2 https://www.cdc.gov/tb/. 3 http://www.who.int/tb/en/. 4 http://www.who.int/mediacentre/factsheets/fs104/en/ ... COMPAN
R&D Pipeline for
TUBERCULOSIS DISE A SE IMPAC T 1, 2 Tuberculosis (TB) is caused by bacteria (Mycobacterium tuberculosis) that most often affect the lungs, but may also attack any part of the body such as the kidney, spine, and brain. Not everyone infected with TB bacteria becomes sick, hence two TB-related conditions exist: latent TB infection (LTBI) and TB disease. TB is curable and preventable, yet without treatment, the disease can be fatal. Common symptoms of active lung TB are cough with sputum and blood at times, chest pains, weakness, weight loss, fever and night sweats. Another form of the disease is multidrug-resistant tuberculosis (MDR-TB), which emerges when bacteria that causes the illness do not respond to the two most powerful, first-line anti-TB drugs (isoniazid and rifampicin). MDR-TB is treatable and curable by using second-line drugs, however treatment success rates are low given the complexity of managing the disease.
© Otsuka
KE Y FAC TS3, 4 •F rom 2000 to 2015, TB incidence has fallen by an average of 1.5% per year, with 49 million lives saved through effective diagnosis and treatment. • I n 2015, 10.4 million cases (estimated 1 million children) and 1.8 million deaths (estimated 170,000 children, not including those with HIV) occurred from the disease, 480,000 people developed MDR-TB worldwide. •T B is one of the top 10 causes of death worldwide, it is a leading killer of HIV-positive people with 35% of HIV deaths occurring due to TB in 2015. • I n 2015, six countries accounted for 60% of the total cases, with India bearing the brunt, followed by Indonesia, China, Nigeria, Pakistan and South Africa. •O nly 52% of the multidrug-resistant TB (MDR-TB) and rifampicin-resistant TB (MDR/RR-TB) patients who started treatment in 2013 were successfully treated. A B B R E V I ATIO N S
PA RT N E R’S FU L L N A M E
A B B R E V I ATIO N S
PA RT N E R’S FU L L N A M E
Aeras
Aeras Global TB Vaccine Foundation
NIH
National Institutes of Health
BHAM
Birmingham University
OOPD
The FDA Office of Orphan Products Development
BMGF
Bill & Melinda Gates Foundation
PHRI
Public Health Research Institute
British Columbia Uni
University of British Columbia
RIT/JATA
Research Institute ot Tuberculosis
Cornell Uni
Cornell University
SAMRC
South African Medical Research Council
CS Uni
Colorado State University
SSI
Statens Serum Institute
Dundee Uni (DDU)
Dundee University (Drug Discovery Unit)
TAMU
Texas A&M University
GHIT
Global Health Innovative Technology Fund
TB A
Global Alliance for TB Drug Development
HMS
Harvard Medical School
TBDA
TB Drug Accelerator
IDRI
Infectious Disease Research Institute
TBTC
Tuberculosis Trials Consortium
IMI
The Innovative Medicines Initiative
TCOLF
Tres Cantos Open Lab Foundation
JHU
Johns Hopkins University
UAB
The University of Alabama at Birmingham
KNCV
KNCF Tuberculosis Foundation
UCT
University of Cape Town
MLU
Martin Luther Universität Halle-Wittenberg
Weill Cornell
Weill Cornell Medical College
MM4TB
More Medicines for TB
Wellcome
Wellcome Trust
NIAID
National Institute of Allergy and Infectious Diseases
1 http://www.who.int/mediacentre/factsheets/fs104/en/ 2 https://www.cdc.gov/tb/
3 http://www.who.int/tb/en/ 4 http://www.who.int/mediacentre/factsheets/fs104/en/
CURRENT R&D PROJEC TS CO M PA N Y AbbVie
AstraZeneca Bayer Celgene Daiichi Sankyo Eisai
PA RT N E R S
PROJ EC T
PH A S E
T Y PE
TB A
Technical consulting and preclinical support Whole-cell screening program, collaborative drug discovery
Preclinical
Medicine
Lead identification
Medicine
BMGF TBDA TB A
Joint research collaboration agreement
BMGF TBDA NIAID BMGF TBDA, Dundee Uni, UCT Weill Cornell Weill Cornell
Whole-cell screening program AZD5847 Whole-cell screening program Development of treatments Development of treatments
UCT
Development of treatments
TB A, GHIT TB A, GHIT BMGF TBDA Company BMGF TBDA TB A TB A Wellcome, BioVersys TB A Aeras TCOLF, Dundee Uni (DDU)
Identification of lead compounds as novel anti-TB agents Screening program (Natural Products Library) Whole-cell screening program GSK 070 Whole-cell screening program Whole-cell screening program Whole-cell hit to lead screening program (SDD) Ethionamide Boosters Mtb DprE1 inhibitors Vaccine (GSK M72) Tuberculosis InhA focused fragment based drug discovery Whole-cell assays for the identification and classification of Mtb growth inhibitors Intra-macrophage driven optimization of confirmed hit GSK421197A Optimisation of Fidaxomicin analogs Self-poisoning of Mycobacterium tuberculosis by inhibiting siderophore secretion Exploring TB Space: Optimization of novel, high quality phenotypic hits Whole cell protein synthesis inhibition assay for high-throughput Studies towards the identification of orally available beta-lactams with efficacy against M. tuberculosis Diarylquinoline bedaquiline (SIRTURO®) for treatment of MDR-TB Diarylquinoline, bedaquiline for treatment of drug sensitive TB Next generation diarylquinoline CPZEN-45 Screening program Lead generation/optimization portfolio Whole-cell screening program Protein synthesis inhibitor Compound screening ALIS (MOA) Protein synthesis In vivo preclinical PK / PD dose ranging Exclusive worldwide licensing agreement Lamprene® (clofazimine) in MDR-TB Deltyba® (Delamanid) for adult patients with pulmonary MDR-TB: evaluation of the safety and efficacy Deltyba® (Delamanid) for pediatric patients with pulmonary MDR-TB: evaluation of long-term safety, tolerability, and pharmacokinetics
Weill Cornell GlaxoSmithKline
UBC BHAM UAB BHAM BHAM, TAMU TCOLF, Weill Cornell Company
Janssen (J&J)
Lilly
MSD
Novartis
TB A TB A IDRI, NIH IDRI, NIH, TB A IDRI, NIH, TB A BMGF TBDA BMGF TBDA, NIAID, CS Uni, PHRI BMGF TBDA, TAMU TB A JHU TB A Company Company
Otsuka Company
Pfizer
Sanofi
South Korean Ministry of Health & Welfare SAMRC OOPD Pfizer Foundation IMI Regeneron TBTC Company Company Cornell Uni TB A BMGF TBDA SSI, Aeras, Intercell NIAID UCT NIAID KNCV Company
Shionogi
GHIT, TB A, RIT/JATA
Takeda
TB A, GHIT
Total R&D projects for Tuberculosis: 62
Lead identification/ optimization Lead identification Phase II Lead identification R/NR screening Host-directed screening Hit-to-lead and structureactivity relationship (SAR) Lead identification Hit identification Lead identification Phase I Lead identification Lead optimization Lead identification Lead optimization Lead optimization Phase II Discovery
Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Vaccine Medicine
Discovery (tool)
Medicine
Discovery
Medicine
Lead optimization
Medicine
Discovery (tool)
Medicine
Discovery (tool)
Medicine
Discovery
Medicine
Discovery
Medicine
Phase III
Medicine
Phase II
Medicine
Preclinical Preclinical Discovery Discovery Lead identification Lead optimization TID / Lead identification Phase I Preclinical NA Phase III
Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine
Phase III
Medicine
Phase I & II
Medicine
Linezolid
Phase II
Medicine
Linezolid, Oxazolidinone antibiotic Rifabutin & Rifampin Linezolid, Oxazolidinone antibiotic Operations research Operations research Rifapentine (new regimen development for active TB) Rifapentine (new 3HP regimen development for latent TB) Antimycobacterial screening program Screening on non growing TB phenotypes Lead to candidate portfolio
Phase II Phase II Phase II Basic research Basic research Phase III Registration Discovery Lead identification Lead optimization Lead identification/ optimization
Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine Medicine
Phase II
Vaccine
Phase III Phase II/III Phase I/II Phase III Phase I
Medicine Medicine Medicine Medicine Medicine
Drug discovery
Medicine
Lead identification
Medicine
Whole-cell screening program, hit-to-candidate portfolio Vaccine HyVac4 IC31 (AERAS-404) adjuvanted subunit TB vaccine Rifapentine, new ultra-short course regimen for LTBI - PLHIV Rifapentine 3HP for LTBI, correlate of risk intervention Rifapentine 3HP for LTBI, pregnancy/postpartum Rifapentine for LTBI, periodic 3HP for PLHIV Rifapentine-based new formulation Hit-to-lead development of anti-TB phenotypic screening hits Hit-to-lead
Medicine
