All times shown are EST.

7:20 am Breakfast & Registration Opens

8:20 am Chair’s Opening Remarks

DELVING INTO THE EVOLUTION OF PARP & ATR IN THE PAST YEAR: A REVIEW OF PARP AS MORE AGENTS ARE APPROVED & A DEEP DIVE INTO ATR POTENTIAL & PROGRESSION

8:30 am Laying Out The Current DDRi Landscape and Analysing Future Directions

Synopsis

  • Reflecting on where we’re at right now: an overview of the current DDR landscape
  • A focus on 2nd generation targets: working towards an approval?
  • Evaluating future directions: 2023 and beyond

9:00 am Exploring a Novel Dual PARP-HDAC Inhibitor for the Treatment of Ewing Sarcoma

  • Mads Daugaard President & Chief Scientific Officer, Rakovina Therapeutics

Synopsis

  • kt-3000 series compounds exhibit dual PARP1/2 and HDAC inhibitor activity
  • Co-inhibition of PARP1/2 and HDACs amplifies DNA damage and cytotoxicity
  • Ewing sarcoma cells are highly sensitive to combined PARP and HDAC inhibition

9:30 am ATR: The Target of The Year – How Has this Target Progressed in 2022 & What Are the Current Challenges Faced Clinically

Synopsis

  • EMD Serono unveiled its new oral ATR inhibitor (M1774) with best-in-class potential
  • The search for BM-defined populations sufficient to support monotherapy registration continues
  • While there have been setbacks for chemotherapy-ATRi combinations, combinations with ICI look increasingly promising

10:00 am Speed Networking

Synopsis

A session dedicated to taking advantage of face-to-face networking time. An exciting opportunity to get an understanding of who else is overcoming similar challenges within the DDR space.

11:00 am Exploring drug polypharmacology across kinases and PARPs in live cells with NanoBRET probes

Synopsis

  • Applications of NanoBRET for targets in synthetic lethality pathways
  • Characterizing novel interactions for DDR kinase inhibitors in cells
  • Mechanistic analysis of target engagement across the PARP enzyme family

ANALYZING HOW INHIBITION OF THE DDR PATHWAY AFFECTS THE IMMUNE MICROENVIRONMENT

11:30 am Combining Inhibitors of the DNA Damage Response Pathway with Immunotherapies to Treat Cancer

Synopsis

  • The multiple interfaces between the DDR and the immune response
  • PARP inhibitor immune priming in BRCA deficient cancers
  • The link between ATR inhibition, replication stress and the ability to overcome immunotherapy resistance

12:30 pm Effects of Polymerase Theta Inhibition On the DDR-Deficient Immune Microenvironment

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

Synopsis

  • What pathways drive immune cell infiltration following polymerase theta inhibition?
  • Is an immune response required for maximal efficacy of polymerase theta inhibitors?
  • How can polymerase theta-induced immune responses be augmented further to improve anti-tumor efficacy?

1:00 pm Panel Discussion: DDR Inhibitors & the Immune Response Interface

  • Mark O’Connor Chief Scientist, Early Oncology Discovery, AstraZeneca
  • Geoffrey Shapiro Director, Early Drug Development Center, Dana-Farber Cancer Institute

Synopsis

  • DNA damage checkpoint activation, inducing the expression of antimicrobial peptides and activating immune cell receptor ligands: what are the ways DDRis impact these immune responses
  • Which pathways within DDR are involved in immune signalling?
  • DNA damage and chronic inflammation: what is the link?

1:30 pm Lunch & Networking

ADDRESSING RESISTANCE WITH NEXT GENERATION TARGETS: DRUG DEVELOPMENT & CLINICAL TRIALS OF FAMILIAR TARGETS

Chair By:

2:30 pm Reviewing the Renaissance of WEE1 Inhibitors; an Old Target with a Lot of New Potential

  • Sui Xiong Cai Senior Vice President & Chief Technology Officer Oncology, IMPACT Therapeutics

Synopsis

  • The uprise of WEE1 inhibitor and its impacts
  • Designing of WEE1 inhibitors
  • Recent WEE1 inhibitor clinical data

3:00 pm Next Generation DDR/Synthetic Lethality Targets: Mining DNA Metabolism for Gold

  • Jon Hollick Managing Director & Head of Research, Breakpoint Therapeutics

Synopsis

  • Approaches to drug discovery
  • Overview of Polymerase theta as a tumour selective drug target
  • Exploiting cancer replication stress: spotlight on WRN helicase

LOOKING TO THE FUTURE & NEXT GENERATION TARGETS: EXPLORING NOVEL TARGETS ON THE HORIZON & DISCUSSING THEIR POTENTIAL AS MONOTHERAPY AGENTS

3:30 pm Exploiting Vulnerabilities in Cancer with Next Generation DDR Inhibitors Targeting Cyclin K or PARG

  • Steve Warner Senior Vice President & Head of US Research, Sumitomo Pharma Oncology

Synopsis

  • Cyclin K degrading molecular glues potentially target CDK12/13-driven expression of DDR genes
  • PARG inhibitors may target homologous recombination deficiencies in cancer in a complementary and differentiated way than PARP inhibitors
  • Targeting Cyclin K or PARG may provide opportunities to inhibit DDR pathways that leverage contextual vulnerabilities in cancer, including CDK12-amplified cancers and PARPi-resistant HRD-positive cancers

4:00 pm Afternoon Break & Networking

4:30 pm Exploiting DNA Repair Defects via Direct DNA Modification – A New Paradigm in Oncology Drug Development

Synopsis

  • Overview of DNA modifiers (DMs) and how they can be engineered to exploit DDR defects
  • Strategies to evade known drug resistance pathways using DMs
  • Potential for combination therapies with DMs

5:00 pm A New Generation of DDR Targeting Drugs: DNA Decoy Agonists of DNAPK & PARP1

  • Wael Jdey Head of In Vitro Oncology Research & Innovation Group, Onxeo

Synopsis

  • The DDR pathway is made up of well-orchestrated machinery, with redundant pathways that could take over when one enzyme/pathway is inhibited commonly leading to acquired resistance to small molecules inhibitors
  • Onxeo developed a cutting-edge new technology to trap DDR proteins and abrogate the DNA repair machinery to trap and hyperactivate DDR enzymes, inducing a false damage signaling in tumor cells
  • These Decoy Agonists are under clinical or preclinical investigations

5:30 pm Panel Discussion: How Are Newer Targets Being Validated to Move Towards Clinical Trials?

Synopsis

  • What is the rationale behind selecting novel targets for research?
  • How do these targets differ from previous projects?
  • What do these new targets offer to existing drug development projects?

6:00 pm Chair’s Closing Remarks

6:05 pm Scientific Poster Session

Synopsis

After the formal presentations have finished for the afternoon, the learning and networking carries on. The Poster Session allows you to connect with your peers in a relaxed atmosphere and continue to forge new and existing relationships. During this session, scientific posters will be presented on the latest advancements in the DDR field.

7:05 pm End of Conference Day One