4^thInternational Conference on Drug Discovery, Designing Chemistry and Pharmaceutical Analysis June 27-28, 2018 Vancouver, British Columbia, Canada

Bell frequently testifi es as an expert witness on damages in intellectual property, fi nance and antitrust litigation in courts and arbitration proceedings in North America, Europe, Asia and Australia. Dr Bell’s business consulting engagements focus on the economics of business strategy, working with fi rms to develop sustainable competitive advantages in specifi c product markets. He has led numerous projects concerning game theory and competitive strategy, global launch strategy, product pricing and positioning,capital budgeting and real options and cost-benefit analyses.

Biosimilars and biobetters portend huge changes in the marketplace, from both regulatory and legal perspectives. This talk will focus on the strategic implications of the introduction of biosimilars and biobetters. How will biosimilars and biobetters be marketed? How might those marketing strategies diff er from the perspective of a traditional generic product or a traditional branded product? We will consider the ways through which biobetters could be diff erentiated from biosimilars and how those diff erences might be manifest in the go-to-market strategies supporting the products. We will also address portfolio considerations and what might be the role of a portfolio of biosimilars and biobetters alongside a portfolio of branded products related to a condition.

Kooros Motamed-Larijani has been the Director of Drug Development at Nant-Bioscience Inc. since April 2016. Previously, he served as VP of Strategic Alliances and Clinical Communications and VP of Clinical Development and Nanomedicine at Sorrento Therapeutics Inc. from 2013 to 2016. He also served as a co-founder

and CSO/CTO of Igdrasol Inc. and Biomiga Diagnostics LLC start-up companies from 2011-2013. Prior to that, Dr. Motamed served as the MOA and Molecular Biology Group Head at Celgene Corp. and Abraxis Bioscience LLC. from 2007-2011. Dr. Motamed held an Assistant Professorship position in the Department of Pathology and Vascular Biology Center at Medical College of Georgia, Augusta from 2002-2007. He has over 30 original publications in peer-reviewed journals, over 50 conference presentations and 5 issued patents. He has served on the Editorial Board of Journal of Nanomaterials & Molecular Nanotechnology since 2013. Dr.Motamed received a B.S. degree in Biology from University of San Francisco and a Ph.D. degree from the University of California, Davis in Microbiology.

“Biobetters” or “Biosuperiors” are enhanced versions of approved biological products. Whereas “Biosimilars” are near-perfect copies of the originators, biobetters diff erentiate themselves through displaying superiority over the reference biologics.These improvements in one or more attributes could be in the form of increased effi cacy and/or safety, reduced immunogenicity, changes in route of delivery, reduced dosing frequency/cost of treatment or improvements in manufacturing. Inspite of these potential advantages over the branded biologic or an approved biosimilar, biobetters also face various clinical development, regulatory and marketing hurdles which will be addressed. In summary, biobetters represent an opportunity to establish brand-to-brand competition within treatment indications and can be perceived as a potential path to provide meaningful improvements over the original biologic, sustain innovation and market diff erentiation in order to drive future value.

Ivan Tkac has completed his MD in 1982 and PhD in 1991 in the Šafárik University in Košice, Slovakia and his postdoctoral studies in the University of Toronto, Canada. He is a professor and the head in the Department of Medicine, University of Kosice. He has published more than 50 papers in renowned journals including Diabetes Care, Diabetes, Obesity and Metabolism, Nature Genetics, Clinical Pharmacology and Therapeutics, and Arteriosclerosis, Thrombosis and Vascular Biology. His research focuses on the topics of pharmacogenetics of oral antidiabetic drugs and atherosclerosis in diabetes.

Oral antidiabetic drugs are used for more than a half century in the treatment of type 2 diabetes. Only in the last five years intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of associations detected in these studies were replicated. Th e gene variants in CYP2C9, ABCC8/ KCNJ11 and TCF7L2 were associated with the eff ect of sulfonylureas. CYP2C9 encodes sulfonylurea metabolising cytochrome P450 isoenzyme 2C9, ABCC8 and KCNJ11 genes encode proteins SUR1 and Kir6.2,respectively. Th ose proteins constitute the ATP-sensitive K+-channel which is a therapeutic target for sulfonylureas. TCF7L2 is a gene with the strongest association with type 2 diabetes that infl uences insulin secretion. SLC47A1, ATM and SLC2A2 gene variants were associated with the response to metformin. SLC47A1 and SLC2A2 encode MATE1 metformin transporter and GLUT2 glucose transporter, respectively. The function of a gene variant near ATM (ataxia-telangiectasia mutated) gene is probably related to activation of AMPK. In the recent years, the fi rst studies related to the pharmacogenetics of response to DPP-4 inhibitors were published, although none of them was replicated so far. Among identifi ed genes are TCF7L2, CTRB1/2 encoding chymotrypsinogen, and GLP1R encoding the downstream therapeutic target for gliptins – GLP-1 receptor. With the accumulating pharmacogenetic evidence in type 2 diabetes there are reasonable expectations that genetics might help in the adjustment of drug doses to reduce severe side effects, as well as to make better therapeutic choices among the drugs available for the treatment of diabetes.

Mandla Stanley Makhanya was appointed Principal and Vice Chancellor of the University of South Africa on 1 January 2011 and is a prominent proponent of higher education leadership and advocacy. Prof Makhanya is President of the International Council for Distance Education (ICDE) and is also treasurer of the African Council for Distance Education (ACDE). Professor Makhanya is also the President of the Higher Education Teaching and Learning Association (HETL) –

International Body.

While ‘biobetters’ are meant to be an innovation in provision of aff ordable drugs to all those people engrossed in debilitating poverty, the challenge arises on how to navigate the complex regulatory frameworks, which fundamentally hamper access to the life-giving aff ordable medicines. Th is keynote address grapples with ways of navigating regulatory frameworks in Africa so as to make ‘biobetters’ easily available to the masses of people who are unhealthy but cannot aff ord the expensive life-giving medicines available in the market. Th e entry point of this keynote address is the ‘Right to Health’ and how this has remained an aspiration for the poor people of Africa. It proceeds to documents how the existing regulatory frameworks limits rather than enhance access to ‘biobetters’ in Africa. It ends with explorations of ways of democratizing the regulatory frameworks in such a way that they enable the realization of the ‘Right to Health’ in Africa—A continent where human life is still being lost due to curable diseases.

Eric Ka Wai Hui is a Principal Investigator at ArmaGen, Inc., a biotech company focused in the development of biotherapeutics for the brain. Dr. Hui joined ArmaGen in 2008 following 10 years of academic experience in molecular biology of neuroscience. His responsibilities have been instrumental in the development of ArmaGen’s extensive product pipeline, including potential biotherapeutic treatments for mucopolysaccharidosis, stroke, Alzheimer’s disease and Parkinson’s disease. Dr. Hui has a Ph.D. in Microbiology and Immunology, and he has published numerous papers in his field.

The majority of lysosomal storage disorders aff ect the brain. Enzyme replacement therapy does not treat the brain, because recombinant enzymes are large molecules that do not cross the Blood-Brain Barrier (BBB). BBB-penetration of enzyme therapeutics is enabled by re-engineering the recombinant enzyme as bi-functional IgG-enzyme fusion protein, wherein the IgG domain targets specifi c endogenous receptor-mediated transporter within the BBB, such as the insulin receptor. Brain penetrating IgG-enzyme fusion proteins have been engineered for Hurler Mucopolysaccharidosis (MPS) Type I (MPSI), Hunter MPSII, metachromatic leukodystrophy, Sanfi lippo MPSIIIA and Sanfi lippo MPSIIIB, and validated in Rhesus monkey in vivo and in human fi broblasts in culture. Brain uptake in non-human primates approximates 1% of Injected Dose (ID) per brain.This level of brain uptake is able to replace between 20-100% of endogenous enzyme activity in brain. Confocal microscopy shows that these brain penetrating IgG-enzyme fusion proteins target lysosomal compartments in human fibroblasts, reducing accumulation of sulfated glycosaminoglycans. Bio distribution of the IgG-enzyme fusion protein, as compared to enzyme alone, has been evaluated with whole body autoradiography in Rhesus monkeys. Although enzyme alone does not penetrate the primate brain, there is global uptake of the IgG-enzyme fusion protein throughout the brain of the non-human primate. Conversely, there is comparable uptake of either the enzyme alone or the IgG-enzyme fusion protein by peripheral tissues. The data are consistent with comparable uptake of either the IgG-enzyme fusion protein or the enzyme alone in peripheral organs mediated by the Mannose 6-Phosphate Receptor (M6PR), which recognizes the enzyme domain of the fusion protein. However, the M6PR is not expressed at the BBB. Brain penetration of the fusion protein is mediated via the IgG domain of the fusion protein, which targets the BBB insulin receptor. Successful development of a BBB-penetrating platform is transformational for MPS diseases as well as broader CNS/neurological conditions. Neurocognitive function, somatic effects and safety of a phase II proof of concept clinical trial in Hurler MPSI pediatric patients will be discussed. Th is represents the first in human clinical trial of a fusion protein engineered to cross the BBB.

At Labaton Sucharow, Steve Durham concentrates his practice on representing corporate whistleblowers before the SEC. With a 25 year track record of protecting whistleblower and victim rights as a federal prosecutor and as a senior corporate compliance attorney, Steve helps clients obtain justice and maximize recoveries through the SEC Whistleblower Program. During his two decade tenure as an Assistant United States Attorney in Washington, D.C., Steve was a founding member of the President’s fi nancial fraud enforcement task force and longtime chief and deputy chief of the fraud and public corruption section. As a prosecutor and section chief, his experience included a broad array of complex white collar cases and numerous parallel enforcement actions with the SEC involving corrupt broker-dealer violations, offering frauds, market manipulations, Ponzi schemes, insider trading infractions, FCPA violations and accounting frauds.

In 2010, the Dodd-Frank reform legislation created the SEC Whistleblower Program as a key tool in the SEC’s enforcement framework. Since its inception, the SEC’s Offi ce of the whistleblower has awarded 50 whistleblowers over $160 million for information that has led to many signifi cant SEC enforcement actions. In this keynote address, Labaton Sucharow partner Steven J. Durham will discuss the operation and success of the SEC Whistleblower Program and how every individual plays an important role in protecting corporate integrity.

Michael D Winther is Associate Director at the Genome Institute of Singapore (GIS) and Head of offi ce of strategic alliances and knowledge management as of December 2015. Responsible for all agreements with academic, medical and industry organizations, as well as intellectual property developed by GIS. He is also the senior project manager for the national pharmacogenomics project SAPhIRE: Surveillance and Pharmacogenomics of Adverse Drug Reactions (www.saphire.sg). The SAPhIRE programme is developing the knowledge base and tools needed to implement pharmacogenomics at the wider community level to impact safety and efficacy of biological and small molecule therapeutics. He has over 25 years R&D experience in biologicals and drug discovery with pharmaceutical and biotechnology companies and academia.

The dramatic growth of biologics in the past few decades lead to major advances in medical therapy for patients and brought about a shift in the way drug discovery is approached. While biologicals have many diff erent characteristics from small molecule drugs they both share the same concern in that typically only a fraction of the treated population responds favorably, while others may experience lack of effi cacy or even occurrence of Adverse Drug Responses (ADRs). Pharmacogenomic studies for both small molecule therapeutics as well as biologics have shown that diff erent response are oft en explained by host genetic factors, indicating a need for clinical markers for prediction of effi cacy and ADRs. Th e discovery of such genetic biomarkers is challenging, but if successful could lead to competitive advantage for biologicals when they are partnered with their companion diagnostics. Examples of recently identifi ed genetic associations that infl uence response to biologics will be discussed. An improved understanding of host response through careful pharmacogenomics studies can reveal diff erent pathways that impact efficacy and safety of biologicals. This knowledge in turn can help direct eff orts to improve upon the first generation of biologicals by creating molecules with enhanced effi cacy and reduced occurrence of ADRs. Th is field is only beginning to emerge, but with the advances of pathway characterization and use of AI-guided molecular modelling can predicted to impact the next generation of biobetters.

Asif Mahmood have diverse leadership experience as a health services professional with signifi cant accomplishments in all aspects of pharmacovigilance, clinical development, medical affairs, regulatory affairs, primary health care, project management & international health programs. He have vast experience of working in diverse therapeutic areas including rare diseases, novel preventive & therapeutic vaccines, monoclonal antibodies, cardiovascular, oncology, neurology, nosocomial diseases, generic and OTC medicines. He is currently working as Disease Area Cluster Lead for Biosimilars & Drug Delivery Devices at Pfi zer. Currently Pfizer has the largest biosimilars portfolio in the industry that includes projects on Infl ammation, Oncology, Hematology, ophthalmology etc. His past experience includes working as Associate vice president PV and Therapeutic Area Head (Rare Diseases) for Sanofi Genzyme, working as Senior Director & Director for vaccines PV at Sanofi Pasteur, working as Medical Consultant for Apotex Inc Canada. Prior to joining industry, he has worked as Joint Executive Director for Pakistan Institute of Medical Sciences (PIMS), Registrar of the Post graduate medical institute PIMS and as Deputy Director General, Ministry of Health Pakistan.

Advances in biotechnology have ensured a world of opportunities for biosimilars to enter the market and serve the needs of patients in a cost-eff ective manner. However, pharmacovigilance and risk management for biosimilars present a significant challenge that arise from their unique characteristics as biologics as well as from their diff erences with the reference innovator products. Traditional PV processes may not incorporate suffi cient provisions to meet the particular requirements for biosimilars. While a biosimilar and its reference drug can show similar effi cacy, it can exhibit a diff erent safety profi le with respect to the nature, seriousness, or incidence of reported Adverse Events (AEs). Th erefore, there is a need to clearly identify the specific product associated with the AE. Hence, product naming is an important consideration for biosimilars traceability. Th epotential for immunogenicity represents an important safety concern with all biologics, including biosimilars. The nature and severity of immunogenic reactions may diff er from those observed for the reference innovator and immunogenicity data from the reference product may not be directly extrapolated to the biosimilar. Given the relatively small number/size of clinical trials required for regulatory approval of biosimilars, full characterization of the immunogenicity profi le of a biosimilar may not be established at the time of regulatory approval. Continued post-marketing surveillance of biosimilars is critical for eff ective risk management. Also, the unique nature of biosimilars requires a labeling approach that combines data on the reference product with data specifi c to the biosimilar due to diff erences in their source materials, manufacturing processes and impurities. Finally, the safety specifi cations in the RMP of a biosimilar should include the identifi ed and potential risks of the reference innovator product as well as risks identified from studies on the specific biosimilar product.