8:00 am Registration & Virtual Networking Coffee
8:50 am Chair’s Opening Remarks
Assessing Current Limitations of Cell Engagers including Strategies to Mitigate Toxicities to Ensure Patient Safety
9:00 am IL-15 Containing Trispecific Killer Engagers (TriKETM) To Make NK Cells Antigen Specific
Synopsis
- Understand the biology of NK cells
- Understand strategies to engage the CD16 receptor on NK cells
- Understand the specificity of TriKEs in the immune response
9:30 am XTENylated Protease Activated T Cell Engagers: XPATS – A Novel Format to Mitigate the On-target, Off-tumor Problem
Synopsis
- XPATs represent a novel format of highly-selective bispecific T cell engaged pro-drugs that are activated by the high protease activity in the tumor microenvironment
- XTENylation provides long in vivo half-life and universal masking applicable to any binding domain moiety (ScFv, Fab, VHH etc)
- In vitro activity of XPATs is attenuated >10,000-fold prior to proteolysis and yet they demonstrate potent in vivo efficacy with promising improvement in therapeutic index
10:00 am T Cell Engaging Antibody Circuits (TEAC): Focusing Immune Activation to the Cancer Cell Surface to Widen the Therapeutic Index
Synopsis
- Traditional T cell redirecting therapies can kill tumor cells in therapeutically useful ways but are limited by off-target and on-target/off-tumor toxicities
- The goal of the TEAC platform is to focus T cell redirection to the tumor and limit T cell driven toxicities in the periphery to improve therapeutic index and expand treatment opportunities in both liquid and solid tumors
- TEAC rely on several key principles to increase therapeutic index: (1) a requirement for selective dual antigen binding in the tumor to increase specificity, (2) protease cleavage of the TEAC prodrug to activate the CD3 circuit in the tumor and (3) a dummy associated half-life extension domain that leads to rapid inactivation and clearance of activated TEAC in the periphery to limit off target engagement of T cells
10:30 am The Promise of Vascularized Micro-Organs & Tumors for Drug Discovery
Synopsis
- Aracari Biosciences’ Vascularized Micro-Organ (VMO) and Vascularized Micro-Tumor (VMT) platforms contain 3D, fully human tissues that are supported by living, perfused blood vessels
- Molecules and/or immune cells are delivered through the vascularized system directly to these tissues
- Gene expression and drug responses in the VMO and VMT models closely align with in vivo dose response and gene expression data, whereas data from monolayer and spheroid cultures do not
10:40 am Virtual Speed Networking
Synopsis
Recreating the face-to-face networking in the virtual world. We will pair you up with
fellow attendees to break the ice and make new business relationships!
11:10 am Morning Break
11:30 am Panel Discussion: Exploiting the High Protease Concentration in the Tumor Microenvironment to Reduce Toxicity
Synopsis
- Discussing how different platforms are approaching the tumor microenvironment
- Analyze how the high protease concentration can be exploited to widen the therapeutic index
12:30 pm Networking Lunch
Improving the Therapeutic Window of Cell Engagers: Addressing Half-Life and Cytokine Release Syndrome
1:30 pm Discovering and Designing the Next Generation of T cell Engagers
Synopsis
- Approaches to increasing the therapeutic window of T cell engagers
- Combination therapies to improve efficacy
- Redirecting the immune system with the next generation of multi-specifics
2:00 pm Optimizing Therapeutic Index and Other Properties with Potency Reduction and Bivalent Target Engagement
Synopsis
- Lessons from clinical data on CD123 x CD3 and CD20 x CD3
- Reducing CD3 affinity to reduce CRS and improve exposure
- Bivalent engagement and affinity tuning to increase tumor vs normal reactivity
2:30 pm Afternoon Refreshments & Scientific Poster Session
Review of Current Clinical Data
3:30 pm Translating Preclinical BiTE® Data to the Clinic
Synopsis
- Lessons from blinatumomab
- Understanding which preclinical assays are predictive
- Differences with hematologic malignancies and solid tumors
4:00 pm Flotetuzumab: An Experimental CD123 x CD3 Bispecific DART Molecule for the Treatment of AML
Synopsis
- Clinical study design: Dose and schedule optimization to mitigate cytokine release and deliver target dose
- Pharmacokinetics & pharmacodynamic: Correlation with designed mechanism of action
- Biomarker analysis: Identification of primary refractory and early relapse patients as a responsive population
4:30 pm AMV564 Relieves Immune Suppression Through Selective Targeting of CD33
Synopsis
- AMV564 selectively depletes leukemic blasts in AML
- In addition, AMV564 targets myeloid derived suppressor cells
- T cell activation is apparent with continuous intravenous infusion (AML) or subcutaneous administration (solid tumors)