About The Session Session Agenda 1. Introduction 2. Initial Discussion Point 3. Breakout Sessions 4. Full Group Discussion 5. Conclusions Session Summary • The session aimed to engage key industry stakeholders in a bi-directional conversation that will gather feedback on what TRIDENT needs to do to prove its concept, gain insight about partner expectations, and collect ideas on how TRIDENT can help smoothen the path to regulatory affairs. • Dr. Gold provided an introduction, acknowledging the funding from the New Frontiers in Research Fund (NFRF), which supports high-risk, high-reward academic projects in Canada. The primary goal of the AGM Think Tank was to engage participants in discussions about the TRIDENT project, which involves drug development, and to gather feedback on communication, timelines, and project outcomes. • The specific focus of the Think Tank was on translating research into regulatory processes and exploring how industry partners, patient organizations, and government could benefit from these efforts. The research involves testing potential drug molecules using various models, including humanized models and sex-based analysis, with the aim of creating a robust, open, and data-driven platform for drug development. • The meeting included breakout sessions where attendees discussed key topics such as validating the TRIDENT model, adapting it for the future, and contributing to the regulatory process. The session ended with a full discussion. • Breakout groups were organized into different themes, with assigned leaders and reporters for each group. Breakout Session 1: TRIDENT Now • Session Leader: Dr. Ravi Menon • Reporter: Dr. Liisa Galea • Coordinator: Dr. Sriram Jayabal Discussion Points • What is the extent of proof needed to validate TRIDENT's better translation to clinical success? E.g.: right model + touchscreen cognition + imaging on known failed drugs • Will a one stop shop platform with iPSC organoid, mouse, and marmoset models be leveraged together? • What different combinations of models or single model should be utilized? Session Summary and Key Comments • Platform Validation Challenges How to establish predictive validity for preclinical models. Lack of validated models for neurodegenerative diseases like Alzheimer’s and Parkinson’s. Benchmarks are needed to evaluate platform success. • Key Considerations for Validation Importance of replicability and reproducibility in preclinical studies. Role of cognitive testing as a reliable metric compared to traditional methods. Integrating multiple models and approaches (e.g., in vitro, animal models, and imaging). • Industry Expectations and Limitations Pharma’s preference for faster timelines, even at the expense of deeper validation. Focus on biomarker outcomes (e.g., amyloid reduction) rather than cognitive results. Resistance to adopting slower, more rigorous validation methods due to time and cost constraints. • Recommendations for Improving the Platform Use failed clinical trials as proof points to validate predictive ability. Incorporate cognitive and pathology measures into the pipeline for comprehensive evaluation. Leverage computational models and advanced analytics for predictive insights. Collaboration and Partnerships The need for business development efforts to engage industry partners. Challenges of multi-institutional coordination for funding and implementation. Opportunities to work with industry on next-generation drug testing. • Strategic Considerations Develop adaptable platforms to stay relevant with evolving scientific discoveries. Focusing on combinations of approaches rather than single-model predictions. Balancing academic and industry needs to align goals and expectations. Broader Insights on Neurodegenerative Research Cognitive deficits as a critical yet underexplored aspect of many conditions. Importance of integrating cognition, pathology, and imaging into drug validation. Highlighting gaps in preclinical research, such as limited cognitive testing in models. Breakout Session 2: TRIDENT Future • Session Leader: Dr. Tom Durcan • Reporter: Dr. Joel Watts • Coordinator: Shehrbano Khan Discussion Points • How adaptable and scalable should TRIDENT be? To be your top choice to test a therapeutic, what should TRIDENT do? • What would be an acceptable turn around time for TRIDENT therapeutic evaluation? Evaluation using a current TRIDENT model vs. developing a new model + evaluation. Session Summary and Key Comments • TRIDENT’s Current Focus TRIDENT’s work revolves around creating advanced models, including iPSC-derived cells, organoids, and animal models like mice and marmosets, with an emphasis on Alzheimer’s and Parkinson’s diseases. These models aim to bridge gaps in understanding and testing potential therapies, offering a robust pipeline for research. • Opportunities for Growth Participants explored ways to expand TRIDENT’s scope beyond its current focus: • Broader Applications: Extending the pipeline to study conditions like ADHD, traumatic brain injuries, and other neurological disorders. • Collaboration: Strengthening partnerships with academic institutions, commercial entities, and patient advocacy groups to enhance resources and expertise. • Addressing Sustainability A significant portion of the discussion revolved around what happens after the six-year grant ends. The group agreed on the importance of planning now to ensure TRIDENT’s future: • Diversified Funding: Ideas ranged from seeking philanthropic donations and government grants to forming partnerships with biotech companies. • Defined Wins: The team emphasized showcasing tangible successes—such as validated models, impactful collaborations, and published research—to attract continued investment. • Building Trust and Credibility Maintaining high standards for data quality and transparency was identified as crucial for long-term success. This includes adhering to certifications like ISO or GLP to ensure data reliability and reproducibility. • Celebrating and Showcasing Wins The group stressed the need to identify and communicate TRIDENT’s successes: Models validated as the “gold standard” for preclinical research. Publications that highlight the program’s contributions to science. Collaborative projects that deliver meaningful results. • Sustaining Funding To keep TRIDENT moving forward, participants proposed a multi-pronged funding strategy: Engage philanthropic organizations to support the early stages of research. Partner with biopharma companies for downstream development and testing. Reach out to patient communities for advocacy-driven donations. Smart Growth Expanding the program without overextending was a key consideration: Focus on diseases and models that align with TRIDENT’s existing strengths. Gradually increase capacity through partnerships and infrastructure development. Strengthening Outreach Effective communication is vital for attracting stakeholders. This includes: Sharing TRIDENT’s story through publications, conferences, and media. Highlighting the real-world impact of its work, from training researchers to advancing therapies. Breakout Session 3: TRIDENT Policy Appeal • Leader: Dr. Jackie Sullivan • Reporter: Kate Placide • Coordinator: Sarah Brennan Discussion Points • How can TRIDENT make itself relevant for regulatory affairs? • What aspect of TRIDENT is appealing to the regulators? • Discuss the economy of TRIDENT – savings, faster approval process etc. Session Summary and Key Comments • The discussion centered on the TRIDENT pipeline, a framework for enhancing drug development, particularly focusing on preclinical to clinical transitions. • The meeting covered challenges, opportunities, and strategies for integrating TRIDENT into regulatory and commercial frameworks. • Regulatory Integration and Relevance TRIDENT’s focus on translational models (e.g., touchscreen tasks and multi-species cognitive assessments) is unique but not currently essential for regulatory approval. Regulatory standards prioritize safety and efficacy, with preclinical validation playing a supportive role. • Potential Influence TRIDENT could influence regulatory thinking by providing robust, translational data. Its inclusion of diversity (e.g., sex differences, hormonal impacts) aligns with growing regulatory emphasis on representation and precision medicine. • Challenges and Limitations: Negative Data Risks and Industry Skepticism A negative outcome through TRIDENT testing could harm a biotech company's prospects, especially for smaller firms. Public data sharing was identified as a sensitive issue due to commercial risk. Smaller biotech companies may hesitate to engage if TRIDENT outcomes negatively impact valuation, emphasizing the need for clear predictive value and industry trust. • Commercial and Development Strategy: Biotech Perspective and Value Proposition Companies often aim for proof-of-concept milestones to attract investment or acquisition. TRIDENT’s testing could add value by identifying promising candidates earlier in development. TRIDENT could aid in clinical strategy by identifying biomarkers and refining eligibility criteria, improving trial success rates. However, it must balance rigorous validation with practical commercial timelines and costs. • Expanding Applications: Holistic Considerations and Rare Diseases Beyond cognition, TRIDENT could incorporate quality-of-life metrics, delivery mechanisms, and continuous-use designs, aligning with patient-centered goals. The model could be adapted for rare diseases with small patient populations, offering rigorous preclinical validation where clinical trials are less feasible. • Future Directions Collaborations, Open Data, and Pipeline Refinement Partnerships with regulators, industry stakeholders, and smaller biotechs are critical for scaling Trident’s impact. Managing data sharing (e.g., embargo periods or selective release) to align with both academic and commercial interests is a priority. Tailoring the pipeline for specific disease mechanisms and broadening its application to other therapeutic areas. TRIDENT holds promise for advancing drug discovery by bridging preclinical and clinical gaps, but successful integration will require careful navigation of regulatory, commercial, and scientific priorities • Stakeholder engagement, clear value demonstration, and iterative development are essential for its long-term impact. Overall Think Tank Key Takeaways • Timelines and Flexibility: TRIDENT must balance the need for rigorous validation with industry’s demand for speed. • Proof Points: Demonstrating the platform’s success through small wins will attract partners and sustain funding. • Collaborative Approach: Engage diverse stakeholders, maintain adaptability, and establish credibility through robust science Next Steps 1. Define and Achieve Wins: Identify key milestones for the next several years, such as model validation and impactful partnerships. 2. Create a Business Plan 3. Develop a clear roadmap for funding and operational sustainability post-grant. 4. Engage Stakeholders Strengthen relationships with funders, industry, and patient advocacy groups to build a supportive network. 5. Focus on Standards: Work toward certifications and protocols that enhance TRIDENT’s reputation and data reliability.