Conference Day One
Wednesday March 24, 2024

7:00 am Registration & Coffee Room Networking

7:55 am Chair’s Opening Remarks

ENERGIZING ALZHEIMER’S & PARKINSON’S DRUG DEVELOPMENT TO OVERCOME BOTTLENECKS IN TREATMENT DEVELOPMENT

8:00 am Developing a Reliable Mouse Model to Better Understand and Predict ARIA-E and ARIA-H Observed in Subjects Treated with Anti-Aβ Immunotherapy: Myth or Reality?

  • Thierry Bussiere Scientific Director, Neurodegenerative Diseases Research Unit, Biogen

Synopsis

  • Risk factors for the occurrence of ARIA in patients treated with Abeta immunotherapy are being elucidated, but pathogenic mechanisms involved in ARIA remain hypothetical
  • Deciphering these pathogenic mechanisms, or defining features of new molecules that would prevent the occurrence of ARIA remain a priority for the field
  • Basic research effort is needed to develop reliable models that will be used to investigate the mechanistic hypotheses and test potential treatments

8:30 am Subcutaneous Lecanemab for Early Alzheimer’s Disease: Efficacy of IV Regimen with Convenient at Home Administration

  • Natasha Penner Senior Director & Head of Clinical Pharmacology, Neurology Business, Eisai

Synopsis

  • Overview of strategy for subcutaneous lecanemab
  • PK/PD comparability of subcutaneous and i.v. lecanemab
  • Positioning subcutaneous lecanemab for initiation and maintenance of treatment

9:00 am Panel Discussion: Is Plaque Reduction a Valid Marker of Response & Sufficiently Relevant to Drug Efficacy?

Synopsis

  • Navigating how the recent approval of amyloid clearing antibody drugs will affect regulator perception of plaque reduction as a marker of drug efficacy
  • Reviewing if plaque targeting is relevant for drugs with a different mechanism of action and if this affects the safety profile too significantly
  • Exploring the relevance of plaque clearance in heterogenous pathology of Alzheimer’s disease with varying biological basis
  • Discussing alternative clinically relevant markers of drug efficacy and the route required to validate them

10:00 am Morning Refreshment Break & Speed Networking

Synopsis

As the Alzheimer’s and Parkinson’s drug development community is reunited, this valuable session will ensure you can reconnect with your peers in the room to make new and lasting connections. Also, don’t forget to enjoy some refreshments before we split off into the three different tracks: target discovery, translational and clinical/commercial.

DISCOVERY

Elucidating Protective Variants Resistant to Neurodegeneration to Prolong Time Before Disease Onset

11:30 am Identifying Protective Variants for Alzheimer’s & Parkinson’s with the UK BioBank, Using Next Generation Sequencing (NGS) as a Major Source for Target Discovery

  • Achim Kless Senior Director Pain Genetics, Neuroscience Genetics, Eli Lilly & Co.

Synopsis

  • Harnessing whole exome and whole genome sequencing to identify protective/rare variants and their subsequent prioritization
  • Exploring the influence of causal variants in the context of mutations in the rest of the genome (epistasis and penetrance)
  • Identifying subgroups on the basis of comorbidities and diagnosis using examples from the UK Biobank

12:00 pm Mining Patient Resiliency-Associated Targets for Novel Antibody Therapeutics: Discovery of the CD33 antibody, ATLX-1088

Synopsis

  • Sequencing the B cell repertoire from resilient patient populations to look for protective auto-antibodies in an unbiased manner
  • Identifying resilient autoantibodies to uncover novel targets and pathways for target discovery
  • Harnessing the neuroprotective activity of microglia within the 1088 program as a novel antibody therapeutic

TRANSLATIONAL

Developing Humanized Rodent Models that Exhibit the Full Range of Alzheimer’s Pathology for More Confident Translation to Clinic

11:30 am Modelling Tau Pathology Propagation In Vitro & In Vivo: Insights from Past & Present Explorations

Synopsis

  • Understanding tau propagation pathology over recent history
  • Delving into neuron-glia interactions and how to precisely interrogate mechanisms for tau derived models
  • Translating learnings on in vitro and in vivo models informing drug design and prevent tau propagation

12:00 pm Delving into PFF & GBA Rodent Models of Parkinson’s Disease; Recent Progress & Future Challenges

  • Kelly Glajch Associate Director - Scientific & Neurodegenerative Diseases Research Unit, Biogen

Synopsis

  • Re-evaluating our understand of CBE dosage for similar GK & substrate effect but reduced offshore effects on cell loss
  • Exploring homozygous and heterozygous differences in lipid substrates for GBA models of PD to better model dysfunction
  • Modifications for fibril injections and QC to improve reproducibility and robustness of PFF model

CLINICAL & COMMERCIAL

Next Generation Amyloid Targeting to Reduce ARIA Seenin Clinic

11:30 am 2-Year Effects of Alz-801/Valiltramiprosate on Plasma Fluid Biomarkers, Volumetric MRI Biomarkers & Cognition Support Disease Modification In APOE4 Carriers With Early Alzheimer’s Disease

  • John Hey Chief Scientific Officer, Alzheon

Synopsis

  • Evaluating ALZ-801 in EAD (early Alzheimer’s Disease) patients that are APoE4 carriers as measured by fluid biomarkers e.g. p-tau 181, imaging and clinical outcomes
  • Highlighting a disease modifying effect and dynamic biomarker analysis over a 2-year period
  • Evaluating potential disease modifying effects of ALZ-801 as an oral anti-oligomer agent in phase 3 development that demonstrating safety and tolerability

12:00 pm PM310: the Next Generation of Anti-Amyloid Antibodies that Avoid ARIA to Improve Safety

Synopsis

  • Oligomer specificity can be generated
  • Specificity for oligomers will reduce competition by Amyloid beta monomers
  • Specificity for oligomers will improve safety by reducing ARIA

12:30 pm Lunch Break

DISCOVERY

Integrating GWAS & Multiomic Data Sets into Mechanistic Understanding to Identify & Validate Druggable Targets for Neurodegenerations

2:00 pm Integrating Multi-omics of Human Data Sets to Identify Causal Pathological Changes in Neurodegenerative Disease

Synopsis

  • Integration of genetics and cellular transcriptomics to understand causal links to AD risk genes
  • Modelling human biology derived mechanisms of action
  • Integrating human biology into all steps of the preclinical drug discovery process

2:30 pm Leveraging Population-Scale Genetics & Multiomic Data in Target ID & Validation

Synopsis

  • Landscape of large scale multiomic data in neurodegeneration
  • Methods of integrating multiomic data for target discovery
  • Downstream functional validation – how can we interrogate at scale?

3:00 pm Leveraging Electronic Health Records to Understand the Genetics of Alzheimer’s Disease at Scale

  • Neelroop Parikshak Associate Director, Neuroscience & Ophthalmology Genetics, Regeneron Pharmaceuticals Inc

Synopsis

  • Utilizing partnerships with electronic health records systems to power patient-oriented genetics discovery
  • Leveraging genetics and genetic risk scores to understand Alzheimer’s biomarkers
  • Moving toward detailed and longitudinal phenotyping at scale

TRANSLATIONAL

Refining In Vitro Techniques from BioPrinting, to hiPSC to Better Reflect Diverse Neurodegenerative Pathology

2:00 pm Using Precise (Co-)Cultures to Model Cell Interactions Between hiPSC-Derived Neurons, Astrocytes & Microglia

Synopsis

  • Stressing the importance of scalability and applicability
  • Ensuring specificity of cell type to model neurodegeneration in repetitive drug discovery for consistency in performance
  • Demonstrating effect of cell type on disease modelling

2:30 pm Overviewing the Use of Human iPSC Derived Neuronal Models to Enable Preclinical Drug Discovery in Neurodegenerative Diseases

Synopsis

  • Utilizing multiomics to characterize models and understand key aspects of human disease
  • Leveraging monoculture and complex co-culture models to build assays for drug development
  • Understanding disease impact on neurons, glia and neuron-glia interactions

3:00 pm Bioprinting 3D Brain Models as the Next Wave to Induce Neurodegeneration Preclinically

Synopsis

  • Modelling diverse neurodegenerative pathology including autophagy deficits, oxidative stress, mitochondrial dysfunction and ER stress
  • Incorporating a matrix of cellular interactions including protein aggregates in a live 3D environment for drug discovery
  • Using high-content imaging, transcriptomic profiling and molecular biology techniques to understand biological phenotypes and compound profiling

CLINICAL & COMMERCIAL

Alternate Approaches to Treating Neurodegeneration in Clinic: from Protein Degraders, to Insulin Sensitivity & Neuronal Hyperexcitability

2:00 pm Targeted Protein Degradation of Tau & Alpha-Synuclein For Preventing Neurodegeneration in Alzheimer’s & Parkinson’s Disease

  • Mark Shearman Chief Executive Officer, Aprinoia Therapeutics Inc.

Synopsis

  • Harnessing protein degradation technology using dual function target binders and E3-ligase ligands to degrade pathological protein aggregates via the ubiquitinproteasome system
  • Investigating selectivity and specificity of mechanism of action in cells and in vivo
  • Using proprietary diagnostic radiotracers to select patients and provide both target engagement and efficacy readouts

2:30 pm Modulating Metabolic Inflammation & Enhanced Brain Insulin Sensitivity to Decrease Progression of Neurodegeneration

Synopsis

  • Increasing insulin sensitivity to inhibit the inflammatory ERK signalling pathway to reduce neuroinflammation by inhibition inflammation-driven insulin resistance and major pathological inflammatory cascades
  • Reviewing phase 3 data for NE3107 as an anti-inflammatory insulin sensitizer to treat patients with mild to moderate Alzheimer’s Disease
  • Exploring preliminary biomarker findings for NE3107 in modulating progression of neurodegeneration

3:00 pm Examining Progression in MCI Due to AD: Results from a Phase 2b Trial of AGB101

Synopsis

  • Using high resolution structural brain imaging to monitor brain atrophy as a biomarker of progression
  • Consistent with a decrease in clinical & cognitive progression (CDR sum of boxes), brain atrophy was reduced by AGB101 compared to placebo in a 78-week double-blind randomized controlled study
  • Topography of this effect was consistent with the prodromal phase of amnestic MCI (e.g. reducing atrophy of entorhinal cortex)

3:30 pm Refreshment Break

EXPLORING THE LATEST UNPUBLISHED CLINICAL DATA CHANGING THE GAME FOR ALZHEIMER’S DISEASE

4:30 pm Effect of ACU193, an Aβ Oligomer Targeting Monoclonal Antibody, on CSF & Plasma Biomarkers of Alzheimer’s Disease

  • Eric Siemers Chief Medical Officer, Acumen Pharmaceuticals

Synopsis

  • Discussing ACU193’s reduction of ARIA in patients with ApoE4 variants without targeting plaque following the INTERCEPT-AD trial
  • Identifying CSF & plasma biomarkers and exploring the differences and approaches with this target
  • Using a bioanalytical target engagement approach to inform dosing and adaptive trial design for phase 2/3 studies

5:00 pm Session Details to be Confirmed

Synopsis

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5:30 pm Harnessing Alnylam’s RNAi Therapeutic ALN-APP for Treating Alzheimer’s

  • Kirk Brown Vice President, Alnylam Pharmaceuticals

Synopsis

  • Evaluating a phase 1 interim single ascending dose of ALN-APP in early onset AD
  • Working upstream to reduce amyloid production
  • Demonstrating target engagement with the first siRNA to be used in the brain

6:00 pm Panel Discussion: How Will Diagnostics Change With the NIA-AA Revised Criteria for Diagnosis & Staging of Alzheimer’s Disease?

  • Enchi Liu Senior Vice President Translational Sciences, Tranquis Therapeutics Inc.
  • Eric Siemers Chief Medical Officer, Acumen Pharmaceuticals

Synopsis

  • Shifting Alzheimer’s Disease definitions to more biological than clinical definitions
  • Integrating the latest validated findings in plasma-based marker research to establish likelihood of developing AD
  • Exploring how the novel staging might affect diagnosis and staging to understand the potential impact on clinical research

6:30 pm Chair’s Closing Remarks

6:45 pm Poster Session:

Synopsis

Connect with your peers in a relaxed atmosphere and continue to forge new and existing relationships, while exploring the latest innovations in Alzheimer’s and Parkinson’s from discovery to commercial insights. To submit a poster or to find out more, contact info@hansonwade.com

7:30 pm End of Day One