All times shown are EST.

7:00 am Registration & Coffee

8:20 am Chair’s Opening Remarks

  • Laure Escoubet Vice President, Discovery Biology , Zentalis Pharmaceuticals

PARP INHIBITION: NEXT-GEN PARPI’S, PARP RESISTANCE & THE FUTURE OF PARP INHIBITORS

8:30 am Progress in PARP1 Selective Inhibitors: AZD5305

  • Elisabetta Leo Principal Scientist - Associate Director , AstraZeneca

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

  • Kirk Tanner Chief Scientific Officer , National Brain Tumor Society
  • Wael Jdey Lead Scientist , Onxeo
  • Elisabetta Leo Principal Scientist - Associate Director , AstraZeneca
  • Mark O’Connor Chief Scientist & Senior Principal Scientist , AstraZeneca

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

  • Frank Zenke Global Head DNA Damage Response Research , Merck KGaA

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

  • Oren Gilad Chief Executive Officer , Atrin Pharmaceuticals

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

  • Peter Huang Senior Vice President Discovery , Zentalis Pharmaceuticals

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

  • Mark O’Connor Chief Scientist & Senior Principal Scientist , AstraZeneca

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?

  • Frank Zenke Global Head DNA Damage Response Research , Merck KGaA
  • John Pollard Vice President & Global Head of Translational Medicine & Oncology , Bayer
  • Timothy Yap Associate Professor, Investigational Cancer Therapeutics, MD Anderson Cancer Center
  • Sui Xiong Cai Executive Vice President & Chief Technology Officer, IMPACT Therapeutics

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

  • Alan D’Andrea Director: Center for DNA Damage and Repair, Director , Susan F. Smith Center for Women’s Cancers (SFSCWC) Professor Harvard Medical School Dana-Farber Cancer Institute

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

  • Debanu Das Chief Executive Officer , XPose Therapeutics

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

  • Nathalie Agar Director of Surgical Molecular Imaging, Laboratory & Department of Neurosurgery , Brigham & Women’s Hospital Department of Cancer Biology Dana-Farber Cancer Institute

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

  • Geoffrey Shapiro Professor, Medicine, Harvard Medical School, Director of Early Drug Development Center , Dana-Farber Cancer Institute
  • Ranjit Bindra Professor, Departments of Therapeutic Radiology & Pathology , Yale School of Medicine
  • Nathalie Agar Director of Surgical Molecular Imaging, Laboratory & Department of Neurosurgery , Brigham & Women’s Hospital Department of Cancer Biology Dana-Farber Cancer Institute
  • Alan D’Andrea Director: Center for DNA Damage and Repair, Director , Susan F. Smith Center for Women’s Cancers (SFSCWC) Professor Harvard Medical School Dana-Farber Cancer Institute

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?

5:00 pm Chairs Closing Remarks & End of Conference Day 1