7:30 am MORNING REFRESHMENTS & CHECK IN
8:20 am Chair’s Opening Remarks
BRIDGING PRECLINICAL SUCCESS & CLINICAL REALITY: TRANSLATING PROTEIN DEGRADATION THERAPIES FOR NEURODEGENERATIVE DISEASE
8:30 am PROTAC LRRK2 Degrader Molecules as Potential Disease Modifying Therapeutics for Neurodegenerative Diseases
Synopsis
- Overview of Arvinas’ PROTAC strategy for neurodegenerative diseases
- Review of in vitro and in vivo data for potent, orally bioavailable PROTAC LRRK2 degrader molecules
- Biomarker changes in non-human primates consistent with LRRK2 PROTAC mechanism of action
9:00 am Harnessing the AUTOTAC Platform for Development of a First-In-Class Tau Aggregate Degrader: Bridging the Gap Between Discovery, Preclinical Candidacy & Clinical Trials
Synopsis
- Development of a novel targeted protein degradation platform (AUTOTAC) via p62-dependent selective macro-autophagy
- Application of the AUTOTAC platform to develop a first-in-class tau aggregate degrader ready for clinical trials
- Translation of academic discovery into industry-level drug development
9:30 am Navigating the Next Steps in Neurodegenerative Therapies: Assessing Drug Safety, Regulations & Progressing Through Trials to Get Protein Degrader Drugs to Clinic to Improve the Treatment of CNS Disease
Synopsis
- In vitro and in vivo safety and toxicity profiling – overview of the methodologies able to assess safety, toxicity and off-target effects as well as selecting appropriate biomarkers for progressing to clinical trials
- Current regulatory landscape for protein degrader therapies – regulatory requirements and guidelines that need to be met to get approval for use as drugs
- Challenges that novel protein degradation drugs for neurodegenerative diseases face in the approval process – preclinical study design and navigating the FDA/EMA regulatory pathways
10:00 am Panel Discussion – What Do We Need To Do To Get Protein Degraders To Clinic For Treating Neurodegenerative Disease?
Synopsis
- How translatable are the current models to clinic and what do we need to advance them for approved use?
- What are the regulatory hurdles for protein degraders in neurodegenerative disease?
- What lessons have been learnt by past failures in neurodegenerative drug development that can inform the success of protein degraders?
10:30 am SPEED NETWORKING:
Synopsis
Put a face to a name – this session is the perfect opportunity to get face-to-face time with key opinion leaders, leading companies, and innovative researchers in the protein degradation and neuroscience fields. Establish meaningful connections to build upon for the rest of the conference and gain individual insight beyond the papers and press releases into the pioneering research and therapeutic development
11:15 am MORNING BREAK
SOLVING PHARMACOKINETIC & PHARMACODYNAMIC CHALLENGES IN THE BRAIN TO ADVANCE PROTEIN DEGRADER DRUGS TO CLINIC: FROM DISTRIBUTION TO DOSING
11:30 am Evaluating the Progress in PK/PD Research for Optimising Drug Efficacy to Enhance the Translation of Therapies for CNS Diseases
Synopsis
- Review the challenges of drug development for brain tumors
- Overview of pharmacokinetics and pharmacodynamic studies to ensure adequate drug concentration across blood brain barrier
- Strategies to improve delivery across blood-brain barrier in neuro-oncology
12:00 pm Round Table Discussion: Cross-Disciplinary Perspectives on PK/PD in Protein Degradation Drug Development for Neurodegenerative Diseases
Synopsis
Current Challenges and Opportunities in PKPD for Neurodegenerative Diseases:
- What are the unique challenges in developing PKPD models for neurodegenerative diseases?
- How can we leverage existing PKPD frameworks to better understand the efficacy and safety of protein degraders?
Mechanistic Insights and Translational Approaches:
- How do the mechanisms of action of protein degraders differ from traditional small molecules in terms of PKPD?
- What translational strategies can be employed to predict clinical outcomes from preclinical data
Innovative Technologies and Methodologies:
- What are the latest technological advancements in PKPD modeling for protein degraders?
- How can computational techniques and high-throughput screening be integrated into PKPD studies?
1:00 pm LUNCH
EXPLORING MECHANISMS FOR TARGETED PROTEIN DEGRADATION TO COMBAT CNS DISEASES: ADVANCEMENTS IN APPROACH & ENHANCEMENTS IN STRATEGY
2:00 pm Activation of Parkin by a Molecular Glue
Synopsis
- Discovery of the THPP compound series of Parkin activators
- Deconvolution of the mechanism of action of the Parkin activator as a molecular glue
- Broader implications of understanding this binding site and the considerations for designing other ring-between-ring E3 ligase molecular glues
2:30 pm Mechanisms for Extracellular Targeted Protein Degradation in Immune Cells, Neurons & Glia
Synopsis
- Exploring bifunctional small molecule mechanisms for extracellular targeted protein degradation
- Cell-type specific targeted degradation of extracellular disease proteins in immune and neuronal cells
- Targeted degradation of extracellular neuronal aggregates
3:00 pm AFTERNOON BREAK & POSTER SESSION
Synopsis
Want to share your work but not ready for the big stage just yet? The Scientific Poster Session is your prime time to share your work with peers from discovery, preclinical, translational and clinical backgrounds, all working on developing protein degraders for neurodegeneration and neuro-oncology. Get their thoughts on how you can accelerate the progression of your drug pipelines and build connections for potential collaborations to expand your R&D pipelines.
4:00 pm Discovery of First-In-Class Brain-Penetrant NEK7 Molecular Glue Degrader For the Treatment of Neuroinflammation
Synopsis
- NEK7 and its role in neuroinflammation
- NEK7 as a target for targeted protein degradation
- Spectacular properties of NEK7 molecular glue degraders
4:30 pm Focused Ultrasound-Mediated Blood Brain Barrier Opening to Enhance Drug Delivery
Synopsis
- Overview of the use of focused ultrasound in combination with microbubbles to create transient, safe and targeted opening of the blood brain barrier to aid drug delivery
- Review key findings from clinical trials and preclinical studies for a range of disease types that support the safety and feasibility of the technology as a method for enhancing drug delivery
- Future opportunities and challenges for the technology in combination with promising drug candidates for better treatment of CNS diseases
5:00 pm Expanding the Set of Zinc Finger Proteins Accessible to Drug-Induced Protein Degradation by CRBN
Synopsis
- Functional genomics define the ZF degron landscape, revealing ZF targets not detectable in proteomics experiments for CRBN degraders
- Potent degraders can accommodate a broader range of substrates. Contacts outside the core ZF degron can contribute to neo-interaction
- Clusters of CRBN amino acids are linked to patterns of activity. Different substrates or drugs can interact with distinct CRBN surfaces. A single amino-acid change can determine degradation selectivity
5:30 pm Chair’s Closing Remarks
5:35 pm End of Conference Day 1
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- 18+ Expert Speakers
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