Day 1 :
Profectus Biosciences Inc., USA
Keynote: Development of the full length single chain gp120-CD4 (FLSC), a novel vaccine for HIV prevention
Time : 09:05-09:35
Timothy R Fouts is one of the Founders and Principle Scientists at Profectus Biosciences. He directs a team of scientists in the discovery and preclinical development of vaccines, small molecule and antibody based antiviral therapies and microbicides that are within the Profectus research portfolio, in particular HIV and certain biothreat viruses. He has more than 35 scientific publications that have appeared in peer reviewed journals and book chapters. He has received his PhD in Immunology from the University of Maryland, Baltimore and completed Postdoctoral fellowship at the Aaron Diamond AIDS Research Center at Rockerfeller University in NYC.
Obtaining a practical, efficacious vaccine against HIV has been a public health priority for over 30 years. We have developed the Full Length Single Chain (FLSC) in order to induce broader immunity, including against new conserved epitopes, compared to conventional gp120 or trimeric gp140s. The FLSC vaccine is fusion protein consisting of a modified full length gp120 protein derived from HIVBaL and the first two domains (D1D2) of human CD4, genetically fused via a 20 amino acid linker. Immunization with FLSC was able to protect rhesus macaques against rectal challenge of heterologous neutralization resistant SHIV (162P3) and SIVmac251. Efficacy tracked with Fc mediated effector function of the antibody provided that the concurrent anti vaccine T cell response is minimal. Protection is lost over time as requisite antibody titers declined consistent with the evanescent quality of anti envelope humoral responses. To advance the FLSC into clinical trials, a master cell bank expressing human FLSC was prepared from G293H, a derivative of HEK-293 cell that grows in suspension using the GPEx® retrovector transduction system. Bioreactor production rates were consistent from the 2L to the 200L scale, yielding approximately 1 gms/liter after downstream purification. Drug substance was predominately monomeric and expressed the expected CD4 induced structure. Potency studies with the Alum formulated drug product demonstrated a significant relationship between the dose of the FLSC/Alum (IHV01) and the induction of the desired CD4i directed immune response. Immunogenicity studies performed in rhesus macaques showed that the FLSC/Alum formulation induced antibodies directed to CD4i epitopes and mediated ADCC activity while T cell responses were modest. Toxicity studies performed in rabbits and cynomolgus macaques demonstrated that the vaccine was safe and did not induce any deleterious autoimmune effects directed to CD4. A dose escalation phase 1 clinical trial with IHV01 has started at the Institute for Human Virology in Baltimore, MD.
Sanofi Pasteur, France
Time : 09:35-10:05
Rene Labatut has experience in CMC Management in Biopharmaceutical Industry from research & development to manufacturing in highly regulated environment (US, EU, Japan, China etc). He has developed a worldwide international skill set in innovation, technology transfer, licensing in and out and acquisition integration management. He is the Vice President of Manufacturing Technology of Sanofi Pasteur; the vaccines division of Sanofi. He has delivered numerous speeches in reputed conferences and has been serving as a steering Committee Member of Center for Biomedical Innovation at MIT. He has brought significant contribution to several key healthcare product developments like ceredase, thymoglobulin, hexavalent pediatric, flu and dengue vaccines. He holds PhD in Biochemistry, Master in Bioengineering from National Institute of Applied Sciences, Master in Molecular Biology from Lyon I University and Master in Business from Lyon III University.
Vaccines are considered as one the most efficient approach to fight life threatening infectious diseases for a while. Nevertheless there is still unmet medical needs to be addressed. Former and currently in use approaches and technologies had reach their limit. We clearly have to design other ways to cross the current frontier. New technologies should be a key enabler to be created in association with new “business” and operating model. We will broaden the field of application opportunity within the anti infectious areas giving access to more population. Others therapeutic territories should be explore using the immune systems as beyond the historic ways. Let’s explore this new potential space for the benefit of the patient.
Inovio Pharmaceuticals, USA
Keynote: VGX-3100 drives regression of HPV16/18 CIN2/3 and robust cellular immune responses in blood and cervical tissue in a blinded, randomized, placebo-controlled phase 2b study
Time : 10:25-10:55
Prakash Bhuyan received his MD and PhD degrees from the University of Texas, Southwestern Medical Center and completed his Fellowship in Infectious Diseases at the University of Pennsylvania. He was Board Certified in both Internal Medicine and Adult Infectious Diseases and joined Inovio Pharmaceuticals as Vice President of Clinical Development in 2016 from Pfizer and, prior to that, Merck where he helped lead the development and licensure of Trumenba™ and Vaxelis™, respectively. He is an Adjunct Assistant Professor of Infectious Diseases at the University of Pennsylvania School of Medicine. He has published dozens of scientific papers in peer-reviewed journals in the field of Vaccinology.
Objectives: Assessment of the safety, efficacy and immunogenicity of VGX-3100 in women with biopsy-proven CIN2/3 with HPV16 and or HPV18 infection.
Methods: Randomized, placebo-controlled, double-blind study, stratified by age and severity of CIN, evaluated cervical tissue changes after three 6 mg intramuscular doses of VGX-3100 followed by electroporation with Inovio’s CELLECTRA®2000 device at weeks 0, 4 and 12.
Results: Among 167 vaccinated women, the study met its primary efficacy endpoint; the percentage of patients who had regression of CIN2/3 to CIN1 or no disease at 6 months post third dose was significantly higher in VGX-3100 recipients compared to placebo (p=0.034). VGX-3100 cleared HPV16/18 infection concurrent with regression of CIN2/3 (p=0.003). Post-hoc immune analysis revealed significantly elevated immune responses in treated patients who had CIN2/3 regression concurrent with HPV16/18 clearance when compared to those who did not. This included the presence of CD8+ T-cells in the blood exhibiting CD137 expression concurrent with perforin (p=0.032) as well as perforin in addition to granzyme A (p=0.036) as well as an influx of CD8+ T-cells into cervical tissue (p=0.008).
Conclusion: The successful phase 2b results represent a significant milestone in the development of active immunotherapies to treat HPV-related dysplasia and cancer. The data generated from the trial reveal a significant clinical benefit afforded by treatment with VGX-3100 and underscore the mechanism of action of HPV specific T cells. Thus VGX-3100 has the potential to provide an important alternative or adjunct to surgery in treating CIN 2/3.