Conference Day 2

All times in EDT

8:30 am Welcome Coffee & Networking

8:50 am Chair’s Opening Remarks

  • Anwesha Dey Principal Scientist, Discovery Oncology, Genentech

Advancing Development of Safe, Durable & Effective Hippo Targeted Candidates for Patient Intervention

9:00 am TEAD Palmitoylation Inhibitors – From Discovery to the Clinic

  • Len Post Chief Scientific Officer, Vivace Therapeutics

9:30 am Targeting the Hippo Pathway with Conditional Modulation of TEAD Activity

  • Glen Rennie Principal Scientist, Cedilla Therapeutics

Synopsis

  • Mechanistic insights into the allosteric inhibition of TEAD
  • How Cedilla is using multiple methodologies to screen for inhibitors with distinct mechanisms of action
  • Opportunities for treating cancers with Hippo pathway dysregulation

10:00 am Discovery & Development of Novel YAP/TAZ-TEAD Antagonists

Synopsis

  • Activity of the YAP/TAZ-TEAD complex represents a compelling pharmacologic target
  • We have identified novel small molecules that bind to the TEAD autopalmitoylation pocket; these compounds are highly potent, orally bioavailable and active against multiple cancer cell lines
  • In vivo models of Hippo pathway-altered xenografts showed that our inhibitors deliver consistent monotherapy activity, with dose-dependent and durable tumor regressions achieved at well-tolerated doses

10:30 am Hippo Pathway & RAS: Relationship & Therapeutic Potential

Synopsis

  • Overview of Ikena efforts to target the Hippo pathway
  • Hippo & RAS: pathways and mechanisms of resistance
  • IK-930: Ikena’s TEAD inhibitor

11:00 am Morning Break & Speed Networking

Synopsis

As the community if individuals working to drug the Hippo pathway is united, this valuable session will ensure you can reconnect with your peers to make new and lasting connections, as all attendees will have the opportunity to meet and network with academic and industry colleagues

Reviewing Safety, Toxicity & Druggability Concerns for Targeting the Hippo Pathway

12:00 pm Leveraging the Hippo Pathway for Therapeutic Intervention – Optimizing Translation, Animal Models & Safety

Synopsis

As we continue to see more success with drugs targeting the Hippo pathway, it is critical that we consider how to optimize translation and safety to the patient. This panel discussion will consider all important elements to nurture the success of Hippo targeted therapies, including debates on topics surrounding advanced animal models, pharmacology and toxicology, through to patient selection

1:00 pm Lunch Break & Networking

Harnessing Hippo Signaling Vulnerabilities for Therapeutic Intervention

2:00 pm MSC-4106: From TEAD P-Site Binding Fragment into In Vivo Active Lead

  • Timo Heinrich Associate Scientific Director, Head of Laboratory, Merck Healthcare KGaA

Synopsis

  • Fragment hit identification and structure enabled optimization
  • TEAD 1/2/3/4 selectivity investigations based on thermal shift and palmitoylation assays for MSC-4106 and a couple of published covalent and reversible P-site and surface binder
  • In vivo efficacy and PD biomarker correlation for MSC-4106

2:30 pm YAP vs TAZ-Dependence of Different Cancer Cells

Synopsis

  • YAP and TAZ in disease: do they have the same role?
  • Cells from different cancers or from the same cancer indication can be either YAP- or TAZ-dependent
  • Potential implications for patient selection, prediction of response and final outcome in clinical trials

3:00 pm Large Scale Functional Epigenomics Reveal Context Dependent Hippo Vulnerabilities

Synopsis

  • YAP and TAZ are now established oncogenes in multiple cancer types
  • Cancers bearing genetic aberrations in Hippo pathway respond to TEAD perturbations
  • Other cancer types – YAP engages a different cistrome to drive its oncogenic function

3:30 pm YAP-dependent proliferation by a small molecule for regenerative repair

  • Sophia Shalhout Cutaneous Oncology Research Fellow, Mass General Cancer Center, Harvard Medical School

Synopsis

  • Pharmacological activation of YAP through small molecule targeting of a key scaffolding/sensor protein which is contextually essential in relaying inhibitory phosphorylation to YAP.
  • Potential transient or pulsatile dosing of a YAP-activating drug may be beneficial for organ repair in acute clinical settings, such as heart failure or diabetic wounds.

4:00 pm Chair’s Closing Remarks & End of the Hippo Pathway Targeted Drug Development Summit

  • Anwesha Dey Principal Scientist, Discovery Oncology, Genentech