Cambridge Healthtech Institute’s Inaugural

CNS, Gene and Cell Therapy

Progress in CNS and Rare Diseases, Gene and Cell Therapy

September 16 - 17, 2020 ALL TIMES EDT

Significant progress in the fields of genetics, protein science, and drug discovery is driving a renewed interest in emerging indications outside of oncology, and important indications, such as CNS and rare diseases. Moreover, new and exciting technologies, such as cell, gene, and gene-edited therapies are offering a new way of treating previously untreatable diseases, and are quickly advancing through the clinic. CHI's CNS, Gene and Cell Therapy conference provides a platform for pharma, biotech, and academia to discuss and benchmark the latest advances in developing new drug targets and novel therapies across the fields of neuroscience and rare diseases, as well as the unique challenges facing cell and gene therapy development. How do your drug discovery and translational strategies compare?

Wednesday, September 16

MATCHING THE RIGHT MODALITY TO THE RIGHT MECHANISM

9:30 am

Painting Brain Drug Discovery’s Way Out of the Corner: A Proposal to Energize Our Search for Small Molecule Treatments for CNS Diseases

Dario Doller, PhD, Director, Medicinal Chemistry, Alcyoneus ScienceWorks, LLC

This presentation will analyze and present a perspective on some challenges in CNS drug discovery and development, including: where we have been, contemporary neuroscience pipelines, success in CNS drug research, and where to go now.

9:50 am

Exploring the Gut-Brain Axis as a New Therapeutic Approach to Treat CNS Disorders

David H. Donabedian, PhD, Co-Founder, CEO & Director, Axial Biotherapeutics Inc.

Axial Biotherapeutics' vision is to establish a new path for targeting neurological disorders through harnessing the power of the gut-brain axis. This radical idea is based on the groundbreaking work of scientific founder, Dr. Sarkis Mazmanian, who was the first to describe a functional link between the gut-brain axis in Parkinson’s disease and the impact of neuroactive microbial metabolites on autism behaviors. These findings contribute to a paradigm shift and a significant scientific advancement in how we approach the treatment of neurological disorders and the departure from the belief that neurological disorders originate exclusively in the brain.

10:10 am

A Minimally Invasive DREADD-based Therapy Platform: Treating Neuropsychiatric Disease via the Retina

Hannah E. Bowrey, PhD, Research Fellow, Rutgers Brain Health Institute

We have created a minimally invasive designer receptor (DREADD) - based therapy platform that can be used to control activity of the circadian neurocircuitry, including locus coeruleus (LC), a deep brain nucleus that is otherwise impossible to access without brain surgery. We utilize the retina as a target for DREADD expression, from which we can manipulate these key neural structures whose aberrant activity characterizes numerous neuropsychological disorders, including major depression, addiction, attention deficit hyperactivity disorder (ADHD), Parkinson’s disease, Alzheimer’s disease, and sleep disorders. Therefore, this technology has potential applications across several disorders. This presentation will focus on this technology as it applies to depression.

10:30 am LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Dario Doller, PhD, Director, Medicinal Chemistry, Alcyoneus ScienceWorks, LLC
Panelists:
Hannah E. Bowrey, PhD, Research Fellow, Rutgers Brain Health Institute
David H. Donabedian, PhD, Co-Founder, CEO & Director, Axial Biotherapeutics Inc.
10:50 am Session Break
11:10 am Coffee Break - View Our Virtual Exhibit Hall

CNS DRUG DEVELOPMENT AND TRANSLATION

11:25 am Machine Learning Models in CNS Drug Discovery and Penetrating the BBB
Istvan Enyedy, PhD, Director, Black Diamond Therapeutics

The design of therapeutic agents that penetrate the blood-brain barrier is challenging mainly due to the promiscuity of efflux transporters. The structures of P-gp and BCRP have been published, allowing us to build machine learning models that combine the transporter structural information with traditional ligand-based descriptors. The performance of these models will be presented.

11:45 am PET Imaging of Neuroinflammation in Neurodegenerative Diseases
Changning Wang, PhD, Assistant Professor of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School

Molecular imaging, such as PET, has been widely used in medical research and drug discovery. We have developed new imaging tools and applied them in clinical research and drug discovery. In this presentation, I will discuss the development and application of molecular neuroimaging techniques for brain research. Our work is a unique example on the multidisciplinary research, including molecular imaging, medicinal chemistry, clinical research, and preclinical drug discovery.

12:05 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Dario Doller, PhD, Director, Medicinal Chemistry, Alcyoneus ScienceWorks, LLC
Panelists:
Istvan Enyedy, PhD, Director, Black Diamond Therapeutics
Changning Wang, PhD, Assistant Professor of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
12:25 pm Session Break
12:45 pm Lunch Break - View Our Virtual Exhibit Hall
1:15 pm

A Neuroinflammatory Translational Pipeline for Neurodegenerative Diseases

Jonathan Levenson, PhD, Vice President, Translational Biology, Tiaki Therapeutics

Neuroinflammation is a pathological hallmark of CNS degenerative diseases, yet preclinical translational tools to support drug discovery programs are lacking. Tiaki has developed an ex vivo slice culture and an animal model that manifests a neuroinflammatory state that is aligned with Alzheimer’s and Huntington’s diseases. Using these tools, a novel anti-inflammatory target for neurodegenerative disease which was identified using curated human data, has been progressed to lead optimization.

1:35 pm

TANGO (Targeted Augmentation of Nuclear Gene Output) for the Treatment of Genetic Diseases

Isabel Aznarez, PhD, Co-Founder, Vice President & Head, Biology, Stoke Therapeutics

TANGO uses antisense oligonucleotides (ASOs) to prevent naturally occurring, non-productive splicing, and increase productive mRNA and fully functional protein. We identified non-productive events in > 50% protein-coding genes. ASOs targeting these events lead to increased mRNA and protein in a dose-dependent manner. TANGO-ASO treatment of Dravet syndrome mice lead to protein restoration to near normal levels, significant reversal of the survival phenotype, decreased seizure frequency and increased numbers of seizure-free mice. 

1:55 pm Session Break
2:35 pm Refresh Break - View Our Virtual Exhibit Hall
3:00 pm Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Discussion topics and moderators will be listed on the website.

BREAKOUT: Translational Strategies in CNS Drug Development

Dario Doller, PhD, Director, Medicinal Chemistry, Alcyoneus ScienceWorks, LLC
  • What is the most translationally influential technology developed in the last 5 years? (overall, and specifically for brain diseases)
  • What is the biggest translational challenge within CNS drug discovery and development?
  • What it the next translational breakthrough you see coming in the horizon?
3:35 pm Close of Day

Thursday, September 17

EMERGING TARGETS AND PATHWAYS

10:15 am Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions
Matthew Nolan, DPhil, Postdoctoral Research Fellow, Massachusetts General Hospital and Harvard Medical School

RNA-binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle, resulting in various molecular phenotypes, such as aberrant RNA splicing, transport, and stability. Emerging therapeutic approaches to mitigate or reverse alterations of RNA-binding proteins in neurological diseases are discussed.

10:35 am

Alzheimer’s Disease: Pathogenic Mechanisms and Therapeutic Intervention

Can (Martin) Zhang, MD, PhD, Assistant Professor of Neurology, Harvard Medical School, Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital

Alzheimer’s disease (AD) is an ageing-related neurodegenerative disorder. It is the primary cause of dementia in the elderly and presently no effective therapeutics are available to modulate disease progression. Genetics have identified not only mutations in specific genes that are linked to the familial early onset form of AD, but also the cause(s) of the more typical late onset form of the disease. Studies have identified new molecular mechanisms and modifiable risk factors of AD, which may enable the development of effective interventions to prevent or cure the disease. Emerging research has shown that the disease can be potentially prevented; and an increasing number of researchers are developing therapies that can modify disease pathology or risk. This talk will be focused on recently identified molecular mechanisms of AD, and translational potentials of developing effective therapeutics of AD.

10:55 am

Targeting Ataxin-2 against TDP43 Pathology Associated with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Yinghui Hu, PhD, Associate Principal Scientist, Neurodegeneration Group, Merck

Ataxin-2 has been identified as a potent modifier of TDP43-toxicity. We demonstrated that knockdown of Ataxin-2 or inhibition of Ataxin-2 interaction with TDP43 effectively reversed TDP43-induced toxicity in hu-iPSC neurons. Proteomic analysis was also performed to identify a specific set of proteins associated with the aberrant Ataxin-2/TDP43 interaction. These findings led us to explore various approaches and modalities that can be used as novel strategy for therapeutic intervention.

11:15 am LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Matthew Nolan, DPhil, Postdoctoral Research Fellow, Massachusetts General Hospital and Harvard Medical School
Panelists:
Can (Martin) Zhang, MD, PhD, Assistant Professor of Neurology, Harvard Medical School, Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital
Yinghui Hu, PhD, Associate Principal Scientist, Neurodegeneration Group, Merck
11:35 am Session Break
11:55 am Coffee Break - View Our Virtual Exhibit Hall

PLENARY KEYNOTE PROGRAM

12:20 pm

PLENARY KEYNOTE: Tackling Undruggable Oncoproteins: Lessons from the VHL Tumor Suppressor Protein

William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics

VHL tumor suppressor protein (pVHL) inactivation is common in kidney cancer and upregulates the HIF2 transcription factor. PT2977/MK-6482 is an allosteric HIF2 inhibitor now in Phase 3 testing. Thalidomide-like drugs (IMiDs) bind to cereblon which, like pVHL, is the substrate-binding unit of a ubiquitin ligase. IMiDs redirect cereblon to destroy the myeloma oncoproteins, IKZF1 and IKZF3. We have developed new assays for identifying drugs that can destabilize oncoproteins of interest.

12:45 pm LIVE Q&A:

Plenary Keynote Discussion

Panel Moderator:
Stewart Fisher, PhD, CSO, C4 Therapeutics, Inc.
Panelist:
William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics
12:55 pm LIVE PANEL AND Q&A:

Plenary Keynote Discussion: De-Risking Early Drug Discovery

Panel Moderator:
Nadeem Sarwar, PhD, Founder & President, Eisai Center for Genetics Guided Dementia Discovery, Eisai, Inc.
  • Data Sciences
  • ​Novel Chemical Modalities
  • Investment and Partnering Models
  • COVID-19 Progress as Examples of Successful Partnerships
Panelists:
Anthony A. Philippakis, PhD, Chief Data Officer, Data Sciences & Data Engineering, Broad Institute; Venture Partner, GV
Stephen A. Hitchcock, PhD, Head, Research, Takeda Pharmaceuticals, Inc.
1:35 pm Lunch Break - View Our Virtual Exhibit Hall
2:05 pm Close of CNS, Gene and Cell Therapy Conference





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