All times shown are EST.

7:00 am Morning Poster Session: Coffee & Networking

7:50 am Chair’s Opening Remarks

  • Graeme Smith Chief Scientific Officer , Artios Pharmaceuticals

IDENTIFYING RELIABLE DDR/HR TUMOR BIOMARKERS

8:00 am Breakfast Panel: Assessing the Situation: Improving Biomarker Characterization, Aiding Predictive Drug Development & Advancements in Addressing Patient Heterogeneity

  • Ioannis Gounaris Senior Medical Director Cluster Lead DNA Damage Response (DDR) Inhibitors, Global Clinical Development Oncology Group II , Merck KGaA
  • Sotirios Sotiriou Head of Biology & Co-Founder , FoRx Therapeutics
  • Wael Jdey Lead Scientist , Onxeo
  • Shikang Liang Postdoctoral Research Scientist, Blundell Group, Department of Biochemistry , University of Cambridge

Synopsis

  • Discussing target engagement and response biomarkers
  • Exploring similarities between uses of biomarkers in pre-clinical vs clinical settings
  • Debating the reliability of current biomarkers
  • Is a global standard approach needed to evaluate biomarkers? How would we navigate this?
  • Dissecting selecting alternative biomarkers for various populations
  • How close to the route cause should we be going? (genomics, transcriptomic, proteomics)
  • Evaluating how to decide on the most reliable biomarkers to identify TRUE functional deficiency
  • Evaluating the successes of the windows of portion trialing – can you predict the long outcome?
  • Analyzing data for biomarkers of PARPi sensitivity beyond BRCA – mutational signature approaches to identify HR deficiency as a means to expand the web of biomarker options?
  • Thoughts on trends in germline vs somatic DDR mutations

8:30 am ATR Inhibitor-Based Combination Treatments in the Clinic: Biomarkers for Patient Selection

  • Ioannis Gounaris Senior Medical Director Cluster Lead DNA Damage Response (DDR) Inhibitors, Global Clinical Development Oncology Group II , Merck KGaA

Synopsis

  • ATM remains the most studied biomarker for ATRi monotherapy activity and also for ATRi-DDRi combinations
  • Explore how replication stress signatures represent an emerging biomarker, but not ready for prime time yet
  • Learn how to optimally select patients for PARPi-ATRi in both the PARPi naïve and resistant settings remains a challenge

9:00 am ATRi Development & Biomarker-Led Selection; Bridging the Gap Between the Lab & the Clinic

Synopsis

Speaker TBC
Repare Therapeutics

9:30 am Drug-driven HRD: From Bench to Bedside & Back: Discovering Novel Biomarkers for PARP

Synopsis

  • Understanding and utilizing drug-driven Homologous Recombination Deficiency (HRD)
  • Potentials and hope for a Rad51 biomarker
  • Furthering the understanding of primary and acquired resistance to PARP inhibitors

10:00 am Synthetic Lethality-Mediated Precision Oncology

  • Eytan Ruppin Chief - Cancer Data Science Lab , National Cancer Institute

Synopsis

  • Harnessing synthetic lethality to stratify patients to targeted and immune therapy
  • Synthetic lethality-based identification of drug targets, drug re-purposing and combinations

10:30 am Morning Refreshments & Networking

EXPLORING THE EMERGING TARGETS IN THE DDR PATHWAY: STRATEGY, EXECUTION, DEVELOPMENT & PROMISE

11:30 am Targeting Protein-DNA Interactions in the DNA Damage Response: Lead Identification & Optimization for Novel Inhibitors of Replication Protein A (RPA) & Ku

Synopsis

  • Understanding how NERx is positioned to lead the first-in-class and first-in-human trials of novel agents targeting RPA and Ku
  • Delving into how RPAi’s synergy with DNA damage-inducing therapeutics and DDR targeted therapies, and a lead candidate has been selected
  • Exploring Ku inhibitors blockage of the Ku-DNA interaction and serve as a novel approach to inhibit DNA-PK

12:00 pm Developing a PARG Inhibitor

  • Monah Abed Principal Scientist , IDEAYA Biosciences

Synopsis

  • Exploring the drug discovery process: target identification and validation, antitumor effect, pathway understanding, biomarkers
  • Latest data and future directions
    This seminar will be streamed live at the event

12:30 pm Exploring KSQ-4279, a First in Class USP1 Inhibitor for the Treatment of Tumors with Defects in DNA Damage Repair

  • Andrew Wylie Senior Vice President & Head of Oncology , KSQ Therapeutics

Synopsis

  • Proprietary CRISPR screening platform identifies USP1 as a novel target that has a distinct, cancer-selective profile in comparison to other DDR targets that are often broadly cytotoxic
  • Delve into the potent, selective USP1 inhibitor, KSQ-4279, is active in patient-derived xenograft models with DDR defects both as a monotherapy and in combination with PARP inhibitors
  • Leveraging forward directions: KSQ-4279 Phase I trial is actively enrolling

1:00 pm Discovery of a Potent, Selective, Bio-Available & Highly Efficacious DNAPK Inhibitor

  • Claudio Sturino Senior Director, Head of Chemistry & Pharmaceutical Development , adMare Bioinnovations

Synopsis

• The lecture will introduce the importance of DNA-dependent protein kinase (DNA-PK), a serine-threonine protein kinase, in repairing double-strand DNA breaks and in the DNA damage response
• We have optimized an initial lead series to identify a potent and selective DNA-PK inhibitor. An overview of the optimization strategy will be presented, along with the key lessons learned during this discovery process
• The lead molecule’s in vitro, and cross-species PK profile will be presented, demonstrating the excellent profile of the lead DNA-PK inhibitor.
• The efficacy of the lead DNA-PK inhibitor in a mouse FaDu thigh muscle xenograft model, in combination with ionizing radiation treatment, will be presented

1:10 pm Emerging Roles of the ATR/CHK1 Axis in Nucleotide Excision Repair

  • Kent Mouw Assistant Professor of Radiation Oncology , Dana-Farber Cancer Institute

Synopsis

  • The ATR/CHK1 axis has a role in early NER events
  • CHK1 inhibition induces cellular NER deficiency
  • CHK1 inhibition may cooperate with DNA damaging chemotherapy via multiple mechanisms – The ATR/CHK1 axis has a role in early NER events

1:40 pm Lunch Break

2:30 pm Progress in PKMYT1 Inhibition: RP-6306

Synopsis

• PKMYT1 is synthetic lethal with CCNE1 amplification and FBXW7 deleterious mutation and represents a unique targeting opportunity in patients with significant unmet need
• RP-6306 is a potent and selective inhibitor of PKMYT1 that is safe and efficacious in models of CCNE1 amplification and FBXW7 loss
• Combination of RP-6306 with standard of care chemotherapy results in rapid and profound regression in xenograft models at very well tolerated doses and schedules

MANAGING TOXICITY – DOSE, DELIVERY, SCHEDULING, PATIENT SELECTION & STRATIFICATION – MANAGING THE THERAPEUTIC WINDOW & TREATMENT REGIMES

3:00 pm Durability of PARP Inhibition: Implications for Dose & Schedule as Single Agent & Combination Therapy

  • Nicola Curtin Experimental Therapeutics Professor , Newcastle University
  • Asima Mukhopadhyay Gynaecological Oncologist & Clinician Scientist,, Chittaranjan National Cancer Institute India & Newcastle University

Synopsis

  • Understanding different PARPi doses and schedules are needed for single agent and combinations
  • Delving into how the durability of PARP inhibition differs for the approved PARPis
  • Is the MTD/Safe dose and schedule appropriate for the approved dose of a molecularly targeted agent?
  • Clinical implications and improving access
    This seminar will be streamed live at the event

3:30 pm DDRi R&D in CNS Tumors: Landscape & Opportunities

  • Kirk Tanner Chief Scientific Officer , National Brain Tumor Society

Synopsis

  •  Understanding the strong rationale for DDRi’s in CNS Tumors
  • Optimizing systematic and efficient experimental drug qualification as a key opportunity to make profound impact on devastating diseases with a strong commercial case

4:00 pm Afternoon Break & Networking

NEXT STEPS IN COMBINATION APPROACHES – TO HEIGHTEN DRUG EFFECT & OVERCOME RESISTANCE – THE FUTURE?

4:30 pm Understanding Connections Between Immune Response & DNA Damage Defects in Chronic Lymphocytic Leukaemia ( CLL) as a Disease Model

  • Tatjana Stankovic Institute of Cancer and Genomic Sciences , University of Birmingham

Synopsis

  • Exploring how DNA damage defects in CLL lead to the accumulation of DNA damage and activation of nucleic acid sensing pathways
  • Understanding why activation does not lead to the induction of INFI and immune responses in all tumors
  • Delve into how the integrity of sensing pathways and the immune cells’ exhaustion may hamper anti-tumor immunity and this provides an opportunity for therapeutic intervention

5:00 pm Targeting ATR in the Clinic: Novel Agents and Rational Combinations

  • Timothy Yap Associate Professor, Investigational Cancer Therapeutics, MD Anderson Cancer Center

Synopsis

• ATR inhibitors are a promising antitumor therapy
• Patient selection is critical to optimize antitumor efficacy
• Rational combinations will enhance the efficacy and reach of ATR inhibitors

5:30 pm Closing Panel Discussion: Future Directions for DDRi

  • Daniel Speidel Managing Director & Co-Founder , Breakpoint Therapeutics
  • Mark O’Connor Chief Scientist Oncology, Head of the DDR Strategic Biology Area, AstraZeneca
  • Ranjit Bindra Professor, Departments of Therapeutic Radiology & Pathology , Yale School of Medicine
  • Timothy Yap Associate Professor, Investigational Cancer Therapeutics, MD Anderson Cancer Center

Synopsis

  • What is the current status of DDRi combination with IO
  • Thoughts and rationalizing on potential best outcomes DDR-DDR combos
  • Reviewing the various combination approaches and new targets coming in – thought experiment based on pathway
  • What are the combinations and new targets that are going to push the field forward in a durable and effective way?
  • Designing for approval in monotherapy vs comb therapy?
  • PARP combination directions
  • How far to take monotherapies?
  • How can we be equally successful with PARP in other cancer types?
  • What makes DDRis so powerful?
  • Advice on how to take novel targets into the clinic?
  • Where is this field going?

5:30 pm Close of Summit