Conference Day Two
7:30 am Check-In & Coffee + Light Breakfast
7:55 am Chair’s Opening Remarks
TARGETING THE FUTURE: NOVEL DDR PATHWAYS & EMERGING THERAPEUTIC TARGETS
8:00 am FORX-428: A Novel, Potent PARG Inhibitor Demonstrating Strong Anti- Tumor Activity in Preclinical Cancer Models
Synopsis
- Reviewing the rationale for targeting PARG to selectively treat cancers with deficiencies in DNA repair
- Assessing the characteristics of FORX-428, emphasizing its potency, selectivity, and promising efficacy in various cancer models
- Uncovering the for advancing FORX-428 to clinical trials for cancer therapy
8:30 am CTX-439: A First-in-Class Orally Available CDK12 Inhibitor with Anti- Tumor Potential
Synopsis
- Analyzing CTX-439's selective inhibition of CDK12 and its impact on transcription elongation, leading to aberrant RNA accumulation and increased cancer cell stress
- Evaluating the preclinical anti-tumor efficacy of CTX-439 in various carcinoma mouse models, assessing its potential as an effective single-agent therapy
- Exploring the synergistic effects of combining CTX-439 with PARP inhibitors or chemotherapeutic agents, focusing on enhanced DNA damage response and overall treatment efficacy
9:00 am Novel FEN1 Inhibitor with Unique Metal-Binding Pharmacophore to Enhance Synergistic Therapeutic Effects with USP1, PARP, PARG, & ATR Inhibitors
Synopsis
- Highlighting the discovery of BSM-1516, a novel and highly potent FEN1 inhibitor, demonstrating significant selectivity and efficacy, especially against HR-deficient cancer cells—a breakthrough overcoming previous chemistry limitations
- Presenting evidence of strong synergy between BSM-1516 and multiple DDR drug classes (e.g., PARP, PARG, USP1, ATR inhibitors), underscoring its potential to enhance the therapeutic effects of existing DDR-targeting treatments
- Showcasing ongoing in vivo studies that build on preclinical data, positioning BSM-1516 for future clinical testing, particularly in combination with synergistic DDR inhibitors
9:30 am Morning Break & Refreshments
ADVANCED TRANSLATIONAL MODELING FOR NOVEL DDR TARGETS: BRIDGING ANIMAL STUDIES, IN VITRO APPROACHES, & CLINICAL APPLICATIONS TO IMPROVE PATIENT OUTCOMES
10:30 am Enhancing Translation of PKMYT1 Targeting: In Vivo & In Vitro Strategies for Maximizing Efficacy & Patient Impact
Synopsis
- Conducting comparative analysis of the in vitro profile of Evariste’s preclinical candidate PKMYT1 inhibitor, EVT-3023
- Analyzing of the extent to which PKMYT1 is responsible for control of pCDK1 levels in various in vitro and in vivo models
- Exploring translation of a novel biomarker for sensitivity to PKMYT1 inhibition
11:00 am Translating ALC1 Inhibition into Clinical Success: Targeting Genomic Instability
Synopsis
- Leveraging EIS-12656 to disrupt chromatin remodeling and exploit vulnerabilities in tumors with impaired DNA repair mechanisms
- Demonstrating rapid tumor inhibition and strong tolerability in preclinical models
- Highlighting the drug’s translational potential
11:30 am Integration of PDX Modeling & Pharmacokinetics to Inform Clinical Development of the Novel ATM inhibitor WSD0628
Synopsis
- Use of in vitro and PDX modeling to define target drug concentrations for a novel ATM inhibitor WSD0628
- Integration of Kp and Kpuu to define target human plasma concentrations for robust radiosensitization in GBM
- Analysis of human PK data to inform further dose-escalation in the first-inhuman clinical trial of WSD0628 and radiation in recurrent GBM the translation of synthetic lethal strategies into clinical therapies for improved patient outcomes
12:00 pm Lunch & Networking
INNOVATIVE DRUG DISCOVERY & RESPONSE TECHNOLOGIES REVOLUTIONIZE DDR INHIBITOR APPLICATIONS
1:15 pm AI-Powered Target Identification in DNA Damage Repair: Hypotheses for Validation
Synopsis
- Reviewing how AI identifies and analyzes synthetic lethal DNA damage repair (DDR) targets, offering new therapeutic opportunities
- Uncovering the rationale behind selecting WRN and USP1, supported by AI-driven insights into their potential roles in synthetic lethality and cancer treatment
- Progress and speed in advancing chemistry with AI, from target discovery to drug development, optimizing efficiency in the drug discovery process
1:45 pm Predictive Precision Proteomics (AP3) Platform Uncovers Need for Dual WEE1/PKMYT1 Inhibition for Superior Single Agent Activity, Leading to the Discovery of ACR-2316
Synopsis
- Discussing Acrivon’s AP3-based finding that balanced PKMYT1 inhibition overcomes a dominant cellular WEE1 inhibition-induced resistance mechanism resulting in superior single agent activity
- Exploring how Acrivon leveraged its AP3 platform to identify the key signaling nodes associated with maximum on-target activity and guide drug candidate selection
- Analyzing the mechanism of action and potentially class leading potency and selectivity of ACR-2316, translating to superior in vivo efficacy with enhanced therapeutic index compared to single agent WEE1 or PKMYT1 inhibitors
2:15 pm Enhancing Patient Selection in Oncology: Clinical Validation of a Multi- Gene Expression Diagnostic to Predict Sensitivity to DDR Therapies
Synopsis
- Introduction to Allarity’s Drug Response Predictor (DRP)- a multi-gene expression diagnostic for selecting patients likely to benefit from DDR therapies
- Sharing key findings from the phase II advanced, recurrent ovarian cancer study showcasing the impact of Allarity’s novel PARP/ Tankyrase inhibitor, Stenoparib
- A discussion of Stenoparib’s potential in advanced ovarian cancer using the Stenoparib DRP to select patients for therapeutic benefit
2:45 pm Afternoon Break & Refreshments
THE NEXT WAVE: PROGRESSING SECOND-GENERATION PARP INHIBITORS & FUELLING FUTURE DDR INHIBTOR CLINICAL PIPELINES
3:15 pm Clinical Advances in the Development of New Generation PARP1- Selective Inhibitors
Synopsis
- Understanding how next-gen PARP1 selective inhibitors maintain efficacy while mitigating toxic side effects
- Uncovering the ways in which these new molecules diversify the application scenarios of PARP inhibitors in clinic
- Outlining which novel DDR targets are showing preclinical & clinical potential for the next wave of cancer-targeting drug approvals
3:45 pm Exploring Next-Gen PARP Inhibitors without PARP Trapping
Synopsis
- Evaluating next-gen PARP inhibitors that selectively target PARP1 without trapping, aiming to minimize hematological toxicity and enhance safety in combination with DNA-damaging agents
- Focusing on improving blood-brain barrier penetration to address the unmet needs in treating brain metastases and glioblastomas
- Exploring the potential of these next-gen PARP inhibitors in combination with various DNA-damaging therapies to broaden their therapeutic applications
4:15 pm Panel Discussion: What’s Next for DDR Therapeutics? Evaluating Next-Gen PARP Inhibitors, Novel Targets, & the Future of Clinical Validation
Synopsis
- How are biopharma validating novel DDR targets, and what role will next-gen PARP inhibitors play in the evolving landscape of DDR therapeutics?
- What preclinical frameworks are currently in use for DDR inhibitors, and how can they be enhanced to better predict clinical success and viability?
- As we look to the future, could expanding data access—such as sharing DDRi trial results and patient genome sequencing—help create a more patient-centric approach to clinical trials for DDRi-sensitive cancers?
5:00 pm Chair’s Closing Remarks & End of Conference
