On November 12, 2021 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported that preclinical data from its AL009 immuno-oncology program in poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36th Annual Meeting (Press release, Alector, NOV 12, 2021, View Source [SID1234595375]).
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AL009 is a first-in-class fusion protein engineered to block multiple Siglecs. Siglecs (sialic acid binding immunoglobulin-like lectins) are a family of receptors involved in immune regulation that bind to cell surface sialic acid glycans. Siglecs are predominantly expressed on myeloid cells and the overexpression of Siglecs has been linked to immune suppression and evasion by tumor cells, as well as modulating the differentiation of myeloid cells into tumor-promoting macrophages. AL009 acts as a checkpoint inhibitor, blocking the immunosuppressive effect of multiple Siglecs and thereby enhancing both the innate and adaptive immune system response to cancer. 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.
"Siglecs play a critical role in regulating immune activity, and our research into the role of the Siglec family of inhibitory receptors in neurodegenerative disease led to the discovery and optimization of AL009 for immuno-oncology. AL009 is a fusion protein uniquely able to block multiple Siglec receptors and halt Siglec-sialic acid-mediated immune suppression, which may be beneficial in a number of disease states where evasion of the immune system allows disease to progress unchecked," said Daniel Maslyar, M.D., Alector’s Vice President Clinical Development. "As we compared AL009 with other immunotherapies in preclinical models, we observe higher potency in blocking immune cell suppression and promising anti-cancer activity alone and in combination with anti-PDL1 in multiple tumor types, including some that have been found resistant to other immunotherapies. We look forward to advancing AL009 into the clinic to characterize its potential to treat a variety of solid tumor types."
In a poster titled "AL009, a Fusion Protein and Multi-Siglec Inhibitor, Repolarizes Suppressive Myeloid Cells and Potentiates Anticancer Effects," Alector researchers highlighted:
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
The poster is available on Alector website in the Investors section at www.alector.com. Alector management will also be conducting a call for analysts and investors to discussion data presented this week for four of the company’s pipeline programs, AL001, AL101 and AL003 being developed for the treatment of neurodegenerative diseases and AL009.
About AL009
AL009 is a first-in-class multi Siglec inhibitor that works to enhance both the innate and adaptive immune system response to tumors by blocking a critical glycan checkpoint pathway that drives immune inhibition. Alector is initially developing AL009 for the potential treatment of solid tumors, with plans to initiate first-in-human clinical studies in 2022.