OncoC4 presents data indicating immunotherapy has potential to become a ‘new class’ of Alzheimer’s drug.
This week’s Alzheimer’s Association International Conference (AAIC) in Toronto, Canada has spawned a slew of announcements from biotechs presenting their latest research at the conference. However, one announcement in particular stood out from the crowd, in that it came from a company not previously known for working on Alzheimer’s.
Rockville, Maryland-based biopharma OncoC4 is predominantly focused on cancer and immune-related conditions, and is presenting research indicating it may have unearthed a “new class” of treatment for Alzheimer’s disease in an antibody originally designed for oncology. The discovery centers on ONC-841, an immune checkpoint inhibitor that targets SIGLEC 10, a protein involved in immune regulation.
Initially developed as a way to help the immune system better recognize and attack tumors, ONC-841 has also shown promise in addressing the mechanisms underlying Alzheimer’s disease in preclinical models. OncoC4 is presenting research presented at AAIC, which it says demonstrates that inhibiting SIGLEC 10 activity in the brain could restore microglia, the brain’s resident immune cells, to a more functional state. These cells play a critical role in clearing protein aggregates such as amyloid plaques and tau tangles – known hallmarks of Alzheimer’s disease.
In two mouse models of Alzheimer’s disease, ONC-841 treatment improved microglial migration and ability to clear amyloid plaques, reduced levels of phosphorylated tau in plasma and alleviated structural and functional abnormalities linked to disease progression. According to OncoC4, the treated mice also exhibited measurable improvements in memory and learning, suggesting that immune modulation targeting SIGLEC 10 could influence both pathological and cognitive outcomes.
Another poster being presented by the company also provided insight into the biological role of SIGLEC 10 itself. Transgenic mice engineered to express the human SIGLEC 10 gene specifically in microglia developed amyloid plaques even in the absence of mutations traditionally associated with early-onset Alzheimer’s disease. OncoC4 says this suggests that SIGLEC 10 expression may contribute directly to the pathogenesis of late-onset Alzheimer’s, a form of the disease typically unlinked to known genetic risk mutations.
“SIGLEC 10-CD24 pathway, an innate immune checkpoint discovered by the cofounders, is implicated in cancer evasion of host immunity, which OncoC4 has been exploring for cancer treatment,” said OncoC4 co-founder Dr Yang Liu. “These compelling preclinical findings from two AD models highlight the potential of ONC-841 as a first-in-class immunotherapy for neurodegeneration.”
ONC-841 is already in clinical trials for solid tumors based on its capacity to reverse immune suppression exploited by cancers, and the same pathway appears to be relevant in the brain, where microglial dysregulation contributes to neurodegeneration. According to its web site, OncoC4 now plans to initiate clinical trials of ONC-841 in patients with early-stage Alzheimer’s disease in 2025.
