AC Immune SA (ACIU) Reports Progress for Therapeutic Programs Targeting the NLRP3 Inflammasome Pathway

January 29, 2021 7:06 AM EST
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AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, today announced recent advancements in its small molecule- and antibody-based therapeutic programs targeting the (NOD)-like receptor protein 3 (NLRP3) inflammasome, a multi-protein complex that activates downstream inflammatory pathways leading to neuronal damage. The inflammasome is a highly valued therapeutic target implicated in a wide range of neurodegenerative disorders including Alzheimer’s disease (AD), as well as in non-central nervous system (CNS) indications, such as autoimmune and infectious diseases, as well as certain cancers.

Leveraging the know-how of its proprietary Morphomer™ platform, which generated AC Immune’s clinical stage small molecule Tau aggregation inhibitors, the Company has successfully identified, and filed patent applications for, various chemical series of potent small molecule NLRP3 inhibitors. AC Immune has established biological activity for these compounds in multiple functional assays, and initial animal studies show highly potent target inhibition in a model of peripheral inflammation, providing the first evidence of in vivo activity. AC immune is currently evaluating potential lead compounds for further in vivo efficacy and CNS delivery. The Company expects to initiate in vivo proof-of-concept studies for a CNS-optimized lead compound for development in AD and other key neurodegenerative diseases by year end, as well as evaluate the potential of a second lead molecule in a clinically relevant non-CNS disease model.

A critical component of the NLRP3 pathway is ASC (apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain), which is released by immune cells following NLRP3 inflammasome activation. ASC interacts with amyloid beta (Abeta) in Alzheimer’s disease, not only increasing aggregation but also inducing seeding and spreading of Abeta pathology. AC Immune’s SupraAntigen™ platform has successfully generated high-affinity antibodies binding extracellular human ASC and potently inhibiting ASC-mediated inflammatory responses in vitro. Selected antibodies will be further evaluated in in vivo proof-of-concept studies using animal models of human disease, which AC Immune expects to start by year end.

Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: “Accelerating our complementary programs targeting the NLRP3 pathway intra- and extracellularly is a core element of our growth execution strategy in 2021 and beyond. These critical pipeline advancements represent substantial potential value, as the inflammasome has become an important target in both CNS and non-CNS indications. As we continue to develop our small molecule and antibody candidates, I would like to recognize the talent and dedication of our team for establishing a viable development path and enabling us to reach these milestones. Advancing multiple high-value assets targeting the inflammasome pathway further demonstrates AC Immune’s ambition to shape a comprehensive pipeline addressing key targets in neurodegeneration. We look forward to providing further updates as our NLRP3 programs progress towards clinical development.”

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