to the delivery of the
project
Direct overheads
• E.g. office utilities, IT infrastructure, laptop
provision not covered by capital usage
• must be directly attributable to the project
• Provide detailed breakdown together with
methodology/basis of apportionment

Material costs
Please be clear on what the
materials are, just putting
consumables doesn’t
provide enough detail and
we will request more
information should you be
successful

Capital equipment usage
Eligible:
• Used in the project or shared with
day-to-day production
Calculations will need to be in line with your
accounting practices.
Even if the equipment is depreciated fully over the
life of the project this must be added under capital
equipment.

Subcontractors
Eligible:
• Justified and quantified
• If using non-UK sub-contractors
are being used you will need to
provide strong justification on why
an UK-based sub-contractor is not
being used
• If you’re sub-contracting to a
parent or sister company, please
ensure you list at cost and do not
include profit.

Travel & subsistence
Eligible:
Costs must be directly linked to the
project
Please breakdown your costs as
follows:
• Travel
• Accommodation
• Subsistence
If you have an annual trip to visit
the parent company this is not an
eligible cost

Other costs
Eligible:
• Costs that could not be added under
previous headings.
• Do not double count
• Patent filing costs for new IP – SMEs
up to £7,500

Funding
• Funding rules
• The level of funding awarded will depend upon the type of organisation and the type of
research being undertaken in the project
• Funding is calculated by project participant
• IFS will advise the maximum grant % you can request based upon your answers to:
• Type (and size) of organisation
• Research category defined by the lead applicant in the Application Details section of the
application

Organisation /
type of activity
Technical feasibility
studies and industrial
research
Experimental
development
Notes
Business
(economic activity)
Micro/Small – 70%
Medium – 60%
Large – 50%
Micro/Small – 45%
Medium – 35%
Large – 25%
Research
Organisation
(non-economic
activity)
Universities – 100%
(80% of Full Economic
Costs)
Other research
organisations can claim
100% of their project
costs – see note:
Other research organisations must:
• be non-profit distributing and
• disseminate the project results &
• explain in the application form how this will be done
Public Sector
Organisation or
Charity
(non-economic
activity)
100% of eligible costs Must be:
• Be performing research activity &
• disseminate project results & explain in the
application form how this will be done
• ensure that the eligible costs do not include work /
costs already funded from other public sector bodies

Why Je-S?
• We use the Research Councils’ Joint Electronic Submission System (Je-S) to collect academic
finances
• The Je-S system automates the collection of Full Economic Costs (FEC) based costs from academic
partners and tells them exactly what numbers should be used in the application form for their costs
• Also to collect project finance details from non-HEIs (e.g. RTOs) that are claiming they are carrying
out academic quality work and want to be funded on an FEC basis
• Using Je-S means that Innovate UK follows standard Research Council guidelines on funding
universities and enables Research Councils to easily co-fund Innovate UK projects

• Enter the TSB reference number here
• Enter the TSB Contribution column figures
from your J-eS output document into the
project costs section of the application
• Upload the Je-S with council status form
as a PDF at the bottom of the screen
Project costs – academic partners

Je-S application elements
Not just the financials
• E.g. Justification of resources
• E.g Pathways to impact
Full details on the Je-S system
Queries about Je-S via the Je-S Helpdesk
• JeSHelp@rcuk.ac.uk
• 01793 444164

Project cost summary
All organisations can see a
summary of project costs
Ensure the highlighted costs
fits the criteria for this
competition which are
£50,000 to £100,000 for
Feasibility projects and
As a reminder the project
costs for this competition are
£50,000 to £100,000 for
Feasibility projects and
£100,000 to £1,000,000 for
Collaborative Research and
Development.

Checking your finances are complete
IFS checks
• all organisations have marked
their finances as complete
• research organisation
participation is no greater than
30% of the total project costs

Submit your application early!
Be aware of the
potential for last
minute technical
issues!

Scoring
We review scores and feedback to check assessors are adhering to our guidelines and scoring fairly.
In some cases, where we feel a score is unjust and not supported by feedback, we may remove that
score as an outlier and update the total score for the application.
Please be aware that both low and high outliers may be removed and as a result scores may
increase or decrease.

Application assessment
• The score spread shows the difference between the
top and bottom scores
• If score spread is 30 or more we will look to see if an
outlier is apparent
• If there is a 3 or more appear in either the two
columns Count of No Scope or Count of No
Recc’d we review the applications feedback and if
justified, the application will not be eligible for
funding.

• The green box = particular assessors scores on an application
• The purple box = set of scores for a particular question
• The red box = at first glance this looks like an outlier
Identifying outliers

Project setup for
successful applicants

IFS for successful applicants
Project Set up: 8 steps to complete
• Applicable to all grant claiming partners
• Must be completed within 30 days - projects
must start within 90 days or funding may be
withdrawn
• Confirmation of your bank account is required
to ensure we are paying the correct
organisation you may/will be asked to provide a
redacted bank statement to confirm this
• Project change requests cannot be submitted
before the project starts

Project set up
All grant claiming project partners will be required to complete project set up within 30 days of
notification. To avoid delays you should consider:
• Who will be the project manager?
• Who will be the finance contact for each consortium member?
• How will your consortium be set up? (if applicable)

Collaboration agreement
Original agreement signed by all participants
Key Features:
• Who is in the consortium?
• What are the aims, and how is the work divided up?
• Ownership of IPR
• Management of consortium
Negotiating a Collaboration Agreement can be complex and time consuming. Start work on
this at an early stage in the process.

Grant claims and payments
• All grants are claimable quarterly in arrears
• Claims can only be made for costs incurred and paid between the project start and end dates
• Claims may be subject to an independent audit (including all academic partners) according to grant size
• Claims are only paid once quarterly reporting and necessary audits are complete
• Projects over 6 months are monitored on a quarterly basis including a visit from the appointed
Monitoring Officer. Anything outside of this will be discussed on a case by case basis.
• The monitoring will be carried out against a detailed project plan and financial forecast

Project Change Requests (PCR)
• We are unable to process any PCRs before the Grant Offer Letter is issued
• If a member of your collaboration has failed UiD and is unable to resolve you will be advised
to withdraw
• PCRs will only be agreed and authorised by Head of Operational Delivery

Customer Support Services:
0300 321 4357 (Mon-Fri, 9am-5:30pm)
support@innovateuk.ukri.org
Knowledge Transfer Network:
www.ktn-uk.co.uk
Innovate UK:
https://www.gov.uk/government/organisations/innovate-uk
Q&A

@InnovateUK Innovate UKInnovate
UK

Advancing the UK genomics landscape with
whole genome sequencing for cancer
Greg Elgar, Director of Sequencing
30th October 2019

Our Mission: World leading application of
genomic medicine across a national healthcare
system
7401 November 2019
Genomics England formally launched by then Secretary of State
for Health during NHS 65th Anniversary Celebrations, July 2013
CMO’s Generation Genome and Life Sciences Reports in 2017
Commissioning of NHS Genomic Medicine Service October
2018
Reached goal of sequencing 100,000 genomes in December
2018
100,000 Genomes Project announced by then Prime Minister in
December 2012 – an Olympic legacy
Opening of new sequencing centre in 2016, providing
sequencing support on a national level

Our Experience: The 100,000 Genomes Project
in Numbers
7501 November 2019
Samples
122,94
1Samples collected
and received at the
UK Biocentre
Genomes Analysis and Results
genomes sent to NHS GMCs
101,038Results
for
Equivalent
tocancer genomes and
71,546 rare disease
86,073
36,868
• 20-25% actionable findings for
Rare Disease
• ~ 50% cancer cases contain
potential for a therapy or a
trial in our report
Genomes sequenced
83,538
118,11
2
32,324
29,448
Over 97,000 patients and
family members
25+ Petabytes of data Figures as of Oct 2019

Our Future: UK genomics vision for 5 million
genome analyses
7601 November 2019
UK will be a global
leader in genomics
and precision
medicine
Expansion of the 100,000 Genomes Project to
one million whole genomes sequenced by the
NHS and UK Biobank in the next five years
On 2 October 2018, Secretary of State for Health and Social
Care Matt Hancock announced an ambitious vision for
genomic healthcare in the UK…
From 2019, the NHS will offer whole genome
analysis for all seriously ill children with a
suspected genetic disorder, including those with
cancer. The NHS will also offer the same for all
adults suffering from certain rare diseases or
hard to treat cancers
An aspiration to sequence 5 million genomes in
the UK within the next five years
Opportunity to
contribute to 5
million genome
analyses aspiration

Genomics England: Working with Us

Benefits of working with Genomics England
 World-class sequencing and interpretation pipeline including economy of scale savings of this pipeline and
clinically-relevant turnaround times for data provision
 Trusted research environment to undertake bespoke genomic analysis
 Extensive, world-leading data set of whole genome sequences and associated clinical data
 Suite of bioinformatics and analytical tools and technical support
 Ethical framework of informed consent allowing participant re-contact for research and longitudinal life-
course follow-up
 Secondary data sources (such as hospital episode statistics from 1997, mortality returns, etc.) growing
extensively
 Opportunities for collaboration with of Genomics England’s network of researchers
7801 November 2019

Genomics England research environment:
A world-leading data set
7901 November 2019
Figures as of July 2019 (v7 Data Release)
101,162 genomes
• 26,488 Cancer
• 74,674 Rare Disease
Genomes
Primary
clinical data
Secondary
data
• NHSD – Hospital Episode Statistics (HES)
• NHSD – Diagnostic Imaging Dataset (DID)
• NHSD – Patient Reported Outcome Measures (PROMs)
• NHSD – Mental Health Services Data Set (MHSDS)
• NHSD – Office for National Statistics (ONS)
• PHE – Systemic Anti-Cancer Therapy Data Set
(SACT)
Clinically
interpreted
data & QC
• 30,157 families with Tier 1, 2 and 3
variants from interpretation pipeline
• 8,227 with GMC exit questionnaires
• 54,216 tiered and quality checked rare
disease genomes;
24,568 quality checked cancer genomes
New
datasets
• Exomiser output table
• PHE – National Radiotherapy Dataset
(RTDS)
• PHE – Cancer Registration (AV) tables
• PHE – Cancer waiting times (CWT)
• PHE – Lung Cancer Data Audit (LUCADA)
• PHE – Diagnostic Imaging Dataset (DID)
90,643 participants
• 17,682 Cancer
• 72,961 Rare Disease
One billion unique
genotypes
100 trillion
individual genotypes
10 million health
records, over 100
per patient

Suite of tools and analytics
8001 November 2019
Data and
documentation
CollaborationTools and analysis
Genomes (BAM
and VCF files)
Clinical data
in LabKey
Virtual desktop
interface provides GUI
and security
R and Rstudio for
data analysis
Command-line tools
and HPC cluster for
large-scale analysis
Data release notes
User guides
Airlock
Live issues
Domain-
specific and
shared storage
for files
Social media
platform for
support
Research Registry
Promote
collaboration
Enforce publication
moratorium
Data Discovery
Portal for cohort
building

Secure workspace for data access and analysis
8101 November 2019
Included in Full Membership
Research – access to and analysis of >100,000 genomes and linked data
• Define cohorts based on molecular, phenotypic and/or clinical attributes
• Reproduce known phenotypic and/or genotypic associations
• Test novel biological research hypotheses
Compute: High performance compute cluster; 2,136 job slots available for analysis
Support: Expert Professional Services
Governance: Virtual desktop access and managed file transfer
Additional Options
Additional compute or HPC cluster access
Extra Support or Consulting Services

Scientific Impact: Industry and academic
collaborations
8201 November 2019
Genomics England Clinical Interpretation Partnerships
3,579
researchers worldwide
415
academic institutions
Discovery Forum
Figures as of October 2019
R&D Organisations Charities, Trade & Sector Suppliers & Support
91 13 59

The Genomics England model
8301 November 2019
Discovery Forum
Industry Users
Reporting of Analysis

Proposed approaches for working with
Genomics England
8401 November 2019
1. End-to-end
Genomes
 Genomics England end-to-end genome journey (receipt of sample, sequencing,
bioinformatics pipeline, return of analyses)
2. Analytical
Pipeline
 Use of Genomics England analysis pipeline only (importing genome sequence data
generated externally1)
3. Genome Research
 Access to Genomics England research environment, including ability to import non-
genome data (no new whole genome sequencing to be performed)
1. Minimum quality requirements apply

1. End-to-end Genomes
8501 November 2019
Sample QC
Sequencing
Bioinformatics
Analysis Pipeline
Return of
Analyses
Analysis within
the Research
Environment
Sample
Acquisition
 Transport of samples
 DNA extraction and plating (if needed)
 Quality Control
 Sample archiving
 Management of sample flow
to sequencer
 Whole genome sequencing:
3.5 whole genome
equivalents (30x germline, 75x
somatic)
 Sequence alignment and variant
calling
 Interpretation and tiering of variants
 Provision of genome data
within research environment
(9 months exclusivity)
 Linkage to longitudinal clinical
data
 Provision of bioinformatics
tools and computation
environment
 Genomic data files available to
customer

2. Analytical Pipeline
8601 November 2019
Sample QC
Sequencing
Bioinformatics
Analysis Pipeline
Return of
Analyses
Analysis within
the Research
Environment
Sample
Acquisition
 Sequence alignment and variant
calling
 Interpretation and tiering of variants
 Provision of genome data
(9 months exclusivity)
 Linkage to longitudinal clinical
data
environment
 Genomic data files available to
customer

3. Genome Research
8701 November 2019
Sample QC
Sequencing
Bioinformatics
Analysis Pipeline
Return of
Analyses
Analysis within
the Research
Environment
Sample
Acquisition
 Access to genome and
longitudinal clinical data
environment
 Ability to import own tools
and data (pending consent)

Expectations for working with Genomics
England
8801 November 2019
Appropriate
Sample Quality
Appropriate Data
Quality
Appropriate
Consent
Appropriate Legal
Agreements
Genomics England will collaborate on proposals as a service provider
 Minimum sample
requirements apply.
 Guidance on sample
collection and
preparation can be
provided.
 Minimum data
quality metrics apply.
 Associated data to
permit sequencing to
progress.
 Quality of externally
generated
sequencing data for
import into research
environment.
 Where possible, use
of Genomics England
informed consent is
recommended.
 Longitudinal life-
course follow-up and
recall for research.
 Can co-consent
alongside other
consent frameworks.
 Agreements for
services to be
provided.
 Material Transfer
Agreements (MTA).
 Data Sharing
Agreements (DSA).

Additional considerations and opportunities for
collaboration
Experimental approaches to compare sequencing technologies to current
Genomics England gold standard will be considered
 E.g. Oxford Nanopore Technologies (ONT)
 Combinations of ONT with short read sequencing techniques
8901 November 2019
Competitive pricing available on request for all suggested proposals.
Additional costs may be sourced for non-standard approaches.
Networks for sample acquisition (e.g. ECMC) can work with Genomics England to
enable seamless transition of samples from clinic to sequencer
 Genomics England can support sequencing of clinical trial samples; co-
consent alongside existing trial consent possible
 Trial data can be imported, at an appropriate point, into a sealed embassy
of the research environment for analysis alongside whole genome data

Non-standard proposals
9001 November 2019
 End-to-end genome proposal is preferred:
 Best use of world-leading sequencing and analysis pipelines
 Ensures appropriate data quality for seamless contribution to the research environment
 Best value for UK genomics knowledgebase if data is under appropriate consent model for research
 Options outside of Genomics England standard processes are challenging, incur additional cost and will
need additional consideration regarding feasibility and acceptability
 This includes option 2: use of the Genomics England analytical pipeline only, where sequencing data is
generated by a third party
 This includes the importing of non-WGS data (only considered if alongside WGS); applicants would need
to provide a data and analytic pipeline
 These will be considered on a case by case basis

Proposed roadmap for Innovate UK applications
9101 November 2019
SME sources samples
through alternative
mechanism
Filtering based on feasibility and
suitability assessment via ECMC
processes
Samples sourced through
ECMC Network
Sequencing and Analysis
Pipeline with Genomics
England
Feedback on feasibility
and suitability from
Genomics England
Request for Genomics
England research
environment access
Request to import
externally generated
sequencing data

Contact Us
www.genomicsengland.co.uk
innovate@genomicsengland.co.uk

Sample Requirements
 The above demonstrates the preferred sample requirements. Further information relating to minimum
sample requirements, and risks associated with such, can be provided.
 All proposed sample collections must comply with the sample handling requirements outlined in the
Genomics England Sample Handling Guidance (here). Note: This document is focused on NHS requirements,
but standards are applicable to all sample submissions.
9401 November 2019
Plating Requirements WGS Requirements
DNA Concentration 20-100ng/µl 45ng/µl is preferred
Sample Volume
Minimum 115µl*
Volume range is 115-
125µl*
Minimum 100µl
Volume range is 105-
120µl
DNA Quantification Minimum of 2µg*
DNA Purity Assessment A260/A280 ratio must be 1.75 - 2.04

Example research environment tool: Data
Discovery Portal
 Build cohorts using our Data Discovery Portal, export, and complement with clinical and genomic data
9501 November 2019
Dashboards to select appropriate data
sets (e.g. cancer participants only)
Visualise on chosen parameters (e.g.
genome build, cancer primary site)
Compare with associated data and
export cohorts for further analysis

High Performance Compute
 Pegasus: high performance compute cluster where sequenced data and called variants are stored and
analysed
 2,136 job slots available for analysis
 Further information available at: https://cnfl.extge.co.uk/display/GERE
9601 November 2019
Number of
node(s)
Cores per
node
Number of
CPU cores
Memory per
node
/scratch per
node
Queue’s
available
from
24 24 576 740 GB 2.9 TB (2910
GB)
Bio, high
128 12 1,536 370 GB 1.4 TB (1420
GB)
ALL (bio, high,
gecip,
research,
discovery, cip)

MDC - A national asset
Providing hard-to-access
scientific capabilities
Gateway to UK resources
& expertise

We will not
• Compete with pharmaceutical or service companies
• Perform independent medicines discovery
• Replicate readily available UK infrastructure
We will prioritise and exemplify our efforts
• Outside of areas already covered
• In areas where UK science is perceived as ‘strong’
• In areas where SME needs are not met by others
• On development and promotion of cross-cutting discovery approaches
WHO WHY HOW WHAT WHERE WORK WITH US
We are focussed on enabling UK drug discovery

DISCOVERY SCIENCE
& TECHNOLOGY
INFORMATICS SAMPLES & DATA VIRTUAL R&D SYNDICATES
Our unique capabilities
Designed to address the needs of our UK drug discovery community and change the shape of R&D:
BETTER DATA FASTER
ACCESS TO UK RESOURCES & EXPERTISE
Establishing patient-related
testing models and new
technologies
Discovering and connecting
data to build new algorithms,
AI and machine learning
approaches
Brokering easier access to
consented patient data
and samples
Leveraging the UK’s
renowned leadership in
drug discovery – a modern
approach to R&D
Enabling patient-centred
drug discovery – a collective
approach to R&D

Increasing need for scientific collaboration
• Increasing amount of ‘Team Science’
• Increased funding towards highly
collaborative ventures, Horizon 2020, IMI, etc.
• Companies look to outsource capabilities and
slim down in-house capabilities
• Drug Discovery is becoming increasingly a
data science activity
• Therefore the need for facilitating
collaboration of data and knowledge in a
secure, systematic and supportive format
Science March 2018: DOI: 10.1126/science.aao0185

Who do we help?
We work collaboratively with all sectors of the UK Medicines Discovery Industry
with the primary aim of developing and growing SMEs

UK SMEs see unrealized value in NHS samples and data
10
2
-100% 0% 100%
Access to biosamples for commercial development
is hugely important
It is easy to access high quality NHS biosamples for
commercial research
Access to the right health data such as registries
and activity is hugely important for innovative…
It is easy to access the right health data such as
registries and activity
The UK has a clear framework and process for the
commercialisation of NHS health data
Please could you indicate how much you agree / disagree with these statements about
the NHS?
Neither agree nor disagree Somewhat agree Strongly agree Somewhat disagree Strongly disagree
Why Samples & Data?

Providing support for small medical research companies
We have developed a strong understanding of the UK-wide capabilities in medicines discovery,
so we can help find the right partner or supplier for data via Signposting and Introductions
When researchers are unsure were to find the data they need, we will conduct a full search of
the data landscape and provide a Data Availability Report, detailing suitable data holders,
access procedures and requirements
We have compiled a series Data Access Guides for a number of the main UK data holders.
These impartial overview documents aim to help SMEs consider if and how they can access
data
We can provide practical support in completing Data Access Requests and Data Transfer
Agreements

Biomarkers for Precision Medicine
• Aim to establish a range of targeted and untargeted biomarker
analysis workflows from a wide range of sample types - ex vivo and
clinical tissue, blood, urine; cells grown in 2D and 3D
• Core technologies: Nanostring; Mass Spectrometry; Digital Droplet
PCR
• Many workflows are established today, more to follow..
• Initial focus on transcriptomics, lipidomics, metabolomics; building
proteomics capability in 2019
• Building capability to incorporate spatial biomarker analysis
into our offering
• Mass Spectrometry Imaging available today
• Nanostring GeoMx Digital Spatial Profiler
Biomarker Discovery
Biomarker Assay
Development
Biomarker Validation
Biomarker
prevalence
Early disease
linkage
studies
Human
tissue

DISCOVERY SCIENCE
& TECHNOLOGY
INFORMATICS SAMPLES & DATA VIRTUAL R&D SYNDICATES
Our unique capabilities
Designed to address the needs of our UK drug discovery community and change the shape of R&D:
BETTER DATA FASTER
ACCESS TO UK RESOURCES & EXPERTISE

Delivering Informatics Approaches to Drive Smart
Decision Making in Drug Discovery
• Medicines R&D is fundamentally a data-science, relying on
an increasing diversity and volume of complex R&D and
health data.
• The ability and requirement to build tools that support
interpreting the data are key.
• Informatics and AI offers a competitive edge and
opportunity to both large and small industry alike.
“I need to understand the network of
medicines discovery organisations that
can support me developing my early
stage chemical asset”
“For a class of marketed drugs I need to
understand all of the associated data for those
molecules, to include PK properties, bioactivity,
phys.chem etc.”
“I am considering a number of drug
candidates for different disease
indications, which preclinical tests and
with what budget can I expect to achieve
first-time-in-man milestone?”

Cancer WGS Analysis Capabilities
at Medicines Discovery Catapult
• Identification of somatic structural
variants (e.g. deletions,
duplications, translocations, gene
fusions)
• Detection of cryptic
pathogens (e.g. viral DNA)
• Identification of somatic
mutations

Infections in cancer
• Currently known oncoviruses
• Hepatitis B (HBV) and C (HCV)
• Human T-lymphotropic virus (HTLV)
• Human papillomaviruses (HPV)
• Kaposi’s sarcoma-associated herpesvirus (HHV-8)
• Merkel cell polyomavirus (MCV)
• Epstein-Barr virus (EBV)
http://canceratlas.cancer.org/
Dambuza and Brown - Nature 574, 184-185 (2019)
Aykut, B. et al. - Nature 574, 264–267 (2019).

Cryptic viruses in cancer
• Potential for discovery of novel oncogenic viruses in
sequencing reads not mapped to the human genome
reference in cancer samples, especially of unknown
aetiology
• De novo assembly of viral reads
• Horizontally acquired eukaryotic genes in viral
genomes → Novel mechanisms of oncogenicity and
novel drug targets – allowing for targeted therapies
• Our understanding of commensal microbiota is likely
to be a key factor in understanding the epidemiology
of cancers and for cancer immunotherapy
Routy et al. Science 05 Jan 2018:
Vol. 359, Issue 6371, pp. 91-97

T790M Mutation effect on EGFR+Erlotinib interaction
• EGFR + Erlotinib (PDB:1M17)
• T790M (Threonine 790 to Methionine mutation)
• Explicit solvent: water molecules
• No. Atoms: 60k+
• Active site
• Threonine (green)
• Methionine (magenta)
[1] Stamos, J.; Sliwkowski, M.X.; Eigenbrot, C.; J. Biol. Chem. (2002). 277. 46265-46272
Epidermal Growth Factor Receptor tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib1

Thermodynamic Cycles
"Free Energy Calculations. Theory and Applications in Chemistry and Biology“
Christophe Chipot and Andrew Pohorille (Eds.)
Springer Series in Chemical Physics, Volume 86. (2007)
ISBN: 978-3-540-73617-2. DOI: 10.1007/978-3-540-38448-9
PROTEIN MUTATION SITE-DIRECTED MUTAGENESIS
ΔGA-X
ΔGB-Y
ΔGC-Z

Intelligent Capture
• Data, even from a single publication can be found across multiple data repositories
and formats
• Yet valuable structured and unstructured public data sets are not linked and readily
findable
• Development of AI based approaches is dependent upon robust data capture

Search
• We seek out wide range of linkable data
sets.
• To capture the underlying structure we
have a developed a live knowledge-
graph of UK drug discovery assets and
capability
• Intelligent semantic search capability
allows for a wide range of Medicines
Discovery questions:
• Difficult to find the best
collaborators
• Offering insights to the disease
and therapeutic landscape

Analysis and Interpretation
• Taking these data sets and applying expert interpretation
to:
1. Finding Assays:
– Text-mining across papers, patents, vendor catalogues
2. Indexing of Assays:
– specialist dictionaries - techniques, equipment, genes, end-points,
….
3. Classification of assays:
– Efficacy/ADMET & biochemical, cell-based, organoid, tissue, ….
4. Similarity of Assays:
– how ‘similar’ are two assays?
5. Chaining of Assays:
– constructing the directed graph
6. Learning thresholds:
– Identification of ‘triggers’ from chained, directed assay pairs

Biochemical
assays
Cell-based
assays
Functional
assays
In vivo
assays
Human studies
What is the flightpath through Drug Discovery and Development?
$3b
n
$1.2bn
$2bn
$0.4bn
$0.3bn
Market
Value
stop
stop
stop

Case Study – MS Society
• To enable new treatments to reach patients faster,
the MS Society and its expert consortium wanted to
investigate drugs used in the treatment of other
diseases as potential clinical candidates for
repurposing in MS, therefore:
1. Identifying all drug candidates already tested in
clinical studies for MS
2. The subsequent identification of the known
molecular targets and mechanisms of these drugs
3. The identification of further drugs that were
predicted to impact these molecular targets, that
are approved and licensed, or currently in clinical
studies, for another disease
The MDC informatics workflow identified 878 drugs
tested in 1,976 MS trials and was able to filter these by
distinct drug intervention and mechanistic classes (22
mechanisms) in order to prioritise the top 320 drug
candidates with potential to stop or slow MS progression
Work flow

Outcomes
• Through the independent, data-driven
analysis conducted at MDC, the MS
Society’s expert consortium was able to
validate their list of potential drugs
• Allowed the identification of further
potential clinical candidate drugs.
• Additional data for proposed candidates
supported future prioritisation of drug
candidates to enter the MS Society’s clinical
trial platform.
• Drug identifiers (CAS, ChEMBL ID, name, generics)
• Target classification
• Physical /ADME properties
• Route of administration
• AEs/safety, drug label warnings
• Dosing, cost

©2016 Medicines Discovery
Catapult. All rights reserved.
md.catapult.org.uk
@meddisccat
info@md.catapult.org.uk
01625 238734
Visit our website for our latest partnerships and
funding opportunities.
Get in touch for more information, expert guidance,
strategic consultancy and access to our technology.
Or to discuss a potential project or service.
Get in touch now

One-of-a-kind
Research network
ECMC Programme Office

120
Accelerating Innovation in early-phase oncology research
• A unique network integrating NHS and academic
research centres
• World-class clinical, scientific and operational
expertise
• Access to a broad UK adult and paediatric patient
population
• A single point of entry to facilitate site engagement,
feasibility and study placement
• Academic Engagement to progress innovation
• ~ £7M infrastructure funding annually

World-class clinical and
scientific expertise
Adult ECMC Network
Belfast
Vicky Coyle
Daniel Longley
Birmingham
Gary Middleton
Cambridge
Duncan Jodrell
Rebecca
Fitzgerald
Cardiff
John Chester
Oliver Ottmann
Edinburgh
David Cameron
Stefan
Symeonides
Glasgow
Jeff Evans
Richard Wilson
London - Barts
Peter Schmid
Rowan Miller
London - ICR
Johann Sebastian de Bono
Udai Banerji
London - Imperial
Michael Seckl
Eric Aboagye
London - Kings HPs
James Spicer
Anand Purushotham
London - UCL
Tim Meyer
John Hartley
Leicester
Anne Thomas
Karen Brown
Liverpool
Daniel Palmer
Andrew Petitt
Manchester
Natalie Cook
Caroline Dive
Newcastle
Ruth Plummer
Yvette Drew
Oxford
Sarah Blagden
Adam Mead
Sheffield
Sarah Danson
Ingunn Holen
Southampton
Andrew Davies
Simon Crabb
Paediatric ECMC Network
Birmingham
Bruce Morland
Pamela Kearns
Andrew Peet
Bristol
Helen Rees
Cambridge
Amos Burke
Richard Gilbertson
Glasgow
Milind Ronghe
London - ICR
Lynley Marshall
Louis Chesler
London - UCL
Darren Hargrave
John Anderson
Leeds
Martin Elliot
Liverpool
Lisa Howell
Manchester
Guy Makin
Newcastle
Quentin Campbell-Hewson
Gareth Veal
Deborah Tweedle
Southampton
Juliet Gray

What can the network provide?
• 20 leading sites with expertise in experimental cancer medicine
• 100+ clinicians with expertise across all cancer types and all age groups
• A network that recruits over 3,000 patients to early phase cancer studies annually
• 70% commercially sponsored studies, 30% academically sponsored
• Sites with experience and capability to collect samples suitable for WGS
• A dedicated Programme Office that supports companies in accessing the network
• Expedited process that can identify interested sites and investigators in days
• Assistance with feasibility and site selection

What does the typical ECMC patient look like?
• Patients generally come in via the Phase I clinic
• Usually have had one or more rounds of therapy (chemotherapy/targeted therapy/immunotherapy,
some will have had surgery and/or radiotherapy)
• Patients are usually facing disease progression or relapse and have no other standard lines of therapy
available – early phase trials may be the only treatment option available
• They usually have good performance status, but poor prognosis and can deteriorate quickly
• Most will have had tissue samples taken at diagnosis and/or during surgery (likely to be formalin fixed)
• Patients are match to trials based on eligibility criteria, including disease type and molecular markers
• Many early phase trials require a re-biopsy for entry into the study
• All ECMC locations have access to molecular testing for Phase I patients to assist in matching with trials,
but none has standard access to WGS

What does the network gain from participation?
• ECMC investigators will want to see proposals that seek to generate clinically meaningful data
in a clinically relevant time frame for their patients
• They will want sequencing data returned in a format that will allow them to identify actionable mutations
and other factors such as tumour mutational burden and microsatellite instability, this will help match
patients with suitable trials
• They will need the sequencing data to be returned within a maximum of calendar 12 days
• Clinicians should also be informed of any clinically relevant findings from subsequent analysis of
the tissue sample and/or the sequence generated
• All costs for additional sample collection (e.g. radiology, pathology, DNA extraction shipping) must be
reimbursed via the Innovate UK award

WGS data will be used to match patient to trials using our
TrialFinder Tool, unique to the network
Purpose: Drive trial recruitment by easily matching patients to early
phase clinical trials within the ECMC network
Uniqueness: The power of the Network is utilised to address known
challenges with existing databases i.e. lack of visibility of early phase
trials, out of date and inaccurate trial and recruitment information.
How: Easy search using customised criteria. Recruitment site contact
details published to allow users to quickly determine patient eligibility
and slot availability. Data updated on a monthly basis.
Opportunity to drive faster trial
recruitment
For more info contact: ectrialfinder@cancer.org.uk
Improved patient access
to trials
Visibility of clinical trials to allow
easier patient referrals

• Site engagement, feasibility and study placement enabled by the ECMC Programme Office
• Network level CDA, EOI and Feasibility template
Standard industry access route to the network
EoI Feasibility Site
Selection
5 days 5 days 5 days Site-level intelligence
ECMC
NDA

Proposed access route for submission to the Innovate UK
call - DRAFT
SMEs with ideas requiring tissue samples
Programme
Office
Precision Medicine working group
Feasibility & Suitability Assessment
Feedback
If feasibility favourable
Programme
Office
Identifies interested
collaborators
and informs SME
Other sequencing
provider
Feedback Feedback

Contact us
Programme Office
W: www.ecmcnetwork.org.uk
E: ECMCadmin@cancer.org.uk
Combinations Alliance
W: www.ecmcnetwork.org.uk/ca
E: combinationsalliance@cancer.org.uk

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