ECCMID Copenhagen 2015, Pipeline Corner

Antibacterial Drug Research&Development

Ursula Theuretzbacher – Center for Anti-Infective Agents, Vienna, Austria

Antibacterial drug discovery has declined in most large pharmaceutical companies and has shifted to small companies usually having their background in an academic setting.

Where is the innovation coming from? Major antibacterial drug research and Ceftobiprole (Zevtera) Roche * Basilea (marketed in development (R&D) programmes and Europe) Dalbavancin (Xydalba) Lepetit Research Pfizer Durata Actavis their phase of clinical development Center/Vicuron Oritavancin (Orbactive) Eli Lilly * Intermune Targanta The Medicine Approved Company 10 (Sivextro) Dong-A Trius Bayer/Cubist (Merck) Ph 3 9 Ceftolozane (+Tazobactam) Astellas* Calixa Cubist (Merck) (Zerbaxa) 8 Ph 2 (Ceftazidime+) Avibactam Sanofi * Novexel AstraZeneca- (Avycaz) Forest/Actavis 7 Paratek Novartis (colllab. Paratek Ph 1 discontinued) 6 , oral, iv-oral Optimer Cempra

Phase 3 5

Delafloxacin, iv, oral Wakunaga Abbott Wakunaga Rib-X =Melinta compounds Therapeutics (TP-434) Harvard University Tetraphase 4 Isis Achaogen

Number of 3 Carbavance (+Meropenem) ?? Rempex The Medicines Comp. Nemonoxacin (approved Taiwan) TaiGen Procter & Gamble Warner Chilcott TaiGen 2 Radezolid Yale University Rib-X =Melinta 1 Therapeutics Phase 2 (BC-3781 ) Sandoz/Novartis * Nabriva Forest/Actavis Nabriva 0 Avarofloxacin (JNJ-Q2 ) J&J (Janssen Pharm.) * Furiex Forest/Actavis Gram-pos. old Gram-pos. Staph. only Gram-neg. old Gram-neg. Pseud. only (PMX-30063 ) University of Polymedix Cellceutix novel novel Pennsylvania Corporation Focus of activity AFN-1252/Debio 1450 University of Toronto Affinium Debiopharm Old: Analog of used antibacterial class POL7080 University Zürich Polyphor Roche Novel: New antibacterial class

University/Small company * More than 10 years ago Larger company (>500 employees) Global pharmaceutical corporation The red arrows indicate the origin of a R&D program in a university/small company and/or the current late clinical development stage pursued in a small company.

European “antibacterial” SMEs

In Europe, more than 60 small companies engage Though most European „antibacterial“small The European „antibacterial“SMEs are located in anti-bacterial drug R&D. More than half of and medium sized enterprises (SMEs) are across Europe with most companies in the UK. them focus entirely on and about 30% engaged in the discovery and early research are active in diverse fields. The antibacterial stages of new antibacterial drugs, increasingly approaches range from classical antibiotics and more companies are transitioning from peptides to antibodies, vaccines, adjunctive discovery to clinical stage companies. approaches, phages and potentiating strategies. SME: Phase of programme >1 “antibacterial” SME R&D focus 50 20

40 15

Diverse 30

programmes companies 10 Antibiotics 20

Anti- Number of Number of 5 10 infectives only 0 0 Phase 3 Phase 2 Phase 1 Preclinical Discovery UK FR DE IT AT CH ES NL DK SE

DRIVE-AB (Driving reinvestment in R&D and responsible use) is a collaborative project funded by the European Innovative Medicines Initiative (IMI). DRIVE-AB has been launched to find ways policymakers can stimulate innovation, responsible use and global access to antibiotics to meet public health needs. DRIVE-AB engages with all interested stakeholders during the three year project to develop and test new economic models for antibiotic development and use. SMEs are critical stakeholders with a wide range of innovative approaches to treat or prevent bacterial infections. Though small companies face considerable financial barriers and challenges inherent to small organisations „antibacterial“ SMEs – powered by academic research - provide critical basic discovery efforts that are transformed into antibacterial drug R&D programmes. Contact: www.drive-ab.eu Dr Ursula Theuretzbacher [email protected] @DRIVE_AB