Advancing Neurodegenerative Disease Research With Innovative Targets and Platforms: Xiao Xu, PhD; Mark Carlton, PhD

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"From all the data we generated in [the phase 1] study, we can conclude that [CVN293] meets our safety criteria and is now ready to advance into a phase 2 clinical trial. That trial will evaluate whether the preclinical efficacy we've seen across a range of neurodegeneration models like ALS, FTD, AD and even obesity, translates into clinical benefit for patients, and does so in a safe, well-tolerated fashion."

At the recently concluded 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, Cerevance, a clinical-stage pharmaceutical company, presented new data from 2 posters. The first poster reported findings from a phase 1 study assessing CVN293, an investigational KCNK13 inhibitor targeting NLRP3-mediated neuroinflammation in neurodegenerative diseases, with results that revealed a favorable tolerability profile in healthy adults. The phase 1 trial was a single/multiple ascending dose (SAD/MAD) study where participants received either CVN293 or placebo with SAD cohorts receiving single doses up to 1000mg.¹

Investigators observed that CVN293 was generally well-tolerated following single and 14-day multiple dosing, with no severe or dose-limiting adverse events (AEs), treatment-related discontinuations, or clinically meaningful changes in vital signs or laboratory parameters. Notably, all related AEs were considered mild by researchers. In both dose cohorts, researchers reported that CVN293 plasma exposure increased in a general dose proportional manner. Moreover, penetrance of CVN293 into the cerebrospinal fluid was displayed in both dose cohort studies.

The second poster presented at the conference highlighted Cerevance’s NETSseq proprietary technology platform, which could enable the understanding of temporal dynamics of chromatin and gene expression changes across disease progression. In the study, researchers generated a comprehensive dataset by applying NETSseq to brain tissue from control, early-, and late-sporadic Alzheimer disease donors. From this dataset, investigators could identify relevant pathways and genes to target as novel therapeutic strategies.² Following the conference, Mark Carlton, PhD, chief scientific officer at Cerevance, and Xiao Xu, PhD, director of computational discovery at Cerevance, spoke with NeurologyLive^® to share their insights on findings from the 2 presented posters.

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REFERENCES
1. Dickson L, Tolando R, Scholl C, et al. CVN293, an Investigational Inhibitor of KCNK13 Targeting NLRP3-Mediated Neuroinflammation in Neurodegenerative Disease: A Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics. Presented at: 2025 Alzheimer’s Association International Conference; July 27-31; Toronto, Canada. Abstract 106386.
2. Xu X, Ugbode C, Bayraktar G, et al. NETSseq unveils deep molecular insights into astrocyte function in Alzheimer’s disease in the human brain. Presented at: 2025 Alzheimer’s Association International Conference; July 27-31; Toronto, Canada. Abstract 106433.