* Please note that the following agenda timings are Eastern Standard Time.
Coffee morning to meet your peers ahead of the conference
9:00 am Chair’s Opening Remarks
Driving Future Clinical Success
9:10 am Lessons Learned & Looking Beyond – Novartis’ Journey with TGF-β
Synopsis
- First-in-human data – from biomarker and clinical outcomes
- Potential insights into patient selection
- What did we learn from other studies so far and how does this inform Ph2+ design?
9:40 am Panel Discussion: Realizing a Circular Approach to Enhance Clinical Success
Synopsis
- Developing a closer relationship between preclinical and clinical investigators
- Coming back to models to understand mechanisms behind what is seen in human
- Leveraging feedback from preclinical models to guide clinical decisions
10:20 am
Morning Networking Break
Synopsis
Meet and connect with your peers in this dedicated networking session
Preclinical Track
Overcoming the Complexity of TGF-β Pathways & Immune Cell Interactions
Chair: Divya Mathur, Director of Immuno-Oncology, Regeneron Pharmaceuticals
11:00 am Cancer Immunotherapy using TGF-β Conditioned Gamma Delta T-Cells
Synopsis
• TGF-β enhances the yield and intrinsic anti-tumour activity of gd T-cells expanded from peripheral blood
• Both unmodified and CAR-engineered cells demonstrate superior anti-tumour activity in a range of disease models
11:30 am Exploiting TGF-β Biology in Genotoxic Cancer Therapy
Synopsis
• Radiation and chemotherapy induce TGF-β activity
• TGF-β regulates DNA repair pathways
• Transcriptomic signatures classifying cancers according to TGF-β signaling competency identify a specific DNA damage vulnerability
Clinical Track
Defining Clinical Biomarkers to Maximize the Therapeutic Potential of TGF-β
11:00 am Development of a Comprehensive Biomarker Strategy to Support DRAGON, a Phase 1 Clinical Trial of SRK-181, the Latent TGFβ1 Inhibitor
Synopsis
• Preclinical data demonstrate that combining SRK-181 with a PD-1 inhibitor modifies the immune profile within the tumor immune microenvironment
• A comprehensive biomarker strategy is being developed to support the ongoing DRAGON trial and further explore the mechanism of action of SRK-181
• Ongoing evaluation of immune biomarkers and establishment of image analysis-based methods in preclinical studies will be presented
11:30 am Determining the Promise of TGF-β With Chemotherapeutic Agents
Synopsis
• Exploring the different mechanisms seen when combining TGF-β inhibitors with chemotherapeutic agents
• Investigating the clinical development of this combination approach in pancreatic cancer
• Addressing the importance of patient selection in this clinical success
12:00 pm Networking Lunch
Diving into the TGF-β Paradox in Immuno-Oncology
Chair: Divya Mathur, Director of Immuno-Oncology, Regeneron Pharmaceuticals
1:00 pm Fibroblast Subpopulations & their Role in the Tumor Microenvironment
Synopsis
• Cancer associated fibroblasts are one of the most abundant cell types in the TME
• Recent advances in our understanding of fibroblast populations gained through single cell sequencing and other technologies demonstrates that different populations of fibroblasts are present in the TME
• These insights are helping us understand some of the cues (for example TGF-β and IL1) that are important in regulating these populations and their ability to play key roles in the TME such as promotion of immune suppression and tumor progression
1:30 pm Exploring the Role of TGF-β in Regulating the Immune Environment
Synopsis
• Reviewing the suppressive impact of TGF-β activation on immune cells in health and disease
• Advanced study of the activation of TGF-β via different immune cells
• Potential of targeting TGF-β activation mechanisms in the TME
Preventing & Understanding Toxicity of TGF-β-Targeted Therapeutics
1:00 pm Safety Observations from Small Molecule Inhibitors of ALK5 in Patients
Synopsis
• How to overcome the non-clinical toxicity in animals
• PK/PD modelling and the subsequent validation in patients
• Safety monitoring in the clinic
1:30 pm Determining the Side Effects of TGF-β Inhibition to Drive Safe Clinical Trials
Synopsis
• Highlighting the common side effects with TGF-β inhibition including increased breathing risk and hypertension
• Understanding these side effects in order to manage them correctly in clinic
• Determining the optimal therapeutic window and dosing regiment to balance efficacy and side effects in clinical trials
2:00 pm
Afternoon Networking Break
Maximizing TGF-β’s Therapeutic Potential Beyond IO
2:30 pm A Novel IL-2-TGF-β Fusion Protein for Induction & Expansion of Regulatory T Cells for Autoimmune & Inflammatory Diseases
3:00 pm Harnessing the Parallels of TGF-β Drug Development in Fibrosis & Oncology
Synopsis
- Assessing how TGF-β contributes to fibrosis through signaling pathways and it’s effect on myofibroblasts
- Evaluating what treatments are in the field to date
- Understanding TGF-β in lung fibrosis and the use of biomaterials