Cambridge Healthtech Institute’s 3rd Annual
CNS Targets and Translational Strategies
Advancing CNS Drug Development
June 18-19 2019
A greater understanding of CNS related disease biology and the emergence of new, improved targets and technologies is bringing renewed interest, excitement and investment into this transformative area of medicine.
Cambridge Healthtech Institute’s CNS Targets and Translational Strategies conference focuses on the key issues of CNS drug development – including CNS target discovery and validation, biomarkers, bridging the preclinical/
clinical translation gap, evaluating the strengths and weaknesses of current preclinical models, challenging “gold-standards”, understanding mechanism of action, dose selection, neuroimaging, neuroinflammation, neuroimmunology, and more.
2019’s meeting will focus on progress being made in the field of CNS drug development rather than historical reflection.
Final Agenda
Day 1 | Day 2 | Download Brochure | Speaker Biographies
Tuesday, June 18
7:00 am Registration Open and Morning Coffee
8:00 Chairperson’s Remarks
Dario Doller, PhD., Drug Research Consulting, Alcyoneus/ScienceWorks
8:10 KEYNOTE PRESENTATION: Increasing the Odds of Success in CNS Drug Development: New Horizons
Nadeem Sarwar, Founder & President, Eisai Center for Genetics Guided Dementia Discovery (G2D2), Eisai Inc.
8:40 KEYNOTE PRESENTATION: Translational Opportunities for Brain Proteinopathies, Alzheimer’s Disease and Parkinson’s Disease, through Pathophysiology-Based Imaging and Biofluid Biomarkers
Johan Luthman, PhD, EVP, Research and Development, Lundbeck
Amyloid pathophysiology-based PET imaging and CSF biofluid biomarkers are now used routinely in major clinical Alzheimer’s disease trials for eligibility screening when studying amyloid-directed therapeutics. Moreover, quantitative amyloid PET
imaging is providing important possibilities to conduct clinical proof of principle trials for anti- amyloid investigational therapeutics. Tau PET imaging and CSF tau markers are now emerging as a similar tool for patient identification as well
as PoP in studies on tau-directed therapeutics.
9:10 KEYNOTE PRESENTATION: Lysosomal Dysfunction in Parkinson’s Disease: From Genetics to the Clinic
Pablo Sardi, PharmD,
PhD, R&D Director, Sanofi
This presentation will discuss: clinical, genetic and experimental evidence underlies the relevance of lysosomal dysfunction in Parkinson’s disease (PD); mutations in the lysosomal glucocerebrosidase gene (GBA) accelerate PD progression; First
trial has begun testing a GBA pathway modulator in a genetically defined population, and Modulation of the lysosomal pathway may also benefit a larger sporadic patient population.
9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:25 Featured Presentation: Targeting KCC2 for Epilepsy and Other Brain Disorders
Ross A. Cardarelli, PhD., Lead Scientist, AstraZeneca-Tufts University Laboratory for Basic and Translational Neuroscience, Tufts University
Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Here
we discuss the growing evidence that 2K+-Cl- cotransporter (KCC2) dysfunction has a central role in the development and severity of the epilepsies.
10:55 Behavior & Biomarker Characterization of the SOD1G93A Model of ALS Following Chronic Dosing with a Brain Penetrant HDAC6 Inhibitor Compound
Shahriar Niroomand, PhD, Associate Principal Scientist, Neuroscience, Merck Research Laboratories
Our three month in vivo study aimed to investigate whether pharmacological inhibition of the -Tubulin deacetylase HDAC6 would be sufficient to preserve axonal transport and attenuate disease phenotypes in the ALS SOD1G93A mice as demonstrated in
vitro using ALS patient iPSC neurons and in vivo after HDAC6 genetic ablation. We designed a novel brain penetrant HDAC6i compound to achieve sustained target engagement in the CNS, followed by repeated assessment of motor function using rotarod
and CMAP with concomitant measurement of disease progression biomarker pNfH. Our results indicate that sustained inhibition of HDAC6 in the SOD1G93A mice from a post wean pre-symptomatic age did not delay onset or slow the progression of motor
dysfunction as they aged. This suggests that SOD1G93A may not be a suitable model to test the modulation of axonal transport in ALS, reinforcing the need for additional pre-clinical models for such a heterogenous disease.
11:25 Zebrafish Models for Early Research and Development in Neurodegenerative and Neuromuscular Diseases
Arantza Muriana, Co-Founder & CEO, Biobide USA
Zebrafish presents numerous advantageous that make it a powerful animal model in neuroscience research. During this presentation we will review several neurodegenerative and neuromuscular rare disease zebrafish models (ALS, Duchnne, Dravet Syndrome),
their application in CNS drug screening, target validation and other early research and development activities.
11:55 Transition to Lunch
12:00 pm Enjoy Lunch on Your Own
12:30 Session Break
1:05 Chairperson’s Remarks
Dario Doller, PhD., Drug Research Consulting, Alcyoneus/ScienceWorks
1:10 Targeting Nucleocytoplasmic Transport in Amyotrophic Lateral Sclerosis and Dementia
Fernande Freyermuth, PhD, Massachusetts General Hospital, Mass General Institute for Neurodegenerative Diseases
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons leading to fatal paralysis. Mutations in the FUS gene are responsible for familial cases of ALS, and cytoplasmic mislocalization
of the protein is a pathological hallmark in a form of frontotemporal dementia. We determined that FUS mutations lead to defects in the nuclear membrane integrity that can be restored by targeting FUS nuclear cytoplasmic transport.
1:40 The TSC Preclinical Consortium: De-Risking Drug Discovery and Repurposing for Tuberous Sclerosis Complex
Steven Roberds,
PhD, CSO, Tuberous Sclerosis Alliance
The TSC Preclinical Consortium is a public-private partnership catalyzing development of new treatments for tuberous sclerosis complex. The TS Alliance holds licenses to use specific mouse models at CROs, including rights to test compounds for commercial
entities. This has attracted nine pharmaceutical companies to join the consortium, testing 15 proprietary drug candidates. Fifteen additional compounds have been tested by the TS Alliance, with data shared to all consortium members.
2:10 Beyond iPSC Based Disease Models: A Translatable Drug Discovery Platform for Status Epilepticus
Daniel Haag, CSO and Co-Founder, NeuCyte
Using direct reprogramming of iPSCs to generate defined human neural tissue, NeuCyte developed cell-based assays with complex neuronal structure and function readouts for versatile pre-clinical applications. Focusing on electrophysiological measurements,
we demonstrate the capability of this approach to identify adverse neuroactive effects, evaluate compound efficacy, and serve phenotypic drug discovery.
2:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:30-2:45 Speed Networking: Young Professionals
3:10 New Targets and Biology in Neuroimmunology
Samuel Hasson, PhD, Senior
Scientist, Neuroscience, Amgen
Information coming from human genetic studies has implicated several key pathways in the pathogenesis of Alzheimer’s disease (AD). These include processing of the Amyloid Precursor Protein and activation of the innate immune response. Here we
describe efforts to understand the biology of targets in each of these pathways in order to help translate that into potential, disease-modifying therapeutics for the treatment of AD.
3:40 Microglial Immune Checkpoint in Neurodegeneration and Brain Tumors
Joseph El Khoury, MD, Associate Professor of Medicine, Harvard Medical School
Similar to lymphocytes, microglia, the innate immune cells of the CNS, have several immunological checkpoints that prevent their overreaction to external stimuli. These checkpoints are different from those of lymphocytes. They include Trem2, Cx3cr1/fractalkine
and progranulin that keep the inflammatory response in check. Dysregulation of any of these checkpoints occurs in neurodegeneration and affects the response to brain tumors. As with T cell immune checkpoints, microglial immune checkpoints may
be important targets for therapy.
4:10 Transition to Keynote
4:20 PLENARY KEYNOTE SESSION
5:20 Taste of New England Welcome Reception in the Exhibit Hall with Poster Viewing
5:25 Meet the Plenary Keynotes
6:25 Find Your Table, Meet Your Moderator
6:30 Breakout Discussion Groups
7:30 Close of Day
Day 1 | Day 2 | Download Brochure | Speaker Biographies
Wednesday, June 19
7:00 am Registration Open and Morning Coffee
8:00 Chairperson’s Remarks
Dario Doller, PhD., Drug Research Consulting, Alcyoneus/ScienceWorks
8:05 Harnessing the Gut-Brain Axis to Discover Novel CNS Therapeutics
David
H. Donabedian, PhD, Co-Founder & CEO, Axial Biotherapeutics
In ASD, a human commensal bacterial therapy has shown to correct gut permeability, restore a healthy microbial composition and ameliorate core and non-core behavioral symptoms associated with ASD. In addition, Axial has developed a gut-selective,
nonbacterial-based therapy that has shown to improve barrier integrity and ameliorate core and non-core behavioral symptoms associated with ASD. The findings suggest that targeting the gut microbiome may provide a new approach for diagnosing
and treating PD and ASD.
8:35 Preclinical Translational Strategies for the Neuroinflammatory Aspects of Neurodegenerative Disease
Jonathan Levenson, PhD, Vice President, Translational Biology, Tiaki Therapeutics
Chronic neuroinflammation is a hallmark of Alzheimer’s disease and other neurodegenerative disorders. Tiaki Therapeutics has developed a novel ex vivo platform that faithfully models the neuroinflammatory
signature observed in patients afflicted with a neurodegenerative disease. Tiaki has focused on the role of neuroinflammation in Alzheimer’s disease, specifically microglial dysfunction. Tiaki has identified druggable, molecular targets
on microglia that when modulated mitigate neuroinflammation and improve neuronal health.
9:05 Utilization of Blood Biomarkers in Neurodegenerative Disease Research
Greg Warner, PhD, Senior Field Applications Scientist, Quanterix Corporation
We will describe the use of Simoa technology to measure neurogenerative disease-associated proteins in serum and plasma and their relation to traditional measurements in CSF. We will also discuss how these biomarker measurements can be combined
with traditional monitoring methods such as PET and MRI in patient response to therapeutic regimens.
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:05 Poster Winner Announced
10:20 The Development and Application of New PET Neuroimaging Probes
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. In the past few years, we have developed the first generation of epigenetic PET probes for HDACs an bromodomains. The first probe for class I HDAC imaging has successfully
advanced to human imaging studies and shows promising results so far. With these tools, we know the epigenetic changes in patients for the first time, and we also developed a series of new epigenetic inhibitor. Our work is a unique example
on the multidisciplinary research, including molecular imaging, medicinal chemistry, clinical research and preclinical drug discovery
10:50 Novel Markers that Significantly Enhance the Prediction of Alzheimer's Disease Progression
Viswanath Devanarayan, PhD, Adjunct Professor, University of Illinois, Chicago
The 2018 NIA-AA research framework proposes a ATN classification system with beta-Amyloid deposition (A), pathologic Tau (T), and neurodegeneration (N) for the diagnosis and staging of Alzheimer’s Disease (AD). We use proteomics data
from the AD neuroimaging initiative to develop simple cut-point based signatures that reinforces this ATN research framework. When applied to a separate MCI group at baseline, subjects satisfying these signature criteria experience over
two-fold faster progression to AD compared to signatures based on the ATN research framework.
11:20 Translational Potential of Neuropeptide Derived “stapled” Peptides in Metabolic and Neurological Disorders
Subhi Marwari, PhD, Postdoctoral Fellow, Department of Psychiatry, SUNY Upstate Medical University
The blood-brain barrier poses a significant challenge to drug development efforts for central nervous system disorders. Introducing an innovative “hydrocarbon-stapling” approach and combining with intranasal delivery technology
in neuropeptides, relaxin-3 and NPY, we have demonstrated the potential of the neuropeptide-receptor system in pursuit of the most effective translational pharmacological strategy to reversing depression, anxiety, and related metabolic
disorders.
11:50 Transition to Lunch
12:00 pm Enjoy Lunch on Your Own
12:30 Transition to Plenary
12:50 PLENARY KEYNOTE SESSION
2:20 Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing
2:25 Meet the Plenary Keynotes
3:05 Close of Conference
Day 1 | Day 2 | Download Brochure | Speaker Biographies
Stay on to attend Wednesday, June 19 - Thursday, June 20
Blood-Brain Barrier