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Conference Day One, Thursday, 27 June, 2019


Registration & Breakfast


Chair’s Opening Remarks

Speaker:  Stephanos Ioannidis, VP of Chemistry, H3 Biomedicine

Rising to the Undruggable Challenge: Targeting the Entire Proteome through Small Molecule Innovation

Limitations in our understanding of proteome biology and a lack of small molecule innovation has meant that whilst there is a huge number of highly desirable, yet difficult to reach “undruggable” proteome targets, small molecule drug discovery scientists have barely scratched the surface of the drug discovery opportunity hidden within the entire proteome. However, with game changing technology and discovery breakthroughs, join your peers for a day packed with the latest target discovery case-studies, innovative small molecule approaches and collaborative conversations focusing on novel ways to identify, validate and successfully drug the remaining 85% of currently un-drugged proteome targets.


Drugging Undruggable Protein Tyrosine Phosphatase for Neoplastic Diseases

• What are the challenges of finding and optimizing small molecules that perturb undrugged targets?
• What are the pharmacological opportunities for small molecules that perturb protein tyrosine phosphatases?
• What are the most promising approaches for targeting protein tyrosine phosphatases?

Speaker:   John S. Lazo, Harrison Distinguished Professor of Pharmacology, University of Virginia


Small Molecule Mediated Protein Degradation – From Art to Science

• Overview of current trends, challenges and opportunities
• Need for community endorsed standards
• Power of small molecule degraders as research tools

Speaker:   Milka Kostic, Program Director- Chemical Biology, Dana-Farber Cancer Institute


Targeting the Dark Kinome: Introduction to the NIH National Illuminating the Drugable Genome (IDG) Program

•Introduction and rationale of the NIH IDG program on prioritizing understudied yet likely targetable proteins as drug targets
•Presentation of a computational workflow to identify novel small molecule for understudied dark kinases with no known small molecule binders and no protein structure
•Examples and biology of novel understudied kinase targets and first in class small molecule inhibitors

Speaker:   Stephan Schürer, Associate Professor- Department of Molecular and Cellular Pharmacology, University of Miami


Monitoring Dynamics of Protein Degradation in Living Cells

• Three case studies of PROTAC mechanism of action in different systems
• The Degradogram: Live cell kinetic degradation profiles and quantitative analysis
• Relationship of cellular ternary complex formation and ubiquitination to degradation rate
• HTS screening of compounds in cellular assays

Speaker:  Richard Somberg, Director- Pharma Biotech Strategic Business Unit, Promega

10.45                                                    Speed Networking & Morning Refreshments


Principles of Small Molecule Mediated Protein Degradation

• Structural principles of small molecule mediated protein degradation
• New ‘Molecular Glue’ molecules and mechanisms
• Targeting proteins without classical binding pockets for degradation

Speaker:   Eric S. Fischer, Assistant Professor of BCMP- Harvard Medical School, Dana-Farber Cancer Institute


Drugging the Mammalian SWI/SNF Complex

• Highlighting the therapeutic opportunity within the mSWI/SNF complex
• Exemplify drugging opportunities and approaches
• High level progress on Foghorn’s platform build and programs

Speaker:   David Millan, VP- Chemistry, Foghorn Therapeutics


Discovery of Covalent DUB Inhibitors Using Chemotype Evolution

• Chemotype Evolution is an iterative technology that can rapidly generate tens of thousands of covalent molecules from a single warhead
• Covalent libraries can be used to identify new opportunities for intervention for challenging targets and pathways
• nM, cell-active inhibitors have been identified for multiple DUBs

Speaker:   Jeffrey Iwig, Senior Scientist, Carmot Therapeutics

13.15                                                                  Networking Lunch

Identification, Validation & Successful Targeting of Highly Desirable Proteome Targets: Latest Progress & Reaching the Optimum Target


Chemical Biology to Provide Insight into Small Molecule Targeting of BCL6

• Chemical Biology contributed many important tools which have increased our ability to measure and perturb biological functions

• Chemical proteomics and other emerging techniques such as cellular thermal shift assay (CETSA®) and targeted protein degradation allow characterization of small molecules to determine target engagement, selectivity profiles, off-target liabilities and target validation

• Oncology BCL6 target as a case study to discuss the above methods and gain an understanding of the distinct value that each method can bring towards the development of safe and efficacious therapeutics

Speaker:    Paola Castaldi, Associate Director & Head of Chemical Biology, AstraZeneca


The Zinc-Finger Degrome

• Structure of CRBN-IMiD complexes bound to different zinc-fingers
• Definition of the zinc-finger degron recognised by the CRBN-IMiD E3 ligase
• Computational prediction of additional CRBN-IMiD targets

Speaker:   Nicolas Thomä, Group leader, Friedrich Miescher Institute for Biomedical Research


Targeting KRAS via Inhibition of the KRAS-SOS1 interaction

• Combination of high-throughput & fragment screening enabled a new approach to target KRAS

• Guided by intensive structural biology efforts and multiple biophysics approaches

• Discovery of nanomolar, selective and cell-active SOS1 inhibitors

Speaker:    Roman C. Hillig, Senior Scientist, Bayer AG



Allosteric Inhibition of SHP2 Phosphatase

• Creative hit finding strategies on a difficult target
• Advancing medicinal chemistry & lead optimization

Speaker:   Matthew LaMarche, Senior Investigator & Team Leader, Novartis

16.15                                                      Afternoon Refreshments & Networking


Attenuating Oncogenic Transcription with Small Molecules

• High-throughput binding assays provide a foothold into probe discovery for transcription factors, enabling the identification of compounds with different mechanisms of action in a single screen
• Screens for binders of transcription factors in cell lysates can enable the identification of compounds that target ‘nearest neighbor’ partners and that impact function of the transcription factor indirectly
• Chemical stabilization of Max homodimers attenuates Myc-driven transcriptional programs

Speaker:   Angela N. Koehler, Associate Professor- Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT


OncoPPi: a Network of Cancer associated Protein-Protein Interactions to Inform Therapeutic Strategies

• How to successfully establish a network of protein-protein interactions?
• The integration of genomics, targeted-proteomics & patient data to establish OncoPPi network to inform therapeutic strategies
• Investigation of the function of oncogenic targets through their non-enzymatic domains
• The application of High-Throughput Immunomodulator Phenotypic Screening Platform (HTiP) to search for novel drug candidates that could enhance antitumor immunity

Speaker:   Haian Fu, Professor of Pharmacology and Chemical Biology; Associate Dean for Innovation & International Strategies, Emory University School of Medicine


Inhibitors of Proteasome-Associated Deubiquitinating Enzyme USP14

• How does USP14 regulate the proteasome?
• How do the inhibitors suppress USP14 activity?
• What are the physiological effects of the inhibitors?

Speaker:   Daniel Finley, Professor of Cell Biology, Harvard Medical School


Chair’s Closing Remarks & End of Day One

Speaker:  Stephanos Ioannidis, VP of Chemistry, H3 Biomedicine