CF AMR Syndicate: Collaborative Discovery Programme

© 2021 Medicines Discovery Catapult. All rights reserved.
Webinar will start at 2pm GMT 30th March

Collaborative Discovery Programme: a
new funding call for antimicrobial
innovators

1. Opening Remarks Dr Katy Kettleborough
2. Introduction to the CF AMR Syndicate Dr Paula Sommer
3. Living with CF – A Personal Perspective Angelo Micciche
4. The need for new antimicrobials in CF & what good
looks like – Target Product Profiles
Professor Jane Davies
5. The Syndicate Collaborative Discovery Programme
• Scope
• Eligibility
• Process & Timelines
• Selection Criteria
• Resources available
Dr Neill Gingles & Dr Ed McIver
7. Opportunity for Q&A CF AMR Syndicate Management Team
Webinar – Launch of the First CF AMR Syndicate Funding Call

Introduction to the CF AMR Syndicate

• CF is a life-limiting condition that affects over 162,000 people
globally
• People with CF are susceptible to lung infections – once
these adapt to the CF lung environment they can be difficult to
treat and permanently reduce lung function – AMR is frequently
seen and is a cause of mortality1
• Antimicrobials and related diagnostic tools remain a key and
necessary therapeutic in CF2. Key CF pathogens are included on
the WHO Priority list.
Cystic Fibrosis and Antimicrobial Resistance
1 UK CF Registry Annual Data Report 2020 Annual data report - Version 2.pdf (cysticfibrosis.org.uk)
2 Cystic Fibrosis Refresh Top 10 priorities (priority setting in association with the JLA) | James Lind Alliance (nihr.ac.uk)
2 World Health Organisation. (2017). Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antiobiotics
Lung Infections in 2020 across the UK Population
of People with CF (N=9922*)1

The CF AMR Syndicate
Our Mission: to accelerate the translation and adoption of new CF
antimicrobials and diagnostics to the clinic, through collaboration. Bring new
treatments to people with CF, faster.
Our Aims:
• Provide guidance on the medicines discovery roadmap for lung
infections in CF in keeping the needs and priorities of people with CF
• Catalyse the development of and access to specialist enabling research
resources to accelerate translation.
• Facilitate the formation of virtual medicines discovery teams and R&D
collaborations across the CF AMR network.
• Enable innovators globally to access specialist support and funding to
advance diagnostics and antimicrobial projects for lung infections in CF

Our Approach and Who we are
Working together to accelerate the
translation of CF antimicrobials and
diagnostics to the clinic
People
with CF
Commercialisation and
Translation Experts
including regulators
Managing partners
Funders and
investors
Leading experts
from academia
and industry
Clinical Teams
Identifying areas of
unmet need
Leveraging
cross-sector expertise
Catalysing drug
discovery efforts
Involving patients

Despite global activity
in CF antimicrobial
development, key
challenges remain:
The UK CF Infection
Biorepository
• Lack of access to clinically
relevant samples & data
• No agreed preclinical testing
pathway
Evidence-based Preclinical
framework for the
development of CF
antimicrobial therapeutics
Patient-focused Target
Product Profiles for
antimicrobials and
diagnostics
Funded by: Funded/Delivered by:
PI: Prof Jo Fothergill University of Liverpool
Funded by:
Progress to Date: Catalysing the build of required resources

Community Action: The CF AMR Network
The Syndicate has formed the CF AMR Network to help the community to work together to address the challenges
CF AMR Syndicate Website &
Newsletter
Blogs News Resources
Events, Workshops &
Focus Groups
Knowledge exchange & problem solving
Networking & Signposting
Catalysing collaborations
Join the Network here: https://cfamr.org.uk/network/

Growing our Impact
Continue to build supporting
tools and resources for CF
antimicrobial and diagnostic
development
Nurture the cross-sector CF
AMR network to facilitate
collaboration and knowledge
exchange
Identify, enable and support
CF antimicrobial and
diagnostic programmes
The Collaborative Discovery Programme

Living with Cystic Fibrosis – A personal
perspective

The need for new antimicrobials in CF
& what good looks like – Target Product Profiles

IVACAFTOR
Continuing problem of lung infections in the era of CFTR
Modulators
? Infection impacts

Continuing problem of lung infections in the era of CFTR
Modulators

https://www.cff.org/Trials/Pipeline
Preclinical
• NO-donor molecules
• Antimicrobial resistance
breakers
• Repurposed drugs
Current pipeline

Considerations in the development of new
antimicrobials
Develop target product profiles with a focus directly from people
living with CF
Build enabling tools/resources for CF antimicrobial development
CF AMR Syndicate: identified an unmet need of a lack of target product profiles to facilitate a structured
approach to develop new CF antimicrobials including consideration of the people living with CF who mostly
have long term antimicrobial treatment
TPPs are used:
• As drug development planning
tools
• To provide a regulatory context to
drug development e.g. alignment to
regulatory submission documents
• As a guidance document align
unmet medical need and R&D targets
for public health

The process of developing patient-focused TPPs
Being involved in the
meeting to identify TPPs for
the development of new
antimicrobials was
extremely helpful to me
as a patient.
We hope that these TPPs
influence the development of
future treatments to be easier
to manage and more tolerable
without loss of efficacy.
Focus group
of people
with CF
Clinical
focus group
Industry
insights and
expertise
Delphi
Survey
Virtual
Symposium
TPP Development Process
CF AMR Syndicate TPP project (completed in 2022): developed TPPs to help guide and catalyse the discovery and
development of CF antimicrobials that meet the needs and priorities of people living with CF
Angelo, who has CF Lorna, who has a child with CF

Target Product Profiles for Specific CF Pathogens
CF AMR Syndicate TPP project outcome: through engagement with the UK CF community priority areas of unmet
need were defined and developed into three main TPP themes
Patient-focused TPP
Pseudomonas aeruginosa
infection
TPP for eradication and/or suppression
of chronic infection
TPP for treatment of acute pulmonary
exacerbations (PEX)
Mycobacterium abscessus
infection
TPP for eradication of infection
TPP for maintenance treatment or
suppression of chronic infection
TPP for treatment of acute PEX
CF AMR Syndicate TPPs for CF infection Aspects of these TPPs are relevant to other CF
pathogens
Other important and emerging pathogens
associated with CF
Other NTMs: Mycobacterium avium
Strenotrophomonas maltophilia, H.influenzae, B.cepaci
a and related species such as B.cenocepacia,
B. multivorans), Achromobacter spp. Pandoraea spp, R
alstonia spp, S. aureus
Fungal pathogens: Aspergillus, Candida albicans

Where did we start?
1 Burden of Healthcare
2 Quality of Life
3 Stability of Health
A generic overarching TPP defined outlining the needs and priorities of people living with CF for any
new antimicrobial
Key characteristics
defined*
• Patient population
• Treatment duration
• Route of administration
• Regimen
• Polypharmacy
• Monitoring of treatment
• Risks/side effects
• Clinical trial endpoints
Storage
* Specific details on the published TPPs
available via the CF AMR Syndicate website
Adverse effects from multiple medicines
negatively effect Quality of Life
Long-term oral and nebulised medications
multiple times per day, daily physiotherapy and
demanding nutritional regimes.
Requirements set in this TPP should be
considered alongside each of the organism
and indication TPPs and key considerations
considered
Patient-focused TPP

TPPs: Pseudomonas aeruginosa infections (summary)
TPPs aligned to Pa
infections
TPP for eradication and/or
TPP for treatment of acute
pulmonary exacerbations (PEX)
TPPs defined outlining the unmet needs around Pseudomonas aeruginosa (Pa) infections
Key characteristics defined*
• Treatment aims
• Evidence of efficacy from
preclinical assessment
• Clinical outcomes
• Concept of use
*Refer to specific details on the published TPPs
The ideal product should have:
• Activity against the majority of MDR clinical
isolates, in particular CF-related endemic strains
• Demonstrable ability to break existing intrinsic or
acquired resistance mechanisms
• No significant pre-existing resistance profile in
clinical isolates of Pa
• Evidence of synergies with other standard of care
antibiotic classes to reduce resistance emergence
To address newly acquired or chronic lung
infection with the goal to eliminate or
reduce burden return to baseline lung
function
To address acute flareup in infection and
restore normal function and symptoms.
Reduction in frequency, duration and/or
recurrence of PEX

TPPs: Mycobacterium abscessus infections (summary)
TPPs aligned to
M.abscessus infections
TPP for maintenance treatment for
TPPs defined outlining the unmet needs around Mycobacterium abscessus infections
Key characteristics defined*
• Treatment aims
• Evidence of efficacy from
preclinical assessment
• Clinical outcomes
• Concept of use
*Refer to specific details on the published TPPs
The ideal product should have:
• Efficacy against one or more species of
M.abscessus complex
• Be able to break existing intrinsic or acquired
resistance mechanisms
• No pre-existing resistance profile in clinical
isolates of M.abscessus
• Evidence of synergies with other standard of care
antibiotic classes to reduce resistance emergence
Unmet set out in this TPP is to address
newly acquired or NTM lung infection with
the goal to eliminate or reduce burden
return to baseline lung function
M.abscessus lung infection, unstable on
maintenance treatment, unresponsive to
curative treatment. Reduce burden, reduce
rate of respiratory decline
TPP for treatment of acute
pulmonary exacerbations (PEX)
acute flareup linked with M.abscessus
infection and restore normal function and
symptoms.

Syndicate Collaborative Discovery Programme:
Overview & Key Features

Purpose and Overview
£3 million over a 2-year timeframe with the intent to have selected
between 3-5 projects to fund and support by end 2023
A new programme to create
and advance an exciting and
diverse pipeline of preclinical
phase antimicrobial projects
aimed at treating lung
infections in
people with CF
Aim to provide participants with funding and support that secures
delivery of key data for onward development and investment
The portfolio will be actively managed. Projects will receive drug
discovery advice and project management input from the Syndicate

What projects are we looking for?
Projects directed at addressing the CF AMR Syndicate therapeutic
target product profiles (TPPs) will be prioritized
Patient-focused TPP
Pseudomonas aeruginosa
infection
TPP for eradication and/or suppression
of chronic infection
TPP for treatment of acute pulmonary
exacerbations (PEX)
Mycobacterium abscessus
infection
TPP for maintenance treatment or
TPP for treatment of acute PEX
Strenotrophomonas maltophilia,
H.influenzae,
B.cepacia and related species such
as B.cenocepacia, B. multivorans
Achromobacter spp.
Pandoraea spp,
Ralstonia spp,
S. aureus
Other important pathogens
associated with CF
Fungal pathogens: Aspergillus,
Candida albicans
Other NTMs: Mycobacterium avium

What is in Scope?
Target
ID
Hit ID
Hit
Validation
Hit-Lead
Lead-
Candidate
Preclinical IND P1 P2 PIII
Syndicate CDP
• Phase: Projects at Hit Validation stage, Hit-Lead, Lead Optimisation, Candidate Selection and Early Preclinical
• Target Class/ Mechanism: Any novel targets OR novel chemical classes including but not limited to the following
mechanisms; direct-acting and non-direct acting antimicrobials, anti-virulence approaches, host immune-
modulation, potentiators, modulators of microbiota
• Therapeutic Modality: Any including but not limited to small molecules, biologics (antibody, peptide, CRISPR,
complex/targeted modalities), phage

What is out of Scope?
• Target Identification
• Hit Identification
• Projects focused solely on IND-enabling studies
• Clinical Phase R&D
• Projects not directly focused on antimicrobial development (e.g. diagnostics, delivery methods,
biomarkers)
Target
ID
Hit ID
Hit
Validation
Hit-Lead
Lead-
Candidate
Preclinical IND P1 P2 PIII
Syndicate CDP

Key Eligibility Criteria
The project
The applicant(s)
• can be academics and researchers from SMEs worldwide
• applications should have a single lead applicant and co-applicants also welcome
• should last up to two years
• will be milestone driven with clear go/no go progression criteria defined upfront
• with up to £500,000 UK GBP of direct costs

More than just funding – what we will offer
Our intention is not just to fund but to add additional collaborative support to enable
the best chances of success for projects to attract further investment
Support throughout the project funding journey tailored to individual project
needs (defined at full application stage);
 Drug discovery and disease area insight and advice
 Support to develop actionable project plans aligned to TPP
 Drug discovery capabilities through
• Resources of the managing partners
• Syndicate enabling resources
• Wider discovery services network
 Commercial know-how (e.g. IP, pitch-deck preparation)
 Facilitating involvement from people living with CF
 Connections across the Syndicate CF AMR Network
 Access to potential downstream funders
UKCFIB

Summary of Key Terms and Conditions
IP, Ownership of results and Revenue Share
• Funding is non-dilutive
• Background or arising IP remains with the recipient
• A revenue share clause will apply upon successful commercialisation
(Agreed case-by-case and giving consideration to the AMRC guidelines at the time)
Funding
Direct costs associated with the project will be funded. Typically, this will cover:
• An appropriate %FTE of staff (Post Docs), plus consumables, directly related to funded work
• Access to specialist equipment/reagents
• Contract Research Organisation work
• Use of centralized platforms enabled by the CF AMR Syndicate
• Defined lab activities at the Medicines Discovery Catapult or LifeArc
Receipt of funding will be linked to achieving milestones. Some payment could be made in advance on a case-by-case basis
Full terms and conditions available here: https://cfamr.org.uk/collaborative-discovery-programme/

Call Process Overview, selection criteria
and next steps

Expression of
Interest (EOI)
•EOI Opens 30th March
•Applicants apply
online
•Option of booking a
call to discuss
application
•EOI closes at 23:59
BST on 9th May
Triage
•Internal review by
Syndicate select up to
10 proposals to
progress to full
application
•Successful applicants
invited to online
Workshop in June
•Unsuccessful
applicants given
feedback
Full application
(10 proposals)
30th March - 9th May 9th May - June
•Workshop for
Applicants
•Full application
developed with
support from
Syndicate
•Deadline 28th July
Final selection
(3-5 projects)
•Due diligence
conducted on
applications by
the Syndicate
•Successful applicants
notified (3-5 projects)
•Unsuccessful
applicants given
feedback and
recommendations
Project
initiation
•Finalise project
plans based on
panel feedback
•Finalise budget
and resource
requirements
•Finalise T&Cs
•Contract work-up
•Project launch
June-28th July July-Oct Oct-Dec
Call process overview and timelines

EOI – information required and submission process
• Name, affiliations of lead applicant and any co-applicant(s)
• Project Category e.g. therapeutic approach, modality, phase, funding
need, duration & start date
• How the project will address the need(s) identified in the Syndicate
therapeutic TPPs (max 200 words)
• The scientific rationale for the project (max 400 words)
• High level plan of work – key goals, milestones and deliverables along
with indicative budget (max 400 words)
• Project outputs and future exploitation plan (max 200 words)
• IP Position (max 200 words)
• What does your team bring to the project?
• What support would you like to receive through the programme?
In order to be considered as a
participant on the programme
your expression of interest must
be submitted between
30th March and 23:59 BST on 9th
May
via the online portal

• Since the 1980s, very few genuine novel classes of antibiotics have been discovered. Recent approvals are mainly drugs targeting
existing mechanisms of action and face the same resistance mechanisms.
• Both GSK and AZ screened against numerous antibacterial targets and were unable to generate any drugs:
• Obtaining hits was not the main issue –the main challenge was converting hits into leads with
cellular activity (especially in gram negatives).
• Most HTS libraries are designed around orally active compounds for host targets and have very
different physiochemical properties than typical antimicrobials.
• It is important to understand the level of target engagement required to drive the desired
phenotype.
• Understanding compound permeability early may facilitate optimization.
Antimicrobial R&D: challenges and opportunities
GSK: Antibacterial screening campaigns:
Nature Reviews Drug Discovery, 2015, Vol 14 (9), 662-
662
Nature Reviews Drug Discovery, 2007, Vol 6 (1), 29-
40
67
HTS
16
Hits
5
Leads
0
Drugs
65
HTS
57
Hits
19
Leads
0
Drugs
AZ: Antibacterial screening campaigns

Cell surface or
periplasmic targets
• An effective drug will need to reach the target in sufficient concentration for a
sufficient duration following a chosen route of administration.
• This is challenging to achieve for any drug but much more so for antimicrobials due
to:
• Bacterial permeability – membranes are very different to mammalian cells.
Many drugs which do enter the cells are rapidly eliminated by efflux
mechanisms.
• Significantly higher doses are generally required which can lead to more side
effects and late-stage clinical failure.
• Clinical trial recruitment.
• Successful applicants will have a credible plan for drug development in the
EOI
Novel technologies
Non traditional
modalities (e.g.
Phage, antisense
oligos)
Host and virulence
targets
Well validated with a
strong data package
Small and large
molecules
Future opportunities for AMR drug discovery
Theuretzbacher and Piddock, Cell host & microbe, 2019, Vol 26 (1), 61-72

Alignment to CF Syndicate Therapeutic TPPs
• How likely is the project to deliver on the CF-patient
TPPs? For example, target pathogens, route of
administration, side-effects.
Collaboration
• What does the applicant bring to the
collaboration? (e.g., novel technology, target
expertise, access to assays or platforms, IP,
screening etc.)
• What additional platform access is required?
Druggability
• Evidence for binding site ligandability.
• Target localization (e.g., cell-surface, periplasmic).
• Does the approach address known challenges of
bacterial permeability?
• Off-target activity, toxicity and drug-drug
interactions
• PK/PD considerations
Novelty and freedom to operate
• How much has this target been worked on previously or
is the approach, modality or technology novel?
• Are there any competing IP considerations?
Mechanistic validation
• Evidence that pathway modulation is linked to desired
phenotype in relevant CF pathogens.
• Evidence of low propensity for resistance
• Evidence of target engagement.
Reagents and Tools
• Accessibility of proteins, ligands, cell lines.
• Access to screening assays (e.g., biochemical or cellular).
• Is there a crystal structure known for the target to facilitate
structure-based drug design?
Progression plan
• Is there a credible progression plan within budget
to take the project to a point of securing onward
funding?
Key criteria for project selection

Criteria at end of hit validation at end of hit to lead at end of lead optimisation
Potency &
SAR
• Inhibition of defined target in at
least 1 relevant assay
• Understandable SAR with clear
scope for optimization
• Selectivity against any relevant
human targets
• Significant SAR and chemical design
across lead scaffolds
• Excellent selectivity against any relevant
human targets
• Candidate identified for progression into IND-
enabling studies
In vitro ADMET • Promising in vitro ADME
properties
• No cytotoxicity in relevant
human cell lines
• Good microsomal and plasma stability
• Acceptable plasma-protein binding
• Any significant liabilities understood with
credible strategy to address these
• No significant in vitro safety pharmacology (e.g.
Eurofins 44) panel
• No predicted drug-drug interactions (CYP
inhibition / induction assays)
Microbiology • Demonstration of cell-based
MoA in CF relevant bacteria
(e.g. MIC)
• Significant cellular activity against TPP
relevant pathogens (including clinical
isolates)
• Extensive microbiological evaluation (e.g.
Frequency of mutation, time kill kinetics, MIC90)
In vivo • Promising in vivo PK
• Preliminary in vivo efficacy data
• Demonstration of in vivo efficacy in a relevant
model with clinical isolates. Efficacy endpoint
should be comparable or better than standard of
care.
• Non-GLP toxicity study (MTD and repeat dosing)
in line with intended use.
Other • Synthetic route amenable to scale-up to
support LO and IND enabling studies.
Successful completion of CDP projects will have generated robust data packages making the asset well positioned to
Typical data packages expected at the end of a
project to achieve follow-on funding

Visit our stand at
ECCMID, Copenhagen,
15-18th April
TPP document
Webinar recording
Book a call
FAQs
Terms & Conditions
Access our website for support:
https://cfamr.org.uk
Key Date:
Online EOI closes
23:59 BST on 9th May
Please note – all applicants must complete the online EOI before 23.59 BST on May 9th to be considered for
Helpful resources

Q&A

Visit our website for more
information
https://cfamr.org.uk

CF AMR Syndicate: Collaborative Discovery Programme

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