7:00 am Registration Opens
7:50 am Chair’s Opening Remarks
Keynote Plenary Session: Harnessing Key Discoveries of Bifunctional Degraders to New Targets
8:00 am Exploiting Tissue Sparing E3 Ligases for Next Generation TPD Medicines
Synopsis
- Highlighting the promises and challenges of exploiting tissue sparing E3 ligases
- Pinpointing LED selection criteria for novel E3 ligases for TPD application
- Showcasing tissue sparing E3 ligases to unlock clinically validated targets
8:30 am Oral, Blood-Brain Barrier Penetrant CDK4/6 Bifunctional Degrader for Breast Cancer & Other Solid Tumors
Synopsis
- Highlighting Biotheryx's PRODEGY platform which has enabled the discovery of bifunctional molecules that demonstrate highly selective, rapid, and deep degradation of CDK4 and CDK6
- Spotlighting BTX-9341's excellent PK/ADME properties and sustained exposure in the brain, which is currently in IND-enabling studies
- Demonstrating potent tumor growth inhibition superior to the FDA-approved CDK4/6 inhibitors in breast cancer xenograft studies, including intracranial models
9:00 am Molecular Glue Degraders for Non-Oncology Indications
Synopsis
- Molecular glue degraders (MGDs) have historically been developed for oncology indications
- Our platform has enabled programs in non-oncology indications, such as diseases associated with autoimmunity and inflammation
- An overview of the additional challenges associated with degraders for non-oncology diseases will be provided, together with updates on our programs highlighting our rational design of selective and orally active MGDs
9:30 am Panel Discussion: KOL Future Advisory Panel
Synopsis
At a time when the TPD community is poised for more clinical success yet continues to battle for available funding to progress this pioneering drug modality, its crucial we heed the knowhow and experience of the field’s thought leaders. Here we have our TPD Future Advisory Panel
- Where should the field’s focus be on tackling future challenges and defining best practice to fulfil that mission?
- Where is the field of TPD heading and what can we learn from the past?
- What is the next ‘big thing’ in TPD and why?
10:15 am Morning Break
TARGET ID & HIT VALIDATION
11:15 AM - 2:45 PM TARGET ID & HIT VALIDATION
Download the Full Event Guide for Presentation Details
Expert speakers on this track include:
AbbVie, NEOsphere Biotechnologies, GlaxoSmithKline, PhoreMost, Kantify, & More.
LEAD COMPOUND OPTIMIZATION
PRECLINICAL DEVELOPMENT
CLINICAL DEVELOPMENT
2:45 pm Afternoon Break & Networking
CLOSING PLENARY SESSION PLENARY SESSION
A First Look at the Road Ahead: Accelerating TPD Success with Novel Ligands, Novel Bi-functionals, & Covalent Therapies
3:15 pm HiBiT-SpyTag: A Minimal Tag for Covalent Protein Capture & Degrader Development
Synopsis
- We show a designed sized protein tag amenable to CRISPR/Cas9 knock-in which can be used for both protein quantification and covalent modification of a protein of interest
- Using BRD4 as a proof-of-concept, we show efficient labelling of HiBiT-SpyTag labelled BRD4 with a SpyCatcher-dTAG protein, which can be degraded through various dTAG PROTACs
- This tag was then used with IRE1α to develop the first PROTAC of this ER-membrane protein
3:45 pm Advances in Covalent Therapeutics
Synopsis
- Outlining the most recent advances in chemoproteomic techniques used to identify nucleophiles in tractable binding pockets
- Providing an overview of the state-of-the-art covalent warhead modalities used for targeting non-cysteine nucleophilic residues
- Describing advancements in Dunad Therapeutics’ novel monovalent covalent degrader platform, and how it can be applied to unlock new target space for the field
4:15 pm Discovery of a Bifunctional Degrader for Targeting of the RAS Pathway
Synopsis
- Biology DepMap and computational analysis reveals a target that represents a top dependency in KRAS mt Pancreatic cancer cell lines and provides alternative to targeting KRAS
- The talk will describe discovery and characterization of a highly selective and potent novel bifunctional degrader, including anti-tumor activity in vivo
- Highlight impact on the RAS pathway biology and potential therapeutic implications
4:45 pm Discovery of Cancer-specific E3 Ligands for Targeted Protein Degradation
Synopsis
- FBXW7 ubiquitinates and degrades many oncogenes such as cyclin E, c-JUN, c-MYC, NOTCH-1, and MCL-1 etc.; its hotspot mutation R465C loses substrate recognition, and drives cancer transformation through up-regulation of oncogene substrates
- Binding specifically to FBXW7 R465C mutant have been discovered through high throughput screening and validated by X-ray crystallography
- Degrading various protein targets in R465C mutant cell lines using PROTACs but not the wild-type cell lines, potentially representing a novel therapeutic approach against FBXW7 R465C mutant cancer
5:15 pm Chair’s Closing Remarks & End of Day Two
