SL-9258 / Shattuck - LARVOL DELTA

Delivery of hexameric TIGIT-Fc-LIGHT as lipid-encapsulated mRNA achieves therapeutic exposures that potentiate immune cell activation and anti-tumor activity in the setting of CPI acquired resistance (SITC 2024) - "The versatility of mRNA therapeutics and the ability to fine-tune expression/exposure could mark a significant advancement in immunotherapy. Ethics Approval All murine animal studies have been conducted by and with the approval of an Institutional Animal Care and Use Committee (IACUC) and reviewed and approved by a licensed veterinarian."

Immune cell • IO biomarker • Preclinical • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • CD31 • CD68 • CD8 • PECAM1 • TIGIT

Delivery of hexameric TIGIT-Fc-LIGHT as lipid-encapsulated mRNA achieves therapeutic exposures that potentiate immune cell activation and anti-tumor activity in the setting of CPI acquired resistance (SITC 2024) - "The versatility of mRNA therapeutics and the ability to fine-tune expression/exposure could mark a significant advancement in immunotherapy. Ethics Approval All murine animal studies have been conducted by and with the approval of an Institutional Animal Care and Use Committee (IACUC) and reviewed and approved by a licensed veterinarian."

Immune cell • IO biomarker • Preclinical • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • CD31 • CD68 • CD8 • PECAM1 • TIGIT

Lipid-encapsulated mRNAs encoding complex fusion proteins potentiate anti-tumor immune responses. (PubMed, Cancer Res) - "Here, we evaluated whether in vivo administration of mRNA/LNP formulations of SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT could achieve oligomerization and extend exposure, on-target activity, and anti-tumor responses comparable to that of the corresponding recombinant fusion proteins...Furthermore, the mRNA/LNPs demonstrated improved efficacy in combination with anti-PD-L1 relative to the recombinant fusion proteins. These data support the delivery of complex oligomeric biologics as mRNA/LNP formulations, where high therapeutic expression and exposure could translate into improved patient outcomes."

IO biomarker • Journal • Oncology • CD40LG • CD8 • IL2 • SIRPA • TIGIT

LIGHT (TNFSF14) Costimulation Enhances Myeloid Cell Activation and Antitumor Immunity in the Setting of PD-1/PD-L1 and TIGIT Checkpoint Blockade. (PubMed, J Immunol) - "Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade."

Checkpoint inhibition • IO biomarker • Journal • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • PD-1 • PD-L1 • TIGIT • TNFRSF18 • TNFSF14

LIGHT (TNFSF14) Co-Simulation Enhances Myeloid Cell Activation and Anti-Tumor Immunity in the Setting of PD-(L)1 and TIGIT Checkpoint Blockade (PEGS 2022) - "TIGIT-Fc-LIGHT does not depend upon DNAM-1 co-stimulation for activity, like TIGIT antibodies, and unlike DNAM-1, HVEM is not down-regulated on TIL in advanced tumors, nor directly inhibited by PD-1. We demonstrate this translates to TIGIT-Fc-LIGHT anti-tumor activity in PD-L1-low and CPI acquired resistant tumors."

Checkpoint inhibition • Immune Modulation • Inflammation • Oncology • CD8 • PD-L1 • TIGIT • TNFRSF18 • TNFSF14

LIGHT (TNFSF14) costimulation with TIGIT blockade broadens the activity of checkpoint inhibitors (CPIs) into CPI refractory and resistant tumors through targeted myeloid cell and effector lymphocyte activation (AACR 2022) - "Lastly, the combination of TIGIT-Fc-LIGHT with anti-PD(L)1 broadened anti-tumor activity of the checkpoint antibodies in aggressive CPI-resistant tumors. These results suggest that LIGHT could be the differentiator that extends the clinical activity of conventional CPIs into PD-L1 low or CPI acquired resistance tumors."

Checkpoint inhibition • IO biomarker • Oncology • CCL2 • CD8 • CXCL10 • IL10 • IL2 • NECTIN4 • TIGIT • TNFRSF18 • TNFSF14

Shattuck Labs Presents Preclinical Data at the 2022 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Shattuck Labs...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....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."

Preclinical • Oncology

Shattuck Labs Reports Fourth Quarter and Full Year 2021 Financial Results and Recent Business Highlights (GlobeNewswire) - "Upcoming Events: American Association for Cancer Research Annual Meeting (AACR), April 8-13...Poster presentation on the preclinical development of SL-9258; Poster presentation on the preclinical development of GADLEN compounds."

Preclinical • Oncology

Shattuck Labs to Present Two Posters at the 2022 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Shattuck Labs...announced that two posters have been accepted for presentation at the American Association for Cancer Research (AACR) Annual Meeting....The first poster will highlight preclinical data from the company’s GADLEN™ platform, while the second will highlight preclinical data from SL-9258 (TIGIT-Fc-LIGHT), derived from the company’s ARC® platform, demonstrating its ability to broaden the activity of checkpoint inhibitors through targeted myeloid cell and effector lymphocyte activation."

Preclinical • Oncology

Shattuck Labs to Present at TIGIT Therapies Digital Summit 2021 (GlobeNewswire) - "Shattuck Labs, Inc...announced its presentation at the TIGIT Therapies Digital Summit 2021 being held virtually December 7 – 9, 2021."

Clinical data • Oncology

LIGHT (TNFSF14) co-stimulation enhances myeloid cell activation and anti-tumor immunity in the setting of PD-1 and TIGIT checkpoint blockade (SITC 2021) - "Conclusions TIGIT-Fc-LIGHT was designed to overcome the limitations of TIGIT blocking antibodies through: 1) preserved costimulation in advanced tumors, 2) direct myeloid cell activation, 3) blockade of all known TIGIT ligands, and with 4) no risk of depleting effector lymphocytes since TIGIT-Fc-LIGHT activity does not require Fc function. Pre-clinical data indicate that these goals were achieved, and further development is warranted."

Checkpoint inhibition • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL2 • CD8 • CXCL10 • CXCL11 • CXCL13 • TIGIT • TNFRSF18 • TNFSF14

Shattuck Labs to Present Clinical Data on SL-172154 and SL-279252 and Preclinical Data on SL-9258 at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Shattuck Labs, Inc...announced it will present four posters at SITC’s 36th Annual Meeting being held Wednesday, November 10, 2021 to Sunday, November 14, 2021."

Clinical data • P1 data • Preclinical • Gynecologic Cancers • Hematological Malignancies • Lymphoma • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

Shattuck Labs Highlights Preclinical Data for SL-9258 (TIGIT-Fc-LIGHT) in an Acquired Resistance Model and Expanded Preclinical Data from the GADLEN Platform at AACR 2021 (GlobeNewswire) - “TIGIT blocking antibodies have shown encouraging clinical activity in combination with PD-1/L1 blocking antibodies in checkpoint naïve NSCLC, if PD-L1 expression is high. Thus, opportunities to broaden the utility of combined PD-1/TIGIT blockade may be evident in either checkpoint inhibitor (CPI) acquired resistant tumors, or tumors with low expression of PD-L1…demonstrated that preclinically, SL-9258 (TIGIT-Fc-LIGHT) retained activity in a PD1 resistance model and outperformed dual checkpoint blockade with anti-PD1 and anti-TIGIT…The second poster highlighted expanded preclinical data from Shattuck’s GADLEN™ platform…demonstrated a multi-layer analysis to uncover the gamma and delta TCR usage in tumors and the butyrophilin expression pattern guiding the design of GADLEN therapeutics, which will target hematologic malignancies and solid tumor indications.”

Preclinical • Oncology

Shattuck Labs to Present Two Posters at the 2021 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Shattuck Labs, Inc...announced that two posters have been accepted for poster presentation at the American Association for Cancer Research (AACR) Annual Meeting, which is being held virtually April 10-15, 2021. The first poster will highlight preclinical data from the company’s GADLEN™ platform, while the second will highlight preclinical data from the development of an in vivo model of checkpoint acquired resistance and the therapeutic potential of SL-9258 (TIGIT-Fc-LIGHT), derived from the company’s ARC^® platform, in an acquired resistance setting."

Preclinical • Oncology