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DAEJEON, South Korea & GAITHERSBURG, Md.

AevisBio, a private biotech company developing novel therapeutics for neurological diseases and cancer by targeted protein degradation (TPD), today announced publication of key research demonstrating 3,6’-dithiopomalidomide (3,6’-DP or AEV103) decreases neuroinflammation and mitigates cognitive decline in the presence of progressive amyloid-beta (Aβ) generation and deposition in an animal model of Alzheimer’s disease (AD). Published in Alzheimer’s & Dementia^®, the Journal of the Alzheimer’s Association, these data address an urgent need for new therapeutic strategies and build on previous research indicating that reducing neuroinflammation in the brain can be a disease-modifying approach for AD.

“The immunomodulatory activity of AEV103 elucidates the role of neuroinflammation in cognitive decline, building upon the amyloid hypothesis and providing a new therapeutic approach independent of amyloid beta clearance,” said Dong Seok Kim, Ph.D., founder and CEO of AevisBio and author on the publication. “We are grateful to our scientific collaborators and investors for their support as we advance a new generation of immunomodulatory drugs that have the potential to be disease-modifying for neuroinflammation-driven neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases and traumatic brain injury.”

AD is the most common neurodegenerative disorder worldwide. In the United States, an estimated 5.8 million people aged 65 and older were affected in 2020, and this number is expected to more than double by 2050.¹ The few approved AD drugs address symptomatic issues, and the recently approved aducanumab clears Aβ deposits but has shown little impact on cognitive decline.² Further research has shown that neuroinflammation induced by Aβ-plaques may act as a critical causative factor in the development of AD.

Scientists from AevisBio and the National Institute on Aging (NIA) part of the National Institutes of Health (NIH) used an immunomodulatory drug, AEV103, to reduce TNF-⍺, a key proinflammatory molecule involved in the onset and potential progression of AD and other neurodegenerative disorders. In cell-based and animal model experiments, treatment with AEV103, reduced Aβ-mediated microglial activation, neuroinflammation, and neurodegeneration. Furthermore, treatment with AEV103 did not affect soluble or insoluble Aβ or Aβ-plaque load but still prevented cognitive impairment in the 5xFAD animal model.

Nigel H. Greig, Ph.D., Chief, Drug Design and Development Section, NIA Intramural Research Program, is the principal investigator on the publication. Greig and his research team emphasize that these data demonstrate the direct involvement of microglia-mediated neuroinflammation in the development of neuronal dysfunction and cognitive impairment and that mitigating neuroinflammation in the brain can be a potential disease-modifying therapeutic strategy for Alzheimer’s disease. Furthermore, this research provides a novel compound, AEV103, to evaluate in Alzheimer’s disease and other neurodegenerative disorders where neuroinflammation plays a key role. ​​Notably, reducing inflammation by lowering TNF-α with AEV103 did not have any effect on brain amyloid beta levels. These results suggest that, once initiated, brain inflammation is a crucial intermediate step in the neuropathological cascade that leads to neuronal and cognitive loss in Alzheimer’s disease.

AEV103 is a next generation immunomodulatory imide drug that binds strongly to cereblon, an E3 ligase that is the most famous drug target in the field of TPD. AEV103 was invented at the NIH, and AevisBio has an exclusive license from the NIH to the series of next generation immunomodulatory imide drugs for the treatment of neurological disorders, including Alzheimer’s and Parkinson’s disease. AevisBio also has a Cooperative Research and Development Agreement (CRADA) with the NIA to evaluate thalidomide analogs in preclinical models of neurodegenerative disorders. The company has raised $10 million in a Series A financing from KB investment, WeVentures, and Timefolio Asset Management. The proceeds of the financing will be used to evaluate the safety profile of AEV103 and other TPD lead drug candidates as potential treatments for neurodegenerative disorders.³

The publication entitled, “Role of chronic inflammation in neuroplasticity and cognitive function: a hypothesis,” was published in Alzheimer’s & Dementia^®, the Journal of the Alzheimer’s Association on March 2 and can be found here: https://doi.org/10.1002/alz.12610.

The research was funded in part by the NIH Intramural Research Program and R56AG057028.

About AevisBio

AevisBio is a biotech company applying targeted protein degradation (TPD) technology to develop new therapeutics for neurological and immunological disorders and cancers. AevisBio integrates the extensive experience of neuroscience, immunology, and biochemistry with a focused approach to medical unmet patient needs. AevisBio is led by a team of experienced scientists and experts in drug development and has collaborations with the National Cancer Institute, National Institute for Aging, and other research institutes in the United States and Korea. The company has research labs and offices in Daejeon, South Korea and Gaithersburg, Maryland. For more info, visit www.aevisbio.com.

¹Hebert et al. Neurology, 2013. https://doi.org/10.1212/WNL.0b013e31828726f5
²Mullard. Nature, 2021. https://doi.org/10.1038/d41586-021-01546-2
³Lin, et al. eLife, 2020. https://doi.org/10.7554/eLife.54726

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