8:30am | Opening Registration & Morning Coffee

Emerging Strategies to Target a Broad Range of RAS Mutations

9:00 am T-Cell Receptor Targeting of Multiple RAS Mutant Forms in Broad Patient Populations

Synopsis

  • Characterization of RAS T-cell receptor (TCR) targets
  • TCR discovery and characterization for multiple RAS mutations
  • Challenge and propose of TCR-modified cell therapies targeting RAS mutations

9:30 am 2nd Generation Antigen Presenting Cells for Multiple KRAS Mutations

Synopsis

  • SQZ APC mechanism overcomes challenges of previous cancer vaccines with CD8 T-cell activation and can be enhanced with mRNA cargo combinations
  • SQZ APC clinical program overview: Safety and manufacturability of SQZ’s APC candidate in solid tumors
  • Preclinical data for SQZ’s enhanced APC platform in targeting KRAS G12D and G12V mutation

10:00 am Chemotype Evolution Platform for Discovering Covalent Inhibitors of KRAS G12C & Beyond

  • Jack Sadowsky Principal Investigator of Discovery Chemistry, Carmot Therapeutics

Synopsis

  • We will present the development of Chemotype Evolution for rapid, highthroughput identification and advancement of covalent inhibitors
  • Challenges faced and overcome in the construction and screening of covalent warhead-fragment libraries will be described
  • We will describe the deployment of our approach to identify potent covalent inhibitors of KRAS G12C

10:30am | Structured Networking & Refreshment Break

Synopsis

As the RAS community is reunited, this valuable session will ensure you can reconnect with your peers in the room to make new and lasting connections. Running concurrently as an in-person and digital session, all attendees will have the opportunity to meet and network with their academic and industry colleagues

Novel Biologics & Degradation Mediated Strategies Against RAS Mutant Cancers

11:30 am PROTAC Mediated Degradation of KRAS

Synopsis

  • KRAS PROTACs that employ novel ubiquitin ligase and degrade different KRAS isoforms will be the subject of this talk
  • Current methods for PROTAC discovery are not optimal. Use of PROTAC mediated in-vitro ubiquitination to expedite discovery of novel PROTACs
  • Me too ligase, VHL and Cereblon do not offer specificity for certain targets. Relationship between in vitro and in vivo ubiquitination and PROTAC mediated degradation will be discussed

12:00 pm Targeting KRAS with Mutant Selective Monoclonal Antibodies

Synopsis

  • Generation of mutant selective monoclonal antibodies
  • Functional characterization of antibodies
  • Anti-tumor activity in a xenograft tumor model

12:30pm | Lunch & Poster Session – Present, Learn & Collaborate

Synopsis

As the landscape of innovative discovery efforts to target RAS G12C &beyond expands, it is more important than ever to collaborate and learn
with your peers as we continue to advance RAS targeted therapies through discovery. Join our dedicated session to share your latest data and have a first look about what your peers are working on!

Tools & Strategies for Drugging High Value Targets Within the RAS/MAPK Pathway

1:45 pm Structural Insights into Pharmacologic Targeting of the RAS/ RAF/MEK/ERK Pathway

  • Michael Eck Professor, Department of Biological Chemistry & Molecular Pharmacology Harvard Medical School

Synopsis

  • Cryo-EM structures show how BRAF, MEK, and a 14-3-3 dimer or organized in autoinhibited and active states
  • Binding of ATP in the active site of RAF is crucial for maintaining auto inhibition, RAF inhibitors that displace it cause activation
  • RAS can engage autoinhibited RAF complexes without disrupting them
  • Stabilizing autoinhibited RAF
  • Complexes may be an attractive therapeutic alternative to blocking binding of active Ras or inhibiting active Raf

2:15 pm MAPK & Hippo-YAP1 Signaling: At the Crossroads of Cancer Progression & Resistance to Therapy

2:45 pm GFH925 (aka IBI351), A Novel Covalent Inhibitor for KRAS G12C

  • Siyuan Le Senior Director of Biology, GenFleet Therapeutics

Synopsis

  • Preclinical enzymatic, cellular and animal studies indicates GFH925 is a highly selective
  • Proteomic studies reveals a covalent binding mechanism of GFH925 to 12C position, and a clean promiscuity profile of GFH925
  • PK result gives a differentiation profile of GFH925, when comparing other leading compounds with same mechanism
  • Now the compound is in Phase I clinical phase

3:15pm | Chair’s Closing Remarks

3:30pm | End of 3rd RAS/MAPK Pathway Targeted Drug Discovery Summit