CONFERENCE DAY TWO
All times in EDT
8:00 am Morning Networking Coffee
8:45 am Chair’s Opening Remarks
A New Paradigm: Modulation of YAP to Alter TEAD Responses within the Hippo Pathway
9:00 am Unearthing Novel Pharmacology Targeting the Hippo Pathway for Regenerative Organ Repair
Synopsis
- Championing novel small molecules and associated cellular mechanisms of action for contextually inactivating Hippo signaling
- Categorizing strategies to overcome off organ hyperplasia
- Pinpointing proof of concept efficacy data in rodents and pigs demonstrating regenerative repair
9:30 am Uncovering Molecular Physiology of Hippo/YAP Activity to Develop Genetic Medicines for Meaningful Tissue Regeneration
Synopsis
- Spotlighting molecular physiology insights from in vivo preclinical data that inform strategies to safely activate YAP for meaningful tissue regeneration
- Leveraging gene therapy tools for controlled cell-targeted delivery of genetic medicines to activate YAP
- Harnessing in vivo models to demonstrate efficacy and evaluate the toxicity of lead drug candidates
10:00 am Panel Discussion: Harnessing YAP/TAZ as an Alternative to Modulating TEAD: What More Needs to be Done?
Synopsis
- What are the key events leading to YAP/TAZ activation
- Should we activate YAP/TEAD by directly binding it or through inhibiting upstream targets including the hippo signaling pathway ? What’s the merit of either approach?
- What are the current limitations of these molecules and potential ways to improve them?
- What are the potential liabilities/concerns with modulating TEAD/YAP activity
- What are the most promising clinical indications?
10:45 am Morning Break & Poster Session
11:30 am Roundtable Discussion: Poster Session Debrief
Synopsis
This is an opportunity to collate new findings and lessons learned from the poster session. Attendees can share thoughts and ideas born from the posters and ensures no stone is unturned , and no piece of information missed.
- What data did you find most compelling amongst the posters?
- Did any posters inspire new areas of interest for you or your group to potentially pursue? Why?
12:00 pm Deciphering the Context of YAP/TAZ Signaling Across Diverse Cells & Tissues in Vivo
Synopsis
- Leveraging molecular and genetic insights to elucidate further understanding of transcriptional regulators, YAP and TAZ
- Spotlighting limitations of in vitro models of disease through in vivo data
- Interrogating genomic data for insight into clinical biomarkers and therapy targets
12:30 pm Lunch & Networking
Future Thinking: Alternative Therapeutic Methodologies to Target the Hippo Pathway
1:30 pm Inhibiting TEAD in Cancer: An Interactomic Approach
Synopsis
- Delineating how TEAD protein interactions mediate their transcriptional function
- Leveraging mass spectrometry approaches to understand TEAD biology and TEAD inhibitors
- Creating deeper understanding of TEAD interactions and TEAD biology is essential for informing the advancement of TEAD inhibitors
2:00 pm Building Towards Subtype Specific Degraders of TEADs Based on Interface 3 Binding
Synopsis
- Elucidating how pan-TEAD binders targeting interface 3 can be used as disruptors of the YAP/TEAD protein-protein interaction
- Showcasing subtype specific degraders of TEADs, based on interface 3 binders, being optimized by using a ternary complex formation assay
- Demonstrating how a TEAD degrader, in contrast to palmitoylation inhibitors, will block all transcriptional activation by TEAD and hence is expected to be more efficacious as a cancer treatment.
2:30 pm Afternoon Break & Networking
3:00 pm Roundtable Discussion: Let’s Talk About Toxicity, Safety, & the Hippo Pathway
Synopsis
- Can we avoid toxicity with TEAD selective compounds?
- How are we testing compound safety versus target safety?
- Can we produce safe combination therapies?
- Can we mitigate possible target safety with intermittent dosing?
3:30 pm Development of Covalent TEAD Inhibitor to Suppress Defective Hippo Signaling
Synopsis
- Covalent Targeting TEAD Palmitoylation cysteine
- Covalent inhibition of TEAD suppresses TEAD-regulated gene expression
- Covalent TEAD inhibitor inhibits the proliferation of the cell with TEAD/YAP dependence
- Orally bioavailable TEAD Covalent Inhibitor demonstrates anti-tumor effect on mesothelioma mouse model.
4:00 pm Accelerating Epigenetic Understanding to Combat Cancer Resistance
Synopsis
- Exploring the rationale for approaching TEAD modulation through the lens of epigenetic impacts
- Demonstrating biological basis epigenetically in using drug combinations to counter resistance
- Proposing some next steps for translation into clinical drug development
4:30 pm Chair’s Closing Remarks
4:45 pm End of 2nd Annual Hippo Pathway Targeted Drug Development Summit
