AL009 / Alector - LARVOL DELTA

[PREPRINT] The multi-Siglec inhibitor AL009 reprograms suppressive macrophages and activates innate and adaptive tumor immunity (bioRxiv) - "In syngeneic mouse tumor models, AL009 engineered with a mouse Fc (AL009m) reduced tumor growth as a monotherapy and in combination with the checkpoint inhibitor anti-PD-L1. In addition, AL009m synergized with the tumor-targeting therapy anti-TRP1 to reduce lung nodules in the B16-F10 intravenous model. Pharmacodynamic marker analysis in syngeneic and humanized mouse tumor models supported an AL009 mechanism of action based on reprogramming TAMs and enhanced T cell activation."

Preclinical • Preprint • Oncology • Solid Tumor

Characterization of suppressive myeloid cells in solid tumors to refine disease selection in a Phase 1 study of the multi-Siglec inhibitor AL009 (SITC 2022) - "This IHC panel will be utilized to retrospectively explore Siglecs, CD163, and CD68 as predictive biomarkers in an upcoming Phase 1 study. Ethics Approval The human tissue microarrays were procured from a commercial vendor that collect human samples with the following ethical considerations: informed donor consent, IRB/EC approval, fully anonymized, and compliant with current US (HIPAA) International and EU regulations."

IO biomarker • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • CD163 • CD68 • CORIN • PD-L1

AL009 is a multi-Siglec inhibitor engineered to bind myeloid cells that enhances innate and adaptive immunity to cancer (AACR 2022) - "This targeting leads to repolarization of myeloid cells and activates an innate and adaptive anti-cancer response. Pharmacologically relevant doses of AL009 appear well-tolerated in initial studies in non-human primates, supporting further development for entry into clinical studies."

Oncology

AL009, a fusion protein and multi-Siglec inhibitor, repolarizes suppressive myeloid cells and potentiates anti-cancer effects (SITC 2021) - "AL009 has the potential to address tumors that are unresponsive or refractory to standard immunotherapies. These data support further development of AL009 in the clinic with IND enabling studies ongoing."

IO biomarker • Oncology • CD163 • CD8 • MRC1

Alector Presents Preclinical Data from AL009 Multi-Siglec Inhibitor Program at the Society for Immunotherapy of Cancer’s 36th Annual Meeting (GlobeNewswire) - "Alector is developing AL009 for the potential treatment of solid tumor cancers and plans to initiate a first-in-human clinical trial of AL009 in 2022...AL009 led to dose-dependent increases in immune stimulatory molecules consistent with the repolarization of myeloid-derived suppressive cells to a proinflammatory state; In vitro, AL009 increased T cell function by approximately 10 to 100-fold compared to other cancer immunotherapies. In syngeneic tumor models in mice that were less responsive to anti-PD-L1, treatment with AL009 showed efficacy in reducing tumor growth both as a single agent and in combination with anti-PD-L1. In a murine model of lung metastasis, AL009 combined with anti-TRP1 therapy to reduce lung nodules."

New trial • Preclinical • Oncology • Solid Tumor