Day 1 :
Keynote Forum
Panayiotis P Constantinides
Biopharmaceutical & Drug Delivery Consulting LLC, USA
Keynote: Development and commercialization of oral peptide and protein therapeutics: Trends and perspectives
Time : 10:00-10:30
Biography:
Panayiotis P Constantinides is President of Biopharmaceutical & Drug Delivery Consulting, LLC in Gurnee, USA that he founded in 2004, and he has more than 30 years of industrial experience in drug delivery and pharmaceutical development. He did diploma in chemistry from Athens University in 1977 and PhD in Biochemistry from Brown University in 1983. He was a postdoctoral fellow in the Pharmacology Department and Associate Research Scientist in the Comprehensive Cancer Center of Yale University School of Medicine (1983-1987). Past industrial positions held included: Vice President of R&D with DOR Biopharma and Morton Grove Pharmaceuticals (2000-2004), Director of Research at SONUS Pharmaceuticals (1997-2000) and from 1987 to 1997 a number of R&D positions of increasing responsibilities with LipoGen, SmithKline Beecham Pharmaceuticals and Abbott Laboratories. He is inventor in 33 patents and patent applications, has authored more than 130 publications including review articles, book chapters and presentations on the parenteral and oral drug delivery of small molecules and peptides/proteins and has presented more than 100 invited talks at many national and international conferences, pharmaceutical companies and universities. Dr Constantinides is AAPS Fellow, Past Chair of the AAPS Formulation Design and Development Section, the Nanotechnology and Lipid-Based Drug Delivery Systems Focus Groups. He has received numerous honors and awards and serves as Associate Editor of the AAPS Open journal since its launch in the fall of 2015..
Abstract:
The oral route is the most preferred non-invasive route of drug administration due to increased patient compliance. However, advancing oral peptide and protein therapeutics from bench to clinic and commercialization has been a formidable task. Despite major investments and scientific advances in this area over the last three decades, there is no oral water-soluble and poorly permeable (BCS III) peptide/protein drug product on the market. Oral drug delivery approaches used alone and in combination in preclinical and clinical studies include, chemical modifications, intestinal permeability/ absorption enhancers, such as lipids, surfactants, and proprietary molecules, and lipidic and polymeric micro-/nanoparticles with and without targetable ligands directed towards M-cells/Peyer’s patches in the intestinal mucosa. Upon introductory remarks on the Biopharmaceutics Classification Scheme (BCS) as applied to peptide therapeutics and characteristics of an ideal oral formulation, advantages and limitations with peptide therapeutics and drug development needs will be presented during the first part of the talk. Then preformulation and formulation development aspects of oral peptides, assessment criteria and development considerations with various delivery technologies will be discussed, followed by lessons learned from preclinical and clinical studies. The last part of the talk will summarize accomplishments to date, address commercialization issues and conclude with future developments in this field.
Keynote Forum
Arwyn T Jones
Cardiff University, UK
Keynote: Activating endocytosis for enhancing cellular delivery and modifying intracellular targeting of therapeutics
Biography:
Arwyn T Jones obtained a PhD in protein-crystallography at Birkbeck College, University of London and undertook postdoctoral endocytosis research at the University of Liverpool, Harvard University, and EMBL-Heidelberg as EMBO and Alexander von Humboldt fellow. Appointed as a lecturer at the Cardiff University School of Pharmacy and Pharmaceutical Sciences in 2001 he is now Professor of Membrane Traffic and Drug Delivery. His research falls within cancer cell biology, endocytosis, and drug delivery. A major objective understands endocytosis to improve the cellular delivery efficiency of drug delivery vectors including peptides, natural and synthetic nanoparticles and antibodies targeting plasma membrane receptors. Recent work has concentrated on strategic approaches to plasma membrane targeting to stimulate endocytosis and intracellular targeting. He has published widely within these fields and his group has made significant contributions to the current understanding of the way drug delivery vectors interact with cells and enter endocytic pathways that govern their intracellular fate.
Abstract:
Targeting disease processes inside cells with biopharmaceuticals represents a major challenge, not least in overcoming biological barriers such as those posed by the plasma membrane and endolysosomal organelles. Investment in this approach is justified when one considers the number individual intracellular targets now available to us as we continue to understand disease processes at the gene, protein and signaling level. This is true for many high-burden diseases such as cancer, infectious diseases and inherited genetic defects such as cystic fibrosis. Our research at Cardiff University is focused on studying endocytosis and specifically on designing methods to analyze individual endocytic pathways to characterize how Drug Delivery Vectors (DDVs) and associated therapeutics bind to and gain access to cells. As vectors, we have paid particular attention to natural ligands, cell penetrating peptides, antibodies and polymer conjugates. We have made significant contributions to the current understanding of the way DDVs interact with cells, enter cells and traffic on endocytic pathways that critically govern their intracellular fate. This lecture consists of work we have performed focusing on technologies and in vitro models, we have exploited to study cell binding and endocytosis of DDVs including cell penetrating peptides, exosomes, ligand decorated nanoparticles and antibodies targeting plasma membrane receptors on cancer cells. Mainly highlights will be on how we recently demonstrated that Internalisation of receptors, and associated ligands, can be significantly enhanced through manipulating ligand and receptor association, and how normal endocytic routes can be modified to reach a desired intracellular location. Our involvement in a €30M FP7 Innovative Medicine Initiative (IMI-EFPIA) consortium (COMPACT www.compact-research.org) will also be discussed. This represents public-private collaboration between 14 European academic institutes and pharmaceutical companies aiming to improve the cellular delivery of biopharmaceuticals across major biological barriers of the intestine, lung, blood-brain barrier and skin.
Keynote Forum
Prakash V Diwan
National Institute of Pharmaceutical Education and Research, India
Keynote: The pursuit of oral insulin is a reality: Is it simply a matter of when?
Biography:
Prakash V Diwan obtained his PhD from Postgraduate Institute of Medical Education and Research, Chandigarh, India. Contributed in the areas of Novel Drug Delivery systems & drug discovery. Published over 200 papers in pre-reviewed journals. He delivered guest lectures in India and abroad. He has many awards instituted by Indian Pharmacological Society. He has served as founder Director of NIPER, Hyderabad and fellow of the Royal Society of London, FRSC (London). Presently working as Technical Advisor, Indian Pharmacopeia Commission, Government of India, Director School of Pharmacy, and Hyderabad. Director, CRL, Maratha Mandal Group of Institutions, Belgaum, and Consultant for Indian Institute of Technology, Hyderabad.
Abstract:
Oral insulin delivery has been a promising and interesting research area and can revolutionize treatment. Several studies have achieved positive results which includes nanotechnology. Considerable problems of developing oral insulin are because of the small therapeutic index and short half-life which limits the success. Several insulin delivery systems, such as tablets, capsules, intestinal patches, hydrogels, microparticles, and nanoparticles, have been explored to deliver insulin without much success. Various types of nanoparticles are currently studied for insulin delivery in diabetes treatment such as polymeric biodegradable nanoparticles, polymeric micelles, ceramic nanoparticles, liposomes, and dendrimers. Exubera as the first and until now only inhaled insulin with a market approval, was not a market success due to insufficient uptake in the market. The intestinal micro patches for oral insulin delivery is the well-thought approach. The colon-specific drug delivery system has many advantages. Encapsulation of insulin in vitamin B12-coated dextran nanoparticles has been considered in complementing diabetes therapy by taking advantage of enhanced insulin absorption through vitamin B12 intrinsic factor receptor ligand-mediated endocytosis via intestine leucocytes. Artificial pancreas: The future of diabetes treatment. It's known that intestinal epithelial cells have insulin receptors on their apical surfaces. Researchers think that beta-cell implants or island of langerhans transplants would be a more feasible and perhaps better option? Current research has been going on to deliver insulin experimentally and this has been achieved by the developing “smart” insulin patch. The oral version of an acylated insulin analog with a half-life of ~70 hours is a great breakthrough. The herbal medicines are a symbol of safety in contrast to synthetic drugs. The lifestyle is becoming techno-savvy and we are moving away from Nature. The 80 % of the world population is using herbal medicines. Gymnema sylvestre also increases the amount of insulin in the body and increase the growth of beta cells in the pancreas and many more in the armamentarium of Indian herbal wealth. Most of the developments of these companies have failed in phase II clinical studies, showing insufficient metabolic control in patients with diabetes. However, researchers are concerned that oral insulin could raise the risk of certain types of cancer. Addressing these issues successfully will create a new paradigm in diabetes treatment. Future advance in drug delivery could still make it a reality.
Keynote Forum
Oleg V Tcheremissine
Atrium Health, USA
Keynote: Amyloid hypothesis and drug development for Alzheimer’s disorder: A critical review
Biography:
Oleg V Tcheremissine, MD, is a Professor of Psychiatry, Department of Psychiatry, Atrium Health. He is a board-certified Psychiatrist with 30 years of medical and more than 25 years of research experience in human behavioral and applied clinical psychopharmacology. He has served as a Principal Investigator for numerous pre-clinical and Phase II-IV clinical trials in a range of neuropsychiatric indications. More recently, his research has been focused on developing new insights into neurodegenerative diseases with a primary emphasis on advancing pharmacotherapy of Alzheimer’s Disorder and other cognitive disorders. He has successfully combined his research interests with his teaching, clinical, and administrative responsibilities while focusing on eliminating external and internal barriers to novel and innovative treatments with the overall goal of reducing health disparities, improving access to care and increasing the generalizability of clinical trials results.
Abstract:
.Alzheimer’s Disease (AD) is a devastating progressive neurogenerative disorder resulting from pathological changes in the brain. AD manifests by a broad range of symptoms affecting memory, concentration, volition, and leading to significant impairment in all activities of daily living. The currently approved pharmacological treatments have only limited efficacy and provide mostly symptomatic benefits as they do not specifically target the underlying pathology of AD. AD pathology is characterized by the accumulation of beta-amyloid protein (Aβ), tau-protein, and associated inflammatory response. The amyloid cascade hypothesis has been the basis for developing an entire new class of disease-modifying therapeutics. In the past 20 years, there have been more than 100 attempts to develop new pharmacological agents, including a wide range of therapeutics targeting different components of the amyloid cascade. Based on their role in the amyloid cascade and the primary mechanisms of action, these new therapies could be divided into three subclasses: a) aimed at reducing production of Aβ; b) aimed at promoting Aβ clearance; and c) aimed at reducing Aβ aggregation. This session will provide a critical overview of the amyloid cascade hypothesis in AD and discuss the future directions in drug development for AD.
Keynote Forum
Edwin G Moore
University of Illinois, Urbana
Keynote: Multivalent polymer conjugate inhibits aggregation of beta amyloid and disassembles amyloid fibrils – potential for a polymer therapeutic
Biography:
Edwin Moore has 40 years of biopharmaceutical, pharmaceutical, and clinical diagnostic industry experience from global companies, Baxter Healthcare Corp and Abbott Laboratories, in R&D product development. Since retiring he has enjoyed research, teaching, and mentoring startup companies at University of Illinois, Champaign-Urbana campus, and consulting with BioPhia Consulting, Inc. He was a postdoc at University of Michigan, and received his PhD from Cornell University in Biochemistry, B.S. from University of Illinois in Biochemistry.
Abstract:
Beta-amyloid (Aβ) is a member of a class of proteins that are intrinsically unstable. Aβ normally exist as random coil polypeptide. However, the protein will rearrange to the beta-sheet structure resulting in aggregation followed by fibril formation in the brain. Fibrils become the plaques that are observed in Alzheimer’s patients. In patients that develop Alzheimer’s disease, abnormal levels of Aβ protein accumulate in the brain and aggregate. Aβ protein aggregates and fibrils are believed to be neurotoxic leading to neurodegeneration and cell death. We demonstrated (Y. Song, et.al. JACS, 2014, 136:5233-5236) that a multivalent polymer-peptide conjugate (mPPC) is a very potent inhibitor of Aβ aggregation. The polymer consists of a linear N-(2-hydroxypropyl)-methacrylamide backbone appended with multiple copies of a pentapeptide. As a monomeric strand, this pentapeptide is known to bind to the beta sheet region of the Aβ protein. The enhanced local concentration of the pentapeptide in mPPC dramatically enhances the interference of beta-sheet formation with Aβ. Moreover, mPPC also disassembles amyloid fibrils leaving nanoparticle complexes of mPPC and Aβ aggregates (Y. Song, et.al. JACS, 2017, 139:4298- 4301). Synthetic polymers, like mPPC, represent an untapped class of therapeutic agents. Polymers offer potential benefit as therapeutic agents when designed with specific binding agents and other selective functionality. To realize this potential further research and development is needed to provide discrete chemical entities with defined molecular weights and uniquely positioned functional moieties. Precision polymers are evolving to create a new class of discrete chemical entities to further enhance medical applications.
Keynote Forum
Luke S Fisher
Collaborative Drug Discovery, USA
Keynote: Solutions for collaborative drug discovery: Connecting researchers globally
Biography:
Luke S Fisher brings twenty years of experience in scientific informatics solutions. Managing Pre-Sales, Post-Sales and working in Account Management has expanded my domain knowledge of scientific informatics and provided me the ability to maintain a successful track record. He have covered a broad range of clients including the world’s leading pharmaceutical, biotech, agricultural, chemicals, academic and government labs. He have extensive experience in scientific software solutions from the smaller scale deployment of point solutions like molecular modeling packages to the larger enterprise scale of ELNs, scientific workflow technologies, data content, analysis and visualization. It also includes managing the support complexity of software integration strategies based on numerous mergers and acquisitions.
Abstract:
Collaborative Drug Discovery (CDD) provides trailing innovation for today’s chemical and biological data needs, differentiated by ease-of-use and superior, secure collaborative data sharing workflows. Within the CDD Vault® software, activity & registration, visualization, inventory and ELN capabilities all address today’s markets. Researchers need to archive, mine, and collaborate around the structure-activity relationships generated from their biological screens. Collaborative hypothesis generation and evaluation allow multiple brains to synergize. In contrast, CDD’s Research Informatics Group invents bleeding edge technologies for tomorrow’s needs. For example, open source descriptors and model sharing capabilities allow for platform-independent collaborations, even for sensitive data and IP, with groups reticent to share. As a second example, the recently developed BioAssay Express (BAE) technology streamlines the conversion of human-readable assay descriptions to computer-readable information. BAE uses semantic standards to mark up protocols, which unleashes the full power of informatics technology on data that could previously only be organized by crude text searching. These two newer web-technologies may be used not only with the CDD vault but also with non-CDD software tools. Case studies will be shared from a virtual distributed company, government (NIH Neuroscience Blueprint, MM4TB), non-profit (BMGF, MRF, NPDI), and numerous leading academic collaborations.
Biography:
Rodney Villanueva completed his M.D. at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. He is an Assistant Professor of Psychiatry at Carolinas Medical Center and an Adjunct Associate Professor of Psychiatry at the University of North Carolina School of Medicine. He also serves as the associate director of psychiatry residency training and the psychiatry clerkship director at Atrium Health. He is a strong voice for minority health issues, raising awareness of the health disparities that arise within marginalized communities. At Atrium Health, he has spearheaded efforts at education and advocacy for LGBT health issues, establishing an annual LGBT Healthcare symposium and speaking locally and internationally issues of LGBT mental health.
Abstract:
Notwithstanding the considerable efforts to increase study generalizability and minimize health disparities, the recruitment of minority and underserved individuals in clinical trials across many therapeutics areas remains to be a challenging task. Despite the increase in the number of countries participating in clinical trials used by the FDA to approve of drugs, racial diversity in such trials has not increased. Drug effectiveness and adverse effects can vary according to the ethnicity of an individual patient. However, when the definition of “diversity” is broadened, other marginalized or minority populations are underrepresented in clinical trials, potentially affecting the applicability of the results of the trials to the population as a whole. This presentation will explore the potential causes of poor participation in clinical trials of ethnic minorities, low-income populations, sexual minority populations, and rural populations. The implications of limited diversity, as well as strategies to address these problems, will be discussed in the context of the study design and methodology, and culturally appropriate recruitment strategies employed.