Uncovering the Translational Potential of Protein Degradation

Transcription

1 Uncovering the Translational Potential of Protein Degradation November 14 th, 2018 Boston, MA Wednesday, November 14 th :00 Registration, Breakfast & Networking 9:00 Chair s Opening Remarks & Setting the Scene Official welcome to the PDT Summit 2018 and look to the day ahead What are the key takeaways this summit is aiming to achieve? Jim Winkler, Vice President, Discovery and Translational Biology, FORMA Therapeutics Inc. Targeted Protein Degradation: A Breakthrough Therapeutic Modality? 9:10 Presentation: Targeting the Ubiquitin-Proteasome System Refresh your knowledge of the ubiquitin-mediated protein degradation pathway An overview of how small molecule degraders, PROTACs or molecular glues, are hijacking this process to earmark disease-causing proteins for degradation Discussion will focus on the molecular features and differences to other modalities, and the opportunities these novel approaches offer. Eric Fischer, Assistant Professor of BCMP, Dana-Farber Cancer Institute

2 9:35 Case Study: Characterizing Degradation Kinetics and Cellular Mechanisms of PROTAC Compounds Measuring real-time degradation kinetics and quantification of degradation parameters in live cells Influence of E3 ligase handle on ternary complex stability and ubiquitination efficiency Differential family member responses to PROTACs and changes in E3 ligase system Kristin Riching, Senior Research Scientist, Promega Corporation 9:55 Keynote Panel and Open Q&A: Scientific Pioneer s - From Basic Research to A New Class of Blockbuster Drugs? This one-time-only session will allow attendees to tap into the leading minds in protein degradation. It s no secret that induced protein degradation has existed in the literature for decades; so this session will allow you to hear from the leaders to discuss why this industry is taking off right now, and how we are going to deliver on this promise. This session will address: Why are protein degrading therapeutics garnering so much attention right now? What can protein degrading therapeutics offer, in theory, that other types of drugs simply can t? Do we have to develop a completely new set of rules in the drug discovery and development process for the potential of these therapies to be realized? What crucial gaps in our current understanding do we need to fill to maximize the chances of clinical success? When should we realistically expect to see more of these therapies undergoing clinical trials? What do we hope to achieve by the end of the summit? Nathanael Gray, Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Larry Hamann, Vice President, Chemistry, Celgene Eric Fischer, Assistant Professor of BCMP, Dana-Farber Cancer Institute 10:35 Morning Refreshments & Networking Breaking Convention: Carving Out New Rules For Drug Discovery, Design & Development During these intimate breakout sessions, attendees will get the chance to freely discuss some of the key chemical challenges involved when developing and producing PROTACs and other methods of targeted protein degradation techniques. These workshops will allow you to get the answers to your burning questions in a way not possible through panels and presentations. These workshops are repeated to ensure you get the maximum value out from these important sessions, and takes away the difficult decision of choosing between them. You are spoilt for choice! 11:20 Repeated Workshop A:

3 Workshop A1: PROTAC Design - How To Go From Tools To Drugs & Methods of Ligand Discovery Understand what makes these heterobifunctional protein degraders chemically unique How druglike is the molecular structure of a PROTAC? Successes and failures of PROTAC structure: What works and what doesn t? How does PROTAC design compare to other small-molecule methods of targeted protein degradation? What approaches to ligand discovery currently exist? What opportunities do DNA-encoded libraries vs. fragment-based approaches offer? How should we orchestrate the reassessment and revitalization of previously discarded drugs? Yusuke Tominari, Chief Executive Officer, FIMECS Inc. Workshop A2: E3 Ligase Targeting, Functionality & Applications An overview of the current E3 ligases targeted by protein degradation therapeutics What E3 ligases are currently being targeted by researchers/biotechs? What makes an ideal E3 ligase target in terms of drug design and tissue specificity? What chemical factors need to be considered when deciding which E3 ligase to target? What E3 Ligase targets do we need tools for? How do we decide what investments are being made? How do we create novel E3 What methods exist to discover more E3 ligase Paola Castaldi, Associate Director, Head of Chemical Biology, AstraZeneca Workshop A3: Assay Development & Chemical Solutions Understand how current methodologies are falling short in PROTAC and other areas of protein degradation research Discussion will focus around how preclinical research is being held back by old-school methods of drug R&D chemistry As PROTAC s move into clinical trials, discussion in this workshop will focus on how solution-providers are looking to advance their offerings to keep up with this increasing demand 12:05 Repeated Workshops B: Time to switch! Workshop B1: PROTAC Design - How To Go From Tools To Drugs & Methods of Ligand Discovery Workshop B2: E3 Ligase Targeting, Functionality & Applications Workshop B3: Assay Development & Chemical Solutions Understand what makes these heterobifunctional protein degraders chemically unique An overview of the current E3 ligases targeted by protein degradation therapeutics Understand how current methodologies are falling short in PROTAC and other areas of protein degradation research

4 How druglike is the molecular structure of a PROTAC? Successes and failures of PROTAC structure: What works and what doesn t? How does PROTAC design compare to other small-molecule methods of targeted protein degradation? What approaches to ligand discovery currently exist? What opportunities do DNA-encoded libraries vs. fragment-based approaches offer? How should we orchestrate the reassessment and revitalization of previously discarded drugs? Yusuke Tominari, Chief Executive Officer, FIMECS, Inc. What E3 ligases are currently being targeted by researchers/biotech s? What makes an ideal E3 ligase target in terms of drug design and tissue specificity? What chemical factors need to be considered when deciding which E3 ligase to target? What E3 Ligase targets do we need tools for? How do we decide what investments are being made? How do we create novel E3 What methods exist to discover more E3 ligase Paola Castaldi, Associate Director, Head of Chemical Biology, AstraZeneca Discussion will focus around how preclinical research is being held back by old-school methods of drug R&D chemistry As PROTAC s move into clinical trials, discussion in this workshop will focus on how solution-providers are looking to advance their offerings to keep up with this increasing demand 12:50 Networking Lunch 1:50 Presentation: What can we Learn from Viral Hijacking of the Cullin-RING Ubiquitin Ligases (CRLs) for PROTAC Design? The discovery of ROC1/ROC2 and the catalytic mechanism of CRLs The modular assembly of CRLs provides the flexibility for targeting different substrates by one enzyme and the basis for PROTAC Viral hijacking of CRLs: what can we learn from the viruses in designing novel PROTACs? Yue Xiong, Professor & Co-Founder, Cullgen Inc.

5 From Bench to Clinic: Translating Promising Science into Clinical Development Protein Degradation holds huge therapeutic promise, but how we are going to successfully translate this into the clinic is still being worked out? The following sessions will discuss how PROTAC s and other related approaches are innovating our thinking and breaking the translational mould. This is a valuable opportunity to hear for yourself some of the remarkable work contributing to the explosion of interest, and where we can expect to see progress being made within the industry. Plus, catch a glimpse into the next wave of emerging research being conducted by up-and-coming teams in this space. 2:10 Panel & Open Q&A: Optimization, Pharmacological Challenges, and the Translational Opportunities Facing Protein-Degrading Therapeutics This session will deep-dive into the optimization of protein degraders, and give attendees the chance to understand the key translational opportunities these promising therapeutic modalities offer. Hear from the leading chemical and translational scientists in this space as they discuss what the current pharmacological challenges facing protein degraders are, plus get exclusive up-to-date information on how leading optimization workflows are being developed to tackle them. With an ever-increasing flux of biotech-pharma collaborations being established, tap into the minds of industry experts to hear in-depth scientific views with a translational focus. Debate and discuss: What is our level of current understanding around the PK/PD challenges facing these molecules? How is QSP being used to help guide the discovery of protein degradation therapies? How is our current understanding of the mechanism of action and fundamental biology impacting the design of these molecules? How does PROTAC technology compare to other novel approaches of targeted protein degradation, and what are its advantages? What work is currently being undertaken to advance the development of targeted protein degradation at the proof-of-concept phase? Oral bioavailability: How can we transform these heavy molecules into sellable, orally bioavailable drugs, and where do we start? What are the risks associated with protein degraders? What have been the preclinical cases of toxicity or off-target effects to date, and how do we design effective toxicological studies? What are the current predictions on how protein degradation platforms will translate in clinic into effective drugs? Will these approaches translate into effective drugs that consistently degrade their targets? Gillian Watt, Director of Pharmacology, Protein Degradation, GSK Andy Phillips, President and Chief Executive Officer, C4 Therapeutics Scott Edmondson, Director and Boston Head of Oncology Chemistry, AstraZeneca 2:55 Afternoon Refreshments & Networking

6 3:45 Presentation: An Overview of the dtag System A look at how the dtag system can provide a generalized strategy to induce rapid targeted protein degradation Understand how this chemical biology system can provide target validation within drug discovery and offer a kinetic resolution to biological investigations. Behnam Nabet, Research Fellow, Dana-Farber Cancer Institute Into the Unknown: A Look Ahead To the Future of the Industry 4:05 Closing Panel and Open Q&A: How are we Going to Deliver on the Initial Promise of Protein Degrading Therapeutics? With exciting scientific research and pharma-biotech collaborations in the field of protein degradation increasing at an exponential rate, there will be many key learnings from this summit that need to be implemented. This final Q&A panel session will be a chance tap into the minds of the leading minds in Biotech who are trailblazing the path for protein degrading therapeutics. Use this session to finalize any genuine takeaways you ve gained from this summit. Debate and discuss: Drugging the undruggable : When can we expect labs to reveal molecules that work against previously undruggable targets? What new protein degradation approaches can we expect to see coming down the pipeline? When will we see the overall scope of these technologies become established? How readily and broadly can these approaches be applied? What can we learn from other industries with regards to Intellectual Property? Taking it into clinic: When will we see multiple clinical trials and proof-of-concept studies coming to fruition? Do we expect to see more pharma-biotech partnerships being established in the near future? What can we expect to see progress within the next few years? John Houston, Chief Executive Officer, Arvinas Sandra Glucksmann, Chief Executive Officer, Cedilla Therapeutics Nello Mainolfi, Founder and Chief Technology Officer, Kymera Therapeutics 5:00 Chair s Closing Remarks What have been the key takeaways from the inaugural PDT Summit? Final discussion points on what needs to happen next for this industry to realize its full potential Jim Winkler, Vice President, Discovery and Translational Biology, FORMA Therapeutics Inc. 5:10 Close of PDT Summit 2018

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