“28,424 cases of Ebola and still counting—what have we learned “28,424 cases of Ebola and still counting—what have we learned?” AAMC Briefing Dr. Jim LeDuc Director Galveston National Laboratory University of Texas Medical Branch 13 October 2015

GNL Mission The mission of the GNL is to assist the NIAID and the nation by conducting basic and applied research designed to improve the prevention, diagnosis and treatment of naturally emerging and purposefully disseminated infectious diseases. Opened in 2008; fully commissioned and operational since 2010 About 300,000 sq ft of laboratory, mechanical and office space—equivalent to most federal biocontainment labs Vision is to bring the strengths in basic and translational research found in academic centers to the challenges of emerging infectious diseases and threats of bioterrorism

From bench to bedside… Basic Research Product Development NIH R01 and other Funded Research Proof of Concept Concept Validation Pre-clinical/ GLP Studies Human Clinical Trials Animal Rule Traditional basic research funded primarily by NIH Translational research funded by NIH, DOD and others, including the commercial sector Focus on Preclinical testing to advance promising candidates to human trialsAnimal Rule Phase I: Safety Phase II: Expanded Safety Phase III: Efficacy FDA Restricted Use Approval GNL UTMB FDA Licensure

Impact of Research on Ebola Important research moved through preclinical phases, into clinical trials, and to patients. ReEBOV Rapid Diagnostic Test for Ebola – commercialized and in use in West Africa. siRNA post-exposure treatment for Ebola went to Phase 1 and Phase 2 clinical trials. Zmapp (human monoclonal antibodies therapy) clinical trials and applications. rVSV (recombinant vesicular stomatitis virus) vaccine trials in Africa and Europe. Adenovirus vectored vaccine trials. Ebola epidemic called to action decades of research on Ebola and related viruses Adenovirus vectors vaccine started in mid-1990’snow in NIH sponsored human trials in West Africa rVSV vaccine started in early 2000’snow most promising vaccine following demonstrated efficacy in “ring vaccination trial” in Guinea. Zmapp validated in animal trials at UTMB; used clinically in US cases siRNA effective in animal testing at UTMB; advanced to human trials in West Africa; trials terminated Diagnostic assays rapidly developed based on access to live Ebola virus and specimens from acutely ill animals used in vaccine and drug development

Current status of rVSV vaccine April 2015 An important questions was, will the vaccines and diagnostics under development work against the new West African strain of Ebolaonce the virus was available, this was quickly answered and the results shared internationally. August 2015 Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial ,

Rapid Test for Ebola 15 min rapid screening assay using whole blood from finger prick Produced by Corgenix (Broomfield, Colorado) Uses antibodies to identify specific Ebola virus protein Anticipated cost about $15/test 92% of infected people identified; 85% of uninfected—confirmation by PCR Approved by FDA and WHO Rapid test for Ebola developed and utility confirmed in laboratory testing at UTMB using live virus and specimens from animals involved in vaccine and drug testing NEXT SLIDE

Team from UTMB and others validated the rapid test on the ground in Kenema, Sierra Leone, at the height of the epidemic using clinical material from acutely ill patients Test quickly approved by FDA and WHO

Cepheid EBOV Diagnostics Collaboration with Cepheid initiated October 2014 in response to West Africa EBOV outbreak; Cepheid has footprint in Africa for Tb work. Worked with Cepheid to build EBOV specific diagnostic test Tested limit of detection (LoD) for EBOV RNA and live EBOV virus Participated in mock clinical study which led to Cepheid receiving emergency use authorization (EUA) to use diagnostic in the West Africa outbreak EUA received by March 2015 through working with UTMB at the GNL. Progress: From no product in October 2014 to diagnostic test used in Africa under EUA by March 2015. 10 minutes ~90 minutes A second diagnostic test developed in partnership with Cepheid, a biotech firm with an established global network of partners already testing for important diseases of public health concern like TB Benefit is that this test builds on existing technology and is already in use globally. By including Ebola testing capabilities, we are enhancing the sustainability of diagnostic testing for this rare but extremely important disease.

Unique Strengths of Academic Medical Centers Highly trained experts in their field. Cutting edge knowledge of current advances, including unpublished work in progress. Immediate access to reference pathogens and reagents. Through the NIH network, access to appropriate biocontainment laboratories. Skilled workforce approved to handle select agents. State-of-the-art equipment and instrumentation. Appropriate biosafety and biosecurity training—skills being passed on to clinicians. Rapid test for Ebola developed and utility confirmed in laboratory testing at UTMB using live virus and specimens from animals involved in vaccine and drug testing NEXT SLIDE

Conclusions The health of the nation is intimately intertwined; an outbreak anywhere is a threat everywhere—pathogens don’t carry passports! Some of today’s health threats—like Ebola—are extremely dangerous and require highly specialized facilities and skilled personnel to develop the drugs and vaccines needed to protect the nation. The investments by NIH have created a network of biocontainment laboratories on academic medical centers that fosters innovation and discoveries to address the most dangerous global threats to health. Challenges going forward include sustained funding to support basic and translational research in these specialized facilities, and a regulatory environment that fosters collaboration and innovation.

Thank You. For more information: www. utmb Thank You! For more information: www.utmb.edu/gnl Jim LeDuc jwleduc@utmb.edu Opened in 2008; fully commissioned and operational since 2010 About 300,000 sq ft of laboratory, mechanical and office space—equivalent to most federal biocontainment labs Vision is to bring the strengths in basic and translational research found in academic centers to the challenges of emerging infectious diseases and threats of bioterrorism