CPTR WorkshopOctober 3, 2012

Drug Development Coalition

CPTR Organization

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• Integrated Sciences Team

• Data Standards& Integration WG

• Biomarkers & Clinical Endpoints WG

• Preclinical & Clinical Sciences WG

• Clinical Disease Progression Modeling WG

• Health Authorities Submission WG

Regulatory Science Consortium

Research Resources Group

Drug Development Coalition

• Global Regulatory Pathways WG

• Stakeholder & Community Engagement WG

• Access & Appropriate Use WG

• Clinical Trials Infrastructure WG

Drug Development Coalition Signatories

AstraZenecaBayerJNJSanofiTB AllianceWHO

Lead Optimization Preclinical Development

GLP Tox. Phase I Phase II Phase III

Delamanid (OPC-67683)GatifloxacinMoxifloxacinRifapentine

AZD5847Bedaquiline (TMC-207)LinezolidNovel Regimens2

PA-824RifapentineSQ-109Sutezolid (PNU-100480)

CPZEN-45DC-159aQ201SQ609SQ641

Preclinical DevelopmentDiscovery1 Clinical Development

DiarylquinolineInhA InhibitorsLeuRS InhibitorsMycobacterial Gyrase InhibitorsPyrazinamide AnalogsRiminophenazinesRuthenium (II) complexesSpectinamidesTranslocase-1 Inhibitors

Chemical classes: fluoroquinolone, rifamycin, oxazolidinone, nitroimidazole, diarylquinoline, benzothiazinone1 Ongoing projects without a lead compound series can be viewed at http://www.newtbdrugs.org/pipeline-discovery.php.2 Combination regimens: first clinical trial (NC001) of a novel TB drug regimen testing the three drug combination of PA-824, moxifloxacin, and pyrazinamide was initiated November 2010 and completed in 2011 with promising results. The second clinical trial (NC002) of this regimen was launched in March 2012 and will test the efficacy of the regimen in drug-sensitive and multidrug-resistant patients. The third clinical trial (NC003) will evaluate PA-824, TMC-207, pyrazinamide and clofazimine in combinations and is scheduled to begin September 2012.

Global TB Drug Pipeline

Updated: August 10, 2012

BTZ043TBA-354

www.newtbdrugs.org

Key Recent Events

Rifapentine in LTBI – CDC recommendation December, 2011Delaminid in MDR-TB – filed in EUBedaquiline in MDR-TB – filed in US, EU

Key New Data ex CPTR

PanACEA high dose rifampinUniversity of Liverpool / Malawi surrogate marker work

Key New Plans

“Universal” myco lab manual“Universal” EBA analytics manualGatifloxacin Oflotub Phase 3 study results

J = bedaquilineZ = pyrazinamideP = rifapentineC = clofazimineM = moxifloxacinU = sutezolidPa = PA-824N = TBA354

6-wk to 2-mo regimensJZPCJZCMJZCUJZPJZCJZNJPaUZ (pending)

NCE regimensJPaU: 4 mosJUC: 4 mosJPaUC: 4 mosJNU: 2 mos

Key New Preclinical Combo Data (Mouse Relapse Model)

Thank You !