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7:45 am

Coffee & Registration

8:45 am Chair’s Opening Remarks

An Update on PARP Development

9:00 am PARP & Immunotherapy

  • Geoffrey Shapiro Director Early Drug Development Center , Dana-Faber Institute

Synopsis

• Exploring crosstalk between PARP and immunotherapy

• Examining PD-L1 & PARP as a case study: understanding lessons learned, extending these lessons to novel DDR targets, moving immunotherapy combination to wider indications

9:30 am On the Cutting-Edge of PARPi

  • Mitch Raponi Vice President, Biomarkers & Translational Research , BeiGene

Synopsis

• Developing PARPi beyond BRCA and in castration-resistant prostate cancer

• Pamiparib (BGB-290) and combination studies

10:00 am Not all PARPs are Alike: Exploring the Therapeutic Potential of PARPi Beyond PARP1 Inhibitors

  • Heike Keilhack Senior Vice President Biological Sciences, Ribon Therapeutics

Synopsis

•Exploring the biology and disease association of PARPs beyond PARP1

• Studying PARP family members that catalyze monoADP-ribosylation, a posttranslational
modification involved in cellular stress pathway signaling

• Discovery and development of PARP7 inhibitors targeting a novel cancer
vulnerability

10:30 am

Morning Refreshments & Speed Networking

11:15 am PARPi’s for BRCAness

  • Ranjit Bindra Associate Professor, Therapeutic Radiology and Pathology , Yale Brain Tumor Center

Synopsis

• Mechanistic review and update on oncometabolite-induced BRCAness and PARPi sensitivity

• Clinical trial overview on PARPi’s for IDH1/2-mutant cancers in the clinic

• Discussing other avenues to exploit DDR defects in oncometabolite-producing tumors on the horizon

11:45 am Over-riding PARP Resistance in Organoid & Mouse Models

Synopsis

• Choosing effective alternative therapies depending on the mechanism of PARPi resistance

• Identifying targetable DNA damage repair defects using genomic analysis and functional testing of patient-derived organoids

• Assessing novel combination therapy efficacy in specific resistance settings using these organoids for rapid testing

12:15 pm Reversing PARP Inhibitor Resistance by Targeting the Replication Stress Response

Synopsis

• Using PARPi in monotherapy and combination strategies across a spectrum of
molecular backgrounds and tumor types means that addressing PARP inhibitor
resistance will be of increasing importance

• Emerging data suggest the majority of resistance mechanisms are linked to the
reactivation of homologous recombination repair, preventing PARPi synthetic
lethality

• Identifying roles for PARP and homologous recombination repair proteins in the
replication stress response to provide a strategy to reverse PARPi resistance

• Presenting data which demonstrates the ability to overcome PARPi resistance
through combinations with inhibitors of the replication stress response proteins,
ATR and WEE1

ATR: An Emerging Target

1:00 pm

Lunch & Networking

2:00 pm ATR: An Emerging DDR Target

Synopsis

• Presentation content to be revealed

2:30 pm Translating ATR & Emerging Targets to the Clinic

Synopsis

• Reviewing the success and challenges of translating ATR inhibitors to the clinic

• Discussing the future direction of ATR inhibitors

• Using companion diagnostics to identify patient populations for specific therapies and combinations

• Highlighting where lessons learnt from PARP have informed ATR inhibitor application in the clinic

• Designing the perfect clinical trial for DDR therapeutics

3:00 pm

Panel Discussion: The Promise of ATR & Other Emerging DDR Targets

  • Daniel Speidel Co-Managing Director , Breakpoint Therapeutics
  • Anish Thomas Investigator , National Cancer Institute
  • Ed Tian Chief Scientific Officer, IMPACT Therapeutics

Synopsis

• A character profile of blockbuster drugs and how to find them

• Challenges and successes in identifying novel synthetic lethal pairs • Identifying potential combinations

• Optimizing DDR discovery and development using lessons learnt from PARP

Novel DDR Targets

3:45 pm

Afternoon Poster Session & Networking

4:30 pm Combination Olaparib and Ceralasertib in Homologous Repair Deficient Cancers

Synopsis

• Exploring how combined PARP & ATR inhibition can overcome PARP inhibitor
resistance in BRCA mutated ovarian cancer patients

• Providing a perspective of PARPi combination in the clinic

5:00 pm DNA-PK

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

Synopsis

• Presenting preclinical and clinical data for the DNA-PK inhibitor M3814

• Opportunities of M3814 in monotherapy or combinations including radiotherapy, chemotherapy and immunotherapy

5:30 pm A Novel Inhibitor of RAD51

Synopsis

• RAD51 inhibitor showing single agent efficacy in preclinical tumor models and combination efficacy with PARPi in vitro and in vivo

• Detailing the development and characterization of novel small molecules

• Expanding on the discovery of RAD51i mechanisms of action

• Testing RAD51i in a range of cancer types using mouse models

6:00 pm Chair’s Closing Remarks

6:15 pm

End of Conference Day One