Explore the Agenda
Welcome to our pre-conference day. You can either attend our Academic Frontiers Day, or our dedicated TPD 101: Tools & Technologies Day or our three workshops covering Strategic Design Principles for TPD. If you have any questions about the layout or agenda, feel free to reach out to us at info@hansonwade.com.
Academic Frontiers Day
8:00 am Check-in & Morning Coffee
8:50 am Chair’s Opening Remarks
Pioneering Next-Gen Molecular Glue Modalities Through Mechanistic Insight, Ligase Expansion & Chemoproteomics Platforms to Unlock Undruggable Targets
9:00 am A Glue Here, A TAC There: Induced Proximity as a Drug Modality
- Discussion of the history of the TPD field
- Discussion of the current projects in the Crews Lab
- Discussion of future Induced Proximity modalities
9:30 am Unveiling the Hidden Interactome of CRBN Molecular Glues with Chemoproteomics
- Developed a scalable affinity purification mass spectrometry workflow for the identification of chemically glued targets
- Screened 20 IMiD analogs and identified over 290 targets chemically recruited to CRBN. Targets were prioritized through computational alignment analysis
- The novel nonZF target PPIL4 was validated and the new selective lead molecule identified through a biochemical screen of over 6,000 IMiD analogs
10:00 am There is More Than One Ligase for Each Target & We Know It …
- Protein Language and biophysical modelling speak ligase dialect, and can rationally, efficiently and quickly find multiple ligases for a given target
- Binary complexes, from structural modelling open the door to novel molecular glue designs
- Novel AI methods can use the above techniques even in disordered proteins
10:30 am Morning Break & Networking
Unlocking Novel Degraders & Substrates with Multimodal Tools & PROTAC Trafficking Insights to Enhance Selectivity & Cellular Access
11:30 am Multimodal Screening Strategy for Discovery of Novel Cereblon-Directing Molecular Glue Degraders & Neosubstrates
- Molecular Glue Degrader (MGD) discovery mostly relies on screening-based approaches, such as cell viability assays. However, one limitation of such screening methods is the risk of overlooking non-essential neosubstrates of potential therapeutic value
- To address this risk, we developed a high throughput deep proteomics screening platform utilizing label-free, data-independent acquisition mass spectrometry for integrated proteomics and “ubiquitinomics” analysis
- Screening a diverse subset of our large CRBN-focused library uncovered multiple potent and selective degraders of previously unreported cereblon neosubstrates
12:00 pm CD36-Mediated Endocytosis of PROTACs
- Identified CD36 as a membrane target for PROTACs through biotinylated probe-based target fishing
- Demonstrated CD36’s role in facilitating cellular uptake of diverse molecules ranging from 543 to 2,145 Da
- Explored the impact of CD36 knock-down/knock-in on the efficacy of the clinical PROTAC ARV-110 in both in vitro and in vivo models. CD36 knockdown wiped out ARV-110 efficacy in vitro and in vivo
- Leveraged endocytic medicinal chemistry strategies to enhance PROTAC potency and improve drug properties
- Clinical responses of large molecules correlate with the expression of CD36
12:30 pm Lunch Break
Advancing Cereblon Ligand Discovery & Molecular Glue Design to Expand the Degrader Landscape
1:30 pm Ligands for the E3 Ligase Substrate Adapter Cereblon
- Endogenous ligands that regulate cereblon
- Cyclimid ligands derived from the natural cereblon degron
- Contributions of allostery to degradation outcomes
2:00 pm Advances in the Systematic Discovery of Molecular Glue Degraders
- Recent work on understanding the principles that govern molecular glue interactions
- Recent examples of success in expanding the repertoire of ligases enabled for molecular glues
- Updates on our discovery platforms
2:30 pm Afternoon Break & Networking
Driving Scientific & Strategic Progress in Induced Proximity with Next-Gen Therapeutics & Visionary Academic Insights
3:00 pm Proximity Induced Glue Molecules for Protein Degradation & New Pharmacology
- Discovery of degrader glue through covalent warhead
- Bivalent glue for transcription rewiring
- Bivalent glue for a selective pharmacology
3:30 pm Roundtable Discussion: Where Will Academia Trailblaze and Identify New Directions for the TPD & Induced Proximity Industry?
Join academic KOLs for a discussion on things yet to come for induced proximity therapeutics. Expect to cover next-generation PROTACs, degrader
antibody conjugates, the new focus on cooperative molecular glues, and non-degrading proximity therapeutics. This will be a chance to hear about the latest academic research, opportunities for growth in biopharma, and first-hand opinions from leading pioneers on where the TPD and induced proximity community is headed.
4:30 pm Chair’s Closing Remarks
4:45 pm End of the 2nd New Frontiers in Induced Proximity Day
TPD 101: Tools & Technologies Day
8:00 am Check-in & Morning Coffee
8:50 am Chair’s Opening Remarks
Accelerating Next-Gen Molecular Glue Discovery with Novel CBM/PDL Libraries & Lysate-Compatible High-Throughput Screening Platforms
9:00 am Accelerating Molecular Glue Discovery with CBM/PDL Platforms for Novel Target Engagement
- Leveraging a structurally distinct cereblon-binding module (CBM) library to recruit novel neosubstrates beyond traditional thalidomide analogues
- Deploying a proteomics-based degron library (PDL) to predict degron motifs and prioritize new molecular glue degrader (MGD) targets
- Highlighting case studies of MGD discovery and optimization to expand druggable target space
9:30 am Optimizing Drug Discovery with the Development of an Ultra High-Throughput, Lysate-Compatible Induced Proximity Screening System
- Advantages of cell lysate-based screening over recombinant protein screens
- Adapting high-throughput combinatorial chemistry to improve upon their sensitivity, enable their compatibility with cell lysates, and allow their discovery of induced proximity small molecules
- Sharing proof-of-concept data (either full scale, or if not yet available, model system) for Birdwood’s platform
10:00 am Application of Plexium’s Picowell Screening Technology to the Identification of Helios Molecular Glue Degraders
- Application of Plexium’s proprietary ultrahigh density Picowell screening technology to the identification of cereblon mediated molecular glue degraders (MGDs) of Helios (IKZF2) will be described
- Hits from the screen were shown to bind to cereblon, and degradation of Helios was independently confirmed in a Helios-GFP assay and by global proteomics. Loss of Helios was rescued by co-treating with a proteasome inhibitor confirming dependence on the ubiquitin proteasome system
- Collectively, these results demonstrate that Plexium’s Picowell screening platform enables the discovery of MGDs of Helios
10:30 am Morning Break & Networking
Building Smarter Discovery Funnels with High-Throughput Screening, Predictive ADME Tools & Data-Driven Degrader Optimization
11:30 am Developing a Screening Funnel for Targeted Protein Degraders
- Establishing high-throughput assays for on and off-target degradation
- Applying learnings from drug discovery efforts in the “beyond rule of 5” chemical space to predict and assess oral bioavailability
- Profiling PK/PD in vivo and conducting lead optimization studies (Tier 2 ADME, selectivity, and cross-species DMPK)
12:00 pm Streamline the Process for Rational Molecular Glue Development
- How to pair your target with the right E3 ligases
- Applying the right screening strategy to improve the chance of finding glue hit
- Developing a screening funnel for molecular glue degrader ID
12:30 pm Lunch Break
Pioneering Non-Degrader Glue Modalities to Modulate Challenging Targets & Reprogram Protein Function to Unlock New Treatment Opportunities
1:30 pm A Pursuit of the Development of Non-Degrader Molecular Glues Targeting Different Protein Complexes
- Advances in cryo-EM and structure determination have accelerated drug-discovery and development
- Screening strategies for molecular glue stabilizers of different macromolecular targets
- Structure and computational based approaches to accelerate drug discovery
2:00 pm Towards a Comprehensive, Fit-for-Purpose Induced Proximity Platform
- Optimal Screening strategies
- Phenotypic approaches to Target Selection
- Induced proximity beyond CRBN Glues
2:30 pm Afternoon Break & Networking
Harnessing Targeted Delivery & AI-Driven Discovery to Overcome Challenges in Protein Degradation & Accelerate Therapeutic Development
3:00 pm Utilizing AI / ML to Explore Glue Degrader Chemistry & Target Discovery in Early Hit Identification
- Mapping degrader-target interactions using surface fingerprinting and internal/external datasets
- Enhancing glue library design through mechanistic insights and data-driven approaches
- Applying deep learning models to predict degrader efficacy and uncover novel degradation rules
3:30 pm Targeted Delivery of Biological PROTACs: A New Approach for Degrading Challenging Protein Targets
- Biological PROTACs act as novel intracellular mechanisms to degrade undruggable proteins
- Antibody-based nanoparticles effectively address challenges in intracellular protein delivery
- Achieving efficient, targeted degradation offers new treatments for various diseases, including autoimmune disorders
4:00 pm Chair’s Closing Remarks
4:15 pm End of the TPD 101: Tools & Technologies Day
Strategic Design Principles for TPD Workshop Day
8:30 am Workshop A – Discovering Ligase-Target Pairings & Kick-Start Molecular Glue Discovery Program & Enable Rational Drug Design
When starting molecular glue development from scratch, finding the right interaction to stabilize is the most crucial
step. In this workshop, you will learn to decode targetligase pairs and accurately visualize ternary complexes to accelerate molecular glue discovery. We will cover:
- How to identify the right target-ligase pairings with high-throughput assays
- Choosing the best libraries, assays, and biophysical methods to discover and validate hits for molecular glue development
- Using in silico modeling to optimize ternary complex visualization
10:30 am Morning Break & Networking
11:00 am Workshop B – When to Use TPD: Ensuring Your Degrader is the Best-in-Class Approach to Drug Your Target
Identifying why TPD is the best approach for a target is the first step to becoming the standard of care. In this session, you will explore key factors that determine when a degrader is the best strategy for your target and how to differentiate it from traditional inhibitors. We will cover:
- The unique advantages of degraders: When and why TPD outperforms conventional approaches
- The advantages of a TPD approach versus using inhibition only in regulating BRAF-V600 mutant MAPK pathway signaling in cancer
- Discovery of first-in-class potent and selective oral degraders of KAT6A that demonstrate robust anticancer activity in pre-clinical models
1:00 pm Lunch Break
2:00 pm Workshop C – Optimizing the Right Degrader Properties – Developing Efficient & Dependable TPD Design Principles
Effective degrader development relies on precise optimization of key molecular properties to ensure robust, reliable degradation efficiency. Explore how to measure these essential properties, build a process for efficient optimization, and develop a platform to create degraders quickly and reliably. Featuring real-world case studies, this session offers practical strategies to streamline degrader design for maximum therapeutic impact. We will cover:
- The creation of HPB-143/VP-776: an optimized IRAK4 PROTAC modeled against the benchmark KT-474
- Identification and development of BCL-XL protein degraders
- Is ternary complex kinetic stability a key driver of degradation efficiency?