All times shown are EST.
7:00 am Registration & Coffee
8:20 am Chair’s Opening Remarks
PARP INHIBITION: NEXT-GEN PARPI’S, PARP RESISTANCE & THE FUTURE OF PARP INHIBITORS
8:30 am Progress in PARP1 Selective Inhibitors: AZD5305
Synopsis
- Delve into discovery, development and validation
9:00 am Inhibition of PARP7 by RBN-2397 Activates the Type I Interferon Response in Tumors Leading to Robust Antitumor Activity
Synopsis
- Explore how PARP7 negatively regulates the type 1 interferon response in cancer cells
- Delving into discovery, development, and clinical progress of its inhibiton which triggers antitumor immunity
9:30 am Panel Discussion: PARPi’s: The Whole Story? PARP & DDR Biomarkers, Targets & Hope in Indications Outside of Breast & Ovarian
Synopsis
- Sharing insights into future directions and what to anticipate as standards evolve for PARP and other DDRi’s in the clinic
- How is it looking for prostate? leukemia? GBM? pancreatic? endometrial? SCLC?
- What are the differences between cancers in terms of resistance to PARP inhibitors?
- Thoughts on moving to a more genomic rather than indication-specific biomarker-driven treatment strategy?
- Understanding the hope for the more understudied PARP’s
DEVELOPING CLINICALLY SUCCESSFUL WEE1 & ATR INHIBITORS FOR CANCER THERAPY
10:00 am Preclinical & Clinical Exploration of ATR Inhibitors
Synopsis
- Preclinical pharmacology profile of Merck ATR inhibitors (Berzosertib, M1774)
- Preclinical exploration of options for mono- and combination therapy
- Directions of clinical development for ATR inhibitors
10:30 am Progress in ATR & WEE1 Inhibitors: As Single Agents & Synergy in Combination Therapy
11:00 am Morning Refreshments & Networking Break
11:30 am Discovery & Progress of ZN-c3, a Highly Potent & Selective WEE1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer
Synopsis
- Discovery of ZN-c3 as a potent and selective Wee1 inhibitor
- Exploring ZN-c3 antitumor effect as a single agent and in combination
- Diving into recent ZN-c3 clinical data
12:00 pm Targeting Replication Stress in Cancers with Adavosertib, the First in Class WEE1 Inhibitor
Synopsis
- Delving into WEE1 inhibitors, which have the potential for monotherapy activity in cancers with high levels of basal replication stress
- In this monotherapy scenario, in addition to the G2/M checkpoint override resulting from CDK1 deregulation, the activation of CDK2 appears to be the main driver with downregulation of RRM2 and dNTP reduction observed
- Exploring combination of adavosertib with the PARP inhibitor olaparib can overcome of PARPi resistance in both preclinical models and based on emerging data, in the clinic
12:30 pm Panel Discussion: A Comparison; The Challenges & Learnings of Developing ATR inhibitors – What Clinical Space Will They Occupy?
Synopsis
- Analyzing the current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy
- Dissecting toxicity profiles (bone marrow toxicity?)
- Opening the ATR inhibitor black box: what clinical space will they occupy?
- Understanding biomarker indications for ATR sensitivity: Cyclin E, ATM Loss? not as clear as BRCA for PARP
- What patients? What indications? What combinations do you foresee having optimal efficacy?
1:00 pm Lunch Break
DEVELOPING PREDICTIVE PRE-CLINICAL MODELS IN DDR TO ACHIEVE HUMAN-SPECIFIC TRANSLATION
2:00 pm Understanding the Promising Methods for Exploring Novel Biomarkers
Synopsis
- Optimizing Model Systems: CRISPR Screens and Novel Biomarkers
NOVEL METHODOLOGIES & IMAGING TECHNOLOGIES TO REVOLUTIONIZE PATHWAY UNDERSTANDING, COMPOUND OPTIMIZATION & CLINICAL TRANSLATION
2:30 pm HTS & the Best Assays for Compound Optimization & Synthetic Lethal Screening in DDR Quick SAR by X-ray Poses
Synopsis
- Structural biology/crystal structures in DDR drug discovery
- Quick conversion of hits to leads, structure-guided optimization
- Application of the approach for novel oncology therapeutics
3:00 pm Exploring DDR-Specific Companion Diagnostics for Understanding Target Function, Activity, Trial Design & Clinical Response
Synopsis
- Understanding the need for a dedicated diagnostic tool for drug development and a patient selection, prognostic and therapeutic response perspective
- Exploring the tools to interrogate genomic instability to advance development and translation
- Delving into the clinical data and discussion on how to standardize the use of appropriate CDx and biomarkers for your DDRi clinical trials
3:30 pm Afternoon Refreshments & Networking Break
4:00 pm Panel Discussion: Towards Bridging the Gap with the Clinic
Synopsis
- Exploring optimal validation in clinics
- Standardizing the approach in the clinic so we can go back preclinically – which models?
- Gathering early clinical information – robust translational medicine program
- How can you best parallel with translational – ctDNA metabolomics
- Discussing mathematical modeling use potentials for dose adjustment and tolerability
- Why do the colony formation assays take so long and what are the alternatives – reliability? Taking cell proliferation rate into account
- Novel methods to translate drug potency into a cellular format?
- Understanding pharmacodynamics technology platforms and the clinical challenges in the drug discovery program for DDR targets; what target engagement assays, assays, validation, mechanistic, tissue distribution, toxicity, and colony formation assays are being used
- How do you prove target engagement – why a lack of cell viability assay usage?
ESTABLISHING A PRE-CLINICALLY VALIDATED NOVEL TARGET: POLΘ
4:30 pm Exploring Polθ as a New DDR Target
Synopsis
- Discovery and preclinical development of first-in-class inhibitors for oncology in a PARP-resistant setting
- Leveraging synthetic lethality and understanding of the theta-mediated end joining (TMEJ) to determine a validated target
- Latest from the lab, clinical validation, and future directions
- Discussing how it will compare to PARP
- Dissecting how to leverage it as a novel target
- Combination – who, where, what?