All times shown are EST.

7:00 am Registration & Coffee

8:00 am Chair’s Opening Remarks

  • Laure Escoubet Vice President, Discovery Biology , Zentalis Pharmaceuticals

8:10 am Three Generations of DDR Therapeutics – Where Are We Now

Synopsis

• A landscape overview of the DDR Therapeutic landscape, focusing on the first generation of approved PARP inhibitors
• A detailed look at the preclinical and clinical second generation DDR assets, including; specialized PARP-targeted assets, ATR, and WEE1 inhibitors
• A review of a third generation of novel DDR targets, including POL-Theta, WRN, and PARG

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

  • Elisabetta Leo Principal Scientist - Associate Director , AstraZeneca
  • Kirk Tanner Chief Scientific Officer , National Brain Tumor Society
  • Mark O’Connor Chief Scientist Oncology, Head of the DDR Strategic Biology Area, AstraZeneca
  • Mads Daugaard President & Chief Scientific Officer , Rakovina Therapeutics

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 Speed Networking

11:20 am Progress in ATR & WEE1 Inhibitors: As Single Agents & Synergy in Combination Therapy

  • Oren Gilad Chief Executive Officer , Atrin Pharmaceuticals

11:50 am A New Dimension in Precision Oncology with the SPOT-LX DNA Repair Testing Platform

Synopsis

• LXRepair develops funtional repair assays for a comprehensive characterization of major repair pathways in parallel
• Inhibitors specificity and efficacy can be rapidly investigated
• Assays can be used to stratify patients and monitor patients response to various DNA damaging drugs and DDR inhibitors

12:00 pm 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

12:30 pm Targeting Replication Stress in Cancers with Adavosertib, the First in Class WEE1 Inhibitor

  • Mark O’Connor Chief Scientist Oncology, Head of the DDR Strategic Biology Area, 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

1:00 pm Clinical Effectiveness of myChoice® CDx Genomic Instability as a CDx Biomarker

  • Kirsten Timms Vice President, Biomarker Discovery , Myriad Genetics

Synopsis

– Explore the only FDA approved HRD score CDx to prescribe PARPi’s
– Understand the use of broad biomarker offering for patient selection and therapeutic response
– Germline, somatic (myChoice HRD score, and gene panel), TMB, MSI
– Assessing gold standard myChoice HRD vs. other HRD measures

1:30 pm Lunch Break

2:20 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
  • Sui Xiong Cai Executive Vice President & Chief Technology Officer, IMPACT Therapeutics
  • Timothy Yap Associate Professor, Investigational Cancer Therapeutics, MD Anderson Cancer Center
  • Oren Gilad Chief Executive Officer , Atrin Pharmaceuticals

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?

NOVEL METHODOLOGIES, FUNCTIONAL GENOMIC APPROACHES & IMAGING TECHNOLOGIES TO REVOLUTIONIZE PATHWAY UNDERSTANDING, COMPOUND OPTIMIZATION & CLINICAL TRANSLATION

2:50 pm Exploring the Landscape of PARP Inhibitor Selectivity in Cells with NanoBRET

Synopsis

• Introduction to NanoBRET Target Engagement: WEE1, PKMYT1, and CHK1 kinase inhibitor profiling in cells
• Development of a pan-PARP live cell target engagement system
• Revealing unexpected engagement of understudied mono-PARPs in cells

3:00 pm Screening & Best Assays for Compound Optimization: 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

3:30 pm A Transcriptomic Model of Homologous Recombination Deficiency in a Real-World Pan-Cancer Cohort

Synopsis

  • Gene expression can be used to accurately predict HRD-status across solid tumor cohorts
  • This transcriptomic model, HRD-RNA, enriches for samples with biallelic loss in BRCA1/2 and other genes in the homologous recombination pathway
  • Cohorts, outside traditional BRCA-associated cohorts, have samples with biallelic loss of BRCA1/2 and samples predicted HRD+, suggesting new avenues for HRD targeted therapies

4:00 pm Afternoon Refreshments & Networking Break

ESTABLISHING A PRE-CLINICALLY VALIDATED NOVEL TARGET: POLΘ

4:30 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
  • Nathalie Agar Director of Surgical Molecular Imaging, Laboratory & Department of Neurosurgery , Brigham & Women’s Hospital Department of Cancer Biology Dana-Farber Cancer Institute
  • Ranjit Bindra Professor, Departments of Therapeutic Radiology & Pathology , Yale School of Medicine
  • Kalindi Parmar Associate Director, Center for DNA Damage & Repair , 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?

5:00 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?

5:30 pm Chairs Closing Remarks & End of Conference Day 1