Conference Day One

* Please note that the following agenda timings are EDT *

For PDT, please download the full event guide here

08:00 | Morning Networking Coffee

8:20 am Chair’s Opening Remarks

  • Adam Gilbert Senior Director - Design & Synthesis Sciences, Medicinal Chemistry, Pfizer

Keynote Plenary Session

8:30 am Translating Targeted Protein Degradation Beyond Oncology

Synopsis

  • Establishing translating strategies for targeted protein degradation beyond oncology

9:00 am Delivering on a Promise: PROTAC® Protein Degraders

Synopsis

  • Proving the concept of PROTAC degraders
  • Implications of Arvinas’ latest clinical data for ARV-471 and ARV-110
  • Looking ahead to benefitting patients in neuroscience

9:30 am Industry Leaders Panel Discussion | 2021 in Review

Synopsis

  • What is the current state of play of the targeted protein degradation field?
  • What are the most promising therapeutic candidates in the pipeline?
  • What are the major challenges lying ahead in translating novel therapeutics from bench to bedside?
  • Bivalency vs monovalency; what are the key advantages/disadvantages of both?

10:15 am Deconvoluting the Drivers of Targeted Protein Degradation

Synopsis

  • Live cell degradation studies of multiple targets in multiple cells backgrounds
  • Monitoring key mechanistic steps required for degradation
  • Correlative analysis of ternary complex, PROTAC permeability, and ubiquitination with functional outcome

10:45 am | Speed Networking

Accelerating Discovery & Emerging Strategies

Discovering Emerging Monovalent Degraders; Molecular Glues & Beyond

Chairperson:

  • Thomas Smith Associate Director, Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research

11:45 am Molecular Glue Degraders: From Serendipity to Rational Design

Synopsis

  • Monte Rosa’s QuEEN (Quantitative and Engineered Elimination of Neosubstrates) platform enables us to rationally discover molecular glue degraders (MGDs). QuEEN comprises:
  • Degron encyclopedia: A growing catalogue of over 1500 proteins identified through our AI-driven approach, containing proteins of diverse protein classes across therapeutic areas,
    including highly credentialed targets previously deemed undruggable.
  • Proprietary MGD library: A diverse and continuously growing chemical library of drug-like MGDs that are rationally designed based on our expertise in molecular glue anatomy
  • Glueomics toolbox: A tailored suite of biochemical, structural biology, cellular, proteomics and in silico screening tools that connect degrons to MGDs
  • Leveraging QuEEN, we have identified and validated MGDs to highly validated and therapeutically relevant but undruggable proteins

12:15 pm Enabling DNA Encoded Libraries as a High Content Discovery Tool for Protein Degradation Molecules

Synopsis

  • DNA encoded library (DEL) is an optimal discovery tool for protein degradation molecules because both techniques share the same key principles such as affinity binding selection and combination of structural blocks
  • Our pilot study designed an E3 tri-conjugate DEL library where we captured novel dBET1 like compounds validated with BRD4 protein degradation using dual binder DEL selection method developed in house
  • Discovery of novel E3 ligases together with DEL derived ligands creates potent signature to strengthen the chemical design of degradation molecules

12:45 pm Discovery of Novel Molecular Glue Degraders Against Clinically Relevant Targets

Synopsis

  • The Proxygen discovery platform enables identification of novel glue degraders at industrial scale
  • E3 ligase-agnostic screening allows unbiased exploration of the chemical space
  • A multiplexed screening strategy drives systematic identification of targets permissive for degradation by molecular glues

Optimizing Drug Design & Pre-Clinical Validation

Addressing Key Challenges of Penetrating the Brain Using Molecular Glues to Treat CNS Diseases

11:45 am Harnessing Molecular Glue Degraders for CNS Penetration

  • Eunice Park Director - Cell Pharmacology & Chemical Biology, C4 Therapeutics

Synopsis

  • Preclinical evaluation of a highly selective degrader of oncogenic mutant protein
  • Demonstration of in vitro and in vivo activity in the models with clinically relevant resistant mutations to the approved inhibitors
  • Demonstration of intracranial activity showing potential to treat brain metastases

12:15 pm Biophysical characterization of protein degraders in ternary complexes

Synopsis

  • We show how binary and ternary affinity constants, as well as cooperativity values can be obtained with a simple assay design and measurement technology.
  • Characterization of small-molecule PROTACs in ternary complexes of E3 ligase and bromodomain target proteins.
  • Characterization of the interaction of a peptide PROTAC (PRTC) and a pancreatic cancer associated target protein (CREPT).

12:45 pm Molecular Glues Targeting Neurodegenerative Diseases

Synopsis

  • Targeted protein degradation has emerged as a new therapeutic modality in treating cancer. However, development of PROTAC drugs to treat neurodegenerative disorders remains challenging
  • Molecular glues that enable targeted protein degradation can overcome some of the challenges associated with PROTACs and can be a viable alternative
  • This presentation will highlight Progenra’s approaches to the discovery, development, optimization, and characterization of novel E3 based molecular glues for degrading CNS related targets

Robust Translation & Clinical Development Considerations

Clinical Update on Degraders in the Clinic, Key Learnings & Future Directions

11:45 am Turning Degraders into Drugs – NX-2127 & NX-5948

Synopsis

  • Harnessing cereblon to degrade BTK, while tuning in and out IMiD activity
  • Addressing the unmet need of drug resistance

12:15 pm Panel Discussion: The Next Wave of Therapeutics: Applications of Protein Degradation for Oncology & Beyond

Synopsis

  • Delve into the current clinical applications beyond oncology
  • Understanding future directions for protein degraders in the clinic
  • Strategies to address new challenges that present through phase trials
  • What have we learnt so far?

1:15 pm | Lunch Break

Insights into Emerging Induced Proximity Strategies for Targeted Degradation

2:15 pm Induced Proximity Medicines for Targeted Degradation of Proteins & RNAs

  • Ryan Potts Head of Induced Proximity Platform, Amgen

Synopsis

  • Induced proximity medicines are an emerging new drug modality to expand the solution space for difficult to drug therapeutic targets
  • Exploring the use of induced proximity medicines for targeted degradation of proteins and RNAs

2:45 pm Reimagining Druggability Using Chemoproteomic Platforms

Synopsis

  • Using chemoproteomic platforms to discover new E3 ligase recruiters
  • Deubiquitinase Targeting Chimeras (DUBTACs) for targeted protein stabilization
  • Next-generation induced proximity-based therapeutic modalities

3:15 pm Designing Biologics Aimed at the Difficult to Drug Transcription Complexes Resulting from Chromosomal Translocations

  • Terry Rabbits Professor - Molecular Immunology, Institute of Cancer Research

Synopsis

  • Intracellular antibodies are biologics that can be armed with warheads to loss of protein function and induce a phenotype in recipient cells
  • Intracellular antibodies can be guided to sub-cellular locations and therefore able to target difficult to drug transcription complexes
  • Although our focus is in oncology, the techniques are applicable to any clinical indication

Improving Oral Bioavailability of PROTACs invivo for Better Preclinical Outcomes

2:15 pm Identification of Selective & Orally Available VHL-Based PROTACs

Synopsis

  • Strong MedChem use case on PROTAC optimization
  • Provision of design principles leading to oral bioavailability
  • Structural evidence for selectivity

2:45 pm Strategies to Discover Exceptionally Potent & Orally Active PROTAC Degraders

  • Shaomeng Wang Professor of Internal Medicine, Pharmacology & Medicinal Chemistry, University of Michigan

Synopsis

  • Strategies to enhance oral bioavailability of protein degraders
  • How to design degraders with acceptable absorption, distribution, metabolism and excretion (ADME) properties to demonstrate efficacy in vivo
  • Understanding clinical development considerations

3:15 pm Discovery of New Orally Available AR PROTACs for Prostate Cancer

  • Wu Du SVP Medicinal Chemistry, Hinova Pharmaceuticals

Synopsis

  • Prostate cancer remains an unmet medical need and AR is a validated target for prostate cancer;
  • Hinova’s effort on discovery of new orally available AR Protac
  • Dual targeting protac as a strategy for drug resistant prostate cancer

Ensuring Effective Translation, Safety & Efficacy of Degraders to Advance into the Clinic

2:15 pm CC-90009: A First-In-Class GSPT1 Degrader for Patients with AML

  • Michael Pourdehnad VP Early Clinical Development, Hematology/Oncology & Cell Therapy, Bristol Myers Squibb

Synopsis

  • Share CC-90009 activity from first-in-human trial in AML patients
  • Discuss how thresholds for preclinical efficacy translated to patients
  • Discuss how preclinical toxicology studies predicted for clinical safety

2:45 pm Developing Novel Cereblon-Directed PHMs® as First-in-Class Targeted Protein Degradation Therapies

Synopsis

  • Development of BioTheryX’s extensive protein homeostatic modulator (PHM®) library of proprietary molecular glues that uniquely engage and regulate the function of Cereblon.
  • Preclinical data from BioTheryX’s PHM® clinical candidate, BTX1188, which was rationally designed to degrade GSPT1 and Ikaros to provide superior efficacy and therapeutic index over pure GSPT1 degraders, will be presented.
  • BTX-1188 is progressing into the clinic for hematological malignancies such as AML and lymphoma.

3:15 pm Overcoming CRBN Resistance with the Aiolos/ Ikaros Degrader CC-92480 for Multiple Myeloma & the Future of CELMoD Molecular Glues

  • Neil Bence VP Cancer Biology, Bristol-Myers Squibb

Synopsis

  • Changes in CRBN expression can impair the activity of approved Ailos/Ikaros agents
  • CC-92480 is a highly potent Aiolos/Ikaros CELMoD in clinical development that overcomes these limitations
  • Newer CELMoDs are capable of recruiting a number of novel neosubstrates beyond Ailos/Ikaros revealing new opportunities to expand the clinical impact of CELMoD protein degraders

3:45 pm | Afternoon Networking

Harnessing the Power of the Autophagy- Lysosomal Pathway to Achieve Extracellular Degradation

4:15 pm Development of Carbohydrate Conjugates for the Degradation of Extracellular Proteins

  • Weiping Tang Janis Apinis Professor, University of Wisconsin-Madison

Synopsis

  • Comparison of PROTACs and LYTACs;
  • Different lysosome targeting receptors;
  • Triantennary N-acetylgalactosamine conjugates as degraders for extracellular proteins

4:45 pm Degrading Proteins from Outside Using AbTACs

  • James Wells Professor, Department of Pharmaceutical Chemistry, University of California at San Francisco

Synopsis

  • We show a class of transmembrane E3 ligases can be hijacked to degrade membrane proteins using bi-specific antibodies
  • These target proteins for lysosomal as opposed to proteasomal degradation
  • Here we explore how degradation is influenced by the target, degrader, epitope and affinity

Optimizing PKPD to Accelerate in-vivo Studies

4:15 pm Impact of Understanding PKPD for the Development of a STAT3 Targeted Protein Degrader

Synopsis

  • Interrogating degrader PK/PD relationships
  • Defining drug exposure to drug action for a novel STAT3 degrader

4:45 pm Profiling Of AZ’6421, an Orally Available Estrogen Receptor-PROTAC, Highlights the Importance of Evaluating Circulating Metabolites in-vivo

Synopsis

  • Development of potent and orally available ER PROTACs
  • Despite excellent degradation in-vitro, degradation in vivo was suboptimal
  • Experimental data suggested that this was due to the formation of a metabolite that competed with the PROTAC limiting degradation

Exploring the Landscape of BRD9 Degraders in Synovial Sarcoma

4:15 pm Discovery of a Potent & Selective BRD9 Degrader with Activity in a Preclinical Model of Synovial Sarcoma

Synopsis

  • Synovial sarcoma is an aggressive malignancy driven by a characteristic SS18-SSX fusion protein, and recent studies have demonstrated that BRD9, a component of the SS18- SSX containing BAF complex, is required for the survival of synovial sarcoma cancer cells
  • This talk will describe the multiparameter optimization of a series of BRD9 degraders, ultimately leading to the identification of a selective degrader with sufficient intravenous PK profile to enable in vivo proof-of-concept studies
  • The BRD9 degrader described demonstrates in vivo target degradation and efficacy in a mouse xenograft model of synovial sarcoma

4:45 pm Discovery Of FHD-609: A Potent & Selective Intravenous Heterobifunctional Degrader of BRD9

Synopsis

  • Foghorn introduction and overview of our degrader capabilities
  • Rationale for BRD9 as target that requires degradation for a therapeutic effect
  • FHD-609 is a drug candidate with a compelling in-vitro/ in-vivo profile supporting first-in-human studies in Synovial Sarcoma

5:15 pm Chair’s Closing Remarks & End of Conference Day One

  • Adam Gilbert Senior Director - Design & Synthesis Sciences, Medicinal Chemistry, Pfizer