7:50 am Breakfast & Registration Opens

8:50 am Chair’s Opening Remarks

UNPACKING AN ONGOING CLINICAL CHALLENGE & DDR INHIBITION’S BIGGEST OBSTACLE: TOXICITY

9:30 am Understanding DDRi’s In the Clinic: Why is Toxicity Such a Big Issue?

  • Oren Gilad Chief Executive Officer, Aprea Therapeutics

Synopsis

  • On target vs off target toxicological effects; which inhibitors are more likely to
    result in off target side effects?
  • How much inhibition is needed? Identifying the optimum therapeutic window
  • Current strategies employed to minimize toxicological effects when designing clinical trials

10:00 am Addressing DDRi Toxicity: Dosing Schedules, Combination Studies & Biomarkers

Synopsis

  • Weighing up the costs and benefits of alternative dosing schedules and tailoring them to specific patients
  • Refining specificity: targeting tumors using the different screening platform
  • Evaluating common biomarker approaches to patient selection: BRCA screening, HHR gene panel tests and HRD genomic instability assays

10:30 am Morning Break & Networking

PONDERING PATIENT SELECTION: IMPROVING TARGETING USING BIOMARKERS & SCREENING PLATFORMS

11:00 am Session Reserved for Myriad Genetics

  • Paul Bartell Senior Vice-President, Companian Diagnostics, Myriad Genetics

Synopsis

11:30 am Biomarkers Beyond Sequencing: Guiding DDR-Targeted Therapy With PET Imaging

  • David Mankoff Co-founder, Perelman School of Medicine at the University of Pennsylvania

Synopsis

  • PET molecular imaging as a tool to guide targeted precision cancer therapy
  • Assessing PARP-1 expression and PARPi pharmacology with radioligand PARPi analogs
  • Pre-clinical and early clinical results demonstrating the utility of PET PARP imaging for patient selection and drug dosing

12:00 pm Repli-Biom: a Novel Proteo-Genomic Approach to Identify Predictive Biomarkers of DDR Inhibitor Efficacy

Synopsis

  • Repli-Biom combines proteomics, genomics, and synthetic lethality screens through computational approaches
  • Through this analysis, Repli-Biom identifies and prioritizes predictive biomarkers of drug sensitivity
  • This approach has now been used to identify novel biomarkers for ATR inhibitor treatments

12:30 pm Panel Discussion: How Do We Go About Biomarker Selection in Combination Studies?

  • David Mankoff Co-founder, Perelman School of Medicine at the University of Pennsylvania
  • Nimrat Chatterjee Assistant Professor, University of Vermont, Cancer Center

Synopsis

  • Are many different types of biomarkers required?
  • Can biomarker selection help address toxicity issues?
  • How can we bring down the costs of biomarkers, especially when so many are needed for combination studies?

1:00 pm Lunch & Networking

CONDUCTING COMBINATION STUDIES: A TWO-BIRDS-ONE-STONE APPROACH TO TACKLING TOXICITY & RESISTANCE

2:00 pm Adding On to Monotherapy: Combining DDR Inhibitors

  • Greg Korbel Chief Operating Officer, Aprea Therapeutics

Synopsis

  • Combinations to combat emerging resistance; identifying combination agents
  • Can the combination of DDRis result in overlapping toxicity? A case study of combining PARPi and ATRi
  • Circumventing PLK inhibition: combining ATRN-W1051 with Wee1 or ATR inhibitors

2:30 pm Evaluating DDR Combinations in the Clinic: Promises, Pitfalls, Challenges

  • Timothy Yap Medical Director, MD Anderson Cancer Centre

Synopsis

  • DDR combinations have shown promising synergistic activity in preclinical studies
  • Challenges in overlapping toxicity have hampered the development of different DDR combinations
  • Novel agents and clinical trial designs are needed to be implemented to overcome such challenges

3:00 pm Afternoon Break & Networking

3:30 pm Integrating Pre-Clinical Data & Advanced Radiation Therapy Planning to Maximize the Therapeutic Window For Potent Radiosensitizers

Synopsis

  • Use of pre-clinical testing to define biologically effective radiosensitizing regimens
  • Use of in vivo radiation toxicity modeling to define potential dose-limiting drug/ radiation interactions
  • Use of pre-clinical modeling to select radiation fractionation and modification of clinical planning parameters to maximize the therapeutic window

4:00 pm ATM Inhibition Enhances the Efficacy of Radiation Across Distinct Molecular Subgroups of Pediatric High-Grade Glioma

  • Anang Shelat Professor & Director - Compound Management & Discovery Informatics Lead, St. Jude Children’s Research Hospital

Synopsis

  • AZD1390 potentiated radiation across distinct molecular subgroups of pediatric high grade glioma cell lines
  • ATM inhibition improved the efficacy of radiation in both TP53 wild-type and TP53 mutant orthotopic xenograft models
  • We identified a novel mechanism of resistance to ATMi + radiation marked by an attenuated ATM pathway response and synthetic lethality with ATR inhibition

FUTURE OUTLOOK FOR THE DDR LANDSCAPE: MOVING INTO 2023; WHERE IS THE SPACE HEADED?

4:30 pm Roundtable Discussions: Future Outlook of The DDR Space

Synopsis

  • Early drug discovery targets moving into the clinic
  • The future of diagnostic tools and patient selection
  • Novel approaches to overcoming toxicity
  • Combinations to come

5:00 pm Chair’s Closing Remarks & End of Conference