8:00 am Registration & Coffee
CLINICAL PROGRESS WITH INNATE IMMUNE-TARGETING COMPOUNDS
9:00 am Breakfast Panel Discussion: How Far Have We Come & Where Do We Want to Go?
Synopsis
- Dissecting the recent advances in PRR-targeting drugs
- Sharing insights into the directions for more successful immune system manipulation
- Thoughts on modes of action being investigated, conclusions drawn from setbacks and ways to improve the clinical outcomes
- Pathway understanding, indications, toxicity outlooks, combinations, drug formats and delivery mechanisms
- Biological understanding update: pathway, biomarker and translational updates plus validation from the lab
- Update on exciting learnings on the mechanisms, pathways, interactions and key changes in the landscape
- Discussions on gaps in knowledge and how we can fill these: mechanisms, modelling, translation
9:30 am Challenges in Harnessing Innate Immunity for Cancer Immunotherapy
Synopsis
- A broad overview of all of the PRRs, their similarities and differences, and the various modalities by which they are being targeted
10:00 am Networking Break
RATIONALE & PROGRESS IN NOVEL METHODS OF TARGETING STING & TLR
11:00 am Systemic Small Molecule TREX1 Inhibitors to Selectively Activate STING in the TME of Metastatic Disease
Synopsis
- Although STING is a critical innate immune receptor, the clinical activity of STING agonists given by intratumoral administration has not compared well to preclinical studies
- TREX1 is a cytosolic dsDNA exonuclease that modulates the cGAS/STING pathway activation, is a DNA repair enzyme, is upregulated in tumors, and is a target to preferentially activate the STING pathway in the TME
- Systemic small molecule inhibitors TREX1 confer significant anti-tumor activity in mice given in combination with subtherapeutic doses of doxorubicin and are cytotoxic in DNA repair deficient human tumor cell lines
11:30 am Considerations & Progress in Developing a Dual TLR Agonist
Synopsis
- Exploring the drug discovery process: target identification & validation, antitumor effect, pathway understanding, biomarkers
- Discussing potential indications?
- Latest data & future directions
12:00 pm Targeted Immune Activation by Systemic Delivery of Toll-Like Receptor 9 Agonist Antibody Conjugates
Synopsis
- Toll-like Receptor Agonist Antibody Conjugate (TRAAC) platform delivers potent TLR-9 (T-CpG) for targeted immune activation via systemic administration
- TRAAC platform is amenable for immune-targeting, tumor/immune-targeting and tumor-targeting to promote adaptive and innate responses
- TAC-001, CD22 TRAAAC, targets B-cells to drive potent anti-tumor activity in preclinical solid tumor models
12:30 pm Panel Discussion: What is the Best TLR to Target & Why?
Synopsis
- Triggering effective and durable response via the innate–adaptive immune axis
- Dissecting the rationale behind targeting each TLR from different perspectives
- Preclinical analysis, clinical analysis, combination discussion, delivery mechanisms, dosing discussions
1:00 pm Lunch Break
DEVELOPING PREDICTIVE PRE-CLINICAL MODELS IN PRR RESEARCH TO ACHIEVE HUMAN-SPECIFIC TRANSLATION
2:00 pm Lymph-Node Targeted TLR9 Agonists Enable Potent Cellular Immune Responses Against Cancer & Infectious Disease
Synopsis
- Dissecting what exactly is lacking in the current models and bridging the translation gap
- Exploring how we can design/strategize/use the right models to really represent what we want
- Exploring what constitutes sensitivity
- Using models to predict the severe side effects seen in humans
- Understanding what the best setting is to do efficacy/new target discovery for optimizing compounds and biomarker discovery
- Toxicity models – what preclinical models are out there that could help us to identify toxicity of these therapies?
2:30 pm Oral Administration of Tissue-Targeted TLR7 Agonists for Immune Oncology
Synopsis
- Unpicking the mechanistic studies of our tissue-targeted approaches,
- Exploring the preclinical models
- Assessing cytokine responses as it pertains to tissue distribution and residence time
3:00 pm Panel Discussion: Towards Bridging the Gap with the Clinic
Synopsis
- How have clinical results traced back to what was shown preclinically?
- Exploring optimal validation in clinics
- Standardizing the approach in the clinic so we can go back preclinically – which models?
- Gathering early clinical information – robust translational medicine program
- How can you best parallel with translational – ctDNA metabolmics
- Discussing mathematical modelling use potentials for dose adjustement and tolerability
- Why do the colony formation assays take so long and what are the alternatives? Reliability and taking cell proliferation rate into account
- Transition from preclinical to clinical trials
- Collecting preclinical data to demonstrate how initiation of innate immune responses can lead to subsequent adaptive long-term cancer immunity
- Identifying successful localized intratumoral innate immune activation coupled with concurrent systemic adaptive tumor antigen specific cytotoxic T-cells
- Predicting the successful integration of innate immune activation strategies into combination therapies for cancer treatment which lead to more effective and long-term clinical benefit
3:30 pm Afternoon Refreshments & Networking Break
EXPLORING THE EMERGING TARGETS IN PRR TARGETING: STRATEGY, EXECUTION, DEVELOPMENT & PROMISE
4:00 pm Mitochondria as a Central Rheostat of NLRP3 Inflammasome Activation
Synopsis
- Mitochondria Can Both Activate and Inhibit NLRP3 Inflammasome Activation
- Mitochondria Fitness is Essential for Mounting a Proper NLRP3 Inflammasome Response
- Targeting Mitochondria can Regulate NLRP3 Inflammasome Activity