Webinar Slides For PACE Programme 3rd call_Final

Webinar will start at 3pm (GMT) 8 October

PACE and our 2025 Antibacterial Therapeutics Funding Round Dr Bev Isherwood

Webinar Agenda

1

Welcome and Introduction to PACE – Dr Beverley Isherwood

2

PACE 2025 Antibacterial Funding Call: Overview and Key Features – Dr Neill Gingles

3

PACE 2025 Antibacterial Funding Call: Process & application guidance – Dr Tanja Taylor

4

PACE 2025 Antibacterial Funding Call: Selection criteria and resources – Dr Pete Coombs

5

Opportunity for Q&A – Members of the PACE Team and Board

Introduction to PACE Dr Bev Isherwood

PACE

Empowering Innovation: Accelerating Early Translation

Bring together the sector to help innovators with early-stage antimicrobial and diagnostics projects move forward with greater speed and confidence, accelerating the delivery of new innovations to tackle AMR

paceamr.org.uk

PACE: Targeting the translational gap Where we fit in the The (inter)national context

From lab…..

Basic Research

….to launch

Concept Studies

Development

Nurturing innovation

✓ Support to create de-risked investable propositions

Risk

✓ Early-Stage Funding

✓ Access to infrastructure & expertise ✓ Developing entrepreneurial talent Technology Readiness Level

AMR – A precariously thin pipeline New small molecule antibacterial drugs launched from January 2000 to December 2022

There is a lack of novelty in the clinical pipeline

Non-traditional 41%

REF: Butler et al. J Antibiot 76, 431–473 (2023). https://\\doi.org/10.1038/s41429-023-00629-8

Traditional 59%

Novel 27%

Not novel/ unknown 32%

REF: WHO (2024). Global Observatory on Health R&D, accessed June 2024

>80% of preclinical projects are being conducted by SMEs & academics

Investment in AMR R&D is declining 600

$US Millions

550

500 450 400

350 300

250 200 2019

2020

2021

2022

2023*

2024*

*Global AMR R&D Hub Dynamic Dashboard data July 2025 ** Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

REF:. WHO (2024). 2023 Antibacterial agents in clinical and preclinical development: an overview and analysis

11m AMR deaths could be averted through the development of drugs targeting gram-negative pathogens**

PACE: Creating a Path to Value

Empowering Innovation: Accelerating Early Translation

Strengthening

Enabling

Accelerating

Grow a pipeline aligned with unmet needs & routes to market

Collaborative support to build de-risked investment ready assets

Enabling capabilities to advance the portfolio & bring sector benefit

The right funding, at the right time with the right support

Driving Outcomes-focused Innovation PACE funding is highly strategic, centred on addressing critical unmet needs:

• Innovative and differentiated antimicrobials 1 • Diagnostic innovations with health & health system benefits 2

A.Baumannii Carbapenem-resistant P.aeruginosa Carbapenem-resistant

Innovation Assessment of the 2023 Antibacterial Pipeline Only 6 of the 32 clinical stage antibacterials targeting WHO priority pathogens meet at least 3 of the innovation criteria – more are urgently needed.

Antimicrobial Resistance and Diagnostics Appropriate and rapid diagnostics to indicate which antibiotic should be used & reduce inappropriate antibiotic prescriptions are urgently needed.

Enterobacterales Carbapenem-resistant

Health outcome High-burden Indications

PACE aims to drive tangible progress on this pipeline.

1WHO Priority Pathogens & GBD2021 2Unmet needs in AMR diagnostics

Enterobacterales 3rd-gen cephalosporinR

Priority Pathogens & Resistance Novel Diagnostic & Therapeutic Innovations

How we Select and Support Promising Projects •

Funding rounds to attract high-potential innovators globally in academia and biotech.

•

Two-stage selection with intensive 2nd-phase Catalyser: 10-week structured support for shortlisted projects – focused on refining clinical positioning, feasibility/workplan & full application submission.

•

•

•

Rigorous selection, external panel evaluation & involvement of people affected by AMR. Projects actively managed, milestone based nondilutive funding of up to £1m per project.

2024 Diagnostic Innovations Round

2023 Antibacterial Therapeutics Round

171

EOI

177

47/47

% SME/Acad

55/38

34

Countries

37

39

% from UK

36

21

Catalyser Programme Completed

15

11

Portfolio

TBC

Therapeutics progressed through Hit-to-Lead and Lead Optimisation & Diagnostics through TRL3-5.

Helping Projects Progress and Succeed Structured support to provide the critical ‘non-funding’ inputs required to catalyse & better enable asset progression:

Embedding real-world use into asset design and progression

Understanding & navigating endend R&D process

Timely access to required scientific capability for decision-grade data

Funders & investors

Academia

CROs & UK infrastructure

Delivered through partnering across the sector.

Developed resources also made available to the wider community.

Delivery Partner Network

Industry & trade bodies Mentors & advisors

AMR

Acceleration & Innovation

Regulators, payers & HTA bodies Patients, charities, advocacy groups

Our Progress so far: Innovation, Impact, Next Steps

11 Portfolio Projects £11m committed

36 organisations supported through PACE Catalyser

2 Funding Rounds 348 projects assessed

Partnerships with UKHSA, VOCAL & a network of 20 delivery partners

Reports on Unmet Dx Needs & Tx Sector Needs

Programme established

A new national centre aimed at translation new source of sector funding & support

Revitalised national mission for R&D of novel Tx & Dx Strengthened pipeline with more investment ready assets Better ability to tackle AMR through increased international collaboration & enhanced capability

PACE 2025: Antibacterial Funding Call: Overview and Key Features Dr Neill Gingles

Purpose and Overview PACE’s third funding round;

Up to £6m initially available to support up to eight projects focused on developing new antibacterial treatments for the most threatening microbes and resistance mechanisms Up to £1M per project & 2 years in length Innovative, higher risk projects of smaller scales are highly encouraged to apply

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 support and advice from the PACE team

What is in Scope Target ID

Hit ID

Hit-Lead

LeadCandidate

Preclinical

IND

P1

P2

PACE funding call focus

Therapeutics for drug-resistant Gram-negative bacterial infections Phase

Hit-to-Lead, Lead Optimisation

Intervention type

Novel MoA, target and/ or new chemical class, and no observed cross resistance; including direct -acting and non-direct acting

Modality

Agnostic (but must have antimicrobial effect)

Indications

Drug-resistant LRTI, BSI, cUTI

Pathogens

Bacterial species associated with highest-burden indications aligned to GRAM report and WHO BPPL – inclusion of drugresistant priority Gram-negative bacteria essential (Ab, Ec, Kp and/ or Pa) – see preferred profiles for further details

P3

What projects are we looking for?

Projects that are: • Directed at drug-resistant bacteria associated with indications of highest burden of AMR based on the WHO priority list1 and Global burden studies2 • Transformational, with the aim to fill a gap for innovative & differentiated antimicrobials 3 in the clinical pipeline Preferred profiles for therapeutics targeting Gram-negative infections Indication Priority pathogens

BSI

LRTI

cUTI

Ab, Ec, Kp and Pa

Pa and/ or Kp essential. Other Enterobacterales and Ab preferred

Ec and Kp essential. Pm, Pa and other major cUTI pathogens preferred.

Spectrum

Any spectrum of activity (broad or narrow) but requirement, at a minimum, to cover priority pathogen(s) for the indication

Resistance

Activity against carbapenem and 3rd generation cephalosporin resistant strains (e.g. CRE, ESBL, CRAB, CRPA), low FoR, no cross resistance with standard of care antibiotics

Administration

Oral and IV preferred. IV-only acceptable.* *Alternative routes of administration will be considered (e.g. inhaled for LRTI), with strong supporting rationale

Pathogen Key Ab: Acinetobacter baumannii Ec: Escherichia coli Kp: Klebsiella pneumoniae Pa: Pseudomonas aeruginosa Pm: Proteus mirabilis

Oral, or IV and oral* *IV only not acceptable

1 https://www.who.int/publications/i/item/9789240093461 2 European Antimicrobial Resistance Collaborators (2024). The Lancet. PMID: 39299261; Global burden of bacterial antimicrobial resistance

1990–2021: a systematic analysis with forecasts to 2050; Naghavi, Mohsen et al. The Lancet, Volume 404, Issue 10459, 1199 - 1226 3 https://www.who.int/publications/i/item/9789240094000

What is out of Scope?

Target ID

Hit ID

Hit-Lead

LeadCandidate

Preclinical

IND

P1

P2

PIII

PACE funding call focus • • • • • •

Target identification, screening and hit identification Projects focused on late-stage pre-clinical/ IND-enabling studies Clinical Phase R&D Antibiotics based on iterations of existing therapeutics e.g., β-lactams Vaccines​ Interventions focussed exclusively on mycobacteria (including TB), fungal, low-priority Gram-negative or Gram-positive pathogens • Therapeutics solely focussed on out-of-scope indications with no potential to pivot (e.g. topical treatments for skin infections) • Projects not directly focused on antimicrobial development (e.g., diagnostics, delivery methods, biomarkers, standalone technology or model development)

Key Eligibility Criteria

The applicant(s) • Researchers from academia or from SMEs worldwide, including consortia (large Pharma partners permitted, but must cover own costs)​ • Applications should have a single identified lead applicant, however co-applicants are welcome

The project • • • •

Should last up to two years Will be milestone driven with clear go/ no-go progression criteria defined upfront With up to £1 million GBP of direct costs Innovative, higher risk projects of smaller scale are highly encouraged to apply

More than just funding – what we will offer Our intention is not just to fund but to add additional support to enable the best chances of success for projects to attract further onward investment Support throughout the project funding journey tailored to individual project needs, working in partnership with the PACE team: Delivery Partner ✓ Support through the application process Network (e.g. 1:1s, advice on full application, Catalyser workshop) ✓ Drug discovery & disease area insight, advice & mentorship ✓ Access to a collaborative network of potential project delivery partners (PACE DPN) ✓ Access to a unique partnership with UKHSA for evaluation of in vitro antimicrobial activity ✓ Facilitate and support project delivery where applicable (e.g. development of statement of works and acting as point of contact with delivery partners) ✓ Facilitate scientific advisory boards, and public and patient engagement panels ✓ Business support (e.g. orientation to potential downstream funders, commercial know-how such as pitch-deck preparation)

Our Expectations For innovators to maximise impact & reach their potential, it is essential that funded recipients and the PACE team work closely together. Therefore, we have the following expectations of applicants & funded recipients:

✓ Be engaged in the process and work collaboratively with the PACE team, especially R&D advisors, in all aspects of project development and lifecycle if successful (note: our PACE R&D advisers are separated from funding governance and provide support not monitoring). ✓ Each applicant will, if successful, attend (or send a delegate) to the Catalyser workshop (virtual). ✓ Successfully funded projects to start within 3 months of the receipt of an award letter and be committed to the project length specified. ✓ Legal and ethical requirements are followed (e.g., award agreement terms, good research practice in conducting work). ✓ Applicant will highlight and raise any issues or concerns in a timely manner throughout the process.

Summary of Key Terms and Conditions Intellectual Property and Ownership of results

• Funding is non-dilutive • Recipient background and arising IP will remain property of the recipient • No requirement to revenue share upon successful commercialisation Funding Awards shall cover 100% of the direct costs of the project, provided such costs are Permitted Expenditure.

Permitted Expenditure is expenditure which is reasonably incurred and properly evidenced and is directly related to and necessary for the delivery of the Project. Typically, this will cover:

• An appropriate %FTE of staff, plus consumables, directly related to funded work • Access to specialist equipment/reagents • Contract Research Organisation work • Reasonable travel and subsistence Receipt of funding will be linked to achieving milestones and standard payment terms will be quarterly in arrears

Full terms are available at paceamr.org.uk

PACE 2025: Antibacterial Funding Call: Process and application guidance Dr Tanja Taylor

Call process overview and timelines Expression of Interest (EOI) • EOI Opens 1st Oct 2025

•

• Applicants apply online • Queries can be submitted via webform • EOI closes at 23:59 GMT on 5th Nov 2025

Oct 2025

•

Triage

Full application

Final selection

Project initiation

Internal review

by PACE team to select proposals to progress to full application

• Sign Confidentiality Agreements

• Due diligence conducted on applications by PACE team

• Finalise project plans based on panel feedback

Successful applicants invited to Catalyser workshop

• Catalyser workshop for Applicants Jan 2026 • Full application developed with support from PACE team • Application deadline: 27th March

Nov 25 – Jan 26

Jan - Mar 2026

• Review of applications by expert panel and patient representatives.

• Rebuttal to questions

• Finalise budget and resource requirements • Project Award agreements issued • Project launch

• Applicants notified of outcome

Apr - Jun 2026

Projects to start within 3 months from receipt of award letters

EOI – Information required • Name, affiliations of lead applicant and any co-applicant(s) • Application summary: Title, funding requested, duration, category e.g.

To be considered as a participant on the programme therapeutic approach, modality, indication, pathogen and phase your expression of interest must • Project summary (max 500 words) be submitted between • Alignment to clinical need 1st October and 23:59 GMT on 5th • Novelty of approach November 2025 • Scientific rationale & supporting evidence (max 400 words) - includes option via the online portal for 1 file upload • Research plan – key research objectives, work packages, milestones and deliverables (max 1500 words)

• Relevant investigator/ collaborator expertise and experience for project delivery

• Gaps in current resources or capabilities that PACE could advise on or support to improve the impact of the proposed project

• Translational / commercialisation plan (max 300 words)

Guide to Completing the EoI • Project summary Summary • Provide a summary of the approach, including target indication and pathogen(s), modality of intervention and key aims for the project.

Clinical positioning • Explain how the intervention addresses the clinical need, including setting, target patient population(s) and any diagnostic, biomarker or stratification strategies to identify those.

• Would the proposed intervention likely be acceptable to patients (consider treatment burden)? What would be the expected impact on patient outcomes?

• How would the intervention be integrated into the current care pathway (e.g. in addition to or replacing current therapy, what diagnostics may be required and are these widely accessible and available)?

Novelty & competitive positioning • Describe whether the approach is exploring a novel MoA, new target or new chemical class (with no observed cross resistance).

• Is the proposal differentiated from current standard of care, as well as from similar approaches (e.g. approaches with a similar target or mechanism) in development?

Useful Links: WHO novelty criteria Global AMR R&D Hub WHO clinical and preclinical pipeline review

Guide to Completing the EoI • Scientific rationale & supporting evidence • How is modulation of the target linked to the desired anti-bacterial phenotypic effect (e.g. inhibition •

of an essential target for bacterial survival, reduction of bacterial virulence, directing host immune response)?

Is there sufficient evidence (in vitro, in vivo) to support: mechanism, therapeutic effect in relevant strains & models, safety, low propensity for resistance development etc?

• Research plan • Is the plan feasible within the given timeframe, budget and resource as well as appropriate for the • •

development stage? Does the team have access to all required expertise, tools and resource to deliver the plan or reasonable plans to obtain those?

Are milestones clearly defined, realistic, time-bound and measurable?

Will the outputs progress the project towards a value inflection point to secure onward funding?

• Translation/ Exploitation plan • Does the team have access to any required background IP or plans for obtaining access to required • •

•

IP? Does the team have a reasonable IP and commercialisation strategy?

Have the team got credible plans for onward progression and funding of the project (e.g. engagement of downstream funders/ investors/ partners/ regulators) Have potential barriers to patient benefit been identified and how will they be addressed?

PACE 2025: Antibacterial Funding Call: Selection criteria & resources Dr Pete Coombs

Alignment to Clinical Need - Target Product Profiles •

Every application is required to have a clearly articulated target profile outlining the target indication(s), use and drug profile.

•

These should demonstrate consideration for patient and clinical needs, as well as key drug characteristics such as: • Organism coverage • Patient population • Treatment duration and frequency • Route of administration • In vitro and in vivo activity data • Safety and tolerability • Cost and value proposition •

Priority will be given to solutions for indications associated with the highest burden of AMR and tackling MDR pathogens.

•

Examples of TPPs include those developed by WHO, CARB-X and CF AMR Syndicate.

New Target Product Profiles for new antibacterial agents Target product profile for therapy of severe infections caused by multidrug resistant Gram-negative bacteria

WHO Draft Target Product Profiles for new antibacterial agents

Key criteria for project selection Novelty • The project should be sufficiently novel – defined by WHO novelty criteria: novel MoA, new target, new chemical class, no observed cross resistance Scientific rationale & supporting evidence • Evidence that target/ pathway modulation is linked to desired phenotype in relevant pathogens aligned with call scope e.g. MICs (ideally activity against drug resistant strains demonstrated) • Evidence/ rationale for low propensity for resistance • Evidence/ rationale for target engagement and bacterial permeability • Evidence/ rationale for de-risking off-target activity, toxicity (dependent on entry stage) • Data from relevant activities/ assays appropriate for the stage of the project (e.g., hit-to-lead versus LO)

Clinical positioning • The project aligns against a clearly defined clinical unmet need • A credible clinical path to approval and clinical use • The project aligns to an established or has a draft TPP Project plan & resources • The project plan is credible given the timeframe and budget • Appropriate milestones have been set • The deliverables position the project well for onward funding • Additional required resources/ expertise for the project delivery are highlighted and are accessible Translational plan • Applicants own or have access to relevant background IP • IP strategy is established • Competing IP/ FTO considerations are addressed • Consideration of onward funding, clinical progression and business plan

Milestones and the Research Plan • Milestones - a specific point in time within a project plan that aligns to a critical go/ no-go point in which the results generated up until that point are critically evaluated to assess whether the project should continue. Milestones will have associated success criteria which will be agreed by PACE prior to award Month

1 Work Package 1 - Reagent generation Activity 1 Activity 2

Milestone Review Work Package 2 - Early SAR exploration Activity 1 Activity 2 Activity 3

Activity 4 Milestone Review Work Package 3 - Further in vitro profiling Activity 1 Activity 2

Activity 3 Milestone Review Work Package 4 - In vivo POC Activity 1 Activity 2 Activity 3

Milestone Review

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Guidance on determining project stage Minimum Entry Requirements​

Criteria​ •

Potency & SAR

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Inhibition of defined target in at least one relevant assay​ Indication of early, understandable SAR​

Typical activities in Hit-to-Lead​ •

•

• In vitro ADMET

• •

• Microbiology

Demonstration of cell-based mechanism of action in relevant target bacterial species (e.g. MIC for direct acting)​

• •

•

•

In vivo

• Other

Active upon resynthesis, purity >90%​

Typical activities in Lead Op​

Established SAR with clear optimization to improve on in vitro potency, chemical stability, cytotoxicity and drug-like physicochemical properties​ Selectivity against any relevant human targets​

• •

Significant SAR and chemical design across lead scaffold(s)​ Excellent selectivity against any relevant human targets​

Promising in vitro ADME properties (e.g. if oral route demonstration of potential oral bioavailability)​ Low or no cytotoxicity in relevant human cell lines​ Any significant liabilities understood with credible strategy to address these​

• • •

Good microsomal, hepatocyte and plasma stability​ Acceptable plasma-protein binding​ Profiling in in vitro safety and secondary pharmacology assays (e.g. Cyp inhibition, hERG, nephrotox, CEREP)​

Significant cellular activity against TPP relevant pathogens (including MDR clinical isolates)​ Understanding of mechanism of action, target engagement, and potential permeability and efflux liabilities​

•

Improved potency in cellular activity against relevant pathogens in extended clinical isolate panels​ Frequency of resistance, mechanisms of resistance, killing kinetics, MIC90 measurements and confirmed understanding of mechanism of action​

Preliminary in vivo efficacy data (e.g. thigh infection model)​ Promising in vivo PK (associated with intended route of administration)​

•

•

• • •

in vivo efficacy data (associated with intended route of administration & disease-relevant models) against multiple pathogen isolates​ Experiments to understand PK-PD drivers​ Non-GLP toxicity study (MTD, repeat dosing) in suitable species​ Synthetic route amenable to scale-up to support LO, preclinical and IND enabling studies

Helpful Resources

Further questions – contact via website form

FAQs

Key Date: Online EOI closes 23:59 GMT on 5 Nov Please note – all applicants must complete the online EOI before 23.59 GMT on 5 Nov 2023 to be considered for this funding call

Terms and Conditions

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