Antibiotic resistance A threat to global health and development

Dr Manica Balasegaram, Executive Director 1 April 2019 Addressing global public health needs

GARDP is the only global R&D initiative with a focus on AMR and access

Focus and objectives: • Drug-resistant bacterial infections on WHO priority pathogen list. PATHOGENS • Deliver 4 new/improved treatments by 2023 with a robust pipeline. • Appropriate use and access.

Founding partners DRUG RESISTANCE & • World Health Organization UNMET NEEDS • Drugs for Neglected Diseases initiative

KEY DISEASES & Programmes: POPULATIONS SYNDROMES • Neonatal sepsis. • Paediatric . • Sexually-transmitted infections. • Memory recovery and exploratory including adult serious bacterial infections.

2 GARDP - an innovative model and approach

Notably, the flexible and unique model allows GARDP to

GARDP Work from any entry Target important Ensure access and stewardship Invest funding in In-house: point along the R&D indications less likely of products developed by programmes driven and • public health expertise pipeline through to to be developed by GARDP in contractual directly executed by • product development & patient access. other actors. agreements with the private GARDP and our partners. clinical trial know-how sector.

Government Civil society/ Research Pharma/ Academia /international Partners NGOs institutions biotech organizations

Sponsors, Prioritize Develop TPPS Embed In- and out- research The way we work public heath End to end & scientific apropriate licensing, studies & needs road maps use & access generics clinical trials

3 Programme highlights: status and update

Sexually-transmitted Neonatal sepsis Paediatric antibiotics infections

Status Status Status

• Launched a global • Development • Completed phase 1 observational study to programme launched dose evaluation study understand prescribing for an for lead antibiotic practices in Africa, Asia, treatment of MDR (Zoliflodacin). infections. • Set up activities to start EU and US. • Agreement signed with phase III clinical trial in • Completed recruitment Sandoz. Africa, Asia, EU and for PK and safety study • Supported update of USA. of . paediatric evidence- • Progressing based guidelines. pharmaceutical development including alternative formulations.

Update Update Update

• Complete fosfomycin • B: submit • Initiate a phase III PK study analysis and plan for regulatory clinical trial in Africa, reporting. approval and conduct Asia, EU and USA in • Observational study: initial work required by May. complete enrolment of EMA. • Initiate full-scale good 2500-3000 cases. • Develop a global manufacturing practices network of sites with batches of zoliflodacin. capacity and capability.

4 R&D highlights: status and update

Discovery and exploratory Memory recovery and asset evaluation

Status Status

• Established agreements to access • Evaluated over 50 chemical entities, libraries in search of new between new and ‘recovered’ drugs. antibacterials with: • 2 recovered assets moving into further Takeda (JP), Eisai (JP), HIPS (DE), Calibr evaluation: Flomoxef & Sitafloxacin. (US). • 2 recovered assets in clinical development: fosfomycin & polymyxin • Agreements in place with CoADD B. Australia and Institute Pasteur Korea • Up to 6 new assets identified as for library screening. potential portfolio candidates. • Project initiated (University of Verona) to identify effective combinations to treat bacterial sepsis.

Update Update

• Library screening to commence in Q1 • Launching serious Gram-negative 2019. infection programme.

5 GARDP pipeline (Jan 2019)

RECOVERY/ TRANSLATIONAL DEVELOPMENT IMPLEMENTATION EXPLORATORY/ Phase IIa Pre-clinical Phase I DISCOVERY PoC Phase IIb/III Registration Access-Stewardship

Approved in EU limited Strategy for WHO Fosfomycin PK/PD studies Neo&Peds label pre-qualification NEONATAL Sandoz/Infectopharm SEPSIS Beta-lactam Approved in Asia: Neo&Peds data

FDA approved, limited Peds label (no EU) Potential Ready for Adult Asset: A Phase 3 Potential Ready for Adult PEDIATRIC Asset: B Phase 3 - cUTI Potential EMA/FDA Asset: C Approved-Adults Potential Ready for Adult Asset: D Phase 3

Zoliflodacin Working on cost of Entasis-Therapeutics Approved in Asia: goods reduction Quinolone STIs CABP/cUTIs Potential Potential Phase 2 NDA-4Q2018 Asset: F Asset: E ABSSI CABP

HIPS library Screening Potential Considering for CRE SERIOUS CALIBR ReFRAME Asset: B (HAP/VAP?) G-NEG INFECT library screening Japanse Consortium library screening (Eisai & Takeda)

6 REVIVE: status and outlook

An online space to support the antimicrobial discovery, research, and development community

Facilitate learning Connect people Share knowledge Status • 5 webinars with 1,500 registered • Network of 120 leading experts • 6 blogs by invited authors to participants. in the field. share knowledge and spark • Open access. • Sessions and networking events discussions. at key conferences.

Outlook • Develop and launch new content • Extend and diversify the expert • Launch new blogs and implement a for webinars, and resources. network. virtual ‘AMR dictionary’.

7 GARDP facts and figures

R&D • 1 first in class antibiotic entering phase III clinical trial. • 4 recovered antibiotics in different phases of development. • 10 antibiotics under discussions with potential biotech and pharma partners. 37 FTEs & 11 • 4 libraries to be screened for antibiotic activity. additional • 3 clinical studies completed. recruitments projected in 2019. Status • Independent Swiss legal entity – in the process of seeking international organisation status. Governance • Scientific Advisory Committee (14 members, 4 observers). • Board of Directors (currently 6 members, set to grow to 10).

WHO cooperation on • Technical advice, including on stewardship and access. • Priority setting and developing target product profiles • Liaison with member states. DNDi cooperation on • Sharing specialized R&D expertise and capacity • Leveraging regional networks • Sharing some infrastructure to ensure value for money

Funding • 24% of 270 million raised in support of 2017- 2023 plan and budget. • 94.6% of funding from governments.

8 KEY WHO DOCUMENTS FOR ANTIBIOTIC R&D KEY ISSUES FOR DRUG DEVELOPMENT

• WHO Priority Pathogen List: priority bacteria to target.

• FDA / EMA: increased clarity on regulatory pathways; trials are relatively small and non-inferiority based; tendency is largely to develop for cUTI.

• Less clarity on what are the important syndromes and populations to consider, in relation to WHO PPL.

• Reimbursement mechanisms and future pull incentives may be linked to the ability to generate relevant evidence for efficacy against MDR pathogens, key indications / syndromes and populations.

10 KEY ISSUES FOR DRUG DEVELOPMENT

• Therefore GARDP is approaching drug development with two overlapping pathways:

1) Regulatory: for market authorization - Key relevant phase II and III trials, CMC/ formulation - Commence paediatric development as early as possible (when some adult efficacy data available)

2) Public Health: for policy, guidelines and use - Adult trials in MDR populations, specific indication studies - Strategic trials in paediatrics

11 CONSIDERATIONS FOR EML AND ‘AWARE’

• Many of the new and late stage pipeline antibiotics target important MDR pathogens. • These drugs may largely be falling by default into Reserve list (note: where do we place future important BL/ BLIs).

• What level of evidence is required to understand their relative importance within the list?

• Could some of the new antibiotics conceivably end up as ACCESS or WATCH drugs (e.g. new drug for STI). • Certain older drugs in the Reserve List could be repurposed for certain important needs, and may be an important second line agent.

• Should there be strategic positioning of some old and new antibiotics? Guidance to developers would be useful.

12 Thank you