Conference Day One

10.00 - 17.00 EST | 7.00 - 14.00 PST

* Please note that the following agenda timings are Eastern Standard Time.  

For Pacific Standard Times, please download the full event guide here

10:00 am Chair’s Opening Remarks

TGF-ß in Immuno-oncology Drug Development: Current State of Play

10:15 am TGF-β’s Significance in the Cancer Immunotherapy Landscape

Synopsis

• Role of TGF-ß in Immuno-Oncology: Interplay between the TGF-β signaling network and the TME
• Challenges with Systemic Pharmacologic TGF-ß Inhibition
• Overview of current approaches to inhibit TGF-ß signaling in the tumor to enhance the efficiency of IO and combination approaches

10:45 am Panel Discussion: Debating the Best Approach to Target TGF-ß

  • Rik Derynck Professor - Departments of Cell, Tissue Biology & Anatomy, University of California San Francisco
  • Thomas Schurpf Associate Director, Scholar Rock
  • Yulei Wang Principal Scientist, Oncology Biomarker Development, Genentech
  • Marc Pelletier Translational Immune Oncology, Novartis
  • Rick Gregory Associate Director, Takeda Oncology

Synopsis

• Which TGF-ß isoform to target to maximize therapeutic potential in IO and minimize adverse risk
• Combination approaches vs monotherapy?
• Is there one therapeutic approach with greater potential than others?

11:30 am Speed Networking – Get Matched With Your Peers on the Platform for 1-2-1 Introductions

12:00 pm Morning Coffee Break & Networking Chat Rooms

12:30 pm RNAi Therapeutics for Oncology: Silencing TGFb and Cox2 in HCC and NMSC

Synopsis

– We have demonstrated the ability for a Histidine Lysine Polypeptide (HKP) nanoparticle to be used to deliver siRNAs against TGFbeta and Cox2 systemically (using STP707 in a preclinical HCC model) or locally (using STP705 in a Phase 2a study in isSCC (In situ Squamous Cell Carcinoma))
– Silencing TGFbeta1 and Cox2 (using STP707) demonstrated dramatic single agent action against orthotopic HCC tumors with the ability to increase CD4+/CD8+ T-cell penetration into the tumors. Combining the treatment with immune checkpoint mAbs (against PDL1) demonstrated robust efficacy – wiping out the tumors.
– Exceptional results demonstrating histological clearance from the Phase 2a study using local administration of STP705 will also be presented
– Immunohistochemical evidence suggests that the clearance of the isSCC tumors is also driven (at least in part) by increased T-cell penetration into the tumor

Targeting TGF-ß through Integrin Inhibition: Small Molecule vs Antibody Approaches

1:00 pm Integrin αvβ8-Expressing Tumor Cells Serve as a Platform for TGF-ß Activation

Synopsis

This discovery offers a promising novel target to safely and effectively overcome TGF-β-driven immuno-suppression in a variety of tumor types.

• Venn Therapeutics is driven by a paradigm-shifting discovery by Dr. Stephen Nishimura on how transforming growth factor-beta (TGF-β) is activated by integrin αvβ8, published in Cell in January 2020. Dr. Nishimura’s paper showed that TGF-β can be activated in its latent form in the tumor microenvironment, without its release into soluble form. Dr. Nishimura’s pioneering discovery has the potential to enable immuno-oncology therapies to markedly expand benefits to previously unresponsive tumors

• Our lead asset, VTX-001, is a monoclonal antibody that targets integrin avβ8 and has shown single-agent activity in multiple preclinical cancer models. VTX-001 has also been shown to safely target TGF-β1 and TGF-β3 and completely avoid blocking TGF-β2. The blockage of TGF-β2 has been associated with cardiac toxicity

• Integrin αvβ8 is highly expressed by tumor cells in a variety of human carcinomas and high β8 expression is associated with decreased survival in many cancers. This may help us overcome a major challenge in immuno-oncology, which is selecting the right patients for clinical trials. Using our proprietary diagnostic VTX-001DX we can detect the expression of avb8 in tumors, which we hope will lead to better patient outcomes in upcoming clinical trials

1:30 pm Round Table Discussion: Small Molecule Approach to Inhibiting the Moderation of TGF-ß

  • Bruce Rogers Chief Scientific Officer, Morphic Therapeutic

2:00 pm Networking Lunch

Exploring Mechanism of Action and Biomarker Development

2:30 pm Poster Session

Synopsis

Head to our poster competition to explore the latest and greatest research in TGF-ß

3:00 pm Understanding the Mechanisms of Action of TGF-ß Inhibition as Immunotherapy and How Somatic and Germline Genetics Influence Variable Responses Between Individuals

Synopsis

• Work in syngeneic mouse models to explore mechanisms of action and how this differs between tumor types
• Work in syngeneic mouse models to investigate how germline genetic variation influences response to therapy
• Translation to the clinic

3:30 pm Clinical Biomarkers to Inform Therapeutic Development of TGF-ß Blockades in Immuno-Oncology

  • Yulei Wang Principal Scientist, Oncology Biomarker Development, Genentech

Synopsis

• TGF-ß as a key mediator of immune exclusion and resistance to checkpoint inhibitors
• Clinical biomarker development to inform diagnostic strategy, pharmacodynamic effects and mechanisms of action and resistance
• Application of single-cell genomics to understand TGF-ß isoform biology

4:00 pm Evaluating TGF-ß Blockers in Combination Therapies: The Challenges of Preclinical Tumor Models

Synopsis

• Heterogeneity in the TME of preclinical tumor models
• TGF-ß accumulation in some but not all TME: the example of the resistance of spontaneous, not transplanted tumors, to interferon-dependent immunotherapy
• Detection of TGF-ß signaling and associated immune cell modification in the TME

4:30 pm Chair’s Closing Remarks

4:45 pm Close of Day 1