8:00 am Registration & Coffee
CLINICAL PROGRESS WITH INNATE IMMUNE-TARGETING COMPOUNDS
9:20 am Chair’s Opening Remarks
9:30 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
10:00 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
10:30 am Translatable Preclinical Models for Profiling STING & TLR-Targeted Therapies
Synopsis
• hSTING syngeneic mouse models for assessment of STING-targeted therapies
• Immunodeficient mouse model reconstituted with human immune system for assessment of immunomodulators in mono and combination therapy
11:00 am Speed Networking
RATIONALE & PROGRESS IN NOVEL METHODS OF TARGETING STING & TLR
12:00 pm 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
12:30 pm 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
1:00 pm TLR9 Activation & STAT3 Inhibition: a Bifunctional Approach to Immuno-Oncology
Synopsis
- While TLR9 continues to be a high-value target in immuno-oncology, single agent agonists of this receptor have shown limited efficacy in clinical studies.
- This is likely due, in part, to the immunosuppression created by the tumor microenvironment, which acts as a shield protecting the tumor from the activated immune system.
- Duet has developed a suite of bifunctional oligonucleotides that activate antigen-presenting cells (APCs) within the tumor microenvironment, while releasing the immunosuppressive brakes to jump-start T cell-mediated immune responses.
- The unique mechanism-of-action of these synthetic oligonucleotides comes from simultaneously targeting two intracellular immune pathways – signal transducer and activator of transcription 3 (STAT3) and toll-like receptor 9 (TLR9).
- The targeted inhibition of STAT3, a master immune checkpoint inhibitor, reawakens immune cells and allows for the full potential of TLR9-driven innate and adaptive immune responses.
1:30 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
2:00 pm Lunch Break
3:00 pm Bridging Innate & Adaptive Immune Systems with TLR7/8 Activation
3:30 pm Discovery of Innate Immune Agonists Using Deep Learning on High- Dimensional Phenomics
Synopsis
- We apply computational methods to high content imaging of PBMCs to construct highly accurate models that discriminate between many distinct innate immune signalling pathways
- These imaging models are paired with proteomics to build a deep understanding of the relationship between high level cell behaviours and molecular signalling
- This understanding is applied to high throughput screening to identify new compounds that induce inflammation with potential applications as vaccine adjuvants and immunotherapies
OPTIMIZING THE USE OF PRE-CLINICAL MODELS IN YOUR PRR DRUG DEVELOPMENT TO ACHIEVE HUMAN-SPECIFIC TRANSLATION
4:00 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?
4:30 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