Press Release
Shattuck Labs Presents Preclinical Data at the 2022 American Association for Cancer Research (AACR) Annual Meeting
- SL-9258 (TIGIT-Fc-LIGHT) combined with anti-PD(L)1 broadened anti-tumor activity of the checkpoint antibodies in aggressive CPI-resistant tumors -
- Butyrophilin heterodimeric fusion proteins from Shattuck’s GADLEN platform showed enhanced tumor cell killing targeting CD19 and CD20 and demonstrated preclinical proof of concept in the treatment of cancer -
“We have made excellent progress advancing compounds in our preclinical pipeline,” said
Details of the presentations are as follows:
Abstract title: LIGHT (TNFSF14) costimulation with TIGIT blockade broadens the activity of checkpoint inhibitors (CPIs) into checkpoint inhibitor refractory and resistant tumors through targeted myeloid cell and effector lymphocyte activation
Shattuck presented preclinical data for SL-9258 (TIGIT-Fc-LIGHT), a bispecific fusion protein from its ARC platform, demonstrating that SL-9258 simultaneously provides checkpoint blockade to all tumor-expressed PVR ligands and broadens immune costimulation by the TNF ligand known as LIGHT. LIGHT’s ability to bind and activate CD8+ T and natural killer cells through interactions with one of its receptors known as HVEM and myeloid cells through interactions with its other receptor known as LTbR, translates into strong anti-tumor responses in checkpoint primary and acquired resistance murine tumor models, where TIGIT blocking antibodies demonstrate no activity.
TIGIT-Fc-LIGHT was evaluated and well tolerated in non-human primates at doses up to 40 mg/kg and similar on-target pharmacodynamic activity was observed to what was characterized preclinically in mice. Together, these results suggest that TIGIT-Fc-LIGHT may provide clinical benefit to patients that are refractory to conventional checkpoint blockade therapy.
Abstract title: Bispecific gamma/delta T cell engagers containing butyrophilin 2A1/3A1 heterodimeric fusion protein efficiently activate Vg9Vd2+ T cells and promote tumor cell killing
Shattuck presented preclinical data highlighting the potential of GADLENs to direct gamma delta T cells to kill tumor cells and in the process, further elucidate tumor cell markers which are important for the therapeutic activity of gamma delta T cell-based therapies.
Shattuck’s bispecific GADLENs containing heterodimeric BTN2A1 and BTN3A1 extracellular domains fused via inert Fc linkers to scFv domains, targeting CD19 or CD20 tumor-antigens, demonstrated an ability to induce proliferation, degranulation, and cytokine production in Vg9Vd2+ T cells with costimulation of a natural cytotoxicity receptor or T cell costimulatory receptor. Further, CD19 and CD20 directed GADLENs enhanced the specific killing of lymphoma cells that express both antigen targets.
Additional meeting information can be found on the AACR website, https://www.aacr.org. The posters will be available under Posters on the Company’s website shortly after the event.
About Shattuck Labs, Inc.
Investor Contact:
Senior Director, Finance & Investor Relations
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Media Contact:
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Source: Shattuck Labs, Inc.