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LET SCIENCE LEAD: A Special Online Forum on COVID-19

/* custom css */ .td_uid_1_5e52f869a2d15_rand { min-height: 0; } “The only way we will defeat this outbreak is for all countries to work together in a spirit of solidarity and cooperation. We are all in this together, and we can only stop it together.” – Tedros Adhanom Ghebreyesus, Director General, World Health Organization LET SCIENCE LEAD: A Special Online Forum on COVID-19 5-8pm PST Feb 25 | 8-11pm EST Feb 25 | 9am-12pm China time Feb 26 AGENDA (duration: 5PM-8PM PST Feb 25) 5:00 – 5:04 OPENING Hui Cai, Forum Chair, Vice President and Head of Content Division, WuXi AppTec 5:04 – 5:05 A Moment of Silence for the Lives Lost to COVID-19 5:05 – 5:50 Towards Faster and More Accurate Diagnosis Feng Zhang, Professor, MIT McGovern Institute and Broad Institute Charles Chiu, Professor, Laboratory Medicine and Medicine / Infectious Diseases; Director, UCSF-Abbott Viral Diagnostics and Discovery Center Victor Shi, CEO, Adicon Clinical Laboratories; General Partner, Serica Partners Moderated by Nick Naclerio, Founding Partner, Illumina Ventures 5:50 – 6:40 Expediting Therapeutic Intervention George Scangos, CEO, Vir Biotechnology Tomas Cihlar, Vice President of Virology, Gilead Sciences David Ho, Director of Aaron Diamond AIDS Research Center; Professor of Medicine, Columbia University Vagelos College of Physicians and Surgeons Chris Chen, CEO of WuXi Biologics; Chairman, WuXi Vaccines Moderated by Zhi Hong, Co-founder and CEO, Brii Biosciences 6:40 – 7:40 Can We Move Quickly on Vaccines? Gregory Poland, Professor and Director of Mayo Clinic Vaccine Research Group; Editor-in-Chief, VACCINE Johan Van Hoof, Global Therapeutic Area Head IDV, Vaccines, Janssen Pharmaceuticals R&D and Managing Director, Janssen Vaccines & Prevention, B.V. Joseph Kim, President and CEO, Inovio Pharmaceuticals Xuefeng Yu, Chairman and CEO, CanSino Biologics Mark Esser, Vice President of Microbial Sciences, AstraZeneca Moderated by Steve Yang, EVP and CBO, WuXi AppTec 7:40 – 8:00 How to Improve Readiness for the Next Epidemic? Arthur Reingold, Division Head of Epidemiology and Biostatistics, UC Berkeley School of Public Health Moderated by Rich Soll, Senior Advisor of Strategic Initiatives and Head of Boston Office, WuXi AppTec 8:00 CLOSING Click REGISTER to register now. OPENING Hui Cai Forum Chair, VP and Head of Content Division, WuXi AppTec Dr. Hui Cai joined WuXi AppTec in 2009 as Vice President of Business Development, and is currently Vice President and Head of Content Division. Prior to WuXi, Dr. Cai spent 10 years at Johnson & Johnson Pharmaceutical Research and Development leading multiple drug discovery programs in the therapeutic areas of inflammation and autoimmune diseases. She is a co-author and co-inventor to over 50 scientific publications and issued or pending patents. Dr. Cai is a Councilor of the American Chemical Society (ACS), a member of BayHelix, and a member of the UCSD Alumni Board. In her past capacity, she served as a Commissioner at the City of San Diego Science and Technology Commission, Chair of SABPA, and President of SDCA. Dr. Cai received her BS and MS in Chemistry from Peking University, PhD from The Scripps Research Institute, and MBA from UCSD Rady School of Management as a DLA Piper – Athena Scholar. Towards Faster and More Accurate Diagnosis Feng Zhang Investigator, Howard Hughes Medical Institute Core Member, Broad Institute of MIT and Harvard Feng Zhang is a molecular biologist focused on improving human health. He played an integral role in the development of two revolutionary technologies, optogenetics and CRISPR-Cas systems, including pioneering the use of Cas9 for genome editing and discovering CRISPR-Cas12 and Cas13 systems and developing them for therapeutic and diagnostics applications. Zhang’s seminal work provided the foundation for CRISPR-based medicines, and his discoveries continue to fuel the clinical translation of CRISPR technologies. Additionally, he developed the diagnostic platform, SHERLOCK, which is being leveraged to help monitor infectious diseases, including the recent coronavirus outbreak. Zhang is a core member of the Broad Institute, an Investigator at the McGovern Institute for Brain Research, the James and Patricia Poitras Professor of Neuroscience at MIT, and a Howard Hughes Medical Investigator. He is also a member of both the National Academy of Sciences and the American Academy of Arts and Sciences. Charles Chiu Professor, Laboratory Medicine and Medicine / Infectious Diseases; Director, UCSF-Abbott Viral Diagnostics and Discovery Center Charles Chiu, M.D./Ph.D. is Professor of Laboratory Medicine and Medicine, Division of Infectious Diseases at University of California, San Francisco, Director of the UCSF-Abbott Viral Diagnostics and Discovery Center (VDDC), and Associate Director of the UCSF Clinical Microbiology Laboratory. Chiu currently leads a translational research laboratory focused on next-generation sequencing assay development for infectious disease diagnostics and investigation of emerging pathogens, including Borrelia burgdorferi (Lyme disease), enterovirus D68 in acute flaccid myelitis, Zika virus, and the 2019 novel SARS-CoV-2 coronavirus. He is also developing new technologies such as nanopore sequencing and RNA-Seq transcriptome profiling to develop predictive models using machine learning for diagnosis of infections based on a patient’s host response. Chiu’s work is also supported by funding from the National Institutes of Health (NIH), Abbott Laboratories, Department of Defense, philanthropic grants (Charles and Helen Schwab and Steven and Alexandra Cohen Foundations), and the California Initiative to Advance Precision Medicine. Dr. Chiu has authored more than 100 peer-reviewed publications, holds over 15 patents and patent applications, and serves on the scientific advisory board for Mammoth Biosciences, Inc. Victor Shi CEO, Adicon Clinical Laboratories; General Partner, Serica Partners Dr. Victor Shi is CEO of Adicon Clinical Laboratories, a leading independent clinical laboratory in China. Adicon operates more than 22 clinical laboratories across China with 5,000 employees and serves over 12,000 hospitals nationwide. Dr. Shi is General Partner of Serica Partners, a venture capital fund focused on medtech investment. Previously he was President Asia Pacific of QIAGEN, a NASDAQ- and Frankfurt-listed leading company of In-Vitro diagnostics and life science research tools. He held senior positions at Aura Partners, Bridge Pharmaceuticals, Genospectra, and Pappas Ventures. He was also a faculty member at National University of Singapore, School of Medicine and a cancer research scientist at Merck & Co. Dr. Shi is a Founding Directors of Bayhelix Group, a global association of Chinese life science business executives, and was elected Chairman from 2018 to 2019. He also serves on the Hong Kong Stock Exchange Biotech Advisory Committee. Meanwhile, Dr. Shi is a council member of Shoulder Action, a charitable NGO that is dedicated to reading skill development in rural China. Nick Naclerio Founding Partner, Illumina Ventures Nick is the Founding Partner of Illumina Ventures. His passion is building companies at the intersection of technology and human health. Prior to joining the fund, he served as SVP, Corporate & Venture Development for Illumina where he was responsible for strategic planning, business development, licensing, venture investing and acquisitions. In six years, Nick and his team completed ten acquisitions, more than a dozen venture investments, and a multitude of other transactions including the formation of Helix and GRAIL and the creation of a global NIPT patent pool. Nick also served as the founding General Manager of Illumina’s Enterprise Informatics Business Unit. Before joining Illumina, Nick co-founded and was the Executive Chairman of the diagnostics company Quanterix. Previously he was Executive Chairman of True Materials and CEO of ParAllele BioScience, life science tools firms that were both acquired by Affymetrix. Nick got his start in venture investing at Motorola where he led the life science investment team and served on the boards of the SNP Consortium, Genometrix, Clinical Microsensors, and Orchid Bioscience. He founded and led Motorola Life Sciences, an early microarray company that was acquired by GE. Previously he held leadership positions at DARPA and served on the board of SEMATCH. Nick is chairman of Serimmune and Stilla, and also serves on the boards of Baebies, Cradle, DNA Script, and Genome Medical. Nick received a B.S. in Engineering from Duke University, was a Winston Churchill Scholar at Cambridge University, and earned a Ph.D. in Electrical Engineering from the University of Maryland. Expediting Therapeutic Intervention George Scangos CEO, Vir Biotechnology George Scangos, Ph.D., has served as President and Chief Executive Officer of Vir Biotechnology and as a member of the board of directors since January 2017. From July 2010 to December 2016, Dr. Scangos served as Chief Executive Officer and as a member of the board of directors of Biogen Inc., a publicly traded biopharmaceutical company focused on the treatment of serious diseases. From October 1996 to July 2010, Dr. Scangos served as President and Chief Executive Officer at Exelixis, Inc., a drug discovery and development company. From 1993 to 1996, Dr. Scangos served as President of Bayer Biotechnology, where he was responsible for research, business development, process development, manufacturing, engineering and quality assurance of Bayer Biotechnology’s biological products. Before joining Bayer Biotechnology in 1987, Dr. Scangos was a Professor of Biology at Johns Hopkins University. Dr. Scangos has served as a member of the board of directors of various publicly traded companies, including: Exelixis, Inc., since 1996; Agilent Technologies, Inc., a life sciences, diagnostics and applied chemical analysis company, since 2014; and Anadys Pharmaceuticals, Inc., a biopharmaceutical company, from 2003 to 2010. Dr. Scangos served as Chair of PhRMA in 2016, and as the Chair of the California Healthcare Institute in 2010. He was a member of the board of directors of the Global Alliance for TB Drug Development from 2006 until 2010. Dr. Scangos currently serves on the Board of Trustees of Cornell University and the Board of Overseers of the University of California, San Francisco. Dr. Scangos received his B.A. in Biology from Cornell University and a Ph.D. in Microbiology from the University of Massachusetts. Tomas Cihlar Vice President of Virology, Gilead Sciences Tomas Cihlar, PhD is a Vice President of Virology at Gilead Sciences with responsibility for coordinating preclinical antiviral research including projects on treatment, prevention, and cure of HIV, chronic hepatitis B, respiratory viruses, and emerging viruses. Dr. Cihlar joined Gilead after receiving his PhD in Biochemistry from the Institute of Organic Chemistry and Biochemistry in Prague, Czechia. Over the years, he has contributed to the development and regulatory approval of multiple Gilead’s antiviral products including all Gilead HIV drugs and their combinations. Together with his colleagues, he established research programs focused on long-acting antiretrovirals, in addition to a portfolio of projects aiming at the cure of HIV and hepatitis B, and multiple programs for the treatment of respiratory and emerging/neglected viruses. Dr. Cihlar has served as a project leader for Gilead’s program on remdesivir, a broad-spectrum antiviral agent in clinical testing against Ebola infection and more recently against the COVID-19. In past, Dr. Cihlar served on the Board of Directors of the International Society of Antiviral Research and he is currently on the Board of Directors for Global Virus Network. David Ho Director of Aaron Diamond AIDS Research Center; Professor of Medicine, Columbia University Vagelos College of Physicians and Surgeons David D. Ho is the Founding Scientific Director of the Aaron Diamond AIDS Research Center and the Clyde and Helen Wu Professor of Medicine at Columbia University Irving Medical Center. He received his degrees from California Institute of Technology and Harvard Medical School. Dr. Ho has been at the forefront of AIDS research for 39 years, publishing over 400 papers. His elegant studies unraveled the dynamic nature of HIV replication in vivo and revolutionized our basic understanding of this horrific disease. This knowledge led him to champion combination antiretroviral therapy that resulted in unprecedented control of HIV in patients. An automatic death sentence has been transformed into a manageable disease, and over 25 million worldwide are currently on such therapy. Dr. Ho’s research team is now devoting considerable efforts on vaccine and antibody research in order to halt or slow the spread of the AIDS epidemic. He worked on SARS and is now devoted time to develop drugs and antibodies against the new coronavirus. Dr. Ho has received fourteen honorary doctorates. He was named Time Magazine’s Man of the Year in 1996 and the recipient of a Presidential Medal from Bill Clinton in 2001. He was also inducted into the California Hall of Fame. Dr. Ho was also recognized by the Kingdom of Thailand with the Prince Mahidol Award in Medicine, and given the Distinguished Alumni Award by Caltech. He is a member of the US National Academy of Medicine as well as the Chinese Academy of Engineering. Chris Chen CEO, WuXi Biologics; Chairman, WuXi Vaccines Dr. Chris Chen is currently Chief Executive Officer at WuXi Biologics, a Hong Kong listed company with market cap surpassing HK$100 billion. At WuXi Biologics, he has built a world-class open-access integrated biologics discovery, development and manufacturing platform enabling full spectrum of companies ranging from 2-employee virtual companies to Top 20 global large pharmaceutical companies. WuXi Biologics has transformed the global biotech industry by enabling entrepreneurs to build successful biotech companies with no need of investing in infrastructure for people, labs or manufacturing. Under his leadership, WuXi Biologics has assembled one of the largest biologics teams with nearly 6000 employees enabling 60 IND programs and 3 BLA programs per year. WuXi Biologics has also pioneered disposable-bioreactor based state-of-the-art commercial manufacturing facility and built the first 30,000L bioreactor capacity in the world using disposables. The leading globally platform providing end-to-end solutions for biologics developed by WuXi Biologics is now serving more than 200 companies in China, US, Europe, Japan, South Korea, and Singapore. As the first Chinese company producing biologics for clinical trials in the US and Europe, WuXi Biologics is also the first biologics company in China to pass both the U.S. FDA and EMA inspection, and have cGMP biologics manufacturing facility in China approved by the U.S. FDA for commercial biologics products. Zhi Hong Co-founder and CEO, Brii Biosciences Dr. Zhi Hong is the Co-founder and Chief Executive Officer of Brii Biosciences. Prior to starting Brii, Dr. Hong was the Senior Vice President and Head of GSK’s Infectious Diseases Therapy Area Unit. He was widely credited as the key architect of GSK’s comeback and success in HIV & Infectious Diseases Research and development. Under his leadership, GSK’s ViiV Healthcare HIV franchise was revitalized with the approval of Tivicay & Triumeq. Dr. Hong is a public health advocate who has helped establish multiple public-private partnerships with US and EU governments addressing pandemics and bioterrorism threats. He created GSK’s Institute for Infectious Diseases and Public Health in Beijing, China. Dr. Hong also started Ardea Biosciences (later acquired by AstraZeneca). Dr. Hong has 28 years of experience in pharma/biotech R&D and brought many drugs to successful approvals. He had served as a board member of Anacor Pharmaceuticals (acquired by Pfizer) and ViiV Healthcare, and also chaired the board of Qura Therapeutics. Can We Move Quickly on Vaccines? Gregory Poland Professor and Director of Mayo Clinic Vaccine Research Group; Editor-in-Chief, VACCINE Gregory A. Poland, M.D., is the director of Mayo Clinic’s Vaccine Research Group — a state-of-the-art research group and laboratory that seeks to understand genetic drivers of viral vaccine response and application of systems biology approaches to the generation of immunity, as well as the development of novel vaccines important to public health. The Poland lab has developed the field of viral vaccine immunogenetics, the immune response network theory, and the field of vaccinomics and adversomics. Dr. Poland holds the academic rank of professor of medicine and infectious diseases and molecular pharmacology and experimental therapeutics. He also serves as the president of the Edward Jenner Vaccine Society and is the Editor-in-Chief for the journal Vaccine. Dr. Poland has chaired or been a member of every Federal committee involved in vaccine decision-making, including the NVAC, VRBAC, and the ACIP. Dr. Poland advocated for and successfully persuaded the CDC to recommend annual influenza vaccine for all Americans age 6 months and older, and was the initial and primary advocate for requiring influenza immunization for all health care providers. Dr. Poland was the 2013 recipient of the Mayo Distinguished Investigator award by the Mayo Board of Trustees, and the 2012 recipient of the Mayo Clinic Department of Medicine Lifetime Research Achievement Award. In 2012, Dr. Poland was named in the top 25 list of vaccine influencers in the world. In February 2013, he was nominated for membership in the Institute of Medicine (IOM). In addition, he recently received an NIH MERIT Award, an honor accorded to less than 5% of the nation’s NIH-funded investigators. Dr. Poland was awarded the Secretary of Defense Award for Excellence in December 2008. In 2008, he was named a Master of the American College of Physicians. Dr. Poland received the Hsu prize in International Infectious Disease Epidemiology in 2007, and the Charles Merieux Lifetime Achievement Award in Vaccinology from the National Foundation for Infectious Diseases in May 2006. In December 2006, Dr. Poland was elected President of the Defense Health Board, serving two terms. In 2005 he was awarded an honorary Doctor of Humane Letters by Illinois Wesleyan University, his alma mater. He was appointed as the Mary Lowell Leary Professor in Medicine (the highest academic distinction for a faculty member) by Mayo Clinic’s Board of Trustees in 2004. In May 2003, he was awarded the Secretary of Defense Medal for Outstanding Public Service. Dr. Poland served on the Infectious Diseases Society of America (IDSA) Taskforce on Pandemic Influenza, and currently chairs the American College of Physician’s Adult Immunization Advisory Board. Dr. Poland received the inaugural Gold Medal from the Spanish Vaccinology Society in 2001. He is the immediate past president of the Department of Defense’s Defense Health Board and the Armed Forces Epidemiological Board. Dr. Poland received his medical degree from the Southern Illinois University School of Medicine in Springfield, Illinois, and completed his residency and advanced post-graduate work at the University of Minnesota/Abbott-Northwestern Hospital, Minneapolis, MN. He has published over 500 professional papers, book chapters, and editorials. He is actively and regularly sought after by both scientific and lay print, TV, and radio media for his views on vaccine policy. Dr. Poland is a popular conference and seminar speaker on the topics of vaccines, scientific literacy, vaccine hesitancy, scientific writing and publication, and biodefense. Johan Van Hoof Global Therapeutic Area Head IDV, Vaccines, Janssen Pharmaceuticals R&D and Managing Director, Janssen Vaccines & Prevention, B.V. Johan Van Hoof, M.D., is the Global Therapeutic Area Head, IDV Vaccines, Janssen R&D and Managing Director, Janssen Vaccines & Prevention, B.V. He is a member of the Senior R&D Leadership Team, leading Research & Development at Janssen Vaccines, drawing on his extensive experience with Johnson & Johnson and the broader vaccine industry. He joined the Johnson & Johnson Family of Companies in April 2005 as Vice President, Data Management and Early Clinical Development. Following roles as Chief Operating Officer (COO) of Johnson & Johnson Pharmaceutical Research, LLC, and Head of the Global Development Organization, Johan was appointed Global Therapeutic Area Head for Infectious Diseases & Vaccines in 2010. Since 2011, he has been overseeing research & development at Janssen Vaccines as Managing Director. In this role, Johan is tirelessly leading his world-class team to develop transformational vaccines which will prevent, intercept, treat and cure life-threatening infectious diseases. Johan continues to advance Janssen’s efforts in this area, utilizing cutting-edge technology and strategic collaborations to drive research and development forward. Prior to joining the Johnson & Johnson Family of Companies, Johan acquired more than 20 years of experience in the vaccine industry, having worked with Pasteur Mérieux Connaught, Chiron Vaccines and GlaxoSmithKline (GSK) Biologicals. During this period, he held leadership roles with increasing responsibilities, including Head, New Product Development at GSK Biologicals. Johan received his medical degree (cum laude) from the University of Antwerp, Belgium, in the Department of Anatomy and Embryology at Rijksuniversitair Centrum Antwerpen, Belgium. He studied business management at Krauthammer International School and the International Executive Programme INSEAD, Fontainebleau, France. Joseph Kim President and CEO, Inovio Pharmaceuticals Dr. J. Joseph Kim has served as president and chief executive of INOVIO since 2009, leading the company’s transformation into a successful late-stage biotech focused on developing breakthrough DNA medicines that treat, cure, and protect people from diseases associated with HPV, cancer, and infectious diseases. An immunologist by training, Dr. Kim has a deep understanding of the complexities of medical science’s greatest unsolved challenges. He is committed to improving the lives of patients, and this passion permeates the company. Dr. Kim has published more than 100 peer-reviewed scientific papers, holds numerous patents, and sits on several scientific journal editorial boards. Most recently, he was recognized as a Young Global Leader by the World Economic Forum and a Health Innovators Fellow at The Aspen Institute. He previously co-founded VGX Pharmaceuticals, an immunotherapeutic company that he led for nine years before merging VGX with Inovio Biomedical in 2009 to form INOVIO. Dr. Kim earned two B.S. degrees in Chemical Engineering and Economics from the Massachusetts Institute of Technology, a Ph.D. in Immunology and an M.S. in Engineering from the University Pennsylvania, and an M.B.A. in Finance from the Wharton School. Xuefeng Yu Chairman and CEO, CanSino Biologics Dr. Xuefeng Yu was trained as a Microbiologist and obtained PhD from McGill University. He is one of the co-founders of CanSino Biologics Inc., a Tianjin, China based biotech company dedicated for new vaccine development and commercialization. As the Chairman and CEO, he is responsible for the overall strategic development and operation management. Under his leadership, CanSino Biologics has experienced significant growth. He was awarded by MOST as “Leader of Innovation and entrepreneurship” in 2012. Dr. Yu has over 20 years’ biotech industry experiences. Prior founding CanSino Biologics, he had held various leadership positions within Sanofi Pasteur, including director, corporate platform leader for Bacterial Vaccine Upstream Development, director for North America Upstream Bioprocess R&D. During his tenure in Sanofi Pasteur, Dr. Yu had played key roles in multiple new vaccines process development, GMP production as well as regulatory submission. He also had played leadership role in new GMP facility validation and technology transfer. Mark Esser Vice President of Microbial Sciences, AstraZeneca Dr. Esser is Vice President of Microbial Sciences at AstraZeneca. In this role he is accountable for AstraZeneca’s overall drug discovery, translational research and clinical development of innovative medicines targeting the microbiome and in vivo expressed biologics. He is experienced in discovery through registrational and post-marketing effectiveness studies and has contributed to 4 different biologics licensing agreements in the vaccine and infectious disease arena. He has several patents and is widely recognized for his contributions to vaccine research and global health with over 75 peer-reviewed publications. Dr. Esser received his B.S. in biochemistry from Case Western Reserve University, his doctorate in microbiology and immunology from University of Virginia and did his postdoctoral fellowship at the AIDS vaccine program at the NIH. Steve Yang EVP and CBO, WuXi AppTec Dr. Steve Yang is Executive Vice President and Chief Business Officer of WuXi AppTec. He is also WuXi AppTec’ s Head of Research Service Division and Head of Lab Testing Division. His responsibilities include management of multiple business units and commercial operation. WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries worldwide to advance discoveries and deliver groundbreaking treatments to patients. Dr. Yang is a pharmaceutical industry leader recognized for building R&D and service capabilities, delivering research and early development portfolios of drug candidates, and establishing R&D partnerships in US, Europe, China and other Asian and emerging markets. Before joining WuXi AppTec, Dr. Yang was Vice President and Head of Asia and Emerging Markets iMed at AstraZeneca, based in Shanghai. Previously, Dr. Yang served as Vice President and Head of Asia R&D at Pfizer based in Shanghai, and as Executive Director and head of Pfizer’s global R&D strategic management group based in the United States. Dr. Yang received his PhD in Pharmaceutical Chemistry from the University of California, San Francisco. He started his undergraduate study in Fudan University, China and completed his BS Summa Cum Laude from Michigan Technological University. He co-founded the BayHelix Group, a non-profit global professional organization of Chinese life science business leaders, and served as the chairman of the board for two terms. How to Improve Readiness for the Next Epidemic? Arthur Reingold Division Head of Epidemiology and Biostatistics, UC Berkeley School of Public Health Professor Arthur L. Reingold, MD, is Division Head of Epidemiology and Biostatistics at the University of California, Berkeley, School of Public Health. Professor Reingold has worked for over forty years on the prevention and control of infectious diseases both at the national level, including eight years at the US Centers for Disease Control and Prevention, as well as with numerous developing countries around the world. He has directed or co-directed the CDC-funded California Emerging Infections Program since its inception in 1994. His research interests include vaccine-preventable diseases, respiratory infections including influenza, bacterial meningitis, disease surveillance, and outbreak detection and response. He has published almost 300 original research papers on these subjects and teaches a wide variety of courses on related topics at the University of California, Berkeley and at numerous other universities around the world. Among other honors, he was elected to the Institute of Medicine of the National Academy of Sciences in 2003. Rich Soll Senior Advisor of Strategic Initiatives and Head of Boston Office, WuXi AppTec Dr. Richard Soll is presently Senior Advisor, Strategic Initiatives for the Research Service Division at WuXi AppTec and Head of the WuXi office in Boston, Massachusetts. He has held various leadership roles at WuXi as Senior Vice President including head of the medicinal chemistry unit known as the International Discovery Service Unit, business development, and corporate alliances. Dr. Soll’s contributions led to the discovery of the HCV NS5A inhibitor elbasvir (a component of Zepatier®) in the Merck-WuXi partnership, the JAK2 inhibitor fedratinib at TargeGen which formed the basis of the $7B partnership between Celgene and Impact Biomedicines, and more than 10 other clinical stage drugs throughout his career. Dr. Soll is currently a board member at Simcha Therapeutics, an board observer at the Accelerator Life Science Parnters, and an advisory board member with the Blavatnik Center for Drug Discovery at Tel Aviv University, the Children’s Tumor Foundation, and the Pistoia Alliance. Dr. Soll was CSO / VP of R&D at TargeGen and was VP of Chemistry at 3-Dimensional Pharmaceuticals. He started his career at Ayerst Research Labs and was trained as a synthetic chemist at Dartmouth and Harvard. Brought to you by:   /* custom css */ .td_uid_5_5e52f869a5ad3_rand { min-height: 0; } /* custom css */ .td_uid_8_5e52f869a5e11_rand { min-height: 0; } /* custom css */ .td_uid_11_5e52f869a6d18_rand { min-height: 0; } /* custom css */ .td_uid_14_5e52f869a7b88_rand { min-height: 0; } /* custom css */ .td_uid_17_5e52f869a8942_rand { min-height: 0; }

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Amicus Therapeutics: A Patient-First Approach to Treating Rare Diseases

Rare diseases have long posed a dual challenge. First, since there are relatively few patients by definition, they are not the highest priority for most drug makers. Second, many of them have proven quite difficult to effectively treat, let alone cure. The passage of the Orphan Drug Act in 1984 succeeded in spurring greater interest in the field. Amicus Therapeutics is one of the companies focusing on developing drugs for these hard to treat illnesses, one with a unique beginning. Amicus was founded in 2002 and went public in 2007. Leading the company is founder and CEO John Crowley, who has a very personal stake in treating rare diseases. In the middle of an early, successful career at Bristol-Myers, Crowley’s children received a terrible diagnosis: Pompe Disease, a devastating neuromuscular disease. At that time, there was no treatment, so Crowley quit his job, co-founded his own company Novazyme, and then raced against the clock to find a way to help his children. In the end, Novazyme and later Genzyme worked to develop a successful enzyme replacement therapy that saved the Crowley children’s lives. This real-life story has landed the Crowley family on the front page of The Wall Street Journal and served as the basis of the major motion picture “Extraordinary Measures,” starring Harrison Ford. In addition to his highly acclaimed career in the biopharmaceutical industry, Crowley also served as a commissioned Navy Reserve Officer who has served with a special operations team in Afghanistan. He graduated with a B.S. in Foreign Service from Georgetown University, earned a J.D. from the University of Notre Dame Law School, and also completed an M.B.A. from Harvard. Once he’d succeeded in his mission to find a treatment for his kids, Crowley took time to contemplate what to do next. Reflecting on his personal experiences led him to build a new company focused on providing a patient-centered approach to treating rare diseases. This is what gave rise to Amicus Therapeutics, which is named for the Latin word for “friend” to represent the company’s commitment to be the most patient-focused and patient-friendly company in the industry. One key aspect of the culture is for employees to consider and make major decisions from the perspective a patient (or parent of a child) with a rare disease. Although Crowley is optimistic about the current state and future progress of the industry, he identified three main obstacles to treating diseases in a way that serves the best interests of patients. The first is regulation. He praised regulators for moving quickly to work across many facets of treating rare disease, especially regarding incorporating patient voices into the process, but he believes that the regulatory framework has not kept up with the pace of scientific development. The second major concern he has is policy. Specifically, policies that govern patient access to drug companies. Again, he identified the current state as mixed, with some policies (both current and proposed) really ensuring access to patients and others hindering it. “We need to ensure 100% access to all patients in need,” Crowley emphasized. “A number of us have tried to be pretty assertive with our views in terms of what will drive innovation and what’s in the best interests of patients in moving these medicines forward.” However, in his view, there’s still too much that hinders access. The last major concern he has is the biopharmaceutical industry’s commitment to always acting in the best interests of patients. “We have a moral obligation to develop and manufacture the highest quality therapies for patients. We also have the obligation to ensure the broadest access [to needed medicines] possible,” he forcefully stated. He cited this year’s Gallup survey about public perception of various industries and organizations. “For the first time ever this year the biopharmaceutical industry ranked last. We ranked below the federal government and below Big Tobacco,” he said. He believes that the industry needs to improve how it serves patients or else this negative public perception will continue to impede the industry. Shifting his focus from the industry at large to treating rare diseases in particular, Crowley also acknowledged significant challenges even as he maintained his overall positive outlook. Using Pompe Disease as an example, he stated that understanding a disease mechanism does not guarantee the development of a cure. Pompe Disease is an enzyme deficiency resulting in lost function. Replacing lost function is much more difficult in his view. Though there is no cure, Pompe and Fabry now have treatments which Crowley considers an important initial step. “But there are risks and challenges inherent in any small disease population – recruitment of clinical studies for instance.  Even where we do have a first-generation approved therapy, sometimes the harder challenge is to come up with the next generation therapy.” He mentioned that the target for Pompe Disease is particularly tricky. And he cited that in some ways the Orphan Drug Act, while doing a substantial amount of good, has put up huge barriers to second generation therapies on top of the challenge of recruiting study participants. However, he also cited that, despite the challenges, we are truly entering a golden age for medicine and technology. “35 years ago, before the Orphan Drug Act, there were just a handful of approved therapies for rare diseases. Today we have hundreds,” he said. “But it’s still been a tough fight. When we look at some of the results of these approvals in spinal muscular atrophy, in rare eye diseases, I believe we’ve finally turned the corner in gene therapy. When I look at gene therapies, RNA technologies, and also at the promise of a field like gene editing, over the next couple of decades we truly have the chance to change the course of disease and profoundly impact the course of human history to alleviate an enormous amount of suffering. That’s a great, great opportunity for us.” How exactly does Amicus take advantage of this unique turning point? Crowley pointed to Amicus’ patient-centric culture as the key to making the strongest possible scientific and social impact. At the core of this effort is Amicus’ patient advocacy department. “Leading that effort is Jayne Gershkowitz, our chief patient advocate,” Crowley shared. “Her job is to be the voice of patients within the company and (along with the management team) the external face of Amicus to the patient community as well.” Even as the company has grown rapidly, it has stayed true to this commitment. In the nearly fifteen years since its founding, Amicus has grown from five to 600 people across 27 countries while maintaining its patient-centric focus. Indeed, Crowley credited that focus for the company’s success thus far. Amicus has reached the commercial stage with Galafold, which is a precision medicine used to treat Fabry Disease. “Beyond Galafold, in the last year alone we’ve built what is now the largest portfolio of rare disease gene therapies in the industry,” Crowley said. “We still have a very large vision. We decided years ago that at the end of our careers we don’t want people to look back on Amicus and think that we dreamed too small.” It’s a vision driven by the company’s fundamental commitment to patients. Amicus is also currently pursuing a “second generation” treatment for Pompe disease: AT-GAA. “We think it has the potential to become the next standard of care. It is the crown jewel of our portfolio and the only ever second-generation therapy for any lysosomal storage disease to received Breakthrough Therapy Designation,” he stated. AT-GAA is designed to be more highly targeted to muscle cells. This protein with this glycosylation is highly phosphorylated. The mannose 6-phosphate receptor is the uptake mechanism. So, with the higher degree of phosphorylation Amicus has seen much higher penetration into muscles. It is combined with a small molecule to stabilize it in plasma, which appears add some stability and enhanced potency to the protein. Amicus believes that once it’s in the muscle it contributes to the breakdown of the glycogen that’s stored in muscles of Pompe patients. To take this research to the next step Amicus is in the midst of their “PROPEL” study. This phase III study, which is due to complete enrollment by the end of 2019, looks at more than 100 adults living with Pompe Disease. “It is the largest lysosomal disease study ever conducted,” Crowley shared. “We are enrolling more than one hundred patients at more than eighty sites around the world on five continents. It’s also the most expensive study ever done in lysosomal disease field.” As a sign of their commitment to patient welfare, they’re now treating children and, to the best of their ability, meeting requests for expanded access or compassionate use of this still experimental treatment. Being able to produce enough medicine to meet this demand is a challenge. Crowley credits Amicus’ success here (and indeed in many other areas) to excellent collaboration with its partners. “In some areas we needed the expertise and the infrastructure of partnerships, and I think the very best example is our partnership with WuXi AppTec, which began almost six years ago when we only had a cell line in Pompe. Once we saw the early results in animals, we knew manufacturing would be our greatest challenge at that point. And that’s where together with our teams at WuXi AppTec, we really built the processes, ultimately even facilities, geared toward scaling up this product.” Another challenge he cited was how to support the PROPEL study with commercial scale material. “Our team together with our partners and WuXi AppTec really rose to the occasion. It’s because of WuXi AppTec’s manufacturing capabilities that we’ve been able to answer so many [compassionate use] requests for AT-GAA.” Crowley also cited their partnership with Dr. Jim Wilson and the University of Pennsylvania around gene therapy as being particularly important. “We combine our protein engineering expertise and technologies with the gene therapy and vector expertise of Dr. Wilson and UPenn.  And it has just been an extraordinary collaboration and partnership for us.” In this context he also mentioned Brammer (now part of Thermo Fisher Scientific) and Paragon (now part of Catalent) as keys to helping advance several of their programs.           When asked what he would have done differently if he could, Crowley took the time to reflect back on his previous experience with Novazyme. “There we were laser focused on a specific medicine and developing a treatment for Pompe, getting into clinical studies. And that certainly was a noble pursuit. But there were times where I lost perspective of the big picture. Maybe it was partly because we were under such time pressure.” For Amicus he took a different approach. “I instructed the team not to tell me what we’re going to do over the next couple of quarters. Instead I asked, ‘What do you want us to look like in ten or twenty years?’ I told them to dream and dream big. And then think about Amicus. And we ended up brainstorming and thinking really big. So, what I would have done differently is to lay out that bigger vision, that larger purpose to what we’re doing. I think that helps frame the smaller details.” He concluded by expressing his full confidence in his team to achieve these big goals. “We are a persistent and resilient bunch at Amicus.  And I think that’s a great trait for anybody in this industry.” By 2030 Crowley is hopeful that we will get to a world with a complete understanding of mutations, universal (in the U.S. at least) childhood screening, and continuing growth in the number and efficacy of treatments – a world where parents can take full advantage of amazing new treatments to help their children avoid succumbing to an otherwise fatal disease. That, he believes, is a world where we are truly putting the patient first.

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TDI Serves as a Bridge Between Academia and Industry, Leveraging All It Needs for Innovation

By Rich Soll, Senior Advisor, Strategic Initiatives, WuXi AppTec (@richsollwx) and WuXi AppTec Content Team The translation of academic discoveries into therapeutic products remains an issue despite passage of the Bayh-Dole Act (or Patent and Trademark Law Amendments Act) in 1980.  That Act, for first time, allowed academic institutions to capitalize on discoveries that emerged from their faculty’s labs.  Boston, San Francisco and San Diego nurtured cutting-edge entrepreneurial environments for spin-outs from academic science, but New York City, one of biggest recipients of NIH funding, lagged far behind the big-3 bioclusters. Tri-institutional Therapeutics Discovery Institute (TDI) was born in New York City as a not-for-profit research center to explore the early steps of advancing scientific breakthroughs from bench to bedside.  The goal of the Institute is to advance ground-breaking discoveries from scientists at the Memorial Sloan Kettering Cancer Center, The Rockefeller University and Weill Cornell Medicine through preclinical studies. Leading TDI as the Sanders Director since 2018 is Dr. Peter Meinke, a 20+ year industry veteran from Merck Research Laboratories with broad experiences associated with multiple facets of drug discovery and development. He was a recipient of the coveted American Chemical Society’s Heroes of Chemistry team award in 2017 for his leadership in the discovery of the antiviral NS5A inhibitor found in the fixed-dose combination product known as Zepatier,® a therapy for the treatment of Hepatitis C. Dr. Meinke recently sat down with Dr. Rich Soll and members of the WuXi Content Team to share his experience managing a unique organization like TDI as well as provide insights on drug development and observations of the industry’s dynamics and trends over the years. Rich Soll: How does TDI work toward its goal? Peter Meinke: TDI provides industrial-scale technical support for academic projects, making it possible to rapidly assess the utility of specific therapeutic targets in disease-relevant contexts in ways that are unprecedented in scale and scope for an academic environment. This is accomplished through a series of highly favorable academic-industry partnerships established through TDI, as well as our Innovation & Education Initiative, which provides community-wide training and support in order to maximize the impact of these partnerships on academic drug discoveries. We achieve our mission by leveraging the infrastructure, staff and intellectual capital of our academic and industry partners, as well as the generous support of philanthropists. Rich Soll: How many projects do you have and what is the process for selection? Peter Meinke: Currently, we have twenty-three therapeutic programs, almost equally split between biologics and small molecules, and our programs are structured as collaborations so we are able to leverage the expertise of the labs.  And we have built an early portfolio of about twenty-five Early Stage programs, using about 10 percent of our resources, so we now have a pipeline of projects. To decide which programs to undertake, we have an annual RFP process, but we also take in programs on a rolling basis over the course of the year. We have an independent scientific advisory board made up of people who are often former C-Level executives from Pharma and Biotech, all of whom have international reputations. Our SABs look at potential programs and use their best technical judgments, rank ordering them just as in an NIH grant review process, and then we set a funding line. We probably accept somewhere between a quarter and a third of all applicants on a historical basis. We also have project-specific advisory boards to provide technical expertise that we, or the Tri-I labs, lack. Rich Soll: So what about the historical success rates? Peter Meinke: We’ve accepted 60 biologics programs in just about six years, and 68 small molecule programs. Our total output to this date is we’ve contributed to two NewCos (new companies) and licensed six programs to biotech or pharma. We had one program where the PI declined to accept the license because he’s an MD/PhD with unique skills who recognized he could take it close to the NewCo stage and clinical validation before partnering. We have three programs that are available for license, which we validated in animal models. We have 12 additional programs for which we have obtained animal proof of concepts for new mechanisms, five of these are under active licensing discussions and they’re split almost equally between small molecules and biologics. This is a pretty remarkable output. I think it’s about 20 percent overall. Rich Soll:  External collaborations and partnerships are vital, especially in today’s R&D. How is that implemented at TDI? Peter Meinke:  Because of the way we’re structured, we can only work with faculty from these three communities.However, many of the programs that we work on also have a collaboration with faculty from other New York, US or international universities. Takeda is our general partner, but many of the programs that we support do not align with Takeda’s interest and Takeda is happy for that because they get access to cutting edge research in areas that they are of strategic focus. For projects not within Takeda’s strategic interest, the institutions created a for-profit, virtual company called Bridge Medicines to continue translational development of the asset. Being a virtual development company, Bridge Medicines relies heavily on the use of providers, particularly WuXi AppTec. Rich Soll:  How has TDI used WuXi AppTec? Peter Meinke: Currently, we have over 100 providers and platforms under contract with TDI and we have a wide range of specialists that we work with for new things. With respect to WuXi AppTec, we make very heavy use of chemistry services. We do use a lot of biological profiling, but that ebbs and flows depending on the nature of the programs. We use WuXi AppTec very commonly to build assays and miniaturize them for high throughput screenings.  WuXi AppTec has counterscreens for key off-targets which are very important to TDI because we learn more about our compounds’ profiles. We also will perform animal pharmacology studies to support projects. For example, we encountered a situation on one mechanism where an off-target liability required a sophisticated animal study that is in the suite of experience that WuXi AppTec offered.  We worked with WuXi AppTec senior scientists to make sure that we designed the study to de-risk this mechanism-based liability in animals as a key component of advancing the program. If that had been a negative result it would result in program termination, so it was important that study be done right and with appropriate standards. WuXi AppTec scientists were instrumental in ensuring that it was designed properly and appropriately controlled, so that we know it was executed to a high technical standard. Our molecules did not have the adverse signals. We couldn’t possibly do that internally. And we have variations of that on the biologic side in terms of antibody generation, antibody maturation, and so forth. Rich Soll: What is different leading an organization like TDI in comparison to previous positions? Peter Meinke: Leading an organization like TDI has been very different, incredibly enjoyable and very rewarding for me. The environment here is filled with experienced and creative scientists in different scientific disciplines with diverse expertise. TDI is well-resourced, but it is not pharma, so everything we do matters. We continuously ask ourselves “what is the key impediment that stops a program or asset from progressing.” It’s all about quick decision-making and devoting resources to solve the problem, even if deemed risky.  We leverage our externalized networks to augment anything we can’t do internally. I can do that today because of the way industry has evolved. I have a working relationship with WuXi AppTec that goes back to its earliest days. I’ve seen the type of complexity that they can handle on both small molecule and biologic fronts. TDI has its internal labs but, importantly, does not need to build a large chemistry or biologics department because we can leverage the capabilities of WuXi AppTec. Rich Soll: When you take a look at the world of R&D and pharmaceutical discovery, how has it evolved? What trends have you observed? Peter Meinke: The growing role of biotech and academia is clear. There is an increasing amount of large pharma’s pipelines coming from small biotechs and academia. People with real talent and drug discovery experience who once worked for pharma have migrated to the sea of small companies that are doing innovative and highly risky programs that address a recognized unmet need. These small organizations typically only have one, or a few, projects. They have very limited time and bandwidth to be successful, so they are incredibly focused on trying to show that “yes, this hypothesis has legs” and “yes, it will help treat some disease or another.” And then, when they get to a certain point, pharma, which has the resources and the wherewithal, will swoop in and often acquire/partner with these smaller organizations to really move it fast into clinical applications and real-world use. Rich Soll: If you had access to one technology that could make a difference, what would that be? Peter Meinke: One of the greatest challenges in the small molecule world is actually getting a suitable starting point of high quality. So, I pay a great deal of attention to computational technologies that allow me to generate this starting point. We pretty much have unrestricted access to Schrodinger’s software, and we have three full-time computational scientists using these tools, which lets you understand how valuable it is for TDI. Rich Soll:  Do you see opportunities here for cancer to go from treatment to cure? Peter Meinke: It’s pretty clear to everybody that immuno-oncology, for example, is as profound a change for treating cancer as was the discovery of antibiotics, and you know the use of IO is extending past oncology applications. This has led to the development of the Car-T platform which you can view as the next generation, and from this are emerging even more and more changes. People are really starting to learn how the human body’s immune system actually controls disease states, so if you can modulate this in an appropriate fashion, it has really profound impacts, which are already extending beyond cancer treatments.

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SOTIO Arms Dendritic Cells for Immunotherapy Against Cancer

SOTIO has developed a method to generate autologous dendritic cells that express multiple tumor antigens on their surfaces to awaken oncology patients’ immune systems to attack the cancer. Radek Spisek, Ph.D., the company’s Global CEO, observed that cancer cells express many different tumor antigens. In their ongoing effort to elude detection by a patient’s immune system, those tumor cells shed some of their antigens. To counter this evasive strategy, SOTIO arms the patients’ dendritic cells, which Spisek describes as the immune system’s most important cells, with “multiple different tumor antigens,” he explained. “In case two of those antigens disappear from the tumor cell, or five of them, we still have many additional shots on goal. There are still additional targets for the immune response that can be explored and we believe that this is important,” he said. SOTIO is developing its dendritic cell platform for treatment of lung, prostate and ovarian cancers. The Czech company’s most advanced program targets prostate cancer and it expects to complete its Phase III registration trial in Europe and in the U.S. in 2020. Next up is a Phase III trial in ovarian cancer, which will take four years to complete. The company is also in discussions to design a potential registration trial for lung cancer patients. As part of an exclusive series spotlighting the insider perspectives of thought leaders on topics shaping the future of new medicines, WuXi AppTec Communications spoke with Spisek about his company’s technology and the challenges of developing new drugs for cancer. Spisek participated in the founding of SOTIO in 2010 as Chief Scientific Officer and was appointed Global CEO in March 2018. He received his Ph.D. in immunology from the 1st Faculty of Medicine of Charles University in Prague and is a professor at Charles University’s 2nd Faculty of Medicine. Spisek also worked at the Institute de Biologie of Université de Nantes in France and the Center for Immunology and Immune Diseases at Rockefeller University, New York. WuXi AppTec: Is your immunotherapy targeting early stage treatment of solid tumor cancers, including lung cancer? Radek Spisek: In our cancer immunotherapy program, we already have very intriguing data in ovarian cancer, and initial data in lung cancer, that show positive signs of efficacy in our ongoing clinical trials, especially in patients who are at the stage of either minimal residual disease or minimal tumor burden; or patients who are in remission after the standard of care chemotherapy and have low tumor burden. So, our approach seems to be best suited for patients who are diagnosed early, who have low tumor burden, where the immune system is still fully functional and when there is a great chance that successful immunotherapy might lead to induction of anti-tumor response and subsequently result in improvement of the prognosis of the patient. WuXi AppTec: How much progress has been made in lung cancer drug research over the past 10 to 20 years? Radek Spisek: There has been a revolution in the treatment of many solid tumors after the successful introduction with checkpoint inhibitors. They represent a novel class of treatments that exploit the immune system. The outcome is that you delete the immunosuppressive environment in the patients and you give the immune system a chance to get active, attack the tumor cells and eliminate them. Almost 10 years ago, the introduction of checkpoint inhibitors for the treatment of melanoma, then non-small cell lung cancer and then many other solid tumors really represented a change of paradigm, which for me now signals the addition of a new modality to the three classical modalities of radiotherapy, surgery and chemotherapy. Over the course of the past 10 years, checkpoint inhibitors have found their place in the standard of care treatment protocols, including those for lung cancer. It’s fascinating to see that they basically moved to a front-line treatment for lung cancer, and we now see many clinical trials where checkpoint inhibitors are tested as front-line treatments in head-to-head comparison with standard of care chemotherapy or in combination with chemotherapy. This decade-long process in the development of checkpoint inhibitors for lung cancer really resulted in the substantial improvement in the prognosis of the disease. To me this represents a revolution and rightly so was recognized with a Nobel Prize in 2018 for Jim Allison, of the MD Anderson Cancer at the University of Texas, and Tasuku Honjo, of Kyoto University. WuXi AppTec: How does SOTIO’s active cellular immunotherapy platform work in treatment of lung cancer? Radek Spisek: It falls into the category of active immunizations, so it means you are trying to actively induce anti-tumor action in the patient’s body. You are trying to get an anti-tumor immune response that recognizes the tumor cells and eliminates the tumor cells, prolonging survival of patients with lung cancer. There are many approaches that fall into this category of active immunization. What we are trying to explore is an approach based on dendritic cells. Dendritic cells are the most important cells in the human immune system. They are necessary for the induction of the immune response. What dendritic cells do very well is present tumor antigens on their surfaces, which become accessible to the effector cells of the immune system, especially T lymphocytes. When T lymphocytes see the tumor antigens on dendritic cells, the T lymphocytes get activated, they proliferate, they amplify and then they can recognize tumor cells that express these tumor antigens and kill them. In our clinical programs, we enroll patients into the clinical trial and then we artificially, in our cell therapy laboratories, generate hundreds of millions of dendritic cells from a particular cell subset in their blood. Patients go to a blood transfusion center and spend two to three hours there while we collect hundreds of millions of white blood cells from their peripheral blood. From these white blood cells, we generate hundreds of millions of dendritic cells within one week. There is one additional step we do in our laboratories and that is we introduce the tumor antigens into the dendritic cells. Our cell therapy laboratories are in Prague, Czech Republic and in Beijing, China. The tumor antigens are known to be present in lung cancer, and the outcome of their introduction is that the dendritic cells take up the tumor antigens and then they express them on the surface and this results in dendritic cells that are fully capable of inducing anti-tumor responses in the patient’s body. Next we freeze the dendritic cells in liquid nitrogen so they remain viable and when the patient comes to the hospital outpatient clinic, the physician takes up the frozen vial of the dendritic cells, thaws the cells and by a subcutaneous injection, injects the cells and they migrate in the body to the lymph nodes of the organ where they interact with the T lymphocytes. They activate the T lymphocytes, which do their job and kill the tumor cells. This a complicated process that we need to do for every patient involved in the trials. WuXi AppTec: How do you introduce the tumor antigens into the dendritic cells? Radek Spisek: This is a specific element of our program that is patent protected, but most of it has been presented and published in scientific journals. What we decided to do a long time ago and what will differentiate our approach from other ones is that the source of the tumor antigens is the tumor cells. We identified a mixture of two specific lung cancer cell lines that express many of the relevant antigens in lung cancer. We take the cell lines and kill them by a specific method called high hydrostatic pressure. This kills them but it also makes them express high levels of the tumor antigens. When they are killed, they are put together with the dendritic cells, which eat up or engulf the dead tumor cells – it’s called phagocytosis. Then they cleave the tumor cells to the individual tumor antigens and the tumor antigens are presented on the surface of the dendritic cells. This is what normally happens in vivo and we can make this process in vitro as well. WuXi AppTec: How is this different from the CAR-T cell immunotherapy? Radek Spisek: CAR-T cells are a totally different approach. They deal with the last component of this chain. I told you that we inject dendritic cells and we hope that in the patient’s body they activate T lymphocytes and the T lymphocytes then kill the tumor. The CAR-T cell industry does something that is very smart. They take the T lymphocytes, which are the last piece of the chain of immune reaction, and they genetically modify the T lymphocytes so they can specifically recognize a tumor antigen in the body. So, the outcome of the CAR-T cell production is hundreds of millions of T lymphocytes that when injected into the body go directly to the tumor and kill it. It’s cancer immunotherapy at a different level. The main difference is that we are using a response against multiple tumor antigens. Through our approach, we inject the dendritic cells into the patient. They express many tumor antigens – let’s say 25 different tumor antigens – and this results in the activation of the immune response against multiple targets on the tumor cell. I personally believe this is extremely important because then you have an immune response that fights many targets on the tumor cell. What very often happens in the development of the tumor is that the tumor tries to escape the immune response and one way the tumor tries to escape is it loses expression of some of its tumor antigens. If you only have a CAR-T cell active against one tumor antigen and that tumor antigen is gone – it’s not present on the tumor cell – the CAR-T cell cannot do anything. It can’t see the tumor any more. What we have is a complex, robust immune response against multiple targets and in case two of those antigens disappear from the tumor cell or five of them we still have 20 shots on goal. There are still 20 targets for the immune response that can be explored and we believe that this is important. We see this benefit for patients in our lung cancer program and our ovarian cancer program. It’s a very significant benefit in terms of prolonging survival. WuXi AppTec: How are you applying your platform to the development of immunotherapies for prostate and ovarian cancer? Radek Spisek: We have a unique opportunity here. SOTIO started in 2010 and from the beginning we were funded by a very large Czech financial institution, called PPF Group. SOTIO is being built as a company that doesn’t want to be focused on a single program. We have been building for the past 10 years an oncology-focused company with a diversified portfolio of programs that all explore different arms of the immune system. At this stage we have six or seven programs at various stages of development. One program is focused on the dendritic cells and the dendritic cell platform has been optimized for lung cancer, ovarian cancer and prostate cancer. We have very interesting data from a Phase II program in ovarian cancer and in lung cancer where we see statistical significance of survival benefit in patients, which is the most important endpoint in oncology studies. This year we also brought to the clinic, after extensive preclinical work, a program where we have a molecule that very efficiently stimulates T lymphocytes and NK cells. It’s a molecule based on interleukin 15 (IL-15). We call it a superagonist of IL-15. This is now a very popular field in oncology research – proteins that can very efficiently activate those T cells, expand them and make them proliferate. This program is at the Phase I clinical trial stage. We are very close to bringing to the clinic one more program that is in the domain of antibody drug conjugates. We have a monoclonal antibody that recognizes tumor cells in gastric cancer and to this monoclonal antibody we attach a few molecules of a very toxic compound that kill the tumor cells. The idea of this approach is that the antibody brings those toxic molecules very specifically to the tumor cells that express the specific target for the antibody. The tumor cell then takes up the antibody, which releases the toxin and the toxin kills the tumor cell. We believe we may have a very interesting program for clinic trials in the next year and a half. SOTIO is looking for other portfolio programs and also doing minority investments into interesting biotech companies we want to cooperate with. WuXi AppTec: What are some of the other ways your cancer immunotherapy differs from other immunotherapies? Radek Spisek:  There is one more difference that is built into our clinical trials. We always incorporate long-term administration of the compound. In other words, our approach is not that the patient comes to the hospital and receives three shots of the vaccine and then that’s it. We have data that show it’s important to continuously boost the immune response. If you boost it once in four weeks, the tumor response goes down because it’s not very strong and it’s important to boost it again. We basically have in our clinical program one year of treatment for the patients where we continuously boost the immune response. It’s our belief, and it’s now supported by the data, that this long-term administration is important for the clinical efficacy of these approaches. WuXi AppTec:  What major challenges have you faced in developing your immunotherapies? What lessons have you learned that you can share with other CEOs? Radek Spisek: There’s an obvious answer to this one. What we are trying to do is very challenging with respect to the logistics of the process. Manufacturing and administering the cells is very complex – we have built a whole logistical system around it. The fact is we need to produce cells for each individual patient. In clinical medicine, people call this an autologous approach. For every single patient involved in your clinical program you need to generate a compound specific for that particular patient. This has significant logistical challenges. We need to have a network of blood transfusion centers where we collect the cells from patients. Then the cells need to make it from the blood transfusion unit to the SOTIO manufacturing site – one of the largest cell therapy facilities in Europe. And because we are working with living cells, we need to ship the cells within 30 hours to keep them alive, so we can work with them and modify them. Then at the end of the manufacturing process we need to get the cells to the hospital and back into patients’ bodies via subcutaneous injections. The major complication – and the major drawback – of these autologous therapies is the need to produce a specific cellular product for each individual patient. That’s the biggest challenge that we overcame. We have a very sophisticated network of fully functional blood transfusion units. We have very sophisticated software solutions for the logistics of cell shipment. We manufacture the cells in the Czech Republic then ship them and store them in facilities that are close to the clinical side. But this, of course, represents an additional cost of goods that complicates the process and makes it more expensive. WuXi AppTec: How will you maximize the value and benefit of your therapies for patients globally? Radek Spisek: If our clinical trial programs are successful and these cell therapies are approved, the vision of the company leadership and investors is to commercialize them – and we believe that can be done globally. We can already serve the U.S., the Europe and China with the existing process. We are doing a large, global prostate cancer clinical trial that includes sites in the U.S. and Europe. There are almost 1,200 patients enrolled in the trial and there has never been a single mistake in the logistics and the processing of the cells. We have also done all sorts of financial analyses that show us this program might be commercially viable if it gets on the market at a similar price point to other oncology products. WuXi AppTec: How soon will your immunotherapy reach the market? Radek Spisek: We will have the results of the prostate cancer trial in 2020. The next program, is in ovarian cancer. The timeline from the beginning of the registrational trial to the analysis of the results is four years from now. We now have two shots on goal: next year with prostate cancer and four years from now with ovarian cancer. We are still discussing the design of the potential registrational trial for the lung cancer program. WuXi AppTec: What are the top impediments for delivery of better medicines faster and cheaper for patients? Radek Spisek: The biggest issue is one that cannot be solved easily. In SOTIO we’ve been screening more than 300 new oncology programs a year. We are trying to identify oncology programs at the stage of preclinical studies and there are very few approaches, I think, that have a reasonable chance to make it to the market and be successful. This is not an impediment that is caused by the regulatory environment. It is also not caused by the lack of financial resources. It’s really the nature of oncology – of tumor cell biology. We are at the stage where many mechanisms of the tumor cell have been explored. There are many drugs out there and the prognoses of many cancers have improved significantly. And I think what we’ve seen over the past 10 years is there are a very limited number of programs that can be game changers. This is an inherent problem of oncology research at this stage. I see very few effective programs at the preclinical level that make me believe they can become new drugs in oncology. Then, of course, what I see from our experience is the financial need required for text book development in oncology. The cost per patient in clinical trials is increasing tremendously. I have seen a 30 percent to 40 percent increase in the clinical trial costs in the past five years. This is really getting to the point where many companies are struggling to find the financial resources to follow the clinical development program. For me, this is currently the biggest hurdle. You often hear people comment on the complicated regulatory environment in oncology. I don’t share this opinion. I think that regulators, especially the US Food and Drug Administration, are actually trying to create an environment that facilitates the approval of compounds that look promising at the stage of early clinical data. When the compounds look interesting, there are mechanisms to speed up development and accelerate approvals. But really, the financial burden of increasing clinical trial costs is currently the biggest hurdle in the development of new compounds. WuXi AppTec: What would be the one thing that has the most potential to lead a paradigm shift from treatment to cure in cancer? Radek Spisek: I am on the more skeptical side of this. From the 15 years of experience I have in oncology research, it’s very rare to see complete game changers that lead to a cure. I am more a believer in incremental improvements and in the combination of the different treatment modalities. This is what you see in most of the solid tumors. Incremental improvements in the prognosis of the disease come from introduction of new drugs that provide some benefit and then combining these novel treatments with pre-existing ones. This leads to a gradual improvement in the prognosis of the patients. I don’t expect to see a dramatic shift in the case of lung cancer that would result in 100 percent survival from the 20 percent survival you currently see in advanced patients. I doubt there will be a treatment like this.

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Refuge Biotechnologies: Developing “Smart Cells” to Fight Cancer Inside the Human Body

Cell therapy is an emerging treatment with great potential because, unlike small molecules, cells are dynamic. They can migrate, proliferate, differentiate, and respond to their environment both in vitro and in vivo. Cell therapy company Refuge Biotechnologies, based in Menlo Park, CA is leveraging gene engineering technologies known as CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) to develop therapeutic cells that are programmed to make decisions inside the patient’s body. This commitment is aptly summarized by the company’s mission statement: Designing Intelligent Cell Therapies to Fight Cancer. Refuge’s platform connects cell membrane receptors to CRISPR a/i systems, creating a genetically programmable switch that can control multiple gene expressions. Refuge is seeking to enable the integration of multiple therapies into a single type of therapeutic cells, one that combines greater efficacy with fewer side effects. Refuge’s technology enables cells to sense their surroundings and conditionally activate or repress multiple genes when they encounter specific external antigens. In particular, with receptor-dCas, immune cells can now be engineered to conditionally turn on/off certain genes, such as PD-1, to generate more potent CAR-T immune cells when it senses the presence of a tumor cell. Leading Refuge’s research programs is CEO and Co-founder Dr. Bing Wang. Dr. Wang co-founded the company following nearly a decade of life science investment banking experience. He most recently served as director of healthcare investment banking at Barclays Capital. Dr. Wang, a cancer survivor who is passionate about bringing forth “smarter” medicines that will transform cancer care, earned a B.S. in Applied Physics from Columbia University, an MBA from Columbia Business School, and a Ph.D. in Electrical Engineering from Princeton University. WuXi AppTec communications asked Dr. Wang to explain how Refuge’s unique cell therapy platform can fight cancer in vivo and the future benefits of and challenges in developing cell therapies. WuXi AppTec: How has cell therapy research progressed over the past 10 years? Do you anticipate a wave of new approvals coming over the next five to 10 years? Dr. Bing Wang: Absolutely, the expectation is that cell therapies will become much more prominent as a treatment modality across many diseases over the next five to ten years. There has been an immense amount of progress in the cell therapy field over the last decade building on original research into using cells to treat diseases, especially as the Novartis and Kite/Gilead products have come to the forefront to treat hematological malignancies. At Refuge, we are building on this progress and hope to further apply the cell therapy modality with other mechanisms to make cell therapies more effective in oncology and beyond. WuXi AppTec: What kinds of diseases are targeted with cell therapies? Dr. Bing Wang: Recently, cell therapies have been most prominently linked to oncology, but there is a wide range of applications for which cell therapies can be targeted, including regenerative medicine, rare diseases, and metabolic and cardiovascular diseases. Refuge initially focused on furthering cell therapy efficacy in solid tumors, but now we are exploring the potential ways to utilize the Refuge platform beyond oncology indications. WuXi AppTec: What scientific advances are needed to make cell therapies more effective? Dr. Bing Wang: As research progresses further into how cell therapies work and act within the tumor microenvironment, it is expected that better control over these mechanisms will improve the efficacy of cell therapies. Refuge is uniquely positioned to be able to tackle these issues together as its platform technology has the ability to target multiple pathways that underpin these mechanisms at the same time by modulating multiple genes simultaneously in addition to a cell therapy itself, such as CAR-T. This effectively designs an intelligent cell that is fitter and can react to its environment. WuXi AppTec: Will cell therapies ever be commonplace? If so, how soon? Dr. Bing Wang: At the current rate of advancement across various cell therapy fields, it would be expected that cell therapies would become much more common in the clinic and industry. Within the next five to ten years, cell therapies could likely become a common treatment modality in addition to traditional small molecule medicines and antibody-based therapies. WuXi AppTec: What are the risks and limitations of cell therapies? Dr. Bing Wang: As with all medical treatments, there are safety and efficacy risks that need to be managed for cell therapies. With further use in the clinic, as we have seen with the evolution of therapy management in dealing with CRS (Cytokine Release Syndrome), many of the risks can be effectively managed so that patients can really benefit from curative cell therapies. For current cell therapy products on the market, the obvious limitation today is that they are only indicated in hematological malignancies. There are various challenges for getting CAR-T (cell surface chimeric antigen receptor) therapy to perform better in solid tumors, including improving the ability to have CAR-T get into the tumor microenvironment and improving the persistence and fitness of CAR-T therapy cells, which many research and development institutions, including Refuge Biotech, are working towards solving. The field of oncology presents a highly complex range of biology and manifestations that are still being discovered and understood today. It is likely that there are unknown limitations that will cap the ability to have a single solution for all cancers, so combination therapy across cell therapies and other treatments may still be needed. WuXi AppTec: What cell therapies are you developing? Dr. Bing Wang: Our mission at Refuge Biotech is to “Design Intelligent Cell Therapies To Fight Cancer” based on Stanley Qi’s original research in CRISPR interference and activation to allow cells to make decisions in vivo. When the cell therapy comes in contact with a tumor, different genes within the T cell are expressed to react and enhance the attack against cancer cells. To do this, we are leveraging a synthetic biology circuit that combines cell surface signaling with specific multiplexed gene modulation through use of a deactivated CRISPR system. This capability enables us to combine many different cancer therapeutic mechanisms in a single therapy. As it relates to our initial clinical developments, we are applying known cancer biology, combining CAR-Ts against targets such as HER2, among others, with simultaneous modulation of genes responsible for various pathways involved in cancer pathogenesis. This includes checkpoint genes as well as targets in various other co-immunostimulatory and co-immunoinhibitory pathways. Our lead pipeline asset is a HER2 CAR-T plus PD-1 knockdown system for various solid tumor indications. We are also developing various additional pipeline assets focused on other CAR-T targets, with modulation of different genetic target combinations derived through intensive bioinformatics analysis to treat a wide range of cancers. Additional oncology indications will be disclosed in due course. WuXi AppTec: How does your approach differ from other cell therapy companies? Dr. Bing Wang: Our technology platform connects cell membrane receptors to CRISPR interference / activation to facilitate inducible gene modulation of multiple genes simultaneously with cell therapies such as CAR-T therapy. CRISPR interference / activation is very different from standard gene editing technology, such as standard CRISPR, Talens and Zinc fingers, etc., in which there is no cutting of the genome. The CRISPR is “deactivated” to mute the cleavage site while maintaining all the gene targeting specificity through short guide RNA (sgRNA). At the same time a transcription that either down-regulates or up-regulates gene expression is combined to the deactivated CRISPR, so that the cell therapy can use the GPS mechanism of the CRISPR to pinpoint a targeted strand of DNA and switch that gene on or off to varying degrees. This structure is tethered to the cell surface so that it is released only in response to engagement of tumor antigen through activation of a CAR-T on the T-cell surface. On release, the structure travels to the cell nucleus guided by sgRNA to effect specific gene modulation, where gene targeting can be multiplexed through adding multiple sgRNAs. Most DNA editing technologies snip out genes entirely and have an all-or-none effect, but we are able to control gene modulation and up-or-down-regulate multiple gene expressions at different levels. This will be important in combination therapy situations where you may not want to completely knockout endogenous genes since doing so can lead to long term permanent changes to the genome after tumor cells disappear. The advantages of our platform consist of no cutting of genetic material, the ability to multiplex gene modulation through the addition of more sgRNAs, and the capability to simultaneously versus sequentially enhance this process, thereby providing better efficiency for manufacturing. Comparable editing technologies need to be more careful with concurrent edits due to potential translocation and genotoxicity risks, which are irrelevant issues for our technology. By effectively being able to combine multiple cancer treatment modalities together, the Refuge platform will be able to provide better efficacy in the treatment of various cancers while simultaneously achieving a better safety profile. WuXi AppTec: What are your major regulatory and commercial challenges? What lessons have you learned? Dr. Bing Wang: We have a very novel approach to treating cancer that effectively incorporates synthetic biology, cell therapy and gene engineering. Therefore, familiarizing health authorities and regulatory bodies with our technology is essential, especially before we increase the complexity by using multiplexed targets. In parallel, we need to be diligent in manufacturing, as it is central to development and commercialization, alongside impeccable planning. WuXi AppTec: The drug industry is already under enormous pressure in Congress to hold down prices.  And as with other, new medicines, prices for some cell therapies seem to generate “sticker-shock” among patients. What are ways can we make new cell therapies more accessible to patients especially in these times? Dr. Bing Wang: As with any new and complex class of treatments, we must find ways make them effective and ensure patients can access them. One key element to consider is manufacturing. The complexity of manufacturing and delivering cell-based therapies, compared to traditional biologics and small molecules, leads to higher costs. Cell therapies require greater precision and regulatory inspections to ensure quality grade practices, and we face a shortage of capacity in GMP-grade manufacturing facilities to support new cell-based products coming to market. But as more products advance toward the market, the resulting growth in manufacturing capacity and other innovations may help reduce cost.

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