Conference Day One
7:00 am Check-In & Coffee + Light Breakfast
7:55 am Chair’s Opening Remarks
OPTIMIZING DDR INHIBITOR DOSING & REDUCING TOXICITY WITH DATA-DRIVEN PRECISION ONCOLOGY TO ENHANCE PATIENT SURVIVAL & TREATMENT SUCCESS
8:00 am Optimizing Dosage Strategies for DDR Inhibitors Integrating Preclinical & Clinical Knowledge Using Model Informed Drug Development
Synopsis
- Addressing tolerability challenges by optimizing dosage strategies for DDR inhibitors using PK/PD framework, ensuring multicycle tolerability within the expected therapeutic range
- Integrating available preclinical and clinical knowledge using MIDD framework to inform dosage decisions in early phase combination treatment development
- Utilizing predictive modeling to anticipate potential adverse effects and adjust combination therapy regimens for enhanced safety and efficacy in patients
8:30 am Utility of Circulating Tumor DNA (ctDNA) Assessments to Support Early Clinical Development of the PKMYT1 Inhibitor Lunresertib in Combination with the ATR Inhibitor Camonsertib in the Phase I MYTHIC trial
Synopsis
- Examining the role of ctDNA assessments in the early clinical development of the lunresertib and camonsertib combination, with a focus on confirmation rates of enrollment alterations
- Using ctDNA data to support dose and schedule selection for the combination therapy in the Phase I MYTHIC trial
- Correlating early ctDNA kinetics with clinical outcomes to evaluate the effectiveness of the treatment approach
9:00 am Harnessing RNA-Seq for Advancing DDR Inhibitor Therapies
Synopsis
- Analyzing tumor gene expression to uncover critical insights into cellular composition, tumor origin, and the tumor microenvironment (TME), including biomarkers that indicate therapeutic response
- Applying these insights at every stage of drug development, from target discovery and mechanistic studies to clinical trial design, patient recruitment, and biomarker validation
- Identifying biomarkers that inform dosing strategies and assess potential toxicity in DDR inhibitor therapies
9:30 am Speed Networking
Synopsis
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 collectively tackling challenges such as overcoming resistance and identifying novel DDR inhibitor targets.
10:00 am Morning Break & Refreshments
NOVEL & EMERGING PARP COMBINATIONS: CONQUERING RESISTANCE & UNLOCKING NEW POTENTIAL IN DDR THERAPIES
10:30 am Combining PARP & Androgen Receptor Inhibitors in Prostate Cancer: New Insights into the Mechanism of Action
Synopsis
- Explore the interplay between PARPi and AR inhibition in preclinical prostate cancer models and the mechanism of action providing combination activity beyond HRD prostate cancer
- Review of the DNA repair role of AR and regulation by PARP1 and the induction of DNA damage and genomic instability from combination treatment
- Discuss how these insights provide a rationale for the clinical activity of PARPi plus ARi in HRR proficient mCRPC
11:00 am Harnessing Pol Theta Inhibition as a Cancer Specific DDR Target to Overcome Resistance in PARPi-Resistant Cancers
Synopsis
- Discussing the mechanistic role of pol theta in DNA double-strand break (DSB) repair and DNA damage tolerance through translesion synthesis, with potential to address resistance in PARPi-resistant cancers and enhance the efficacy of DNA-damaging agents like chemotherapy and ionizing radiation
- Examining how pol theta inhibitors offer the potential to selectively target tumor cells while sparing normal tissue from toxicity, enabling safer and more effective combination therapies with PARP inhibitors in homologous recombination-deficient cancers
- Exploring genotoxic stress as a biomarker for patient stratification in pol theta combination therapies, highlighting the inhibitor’s promise in expanding therapeutic options and addressing unmet needs in oncology
11:30 am Fireside Chat: How Can We Holistically Prioritise Combination Strategies Across the DDR Landscape & Leverage These to Tackle PARP inhibitor resistance?
Synopsis
- How can we effectively integrate combination strategies that target complementary DNA damage response (DDR) pathways, such as combining PARP inhibitors with emerging DDR modulators like USP1 inhibitors, to enhance therapeutic efficacy?
- What role do biomarkers, particularly those related to homologous recombination repair (HRR) deficiencies, play in guiding the selection of optimal combination therapies tailored to specific genetic contexts?
- How should we address the safety implications and potential resistance mechanisms of DDR combination therapies to ensure balanced strategies that maximize efficacy while minimizing toxicity and long-term resistance?
12:15 pm Lunch & Networking
MAXIMISING TREATMENT OUTCOMES WITH COMBINATION THERAPEUTICS: ENHANCING DDR INHIBITORS WITH RADIOTHERAPY & ADCS
1:50 pm Personalizing Radiotherapy: Deciphering DNA Damage Response Dependent & Independent Mechanisms of ATR Inhibition
Synopsis
- Reviewing the unmet need in early stage and advanced triple negative breast cancer for new strategies to overcome therapeutic resistance, and discuss opportunities to exploit unique DNA damage responses to photon versus proton radiotherapy
- Exploring a novel role for ATR in mediating therapeutic resistance, independent of DNA damage
- Discussing the implications for optimizing ATR inhibitor clinical development and potential biomarkers of response
2:20 pm Combining Azenosertib with Antibody-Drug Conjugates Demonstrates Synergistic Antitumor Effects
Synopsis
- Exploring the synergistic antitumor effects of combining azenosertib with TOP1 inhibitors or ADCs with TOP1 inhibitor/microtubule inhibitor payloads in various cancer models
- Discussing the enhanced therapeutic efficacy observed when azenosertib is combined with trastuzumab deruxtecan (T-Dxd) in HER2+ breast cancer models, analyzing the potential to improve responses to TOP1 inhibitor-based ADCs in HER2+ ovarian and HER2-low breast cancer models, highlighting its broader implications for treating advanced solid tumors
- Discussing the potential for azenosertib as a general enhancer for ADCs with TOP1 inhibitor or microtubule inhibitor payloads
2:50 pm Exploring WSD0628: A CNS-Penetrable ATM Inhibitor for Radiosensitization in Recurrent Brain Cancer
Synopsis
- Investigating WSD0628's pharmacokinetic properties to determine its brain penetration efficacy and systemic exposure
- Evaluating the synergistic effects of WSD0628 combined with radiation therapy in recurrent brain cancer models, focusing on therapeutic outcomes and safety
- Assessing the impact on survival in preclinical intracranial models, including glioblastoma, DIPG, and brain metastases, to understand potential clinical benefits
3:20 pm Session Reserved for IntoDNA
Synopsis
3:30 pm Afternoon Break & Refreshments
PIONEERING CLINICAL ADVANCEMENTS IN DDR INHIBITOR THERAPIES TO PAVE THE WAY FOR FUTURE TREAMENT OPTIONS
4:00 pm A Comprehensive Overview of DDR Therapies: Key Insights & Combination Strategies
Synopsis
- Reviewing 2024 and updating the current state of play in the DDR landscape
- Case study – PARP combinations in key indications
- What to look out for in 2025
4:30 pm Combining CHK1 Inhibitor with Nano Medicine Technology to Reduce Toxicity in Solid Tumor Targeting
Synopsis
- Discussing how CHK1 inhibitors target the DNA damage response by preventing cell cycle arrest and DNA repair in cancer cells, leading to apoptosis under conditions of high replication stress
- Exploring the role of liposomal encapsulation in modifying the pharmacokinetics of CHK1 inhibitors, such as SMP-3124, to enhance anti-tumor activity and reduce systemic toxicity
- Assessing the potential benefits of this combination approach in improving the therapeutic index of CHK1 inhibitors in solid tumor treatments, focusing on reducing side effects and improving patient outcomes
5:00 pm Fireside Chat: Targeting the DDR in Brain Tumors: Trials, Tribulations, & Future Directions
Synopsis
- What evidence supports DDR as a therapeutic target in brain tumors, and are there specific subtypes where it shows more promise?
- Why have DDR-targeting therapies, including PARP inhibitors, faced limited success in brain tumor treatments despite their efficacy in other cancers?
- What strategies could overcome current barriers in DDR targeted therapy for brain tumors and enhance the efficacy of existing treatments?
5:45 pm Chair’s Closing Remarks
5:50 pm Scientific Poster Session
Synopsis
This is an informal session to help you 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.
