25 October 2011Day 1: Working Dinner
Working Dinner
Concurrent Future Planning Discussions for Subgroups
All Sub-Group Members
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All WGND members who attended the events in Lille were invited to a dinner sponsored by the WGND. The dinner was an opportunity for members of each WGND Subgroup (Biology/Targets, Candidates, Critical Knowledge and Tools, Clinical Trial Capacity) to discuss and plan for 2012 activities and provide feedback on 2011 activities.
26 October 2011Day 2: Annual Meeting
WGND Updates
Welcome and Introduction of the New WGND Co-Chair
Mel Spigelman, William Bishai (by video)
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- Welcome and Introduction (Mel)
- Announcement of Barbara Laughon as newly-elected Co-Chair (Mel)
- Welcome and Thank You Message (Bill)
WGND Progress Report: Present new web tools and other WGND updates - Part I
Cherise Scott
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- WGND Clarified its mission
- The WGND accomplished the majority of planned initiatives for 2011 including greatly enhancing and adding to the resources available on the website, hosting PZA Workshop, conducting a strategic planning meeting, integrating into the CPTR and collaborating more with other Stop TB Working Groups
- Several activities are planned for 2012 with continued focus on developing the website, fostering networks and forums around topics such as biology/targets and clinical capacity, working on an updated version of the Blueprint for new TB drugs, and pursue additional funding mechanisms
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- WGND Clarified its mission
- The WGND accomplished the majority of planned initiatives for 2011 including greatly enhancing and adding to the resources available on the website, hosting PZA Workshop, conducting a strategic planning meeting, integrating into the CPTR and collaborating more with other Stop TB Working Groups
- Several activities are planned for 2012 with continued focus on developing the website, fostering networks and forums around topics such as biology/targets and clinical capacity, working on an updated version of the Blueprint for new TB drugs, and pursue additional funding mechanisms
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- Community Representatives can play a great role in facilitating communication between the WGND and the affected community which will enhance community participation in R&D
- Community Representatives can raise public awareness on ongoing TB drugs R&D, advocate for increased funding for TB R&D and empower affected communities and create real ownership of the TB programs
- Community Reps can help in achieving WGND TOR in various activities like CAB, educational workshops, and presenting community concerns at various platforms.
Brief Overview of WGND PZA Workshop
Jacques Grosset
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Main issues addressed by the workshop:
- Mechanism(s) of action including the potential target, the range of susceptible organisms, the role of acidic environment, immune-modulator effect (leishmania)
- The past and new analogues of PZA: Why does the addition of a nitrogen atom in the pyridine ring increase by ~ 7 times the antituberculosis activity of nicotinamide? is nicotinamide, like pyrazinamide, synergistic with rifampin?
- Drug susceptibility test: from phenotypic to genotypic tests? From not possible to be performed on routine basis to "automated" test?
- Timing of PZA use: why is such an unique sterilizing drug used during the initial (bactericidal) phase, only during the initial hase, and not in the continuation (sterilizing) phase of treatment for tuberculosis?
Find out more here:
http://www.newtbdrugs.org/meetings/pza-workshop.php
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- Brief overview of progress made to date on Global TB Drug Pipeline and the TB Drug Discovery Portfolio
AstraZeneca
V. Balasubramanian, Scott Butler
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- Reviewed the progress to date and future plans for the development of AZD5847
- Phase 1 testing completed in healthy volunteers
- Phase 2a EEBA study supported by NIAID is currently in planning stages and will be conducted in South Africa
GSK
David Barros
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- Overview of TB drug discovery projects including DNA Gyrase Inhibitors, 1,5-naphthyridone series, whole cell screening, InhA Inhibitors, TB LeuRS Inhibitors
- GSK's Open innovation strategy includes sharing data, intellectual knowledge and resources.
Novartis
Manjunatha Ujjini
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- Novartis Institute for Tropical Diseases (NITD), Singapore is dedicated to discovery and early development novel treatments for major tropical diseases like tuberculosis, dengue fever and malaria. The main therapeutic objective for TB indication is to develop novel chemotypes active against MDR and XDR TB to enhance cure rates and improve patient compliance. The current TB drug discovery project portfolio includes two lead optimization programmes on scaffolds originated from a cell based phenotypic screen and a few other promising early stage projects.
Pfizer
Robert Wallis
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- Early clinical findings support superior efficacy and safety of sutezolid vs. linezolid
- Combinations including sutezolid, bedaquiline, SQ109 appear likely as candidates for a new universal regimen
- Innovative development strategies for sustainable TB drug development can enhance value to patients, physicians, and sponsors, yet address regulatory concerns regarding the approval of medicines that are safe and effective
Pipeline Updates - Part II
Sanofi-Aventis
Patricia Vita
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- Results of SAR1 alone in in vitro and in vivo activities (acute and chronic models) and in combination using marketed compounds were showed.
- From in vitro results: SAR 1 is a potent bactericidal on replicating M. tuberculosis, with high intra-macrophage activity. No cross-resistance was shown with other TB drugs using laboratory and clinical resistant strains.
- From in vivo evaluation, SAR1 is active alone in M. tuberculosis infected mice acute model from 50mg/kg and in a chronic model from 100mg/kg.
- SAR1 in combination with potent marketed compounds (H, R, Z) during the initial phase of treatment: SAR1 at 100mg/kg is as bactericidal as INH 10mg/kg. SAR1 (100mg/kg) + RIF (10 mg/kg) +PZA (150 mg/kg) has a spectacular activity, especially compared to the activity of the standard regimen, HRZ. During the continuation phase of treatment: SAR1 combined with rifampicin is more active than RH (standard treatment).
- SAR1 is a promising new drug for TB treatment, further work on relapse and activity in combination with new compounds in development is ongoing.
Sequella
Gary Horwith
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- Doses of SQ109 up to 300 mg/day were safe and well-tolerated in 80 healthy subjects administered SQ109 in phase1 SAD and MAD clinical trials.
- SQ109 up to 300 mg/day was safe and well-tolerated in 84 sputum-positive, drug-susceptible patients with pulmonary tuberculosis enrolled in a phase 2a EBA clinical trial in South Africa. Patients were administered SQ109 monotherapy or with rifampicin. The last patient, last visit was mid-September, 2011.
- Assessment of the microbiology and pharmacokinetics data from the EBA clinical trial is in progress.
- A Phase 2b dose escalation study of SQ109 with standard and high-dose RIF in drug susceptible patients with pulmonary TB will commence in PanAcea clinical trial sites mid-2012.
Tibotec
Tine De Marez
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Addition of TMC207 to a 5-drug MDR-TB regimen resulted:
- In faster culture conversion within 24 weeks (p=0.003)
- In median time to culture conversion of 12 versus 18 weeks.
- In a higher sputum conversion rate at 24 weeks 79% vs 58% (p=0.008)
Next steps in 2012: health authority submission and start of phase III study.
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- NC-001 clinical trial results were presented. NC-001 was a 2-week EBA study with treatment arms PA-824+moxifloxacin+pyrazinamide, TMC207, TMC207+pyrazinamide, PA-824+pyrazinamide, TMC-207+PA-824 and rifafour (control). Pyrazinamide greatly enhanced the activities of TMC207 and PA-824, TMC207 and PA-824 were less than additive, and PA-824+moxifloxacin+pyrazinamide performed remarkably well. NC-002 plans and a combined DS/MDR development path were presented briefly. Progress in the REMox Phase 3 trial was also presented; results are expected in early 2014.
TBTC
Andrew Vernon
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TBTC Priorities:
- Treatment of LTBI: shorter, safer, better tolerated, fewer interactions, and (ideally) active against MDR LTBI also
- Treatment of DS disease: shorter, safer, better tolerated, fewer interactions, effective for high risk patients
- Treatment of DR disease: shorter, safer, better tolerated, more effective, less costly
- Key subgroups: HIV-infected; children & mothers
- Trial design: surrogate endpoint for relapse
- Collaborations : effective partnerships
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- NIAID TB Therapeutic Clinical Research Priorities includes new drugs and combinations for drug-sensitive and drug-resistant TB with focus on increasing efficiency of Phase I and II evaluations to be able to get to Phase III faster.
- Sterilizing activity is important consideration for new drugs to kill persisters
- The NIAID is working to enhance/adapt existing clinical research resources for TB, work on coordination and collaborations, develop highly efficient research strategies/agendas and trial designs.
Otsuka
Kelly Stinson
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- OPC-67683 (Delamanid) entered Phase III testing and further information can be obtained at ClinicalTrials.gov
Other Updates
Working Group on New TB Diagnostics
Giorgio Roscigno
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- Overview of progress made in 2011 and objectives for 2012/13 for the Working Group on New Diagnostics.
