CNS and Neurodegenerative Targets

The identification of therapeutic targets based on novel mechanistic approaches is urgently needed for CNS and neurodegenerative diseases, particularly for conditions such as Alzheimer’s which represent extensive unmet medical need and blockbuster potential for the right therapy.

Driven by an improving understanding of CNS disease biology and the emergence of new mechanisms and targets, Cambridge Healthtech Institute’s CNS and Neurodegenerative Targets conference profiles the latest tools, targets and platforms driving today’s CNS drug discovery strategies, with critical updates and findings in key areas such as new targets for misfolded proteins, tau, GCPRs, kinase inhibitors, genetics, gene therapy, and neuroinflammation.

Final Agenda

Choose 2 Short Courses
or 1 Symposium and 2 Conferences/Training Seminars

Wednesday, September 26

7:00 am Registration Open and Morning Coffee (Foyer)

Latest Biology, Pathways And Challenges For Cns Therapeutics
Back Bay B

8:00 Welcome Remarks

Daniel Barry, Senior Conference Director, Cambridge Healthtech Institute

8:05 Chairperson’s Opening Remarks

Dario Doller, PhD, Senior Director, Exploratory Science, SAGE Therapeutics

8:10 FEATURED PRESENTATION: Effects of USP14 Inhibition on Proteasomal Degradation in Mammalian Cells

Qi_WangQi Wang, PhD, Director, Discovery Biology Neuroscience IMED Biotech Unit, AstraZeneca

Inhibition of the proteasome-associated deubiquitinase (DUB) USP14 has been considered a therapeutic strategy for accelerating degradation of aggregation-prone proteins involved in neurodegenerative diseases. In the attempt to validate this target, we studied the effects of inhibiting proteasomal DUBs on protein degradation in mammalian cells. I will present these data and discuss the limitation of USP14 as a target to accelerate proteasomal degradation.

8:40 Translating Targets into Therapeutic Candidates for Alzheimer’s Disease

Stephen_WoodStephen Wood, PhD, Director, Neuroscience Discovery Research, Amgen, Inc.

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.

Machine Learning, AI And Screening To Improve CNS Drug Discovery
Back Bay B

9:10 Machine Learning Models in CNS Drug Discovery

Istvan_EnyedyIstvan Enyedy, PhD, Principal Scientist, Biogen

For CNS targets, the design of modulators that permeate the blood-brain barrier is challenging. The promiscuity of efflux transporters is the main reason for stopping the blood-brain barrier penetration of a large variety of compounds. Machine learning methods have been used for building models for predicting substrates of efflux transporters. The performance of several models will be presented.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

10:25 Phenotypic Screening for Novel Inhibitors of Tau Aggregation in Human iPSC-Derived Neurons

Bhavya_VoletiBhavya Voleti, PhD, Associate Principal Scientist, Neurodegenerative Diseases Discovery WP, Merck Research Laboratories

Tauopathies are neurodegenerative diseases characterized by the presence of aggregates of abnormally hyperphosphorylated tau. Due to the intrinsic differences in clearance mechanisms between neuronal and non-neuronal cells, human iPSC-derived neurons were used to develop a biologically relevant tau model. The goal of this work is to uncover key targets/MOAs of interest involved in the clearance of tau aggregates that could become potential strategies to cure neurodegenerative disorders associated with tau.

10:55 Evolving the Concept of Phenotypic Screening to a New Level of Data-Driven, Systems Oriented Drug Discovery

Peder Svensson, PhD., Director, Comp Chem & Biol, CIO, Irlab Therapeutics

ISP represents a systems-oriented approach to CNS drug discovery, with the potential to significantly improve the discovery process, reducing resource needs, and development risks. The technology emanates from an integrative view on disease states and drug-induced states. Hence, pharmacological evaluation is focused on comprehensive, phenotypic characterization. We discuss theoretical considerations, as well as practical applications of ISP, illustrating with compounds discovered and characterized by the principles outlined.

11:25 Mechanistic Insights into the Use of Mevalonate Pathway Modulators as Cognitive Enhancers

Angela_MabbAngela Mabb, PhD, Assistant Professor, Georgia State University, Neuroscience Institute

To identify specific targets in the mevalonate pathway that promote AMPAR abundance, we established a high-content surface AMPAR assay in mouse primary hippocampal neurons. Using this assay, we found that tocotrienols increased surface AMPAR expression. Tocotrienol-mediated upregulation of surface AM-PARs was also associated with reduced expression of Arc protein, suggesting a mechanistic link of tocotri-enol action on AMPAR abundance.

11:55 Applications of AI in Drug Target Discovery

Jane Yu, Technical Pre-Sales, Life Sciences, IBM Watson Health

With millions of scientific research articles published each year, innovation in the life sciences suffers from knowledge waste and lack of knowledge integration. IBM Watson for Drug Discovery addresses this issue by extensively mining literature and data to help scientists accelerate biomedical research. Using advanced analytics and machine learning, the platform can also predict novel relationships, as demonstrated through our recent work with Barrow Neurological in ALS disease, and Pfizer in immuno-oncology, among many projects.

12:25 pm Session Break

12:35 Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

Targeting and Developing Novel CNS Targets
Back Bay B

1:50 Chairperson’s Opening Remarks

Daniel Klamer, PhD, MBA, Vice President, Business Development & Scientific Strategy, Anavex Life Sciences Corp.


1:55 ANAVEX 2-73, a Sigma-1 Receptor Agonist, in Phase IIb/III for the Treatment of Alzheimer’s Disease

Daniel_KlamerDaniel Klamer, PhD, MBA, Vice President, Business Development & Scientific Strategy, Anavex Life Sciences Corp.

Anavex Life Sciences Corp.’s lead drug candidate, ANAVEX 2-73, recently completed a successful Phase IIa clinical trial for Alzheimer’s disease. ANAVEX 2-73 is an orally available drug candidate that restores cellular homeostasis by activating the sigma-1 receptor. Full genomic analysis of the study participants resulted in the identification of genetic mutations linked to treatment response. Clinical studies in several indications are planned or underway utilizing a precision medicine approach.

2:25 NEW: This presentation has moved to 9.05am, Thursday

2:55 Using Stem Cells to Model Neurological Disease & Advance Personalized Medicine

Evan Y. Snyder, MD, PhD, Professor and Director, Sanford Burnham Prebys Medical Discovery Institute

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced (Grand Ballroom)

4:05 Non-Fibrillar Amyloid-Beta Oligomers – It’s Time to Intercept the Most Relevant AD Target

Grant_KrafftGrant A. Krafft, PhD, Chairman and Chief Scientist, Acumen Pharmaceuticals, Inc.

Alzheimer’s disease (AD) affects more than 45M people worldwide, yet no treatment affords meaningful symptomatic or disease modifying benefits. Recent failures of amyloid-directed therapeutics have cast doubt on the amyloid hypothesis; however, none of the failed drugs directly targeted non-fibrillar amyloid β oligomers (AbOs), now widely recognized as the AD-relevant Aβ structures. This presentation will highlight the AbO-AD linkage and profile ACU193, the first AbO-selective AD immunotherapeutic.

4:35 Oligomerix - Targeting Tau in Alzheimer’s Disease and Related Dementias

James_MoeJames Moe, PhD, MBA, President and CEO, Oligomerix, Inc.

Oligomerix is discovering and developing small molecule disease modifying drugs for Alzheimer’s disease that target the initial step in tau aggregation leading to the formation of tau oligomers, the toxic tau aggregates responsible for neuronal loss, impairment of memory formation and transmission of tau pathology during disease progression. The lead compound from our program inhibited tau aggregation in transgenic mice expressing human tau, best representing tau aggregation in AD.

5:05 Interactive Breakout Discussion Groups - View Details
Room: Constitution A

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.

Table 7: The Use of Precision Medicine in Drug Development for CNS Disorders

Moderator: Daniel Klamer, PhD, MBA, Vice President, Business Development & Scientific Strategy, Anavex Life Sciences Corp.

  • What questions should be asked before adding a new biomarker to your clinical trial?
  • What lessons can we learn from oncology?
  • Pros and cons using biomarkers as surrogate endpoints

Table 8: Machine Learning Models in CNS Drug Discovery

Moderators: Istvan Enyedy, PhD, Principal Scientist, Biogen

Jane Yu, Technical Pre-Sales, Life Sciences, IBM Watson Health

  • Pros and cons of AI in drug discovery
  • Implementing AI in drug development – when and how
  • Methods and building models


6:05 Welcome Reception in the Exhibit Hall with Poster Viewing (Grand Ballroom)

7:10 Close of Day

Thursday, September 27

7:30 am Registration Open and Morning Coffee (Foyer)

8:00 Chairperson’s Remarks

Stephan Schann, Head of Research & Development, Domain Therapeutics

8:05 Targeting Protein Degradation Pathways in Neurodegenerative Disease

Michael_AhlijanianMichael K. Ahlijanian, PhD, Head, Neuroscience, FORMA Therapeutics

Over the past several years, mutations in genes associated with genetic or familial forms of these diseases have been identified. Several of these genes are components of cellular protein degradation networks including autophagy and the unfolded protein response (UPR). This talk will describe the links between genes associated with genetic forms of neurodegenerative diseases, including Parkinson’s disease and Amylotrophic Lateral Sclerosis, protein degradation networks and the potential for developing novel therapeutics that target discrete components of protein degradation in neurons.

8:35 KEYNOTE PRESENTATION: Progress in Deciphering Alzheimer’s and Parkinson’s Diseases Predicts New Therapeutic Approaches

Dennis J. Selkoe, MD, The Vincent and Stella Coates Professor of Neurologic Diseases, Harvard Medical School; Co-Director, Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital

There are specific reasons for the failure of certain clinical trials in AD, and the underlying biological understanding of the disease is sound and steadily improving. Here, we will review the basic science of AD pathogenesis. We will also discuss a new hypothesis for the initiation of dopaminergic neurodegeneration in Parkinson’s disease.

9:05 NEW (Rescheduled Presentation) M3 Biotechnology: Neuro-Regenerative Disease-Modifying Therapies

Leen_KawasLeen Kawas, PhD, CEO, M3 Biotechnology

A clinical-stage biotechnology company with a platform of novel small molecule therapeutics for neurodegeneration with a focus on Alzheimer’s disease. M3’s lead therapeutic is a modulator of a novel neurotrophic growth factor shown to slow disease progression, exhibit neuroprotective and regenerative properties and restore cognitive function in preclinical studies of AD. Currently in human clinical trials, the lead is assessed for safety, tolerability, pharmacokinetics and EEG as a pharmacodynamic biomarker.

9:35 Coffee Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

10:20 Development of translatable biomarkers to aid the clinical interrogation of LRRK2 kinase inhibitors as disease modifying agents for PD

Matt Fell, PhD, Principal Scientist, Neuroscience, Merck

Leucine-rich repeat kinase 2 (LRRK2) gain of function mutations are associated with late-onset autosomal dominant Parkinson's disease (PD) and represent the most common known cause of familial PD. In spite of strong genetic evidence for potential disease modification in PD patients, advancement of LRRK2 inhibitors towards the clinic has been challenging for a number of reasons. Here, we will discuss ongoing efforts to develop translatable biomarkers to aid the clinical interrogation of LRRK2 kinase inhibitors as disease modifying agents for PD.

10:50 Discovery of Foliglurax, an mGluR4 PAM for the Treatment of Parkinson’s Disease

Stephan_SchannStephan Schann, Head of Research & Development, Domain Therapeutics

mGluR4 is an emerging target for the treatment of Parkinson’s disease (PD). However, since the discovery of its therapeutic potential, no ligand has been successfully developed. Starting from the (-) PHCCC, medicinal chemistry efforts lead to the discovery of a novel series of potent mGluR4 PAMs and to the nomination of Foliglurax, the first mGluR4 PAM clinical candidate currently evaluated in a Phase II study for the treatment of PD.

11:20 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

11:50 Conference Registration Open (Foyer)

12:20 pm Plenary Keynote Program (Constitution Ballroom)

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)

2:45 Close of Conference