08.30

Breakfast & Networking

08.55

Chair’s Opening Remarks

Optimizing Discovery & Robust Pre-Clinical Translation into Clinic through Enabling Technologies & Approaches

As the drug development opportunity opens up to drug “undruggable” targets across all therapeutic indications and unlock the entire proteome once and for all, join your peers on this day to hear first-hand about the latest therapeutic methods and enabling technologies to overcome chemistry challenges, and structure-based design of next generation small molecules, such as PROTACS, to successfully translate safe and effective small molecule candidates from pre-clinical into clinical development. Ensure you capitalize on the growing opportunity of proteome-targeted small molecule discovery and ensure these promising drug candidates become a clinical reality for patients in need.

09.00

Reimagining Druggability using Chemoproteomic Platforms

• Chemoproteomics-enabled covalent ligand discovery approaches can be used to discover new E3 ligase recruiters for targeted protein degradation
• Chemoproteomics can be applied for tackling the undruggable proteome
• Natural products can be a source for discover of new E3 ligase modulators

Speaker:  Daniel Nomura, Professor- Department of Chemistry, University of California, Berkeley

09.30

Technologies to Screen for Inhibitors and Hijackers of the Ubiquitin System

• Development of UbFluor probes to measure the activity of HECT/RBR E3 ligases in the presence of biochemical mutations, allosteric activators, and small molecule inhibitors
• Validation of UbFluor in HTS assays to screen for inhibitors or activators of HECT/RBR E3s
• Adopting UbFluor assay to discover protein degraders by monitoring E3 ligase-substrate interactions in real time

Speaker:   Alexander V. Statsyuk, Assistant Professor of Medicinal Chemistry, University of Houston

10.00

Targeted Protein Degradation for Traditionally Intractable Targets

• Showcase of capabilities needs to go after traditionally intractable targets using TPD
• Challenges and pitfalls
• Showcase of successful example(s)

Speaker:   Nello Mainolfi, Founder & CTO, Kymera Therapeutics

10.30                                                      Morning Refreshments & Networking

11.00

Drugging the Undrugged with Protein Interference (PROTEINi)

• In order to break out of current chemical space limitations a new method working on the same level as small molecules is required
• PhoreMost has developed a phenotypic functional proteomics platform to screen millions of peptide “shapes” in live cell assays
• These peptides are used as starting points to inform small molecule drug discovery; we demonstrate this concept on the Ras pathway, in Autophagy and Immuno-Oncology

Speaker:    Markus Muellner, CTO, PhoreMost Ltd

11.30

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

12.00

Structure Based Design of Novel Inhibitors of the Mcl-1’s Protein-Protein Interaction

• Mcl-1, a member of the Bcl-2 family, inhibits pro-death components of the intrinsic apoptosis pathway and thus is a key survival factor in multiple myeloma and other malignancies
• Although compelling, targeting disruption of Mcl-1’s protein–protein interaction to induce tumor cell death was previously thought to be “undruggable” due to the high affinities of Mcl-1 to the pro-apoptotic Bcl-2 proteins and lack of a small molecule binding pocket
• We report here our structure based drug design of novel inhibitors of the Mcl-1 that led to AMG 176, a potent, selective, and bioavailable Mcl1 inhibitor in clinical development

Speaker:   Xin Huang, Head of Structural Biology, Amgen

12.30                                                                Networking Lunch

13.30

Panel Discussion: Structuring the Future of Small Molecule Drug Discovery to Drug the Undruggable as a Collaborative Community

• What do we mean by undruggable targets and how to, as a collaborative community, seize the opportunity of this emerging field?
• How to effectively define and capture the fundamental understanding of the biology to improve target identification and validation within the highly desirable classes of currently difficult to drug targets?
• From covalent inhibitors to protein degradation. From allosteric to fragment-based drug discovery approaches! What are the most exciting breakthroughs that have advanced the field in the recent years?

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

Panelists: Gerald Shipps, Senior Director in the Emerging Science & Innovation (ES&I), Pfizer; David Millan, VP- Chemistry, Foghorn Therapeutics

14.00

Roundtable Discussions: Our breakout roundtables will allow you to have more intimate and open discussions on some of the hottest topics and key areas of debate. Discover multiple perspectives on these key issues, so that you can learn from your fellow experts in the audience. Drive your own learning, crowd-source ideas and get inspired. Immerse yourself in the following discussions:

Roundtable Topics:

•Redefining the rules of small molecule chemistry and entering the modern era of structure-based drug design - how to rationally design and build molecules that consistently and accurately hit “undruggable” targets that do not currently have viable ligands, chemistry or modalities?
• How to overcome the challenge of identify and validate a robust target selection and prioritization process?
• What is the role of enabling technologies such as DNA Encoded Libraries, high throughput/fragment based screening technologies & artificial intelligence in proteome-targeted small molecule drug discovery?

15.00   Chair’s Closing Remarks & Close of Inaugural Proteome- Targeted Drug Discovery Summit 2019