12^th Asian Biologics and Biosimilars Congress August 20-21, 2018 Tokyo, Japan

Tucker holds an MBA with honors from UCLA and a BA with honors from Stanford University. He was one of the Founding Members of ZS’s Biosimilars Vertical

and has led over 30 training sessions across North America and Asia on this topic. He has also advised major biotechnology fi rms on a broad range of sales and

marketing strategy issues related to the biotech industry with an emphasis on oncology and biosimilars. His experience has focused on global quantitative and

qualitative primary market research and forecasting.

When preparing to launch a biosimilar, key distinctions from traditional biologic product launches and increased uncertainty across regulatory, legal and commercial spheres make navigating this landscape especially challenging. It is critical to align incentives of key stakeholders (providers, patients, payers, pharmacists and procurement) as they each can play a critical role in driving/delaying biosimilar uptake. Achieving commercial success in biosimilar’s therefore requires a new approach to understand the market complexity and to engage these stakeholders. Biosimilar developers need to have a strategic plan for forecasting and market research to e ectively maximize the commercial opportunity. Forecasting biosimilar uptake

can be daunting as market events can result in dramatic swings in expected uptake. As a result, a biosimilar forecast should not be an exercise of determining a single share point or uptake curve -rather it should be about understanding the scenarios that could unfold the forecast in each scenario and understanding the key drivers that will determine the success or failure

of a biosimilar. Market research can identify opportunities a manufacturer (innovator or biosimilar) can in uence across stakeholders. Faced with this paradigm shi , manufacturers have struggled to understand the right questions to understand the complexities of the market some they should consider: (1)What are the key drivers and barriers to uptake across stakeholders?

(2) What levers are most successful at encouraging biosimilar adoption? (3)What archetype markets are most appropriate to use as analogs? (4) How can biosimilars di erentiate themselves when clinical di erentiation is not possible? (5) What are the most successful contract pricing strategies in a market with biosimilar competition? These questions are critical to address

through tailored research techniques and modeling to e ectively map the interplay of the incentives of each stakeholder type.

Osama Ibrahim is a highly-experienced Principal Research Scientist with particular expertise in the fi eld of microbiology, molecular biology, food safety, and bioprocessing for both pharmaceutical and food ingredients. He is knowledgeable in microbial testing, microbial screening, culture improvement; molecular biology and fermentation research for antibiotics, enzymes, therapeutic proteins, organic acids and food fl avors; Biochemistry for metabolic pathways and enzymes kinetics, enzymes immobilization, bioconversion, and Analytical Biochemistry. Dr. Ibrahim was external research liaison for Kraft Foods with Universities for research projects related to molecular biology and microbial screening and holds three bioprocessing patents. In January 2005, he accepted an early retirement offer from

Kraft Foods and in the same year he formed his own biotechnology company providing technical and marketing consultation for new startup biotechnology and food companies. Dr. Ibrahim received his B.S. in Biochemistry with honor and two M.S. degrees in Microbial physiology/ fermentation and in Applied Microbiology. He received his Ph.D in Basic Medical Science (Microbiology, Immunology and Molecular biology) from New York Medical College. His research dissertation was on the construction of plasmid for the expression of a fusion protein of VEGF121/ Shiga-like toxin as a therapeutic protein for targeting angiogenesis (cancer treatment). Since 1979 he is a member of American Chemical Society, American Society of Microbiology, and Society of Industrial Microbiology.

Angiogenesis is a highly controlled process of growing new blood vessels under normal circumstances. However, in a large number of pathologies, such as solid tumor growth, angiogenesis is a crucial component of the disease process. Therefore, inhibitors of angiogenesis are being investigated as potential therapeutics for tumor growth. During angiogenesis endothelial cells of existing blood vessels undergo a complex process of reshaping, migration, growth, and organizing into new vessels. Vascular Endothelial Growth Factor (VEGF) is a central mediator of this process and acts via receptors whose

expression is restricted almost exclusively to endothelial cells. Because of its selectivity, VEGF represents a unique vehicle for delivery of inhibitors of angiogenesis to endothelial cells. Among potential inhibitors of angiogenesis, the shiga-like toxin-1 (SLT-I) produced by E. coli O157:H7 has the advantage that endothelial cells appear to be particularly sensitive to its action. The hypothesis that combining an SLT-I toxin with VEGF as a delivery vehicle would serve as a highly selective and active inhibitor of angiogenesis. To this end, fusion proteins containing VEGF121 and two forms of shiga-like toxin-I (SLT-I) were developed and tested in vitro for activities that have the potential to inhibit angiogenesis in vivo. Plasmids encoding the fusion proteins VEGF121/A1 containing the catalytically active fragment of the SLT-I A subunit and VEGF121/A containing the full length A subunit of SLT-I were constructed in pET-29a and pET-32a systems. Escherichia coli BL21 (DE3) pLysS bacteria were transformed with the plasmid constructs for the expression of these two fusion proteins. Both puri ed fusion proteins inhibited the translation of luciferase mRNA as a reporter gene in vitro translation system, indicating that both fusion proteins retain the N-glycosidase activity of SLT-I. However, only VEGF121/A1 fusion proteins displayed the ability to induce

auto-phosphorylation of the VEGF receptor KDR/FLK-1 and displayed a strong, selective growth inhibition of cultured cells expressing KDR/FLK-1 receptors. These results indicated that VEGF/SLT fusion proteins are promising therapeutic agents that can be developed into powerful and selective inhibitors of angiogenesis.

Divya Chadha Manek is the Head of Business Development (Commercial) for the National Institute for Health Research (NIHR) Clinical Research Network (CRN)- the clinical research delivery arm of the NHS. Her role is to establish new and maintain existing strategic relationships with global and UK life sciences companies. She also leads on ensuring that the clinical research network is abreast of new study delivery innovations to ensure that the organization is evolving to service life sciences industry requirements.

Uptake and acceptance of biosimilar medicines in the UK is accelerating and will continue to do so as the NHS (National Health Service) has recently introduced a new commissioning framework for biologic and biosimilar medicines. But there is still work to do to optimize the potential cost-saving bene ts of biosimilar throughout the NHS. This presentation describes how unique challenges in the UK to the delivery of biosimilar clinical trials have been identi ed and overcome. It demonstrates how our biosimilar research delivery strategy was put into practice and will use case study examples and project outputs to illustrate the results. Finally, it will showcase the UK’s ongoing campaign which continues to drive changes in attitudes, appetite and acceptance for biosimilars in the UK National Health Service.

Pankaj S Chaudhari is a Manager in Biotech Division of Ipca Laboratories Ltd., Mumbai. He is a Bioprocess Engineer with more than 10 years of experience in Bioprocess Development R&D, process scale up in GMP and Global regulatory submissions of biosimilars. In Ipca, he actively participates as a Regulatory CMC

team by contributing to the regulatory strategy, identifying the critical issues during product development. He was a key member in success of biosimilar in Europe, Canada, India and ROW market. He has experience in coordinating with Indian as well as international regulatory agencies for biosimilar registrations.

The global biosimilar market is growing rapidly as patents on blockbuster biologic drugs expire. Biologics are among the highest-cost treatments on the global market today, which implies the need for low-cost alternatives. In emerging markets, biosimilars already o er more a ordable prices, which are not only attractive, but indispensable to economies where expensive treatments are not  nancially feasible. Biosimilars have been approved in Europe for more than 10 years. While only recently launched in the United States, biosimilars have enormous potential to save money for the overall healthcare industry and patients. Selection of reference standard is the major challenge in biosimilar development. The country whose manufacturer target is required bridging studies between local and foreign versions of an originator biologic add significant cant costs to biosimilar development yet provide no patient has benefit or scientific rigor for the local approval of the biosimilar. Other challenges are the competitive landscape, frequent changes and uncertainty in approval processes at regulatory authorities, a current pricing system that reflects cost rather than value, the activities to be performed versus outsourced, high technology uncertainty over long time frames and the need for both signi cant complementary assets and substantial financing, naming issue, interchangeability and extrapolation of di erent indications. Regulations are still evolving globally hence meeting regulatory obligations and compliance is difficult in biosimilar development unless company adopts integrated strategic plan at the start of development having opinion from experts and stepwise input on regulatory and market to meet obligations. Strategies and path forward to success are: (1) Take position on fundamental regulatory issues and develop global strategy; (2) Optimizing global, regional and cross-functional collaboration; (3) Conduct in-depth pricing analysis and formulate regional strategy; (4) Develop patient education series/campaign. Patients must be educated so that they are willing to switch to a newer product that may not o er the same level of patient support; (5) Choose markets with limited or no access to innovator biologic; (6) Select country/region where regulatory agencies are willing to work with companies to bring biosimilar market to reduce healthcare cost; (7) Prioritize market entry based on changes in regulatory approval process and commercial viability. Based on scientific cally robust, simpli ed conditions, the selection of a comparator version of the originator for biosimilar development can be established which would be used as a global reference standard global biosimilar pipeline and market prospective are addressing production complexities through risk management and quality by design.

Kurt R Karst provides regulatory counsel to pharmaceutical manufacturers on Hatch-Waxman patent and exclusivity, drug development, pediatric testing and

orphan drugs. He helps clients develop strategies for product lifecycle management, obtaining approval, managing post-marketing issues and defi ning periods of exclusivity. He as the Co-Founder and primary author of Hyman, Phelps & McNamara’s FDA law blog, often leads the response to new rules and regulations, sharing his interpretation with the broader legal community. He has also co-authored and contributed to several text books, including Generic and Innovator Drugs: A Guide to FDA Approval Requirements; Pharmaceutical, Biotechnology and Chemical Inventions; Fundamentals of US Regulatory Affairs; and FDLI’s Drug and Biologic Approvals: The Complete Guide for Small Businesses-FDA Financial Assistance and Incentives.

The biosimilars industry in the United States is still a nascent one. In 2015, FDA approved the  rst biosimilar biological product and several other approvals have followed, with more applications for other biosimilar biological products pending at FDA. Although FDA and industry are tackling the scienti c and data requirements for FDA to approve a so-called “Sectionn 351(k) application” for a biosimilar biological product, legal issues abound. Whether it is the requirements or the contours of the “Patent Dance” for resolving patent disputes between biosimilars applicants and reference product sponsors, the availability and the scope of 12-year reference product exclusivity or the appropriate naming convention for biological products, each issue is critical to the success of biosimilars in the United States and to the future of the industry. And with fast-paced litigation, the landscape for biosimilars seems to change on a monthly or weekly basis. This session will explore the ins and outs of current disputes involving the metes and bounds of the patent dance, non-patent exclusivity, naming and more; explain what each dispute might mean for the future world of United States biosimilars

Rajiv Dua is currently Site ATS Head - Corporate Quality and Compliance at Sun Pharmaceuticals Ltd., India. He is responsible for plant-analytical technical services with respect to analytical troubleshoot and compliance, involved in multiple projects, coordinating in tech-transfer, pharmacopeial evaluation, validations, investigation, exploratory and comparative studies. He holds Masters in Biochemistry and BSc (Chemistry major) from University of Pune, India, as well as holds two Post Graduate Diplomas in Operation Management and Hospital/Healthcare Management respectively. He has over 9 years of experience in Pharma/ Biosimilar industry. His professional life started with Intas Biopharmaceuticals R&D unit and joined Lupin Biotech and later joined USV limited as a part Corporate Quality Assurance. He has co-authored research and review articles related to biosimilars and also hold a formulation patent.

To ensure product safety and efficacy, protein therapeutics must meet de ned quality characteristics after manufacture as well at the end of their designated shelf lives. Many physical and chemical factors can a ect the quality and stability of biopharmaceutical products, particularly during long-term storage in a container-closure system likely to be subject to variations in temperature, light and agitation with shipping and handling. Compared with traditional chemical pharmaceuticals, proteins are considerably larger molecular entities with inherent physiochemical complexities. Proteins are typically sensitive to slight changes in solution chemistry. They remain compositionally and conformationally stable only within a relatively narrow range of pH and osmolarity and many require additionally supportive formulation components to remain in solution, particularly over time. Even lyophilized protein products experience degradation. Advances in analytical chemistry have identi ed many degradation pathways that can occur in recombinant protein therapeutics over time. These pathways generate either chemical or physical instability. Signi cance of Stability studies with reference to cold chain management, types of stability studies and there trend analysis with case studies and temperature excursion studies and its signi cance with case studies will be discussed