– 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 –

AUSTIN, TX and DURHAM, NC, USA I April 08, 2022 I Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, today announced preclinical data at the 2022 American Association for Cancer Research (AACR) Annual Meeting. This includes data from SL-9258 (TIGIT-Fc-LIGHT), derived from the company’s ARC® platform, and the company’s GADLEN platform.

“We have made excellent progress advancing compounds in our preclinical pipeline,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “Data from our SL-9258 compound indicate potent modulation of myeloid cells, T cells, and cytokines, including IL-2, which collectively translated to superior anti-tumor activity in comparison to TIGIT and PD-L1 antibodies in a preclinical model of PD-1 acquired resistance. In addition, multiple compounds from our gamma delta T cell engager, or GADLEN, platform have shown specific anti-tumor activity in preclinical studies, which will help guide our lead candidate selection and clinical development strategy. We look forward to nominating our next clinical product candidate in 2022.”

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.
Shattuck Labs, Inc. (NASDAQ: STTK) is a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease. Compounds derived from Shattuck’s proprietary Agonist Redirected Checkpoint, ARC®, platform simultaneously inhibit checkpoint molecules and activate costimulatory molecules within a single therapeutic. The company’s SL-172154 (SIRPα-Fc-CD40L) program, which is designed to block the CD47 immune checkpoint and simultaneously agonize the CD40 pathway, is being evaluated in two Phase 1 trials. A second product candidate, SL-279252 (PD1-Fc-OX40L), is being evaluated in a Phase 1 trial in solid tumors or lymphomas. Additionally, the company is advancing a proprietary Gamma Delta T Cell Engager, GADLEN™, platform, which is designed to bridge gamma delta T cells to tumor antigens for the treatment of patients with cancer. Shattuck has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit: www.ShattuckLabs.com.

SOURCE: Shattuck Labs