We are pleased to present preclinical data on our multispecific antibody programs in poster presentations at the 40th annual Society for Immunotherapy of Cancer (SITC) Conference, taking place November 5-9 in National Harbour, MD.
Presentation Highlights
Design of a Next Generation Tumor Targeted Masked IL-12Fc for Enhanced Tolerability and Localized Anti-Tumor Activity
Abstract Number: 853
IL-12 is a potent immunostimulatory cytokine whose use as an anti-tumor therapeutic has been limited by severe toxicities associated with systemic administration. We previously engineered a masked, protease activated human IL-12Fc with attenuated potency (ZW270) and demonstrated improved pharmacokinetics and tolerability in mice and NHP3. Next Generation ZW270 combines tumor targeting, conditional masking and attenuation to widen the therapeutic index (TI).
Key Highlights:
- Tumor-targeted masked attenuated IL-12Fc (ZW270) binds to TAA-expressing tumor cells and can be activated by tumor-associated proteases
- Mouse homologous agent mZW270 recapitulates properties of masked, protease activated human IL-12Fc with attenuated potency (ZW270)
- Combination of potency attenuation and masking increases tolerability of mZW270; tumor targeting increases anti-tumor activity in vivo
- Combined strategies of masking, potency attenuation and tumor targeting of IL-12Fc can be incorporated to widen the therapeutic index of an IL-12 based therapeutic
TriTCE Co-stim: A differentiated T cell engager platform with conditional cis CD28 co-stimulation is transferable to diverse targeting strategies
Abstract Number: 1196
TriTCE Co-stim is a modular and adaptable next generation T cell engager (TCE) platform developed to drive enhanced T cell activation, anti-tumor activity, and tolerability. Low T cell infiltration and T cell anergy remain as challenges in the treatment of solid tumors by conventional CD3-engaging bispecific TCEs. To overcome the lack of efficacy and durability of responses in solid tumors, concomitant CD28 co-stimulation provided by a trispecific T cell engager (TriTCE Co-stim) can be used to improve T cell responses.
In the poster, we highlight the novelty and versatility of the modular TriTCE Co-Stim platform enabling potent tumor-associated antigen (TAA)-dependent and tunable anti-tumor and autoimmune applications.
Key Highlights:
- TriTCE co-stim platform CD3/CD28 geometry can be combined with diverse tumor targeting strategies including: monovalent/bivalent Fab, scFv, VHH, 2+1+1, multi-TAA logic-gated designs, and pMHC targeting
- These data highlight the flexibility of TriTCE platform and potential to address unique biological problems across different disease settings
- ZW209 is a DLL3-targeting TriTCE with favorable preclinical in vivo efficacy and tolerability on track to enter Phase 1 in H1-2026
High-throughput quantitative characterization of cytotoxic antibody-drug conjugates using spheroid models reveals important considerations in potential molecular mechanisms of ADC resistance
Abstract Number: 57
There is a need for improved in vitro models that better recapitulate in vivo tumor tissue complexity to aid in the screening and evaluation of novel antibody-drug conjugates (ADCs) during preclinical development. Specifically, we have developed in vitro 3D models from cancer cell lines yielding spheroids in a rapid, robust and uniform manner to functionally evaluate the cytotoxic activity of ADCs in vitro.
Further characterization of ADC activity in 3D cell line models utilized the nCounter® ADC Development Panel. In additional to 3D models, we also validated the ADC Development panel for use with FFPE tissue across 5 different cancer types to assess relevant ADC pathways in both pre-clinical and clinical studies.
Key Highlights:
- nCounter is a robust and reliable platform to assess the gene expression of RNA samples especially using poor quality, fragmented FFPE-derived samples (DV200 < 30%) across multiple tumor types
- Results demonstrate the reliability of the nCounter ADC Development panel for use in ADC-focused clinical studies
- Analysis of in vitro cell culture methods (spheroids vs. monolayer), and different ADC treatments show distinct differences in relevant functional pathways, demonstrating its utility for ADC pipeline development
The posters are available to conference attendees as virtual e-posters on the virtual meeting platform as well as on the Publications page of our website once presented at the conference.
