2023 Industry Workshop Booklet v0.5

NEALS Clinical Trials Workshop

CLINICAL TRIALS OF THE FUTURE

Hosted in partnership with the Healey & AMG Center for ALS at Mass General

March 17, 2023

Kimpton Marlowe Hotel

Cambridge, MA

MEETING PURPOSE

A one-day workshop bringing together invited clinical experts across academia and biopharma to focus on clinical trial design and advancing drug development in ALS

Image by Washinton University School of Medicine

THURSDAY, NOVEMBER 3 2022

Registration and Breakfast

ALS Clinical Trials – Designing for success

Welcome & Meeting Goals

Overview of NEALS (SAB, NEALS Affiliated Trials, ARO, etc)

Jinsy Andrews, MD, MSc and James Berry, MD, MPH

Innovative Digital Assessments

Jeremy Shefner, MD, PhD

Neurofilaments and other ALS Biomarkers in Clinical Trials

Robert Bowser, MD, PhD

Applying Genetics to Clinical Trials

Matthew Harms, MD

Panel Discussion

Break

Patient-Reported Outcome Measures in ALS Clinical Trials: What is “Meaningful”?

Zachary Simmons, MD

Learnings from NEALS-Led Trials and Other ALS Trials

Merit Cudkowicz, MD, MSc

Engaging the ALS Community

Allison Bulat

Panel

Networking Lunch

HEALEY Platform Trial

Adaptive ALS Platform Trial Design, Biomarkers, and Statistics

Panelists: Merit Cudkowicz, MD, MSc (Moderator); Sabrina Paganoni, MD, PhD; James Berry MD, MPH; and Melanie Quintana, PhD

Break

Operational Efficiencies, Industry Experience, and How to Partner

Panelists: Sabrina Paganoni, MD PhD (Moderator), Marianne Chase, Sr Director Clinical Trial Operations, Volkan Granit, MD MSc; Merit Cudkowicz, MD MSc

SPEAKER BIOGRAPHIES

(Listed in alphabetical order by last name)

Jinsy

Andrews, MD, MSc

Dr. Jinsy Andrews, MD, MSc is an Assistant Professor of Neurology, in the Division of Neuromuscular Medicine at Columbia University and currently serves as the Director of Neuromuscular Clinical Trials in the Department of Neurology. In addition to overseeing neuromuscular clinical trials, she cares for patients with neuromuscular disorders, primarily with amyotrophic lateral sclerosis (ALS). Dr. Andrews received her BS from Union College, her MSc in Biostatistics (PatientOriented Research) from Columbia University’s Mailman School of Public Health, and her MD from Albany Medical College. Dr. Andrews completed her residency in Neurology at the University of Connecticut and completed fellowship training in both Neuromuscular Disease and Clinical Neurophysiology at Columbia. Dr. Andrews is board certified in Neurology, Neuromuscular Disease, and Electrodiagnostic Medicine.

Prior to her position, she helped develop and direct a clinical trials unit for neurological diseases at Hospital for Special Care/University of Connecticut. There, she served as the Director of Clinical Trials and Co-director of the MDA/ALS multidisciplinary clinic. More recently, Dr. Andrews was Senior Director of Clinical Research and Development and Head of Neuromuscular Therapeutics at Cytokinetics where she focused on developing investigational therapies for neuromuscular diseases including Spinal Muscular Atrophy (SMA) and ALS. She has experience in conducting human clinical trials in neuromuscular disorders from Phase 1 to Phase 3 from both the academic and industry settings.

James Berry, MD, MPH

Dr. James Berry, is the Director of the Division of Motor Neuron Diseases at Mass General, Assistant Professor of Neurology at Harvard Medical School Co-Director of the NCRI, and is the Director of the Partners Neurodegenerative Clinical Research Fellowship. He serves on the Executive, Technology in ALS, and Biorepository Committees of NEALS. He is a board certified-neurologist and neuromuscular specialist. Dr. Berry completed his medical degree and received his Master of Public Health degree from Northwestern University. He served his internship at the Beth Deaconess Medical Center and his neurology residency and fellowship at Harvard Partners. Dr. Berry leads several biofluid biomarker studies, and the ALS Living Library biofluid repository. He is the principal investigator of several clinical trials in ALS. Dr. Berry also leads the Mass General TelePALS and ALS House Call Program He is the IND holder and led a study of fingolimod, an FDA-approved drug for the treatment of multiple sclerosis, in people with ALS. Dr. Berry has had a leading role in the clinical development of mesenchymal precursor cells for the treatment of patients with ALS with Brainstorm Cell Therapeutics. He has worked closely with, Drs. Merit Cudkowicz and Robert Brown (UMass) to be the first team to test AAV-delivered anti-SOD1 gene therapy in people with ALS. Dr. Berry works with numerous industry and academic partners to design trials of other gene therapies and other novel therapeutics aimed at slowing or arresting ALS progression. He is committed to building better methodology and outcome measures to perform more effective ALS trials.

SPEAKER BIOGRAPHIES

(Listed in alphabetical order by last name)

Robert Bowser, PhD Allison Bulat

Robert Bowser, PhD is the Chief Scientific Officer, Professor and Chair of Translational Neuroscience at the Barrow Neurological Institute and St. Joseph’s Hospital and Medical Center in Phoenix, Arizona. His research interests include the use of biomarker discovery efforts to determine the molecular and cellular basis of neurodegeneration, and translate those findings back to the clinic. He leads efforts to incorporate biomarkers in both preclinical drug development and in clinical trials to monitor target engagement and drug efficacy. He has published over 250 peer-reviewed publications and holds a dozen patents around technologies developed in his laboratory. Dr. Bowser is co-Founder of two biotechnology companies, Knopp Biosciences, LLC and nVector, Inc (formally Iron Horse Diagnostics, Inc.), companies advancing new drug and gene therapy treatments and biomarkers for neurologic disorders. He co-chairs the Northeast ALS (NEALS) biofluids biorepository and the Target ALS Biofluids & Postmortem Tissue Cores.

Allison Bulat graduated with a BA degree in Human Resource Management / Organizational Development and went on to obtain multiple advanced/graduatelevel certifications to include Project Management, Information Systems Management, Technology Quality Assurance, and Clinical Research Management. After holding the position of Senior Director of Software Quality Assurance for Choice Hotels International for 14 years, she “retired” from her full-time career when her son started kindergarten and moved into the field of consulting. As a technology consultant, she has been responsible for many high-profile technology projects within large organizations, centered on organizational development, business strategy, and cybersecurity. Following the loss of her husband to ALS in 2016, Allison focused her time and energy to helping others on the journey, and to doing whatever is possible to enable a cure for ALS to be found. In addition to her current role in Patient Engagement for the HEALEY ALS Center at Massachusetts General Hospital, she serves as a member of the Patient Advisory Committee, EAP Advisory Committee, and Retention and Recruitment Committee for the Healey ALS Platform Trial. She is a Certified NEALS Research Ambassador, serving as the Co-Chair of the NEALS Patient Education and Advocacy Committee (PEACe), the Community Liaison to the Executive Leadership Team of NEALS, the Co-Chair of the NEALS Patient Advisory Committee, and a member of the NEALS Recruitment and Retention, and Information and Education Committees.

SPEAKER BIOGRAPHIES

(Listed in alphabetical order by last name)

Marianne Chase

Marianne Kearney Chase is currently the Senior Director of Clinical Trial Operations for the Neurological Clinical Research Institute (NCRI) and Healey Center for ALS at MGH. The Healey Center, along with key collaborators, designed and initiated the first Platform Trial for Amyotrophic Lateral Sclerosis, which launched in 2020. The NCRI is the Clinical Coordinating Center for the National Institute of Neurological Diseases and Stroke (NINDS) Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT); the Clinical and Data Coordinating Center for the Northeast Amyotrophic Lateral Sclerosis (NEALS) Network and the Parkinson’s Study Group (PSG) Network. Marianne is an active member of the Clinical Trial Transformation Initiative (CTTI) and has over 25 years of experience in both investigator-initiated NIH / foundation-funded and industry-sponsored research including Pre-Clinical Study Design, Clinical Study Coordination, Trial Site Management, Protocol Development, Regulatory Compliance, and Project Management. In addition, serves as an adjunct faculty member for the NINDSfunded Clinical Trials Methodology Course and has developed and presented courses on various topics including; Good Clinical Practice, Good Source Documentation and Data Management Practices, Adverse Event Reporting, Standard Operating Procedures (SOPs), Overall Management of Multi-Center Clinical Trials, and Complexity of Clinical Trial Design: Ethical and Practical Challenges.

Merit Cudkowicz, MD, MSc

Dr. Merit Cudkowicz is the Chief of the Massachusetts General Hospital (Mass General) Neurology Service, and the Julieanne Dorn Professor of Neurology at Harvard Medical School in Boston. Dr. Cudkowicz completed her medical degree in the Health Science and Technology program of Harvard Medical School and a master’s degree in Clinical Epidemiology from the Harvard School of Public Health. She completed her neurology residency and fellowship at Mass General. Dr. Cudkowicz’s research and clinical activities are dedicated to the study and treatment of individuals with amyotrophic lateral sclerosis (ALS). She serves as director of the ALS Center and Neurological Clinical Research Institute at Mass General. She is one of the co-founders of the Northeast ALS Consortium (NEALS), roup of more than 120 clinical sites in North America dedicated to performing collaborative, clinical studies to develop treatments for people with ALS. She codirected NEALS for the first 18 years and currently serves on the Executive Committee and Science Advisory Board. Dr. Cudkowicz has led over 15 clinical trials in ALS and is also the Principal Investigator for the Clinical Coordination Center for NeuroNEXT, a National Institute of Health supported early phase 25 site network that conducts high-impact, efficient early phase trials for neurological disorders. She is the recipient of the 2006 Wings over Wall Street MDA award, 2009 Sheila Essey Award from the American Academy of Neurology, 2012 Prize4life Pioneer Award, 2017 Forbes Norris Award from the International MND Society and the 2018 Pinnacle Award from the Boston Chamber of Commerce.

SPEAKER BIOGRAPHIES

(Listed in alphabetical order by last name)

Volkan Granit, MD, MSc

Dr. Volkan Granit is a neuromuscular neurologist who is Medical Director, Clinical Development at Biohaven. He has 10 years of research and clinical experience in academia, where he served as an investigator in clinical trials targeting ALS, myasthenia gravis, and Guillain-Barré Syndrome, including those using novel modalities (antisense oligonucleotides and CAR-T cells). Before joining Biohaven in February 2022, Dr. Granit held faculty positions at Montefiore Medical Center/Albert Einstein College of Medicine followed by the University of Miami. At Montefiore, he established a Myasthenia Gravis Clinic and served as its Director and was co-Director of the Muscular Dystrophy Association Clinic. At the University of Miami, he served as Medical Director of the multidisciplinary ALS Center and associate program director for the neuromuscular fellowship program.

Dr. Granit obtained his medical degree from Istanbul University (Turkey). He completed a Master of Neuroscience at Albert Einstein College of Medicine (New York), and a neurology residency and neuromuscular fellowship at Montefiore Medical Center (New York).

Matthew Harms, MD

Dr. Matthew Harms is an Associate Professor of Neurology at Columbia University in New York City. Dr. Harms received his A.B. in Biology summa cum laude from Harvard University and his medical doctorate from the University of California San Francisco. He completed clinical fellowships in Neurophysiology and Neuromuscular Medicine at Washington University in St. Louis, where he postdoctoral studies focused on the genetics of motor neuron diseases in general and specifically on ALS.

Since 2015, Dr. Harms’ has been the Director of the Precision Medicine Initiative in ALS at Columbia University’s Institute for Genomic Medicine. With his team in the Motor Neuron Center and in the Eleanor and Lou Gehrig ALS Center, his lab focuses on gene identification for ALS and the use of novel bioinformatic approaches. His efforts have contributed to the identification of five ALS genes and he currently directs the “Genomic Translation for ALS Care” study, North America’s largest prospective study linking genomics to environmental exposures and outcomes. He is the co-chair of the Familial ALS/FTD Committee of NEALS and has served as a site PI for several NEALS clinical trials.

Dr. Harms is an attending in the Eleanor and Lou Gehrig ALS Center at Columbia and also sees adult and pediatric patients in the Muscular Dystrophy/SMA Center.

SPEAKER BIOGRAPHIES

(Listed in alphabetical order by last name)

Sabrina Paganoni, MD, PhD

Dr. Sabrina Paganoni, is the Co-Director of the Neurological Research Institute at the Massachusetts General Hospital, physician scientist at the Healey & AMG Center for ALS, and Associate Professor at Harvard Medical School. Her research focuses on clinical trials and therapy development for ALS. Dr. Paganoni has served as PI of several ALS clinical trials and has been using novel trial designs, novel endpoints and digital technology tools to innovate the way investigational products are tested in ALS. She is the co-PI of the HEALEY ALS Platform Trial, the first platform trial for ALS in the world. She recently reported the positive results of the CENTAUR trial and is the co-Chair of the global PHOENIX trial.

Dr. Paganoni's research has been funded by the NIH, non-profits, and industry; she has published more than 100 peer-reviewed manuscripts and received several awards for her work including the 2021 Top 10 Clinical Research Achievement Award for the CENTAUR trial.

Melanie Quintana, PhD

Dr. Melanie Quintana is a Director of Consulting and Senior Statistical Scientist at Berry Consultants, LLC. She is an expert in utilizing Bayesian statistics to design innovative clinical trials and answer complex clinical questions across a wide range of therapeutic areas. She earned a PhD in Statistics from Duke University and went on to pursue a Postdoc in Biostatistics at The University of Southern California. During her PhD and Postdoc, she worked closely with collaborators within multiple large studies and consortiums around the nation to develop and implement analytical strategies to assess genetic risk factors for various complex diseases. This work led to a passion for consulting and collaborating with clinical experts to find analytical solutions to hard medical problems, which has only expanded since joining Berry Consultants in 2013. At Berry Consultants, she collaborates with a wide range of clinical experts to find the best solution for answering complex clinical questions and mentors and oversees a group of consultants to do the same. Her work includes the design of over 100 clinical trials in a wide range of therapeutic areas including adaptive designs, platform trials & statistical innovation in rare disease and unmet medical needs. Her work in clinical design also involves support for regulatory interactions and guidance on regulatory considerations, and support for clinical trial implementation as a member of statistical analysis committees and data safety and monitoring boards.

SPEAKER BIOGRAPHIES

(Listed in alphabetical order by last name)

Jeremy Shefner, MD, PhD

Dr. Shefner, is Chair of the Department of Neurology, Barrow Neurological Institute and Executive Chair of Neurology, University of Arizona College of Medicine Phoenix. He is also Senior Vice President of Barrow Neurological Institute.

Dr. Shefner’s research focuses on biomarker development and the clinical therapeutics of ALS and SMA. He co-founded the Northeast ALS Clinical Trials Consortium (NEALS), the largest and most active consortium in the world dedicated to ALS. He continues to direct the NEALS outcomes and clinical monitoring cores and is currently the principal investigator for two multicenter clinical trials, as well as a home-based outcomes study with the goals of determining the optimum frequency of outcomes assessments and expanding the number of patients potentially eligible for clinical trials.

Dr. Shefner has published approximately 200 papers in peer-reviewed journals and has served on multiple grant review panels. He has also participated in committees organized by the Institute of Medicine to investigate the relationship between military service and ALS, as well as the health effects of Agent Orange on Vietnam War veterans. In 2014, Dr. Shefner received the Sheila Essay Award for ALS Research, presented annually by the American Academy of Neurology (AAN) and the ALS Association.

Dr. Shefner received his Ph.D. in sensory physiology from the University of Illinois Chicago, and his M.D. with Distinction from Northwestern University Medical School in Chicago. He completed his residency training at the Harvard Longwood Neurology Training Program in Boston as well as a fellowship in neuromuscular disease at the Brigham and Women’s Hospital in Boston.

Zachary Simmons, MD

Dr. Zachary Simmons received his medical degree from the University of Florida, and then trained in neurology at the University of Iowa and in neuromuscular diseases and electromyography at the University of Michigan. He now serves as Professor and Vice Chair for Research in the Department of Neurology at Penn State University, where he founded and directs the ALS Clinic and Research Center.

Dr. Simmons had served as site principal investigator for more than 20 clinical treatment trials, and a large number of investigator-initiated studies in ALS. He has published extensively on quality of life in ALS and was the co-developer of the ALS Specific Quality of Life Instrument (ALSSQOL) and the more recently validated short form (ALSSQOL-SF). Related to this, he has published on ethics of care and end-of-life issues. The Penn State ALS Center has pioneered the use of telemedicine in ALS for clinical and research purposes, including home monitoring of respiratory function, of gait and falls, and of speech and swallowing. Other ALSrelated research interests include symptom management, optimization of multidisciplinary care, psychological well-being and mindfulness.

Dr. Simmons currently serves as Editor-in-Chief of Muscle & Nerve. He has published more than 160 peer-reviewed articles. At the organizational level, he has served on the NEALS technology, bulbar, and upper motor neuron committees, and on the AANEM Board of Directors and multiple AANEM committees. He has been a member of the Ethics, Law, and Humanities Committee of the American Academy of Neurology, and of the Penn State Hershey Ethics Committee.

ABOUT THE NORTHEAST ALS CONSORTIUM (NEALS)

In 1995, the Northeast ALS Consortium (NEALS) was founded as an independent, non-profit group of research sites that collaboratively conduct clinical research in Amyotrophic Lateral Sclerosis (ALS) and other motor neuron diseases While retaining its original acronym and focus on ALS trials, NEALS has since developed into a national, and increasingly an international, consortium of ALS clinical research centers. Together, the scientists at these centers work to improve the efficiency and quality of ALS clinical trials and research, expand access to clinical research, support biomarker development with a robust biorepository, innovate ALS clinical care, and educate the community about ALS research. Through these efforts, NEALS strives to rapidly translate scientific breakthroughs into new therapies and help people with ALS live longer and maintain a higher quality of life

Governed by a seasoned Leadership Team, NEALS has developed into an active network of 147 trial-ready sites with extensive training on conducting clinical research and robust experience in designing and managing FDAregulated clinical trials for ALS. NEALS has successfully partnered with industry and academic researchers to conduct high-quality ALS studies for over 25 years and has grown to be the largest ALS research consortium in the world.

ABOUT THE SEAN M. HEALEY & AMG CENTER FOR ALS AT MASS GENERAL

At the Sean M Healey & AMG Center for ALS at Mass General, we are on a quest to discover life-saving therapies for all individuals affected by ALS. Launched in November 2018, the Healey Center leverages a global network of scientists, physicians, nurses, caregivers, patients and families working together to accelerate the pace of ALS therapy discovery and development.

Under the leadership of Merit Cudkowicz, MD, chief of the Department Neurology, and a Science Advisory Council of international experts, we are reimagining how to develop and test the most effective therapies to treat the disease, identify cures and, ultimately, prevent it

The key to our success is our tightly integrated research and clinical efforts, encouraging opportunities to bring the challenges our patients face every day into our laboratories, focusing investigations on finding solutions that will make a meaningful difference to our patients without delay Our collaborative efforts are designing more efficient and effective clinical trials while broadening access to these trials for people with ALS.

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