8:30 am Chair’s Opening Remarks

8:40 am Kick-off Panel Discussion: Exploring the Biggest Hurdles of Crossing the Blood-Brain Barrier (BBB) & Considerations for Overcoming Them

  • Jonathan Sugam Associate Principal Scientist, Neuroscience Discovery, Merck
  • Felix Schumacher Program Leader Targeted Therapeutics, Roche
  • Danica Stanimirovic Director, Translational Bioscience, Human Health Therapeutics Research Centre, National Research Council of Canada
  • Manuel Sanchez-Felix Senior Fellow, Novel Delivery Technologies, Novartis Institute for Biomedical Research

Synopsis

  • Why are efforts in brain delivery not yet equivalent to CNS drug discovery?
  • Exploring the current state-of-the-art approaches to targeting the BBB delivery of therapeutics
    including receptor-mediated transcytosis, nanotechnology strategies, intranasal drug delivery and BBB disruption technologies
  • Is receptor-mediated transcytosis the most effective option for intravenous drug delivery to the brain?
  •  What approaches can we use to unravel new transport routes?
  • What emerging areas should we focus on to address current deficiencies in brain targeting?
  • Why are we slow to execute brain drug or gene development in parallel with BBB drug delivery technology?

9:30 am Leveraging Tumor Treating Fields (TTFields) to Overcome the BBB

  • Carsten Hagemann Head of the Tumorbiology Laboratory Department of Neurosurgery, University Hospital Wuerzburg

Synopsis

  • TTFields at 100 kHz have the potential to transiently open the BBB in vitro and in vivo
  • The effect was dependent on TTFields intensity and involved delocalization of specific tight junction proteins by cytoskeletal alterations
  • BBB impermeable drugs can target GBM brain tumors in vivo after TTFields induced BBB opening

10:00 am Speed Networking

Synopsis

This session is the ideal opportunity to get face-to-face time (albeit 2D faces) with many of
the brightest minds working on tackling the BBB. Benchmark against the industry leaders and
establish meaningful business relationships to pursue for the rest of the conference and beyond

Evaluating Species to Species Translation of BBB Shuttles & the Neuropharmacokinetics of Brain Penetrating Antibodies

11:00 am Blood-Brain Barrier Delivery in Non-Human Primates by Single Domain VNAR Antibodies to TfR1

Synopsis

  • Ossianix developed multiple BBB shuttles based on single domain VNAR antibody that were shown to deliver functional payloads to brain in mouse models
  • New lead antibody TXP1 with specificity to human and cyno TfR1 showed efficient brain penetration in non-human primates
  • When administered at 1.35mg/kg, TXP1 reached ~4nM concentration in brain at 20-hour timepoint
  • In comparison to negative control, TXP1 showed over 30-fold increase in hippocampus

11:30 am Enabling Peripheral Enzyme Replacement Therapy to Alleviate CNS Pathology in Lysosomal Storage Disease

  • Will Costain Senior Research Officer, Human Health Therapeutics Research Centre, National Research Council of Canada

Synopsis

  • CNS pathology is common in many Lysosomal Storage Diseases
  • The BBB excludes peripherally administered ERT from the brain
  • BBB-penetrating single domain antibodies can affect brain delivery of enzymes
  • Albumin-binding single domain antibodies enhance pharmacokinetic and brain delivery of enzymes

12:00 pm Application of Grabody B, an IGF1R-Mediated BBB Shuttle

Synopsis

  •  Various therapeutic antibodies fused with Grabody B showed higher CNS nexposure than mAb in both rodents and non-human primates, proving Grabody B’s versatile applicability
  • The relation between the improved CNS exposure and pharmacodynamic effect was well-established in both rodents and nonhuman primates
  • ABL301, a bispecific antibody composed of anti-alpha synuclein (a-syn) IgG and Grabody B showed better efficacy than anti-a-syn Ab in both Parkinson’s Disease and MSA models

12:30 pm Bispecific Brain-Penetrating Antibodies – New Possibilities for In Vivo Brain Imaging

Synopsis

  • Radioligands based on antibodies: advantages and challenges for in vivo imaging
  •  Antibody formats and size: implications for imaging
  • Imaging of antibody neuropharamacokinetics

1:00 pm Live Q&A with Your Expert Speakers

  • Sungwon An Director, ABL Bio
  • Stina Syvänen Associate Professor, Uppsala University
  • Pawel Stocki Director of Research, Ossianix
  • Will Costain Senior Research Officer, Human Health Therapeutics Research Centre, National Research Council of Canada
  • James Gorman Brain Targeting Program , Wyss Institute for Biologically Inspired Engineering

1:20 pm Networking Lunch

Exploring CNS Gene Therapy & New Generation Vectors to Overcome the BBB

2:00 pm Crossing the Blood-Brain Barrier to Improve CNS Gene Therapy: From Preclinical Models to Clinical Applications

  • Nathalie Cartier Head of NeurogenCell Lab, Paris Brain Institute (ICM), INSERM, Paris Sorbonne University, CNS Expert, Asklepios BioPharmaceutical, Inc.

Synopsis

  • CNS gene therapy: new generation vectors for intravenous delivery
  • Improving blood brain barrier crossing using focus ultrasounds
  • From genetic to complex diseases: the challenge to treat large numbers of patients

2:30 pm Overcoming the BBB with Direct CNS Delivery: Advantages and Challenges

Synopsis

  • Overview of the evolution of direct CNS delivery
  • Circumventing the BBB with direct delivery and potential safety issues
  • Advantages and disadvantages with direct CNS delivery vs. alternate routes
  • Challenges of scaling up for CNS delivery beyond highly specialized centers

You’ve all been asking for it! COVID & the BBB

3:00 pm Exploring Mechanisms of SARS-CoV-2 Brain Entry: a Focus on the Blood-Brain Barrier

Synopsis

  • SARS-CoV-2 is detected in brains of some COVID-19 patients
  • SARS-CoV-2 spike protein can cross the BBB via adsorptive transcytosis
  • Mechanisms of spike protein uptake vary by tissue
  • Inflammation alters the systemic distribution of spike protein and increases spike protein levels in the brain

3:30 pm Live Q&A with Your Expert Speakers

  • Nathalie Cartier Head of NeurogenCell Lab, Paris Brain Institute (ICM), INSERM, Paris Sorbonne University, CNS Expert, Asklepios BioPharmaceutical, Inc.
  • Amber D. Van Laar VP Clinical Development, Asklepios BioPharmaceutical, Inc.
  • Michelle Erickson Research Assistant Professor, VA Puget Sound
  • Felix Schumacher Program Leader Targeted Therapeutics, Roche

3:45 pm Afternoon Break

Exploring the ‘Other’ Barriers (B-CSF & BRB), the Use of Exosomes & CNS Drug Discovery

4:10 pm BBB-Improving Strategies to Prevent Retinopathies

Synopsis

  • We have developed methods to regulate vascular stability (and BRB integrity) with small molecules, transgenic, and antibody therapies
  • Vascular stabilizing therapies prevent vision loss in preclinical models and in patients with diabetic retinopathy and/or AMD
  • Our lab is focused on developing better models of BBB for drug delivery, and for therapies to prevent ischemic retinopathies

4:40 pm Targeting the “Other” Blood-Brain Barriers for Cerebral Drug Delivery

Synopsis

  • Assessing why we need to understand the other barriers at the CNS
  • Dissecting transport and neuroprotection mechanisms at the developing and adult blood-brain and blood-CSF barriers
  • What advantages are there to target these barriers in addition to the classic BBB? How targeting the blood-CSF barrier can help the penetration of biologics into the brain
  • What are the common and specific hindrances to drug delivery of eachbarrier?
  • Exploring predictive models of the in vivo blood CSF barrier

5:10 pm Neural Extracellular Vesicle Role in Noninvasive CNS Drug Delivery

Synopsis

  • All extracellular vesicles are complex, but origins of extracellular vesicles play a key role in their ability to cross into CNS and delivery products.
  • Unique ligand composition on neural extracellular vesicles play a key role in receptor mediated cell uptake
  • Extracellular vesicles properties can be enhanced with unique surface modifications

5:40 pm CNS Drug Discovery: A Strategy to Develop Freely Penetrant CNS Drugs

Synopsis

  • Designing drugs that are able to freely penetrate the BBB, ensuring adequate drug is available at the site of action to evoke the desired pharmacology is a critical aspect to developing successful CNS drugs
  • A combination of in vitro and in vivo studies were identified to drive rapid design, optimization, and prioritization of chemical matter with good brain penetration
  • A risk assessment strategy was integrated into programs to communicate the impact of the extent of brain penetration on the predicted human dose and exposure parameters in combination with other relevant program data such as safety exposure multiples

6:10 pm Live Q&A with Your Expert Speakers

6:30 pm Chair’s Closing Remarks