Day One

• Highlighting the key reasons DDR programs stall, including weak mechanistic rationale, limited biomarker support, and poor patient stratification

• Presenting real-world case studies from biotech and academia on programs that failed to translate, and the lessons learned

• Exploring how early decisions around target selection, dosing, and trial design impact clinical success

• Identifying practical strategies to improve target validation, including functional assays, predictive biomarkers, and more robust preclinical models

• Illustrating the complexity of PARP-dependent pathways and highlighting underexplored hydrolases, regulators, and effectors with therapeutic potential

• Showcasing emerging early-stage discovery programs targeting alternative hydrolases as biomarkers and drug targets

• Encouraging broader exploration of DDR biology to avoid “PARP tunnel vision” and inspire innovation in next-generation DDR therapies

• Uncovering the rationale for “hot” PARP inhibitors to address resistance seen with conventional agents

• Examining resistance mechanisms and the role of biomarkers like PET imaging in guiding treatment

• Outlining combination strategies to boost efficacy while managing toxicity challenges

•  Unveiling a new generation of precision tools, mechanistic assays, and cellular models that directly measure PARP1 dynamics, replication-fork instability, and DDR pathway engagement—capabilities not accessible with current preclinical platforms.
• Revealing distinct mechanistic modes of PARP inhibitor action and toxicity —a PARP1-retention–driven and a context-specific signalling — providing a mechanistic roadmap for which tumors respond, why resistance emerges, and how to rationally target each context.
• Delivering predictive, high-resolution models of PARPi response across BRCA and non-BRCA tumors, identifying actionable and differential biomarkers for HRDs, combination opportunities, and mechanistic vulnerabilities that can immediately feed into drug discovery and translational programs.
• Defining a new precision-medicine framework for DDR therapeutics and beyond, enabling industry partners to design better molecules, more informative functional screens, mechanistically aligned dosing strategies, and clinically meaningful patient-selection criteria.

A prime opportunity to engage in person with fellow experts and forge valuable connections as new companies enter and established players expand their presence within the DDR inhibitor space. Designed to maximize your interaction with thought leaders, share insights, and spark discussions at this uniquely focused summit tailored for scientists and drug development professionals.

• See how Breakpoint Therapeutics is guiding candidate selection by comparing helicase vs. polymerase inhibition to inform domain targeting

• Presenting Breakpoint’s candidate molecule and second-generation compound with updated preclinical efficacy and safety data

• Contextualizing Breakpoint’s program within the broader Polθ landscape to highlight differentiation and partnering potential

• See how the MD Anderson Cancer Center are advancing first-in-human trial data for WRN inhibitors in MSI solid tumors
• Interpreting translational relevance and biomarker integration
• Positioning WRN as a synthetic lethality target beyond PARP

• Update on on-going Phase I study with the first-in-class ALC1 inhibitor EIS-12656, including safety and tolerability.
• Connecting clinical Phase II plans with mechanistic and biomarker insights to shape advancement strategy
• Building a modular Phase II framework to expand tumor applicability, unlock synthetic-lethal and combinatorial therapy potential to enable ALC1 inhibition in solid tumor therapy

• Introducing Ku as the first responder to DNA double-strand breaks and a novel DDR target distinct from kinase inhibitors

• See how Nerx BioSciences are disrupting Ku-DNA interactions to block DNA-PK activity with greater specificity and reduced toxicity

• Demonstrating how this upstream approach could deliver safer and more effective DDR therapies compared to traditional kinase inhibition

• Reviewing lessons learned from past DNA-PK inhibitor programs and how improved potency, PK, and selectivity address prior limitations

• See how Wayshine Pharma is advancing WN-C001 to enhance radiotherapy efficacy with a favorable safety profile

• Highlighting translational insights and the development path toward clinical validation of DNA-PK inhibition as a radio-sensitization strategy

• See how Theranovir is developing NOV2, a monoclonal antibody targeting the Leptin-dependent NRP-1/OBR complex involved in DDR signaling and nuclear translocation
• Sharing preclinical data demonstrating NOV2’s ability to induce chromosome instability, including centromere disruption and telomere shortening
• Exploring NOV2’s potential to overcome resistance and relapse, and its future use in combination with immune checkpoint inhibitors 

This is an informal session to connect with your peers in a relaxed atmosphere to continue forging new and beneficial relationships. With an audience of preclinical, translational, and clinical scientists eager to hear the latest advancements in DDRi therapeutic development, you will have the opportunity to display a poster presenting your own work and innovations.

• See how CrossBridge Bio is designing dual-payload ADCs to address key clinical questions on efficacy, durability, and safety

• Presenting preclinical evidence that demonstrates how proprietary dual-payload ADCs act synergistically to delay or prevent resistance in tumor models, including activity in resistant settings

• Revealing non-human primate data highlighting an improved therapeutic index and lack of overlapping toxicities compared to single-payload ADCs

• Highlighting oncolytic herpes simplex virus (oHSV) combinations with DDR inhibitors that synergize in treating glioblastoma

• Using patient-derived human and mouse glioblastoma stem-like cells (GSCs) as representative preclinical models to assess therapy

• Targeting cancer stem cells with DNA-PK inhibitors and oHSV

• See the rationale behind PharmaEngine’s combination of CHK1 and PRMT5 inhibitors with preclinical examples

• Understanding alternation of pharmacodynamic markers of CHK1 and PRMT5 post corresponding inhibitor treatments

• Discovering combinations of CHK1 or PRMT5 inhibitors to standard of cares (SoCs) in corresponding indications