the need to increase r&d push incentives and effective pipeline...
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DRIVE-AB conference in Brussels, 5.-6. September 2017
The need to increase R&D push incentives and effective pipeline co-ordination
U. Theuretzbacher, Center for Anti-Infective Agents and DRIVE-AB
DRIVE-AB is supported by the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115618, resources of which are
composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA (European Federation
of Pharmaceutical Industries and Associations) companies’ in kind contribution. DRIVE-AB is part of the New Drugs for Bad Bugs (ND4BB) program.
Innovation
Innovation
Novelty
Usefulness New App
U. Theuretzbacher Antibiotic innovation for future public health needs. Clin Microbiol Infect. 2017 Jun 24. U. Theuretzbacher: New drugs – will they solve the problem of resistance to antibiotics? Clin Microbiol Infect. 2017 August 19
No cross-resistance to existing antibiotics • New class/target/MoA • Substantial improvement of existing class without
cross-resistance
Improved antibiotics from existing classes • Reduced class-specific resistance
Improved features, e.g. • Oral formulation • Improved pharmacokinetics
Scientific definition
Definition not uniformly agreed!
Players in Antibacterial Drug Discovery
„Antibacterial“ SMEs
~90 ~200
~20
~80
Number of SMEs (estimate)
Global pharmaceutical corporations: Novartis, Roche/Genentech, Sanofi, Medimmune (biologics), GSK, Merck
Large companies: Shionogi, Wockhardt
Amount of public and philanthropic funding for drug discovery and preclinical development is not known
No estimate available:
o Academic institutions
o Publicly funded research institutions
o Non-profit research institutions
o Public-Private Partnerships
Clinical pipelines - WHO critical priority pathogens
Ph Class Compound Pathogen activity CR-E | CR-PA| CR-AB
Carbapenems Vaborbactam/merop
3 Relebactam/imip
1 VNRX-5133/merop
3 Sulopenem
1 Cephalosporins Zidebactam/cefep
1 Nacubactam/cefep
2 AAI-101/cefep
1 Tazo/cefep
1 C-Scape
3 Ceph-siderophore Cefiderocol
2 Monobactams Avibactam/aztreon
1 LYS228
1 BLIs ETX-2514SUL
KPC|NDM
Activity
Unclear
No or insufficient activity
WHO critical priority pathogens Carbapenem resistant CR-E: Enterobacteriaceae CR-PA: Pseudomonas aeruginosa CR-AB: Acinetobacter baumannii group
Based on the WHO pipeline analysis 2017, to be published in October 2017
Clinical pipeline: Specific solutions for specific patients for specific situations in specific regions
ß-lactams, ß-lactam-inhibitor combinations
Delafloxacin Fluoroquinolone
3 Sulopenem Carbapenem ESBL
3 Plazomicin Aminoglycoside
3 Lascufloxacin Fluoroquinolone
3 Eravacycline Tetracycline
3 Omadacycline Tetracycline
3 Solithromycin Macrolide
3 Iclaprim DHFR-inhibitor
3 Lefamulin Pleuromutilin*
2/3 MRX-I/MRX-IV Oxazolidinone
2 Gepotidacin NBTI (Triazaacenaphthylene)
2 Zoliflodacin NBTI (Spiropyrimidenetrione)
2 Murepavidn Novel membrane targeting AB
2 Brilacidin Novel membrane targeting AB
2 Afabicin FabI inhibitor
2 Nafithromycin Macrolide
2 Finafloxacin Fluoroquinolone
1 SPR-741 + antibiotic? Polymyxin + antibiotic?
1 TP-271 Tetracycline
1 TP-6076 Tetracycline
1 KBP-7072 Tetracycline
1 TNP-2092 Rifamycin-quinolone hybrid
CR-E|CR-PA|CR-AB
Clinical pipelines - WHO critical priority pathogens
Gram-pos
Activity
Unclear
No or insufficient activity
Based on the WHO pipeline analysis 2017, to be published in October 2017
Biologics, C. diff. drugs, combinations or off-patent drugs not included
Mostly developed by companies with <500 employees (most companies <100)
Carbapenem resistant CR-E: Enterobacteriaceae CR-PA: Pseudomonas aeruginosa CR-AB: Acinetobacter baumannii group
WHO critical priority pathogens
New chemical or functional class
* New for systemic infections
Preclinical pipelines, n=254
CARB-X submissions 2016, n=254
U. Theuretzbacher et al: Innovation potential of the preclinical antibiotic pipeline. Nature Reviews Drug Discovery. 2017. In press
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20
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Small Academic Large Non-profit Medium
Priority grants
Recommendation: push mechanisms ICO
Optimisation
Discovery
Preclinical dev.
Phase 1
Phase 2
Phase 3
Discovery grants improve the entry rates into
the preclinical phase, improve the effect of
pull mechanisms
Increase, Coordinate, Optimise resources
• Address drug discovery and early development hurdles: scientific and financial
• Global coordination hub
Additional annual push funding ~200-500 million
Recommendation: Push incentives - ICO
Push vs pull: Risk due to high attrition rate vs relative certainty what we get
broad
priority
Applied research around AMR Research • Mostly broad topics, add ICO: addressing the most difficult scientific
questions
Broad + priority topics Drug Discovery • Academic, non-profit institutions: ICO, knowledge hub, partnerships
• SMEs: ICO, support with expertise and experience
Priority pathogens and TPPs Drug development • Preclinical: ICO
• Clinical: ICO, clinical trial networks, sustainable use and equitable access conditions apply
ICO – Increase, Coordinate, Optimise resources
Recommendation: Pipeline coordinating models
Public health outcome-driven coordination of pipeline activities
- Identifying gaps in the current R&D pipelines according to public health needs
- Addressing these gaps by
Global Collaboration Hub on AMR R&D
Integrated public health-driven R&D organisation
G20, global
GARD-P
Model: Global Collaboration hub on AMR R&D
Global Collaboration Hub on AMR R&D
Coordinate, align, streamline, increase funding and incentives
Prioritise: WHO PPL WHO PLA WHO TPP
PPL: priority pathogen list PLA: pipeline analysis TPP: target product profiles
Identify gaps and duplication, mapping
Align existing funding
Co-ordinate new funding
Inform public, private, philanthropic decision making, increase efficiency
Co-ordinate new push and pull incentives
Policies for sustainable use and access
Increase therapeutic options and tackle
AMR G20, Global
WHO, IACG, TATFAR, OECD, EU, JPIAMR, CARB-X, GARD-P, …
Model: Integrated public health-driven R&D organisation
Discovery Preclinical Clinical dev. Registration Marketing
Public health focus in all phases
AFFORDABLE, EQUITABLE, SUSTAINABLE
Glo
bal V
irtu
al
Point of entry to patient delivery
In- house scientific and R&D capacity (project management, clinical trials, discovery and preclinical, CMC expertise)
Equal partnerships with agreed principles and based on economically sustainable models
Public and philanthropic funding