Flutriciclamide (18F)

Data highlights [18F]OP-801’s differentiated imaging profile as a promising tracer for visualizing the progression of neuroinflammationREDWOOD CITY, Calif., Aug. 01, 2022 (GLOBE NEWSWIRE) -- Ashvattha Therapeutics (“Ashvattha”), a clinical stage company developing novel hydroxyl dendrimer therapeutics, today announced a poster presentation of preclinical data demonstrating its hydroxyl dendrimer (HD)-based PET tracer, [18F]OP-801, can detect neuroinflammation via activated microglia and macrophages with higher sensitivity than translocator protein 18 kDa [TSPO]-PET, using [18F]GE180, an established and validated PET imaging approach, in a mouse model of Alzheimer’s Disease. The data were presented by Mackenzie Carlson, a scientific collaborator at Stanford University, in a poster titled, “Novel hydroxyl dendrimer-based PET tracer [18F]OP-801 detects early-stage neuroinflammation in 5xFAD mouse model with higher sensitivity than TSPO-PET,” at the 2022 Alzheimer’s Association International Conference (AAIC) taking place at the San Diego Convention Center in San Diego, CA, and online, July 31 – August 4, 2022. “We are encouraged by the data as it supports the potential of our HD-based PET tracer, [18F]OP-801, to be an effective imaging agent for detecting early-stage neuroinflammation, a hallmark of neurodegenerative diseases including Alzheimer’s,” said Jeffrey Cleland, Ph.D., Chairman & CEO of Ashvattha Therapeutics. “The data also build on previous studies and validates our hydroxyl dendrimer’s ability to cross the blood-brain barrier and be selectively taken up by reactive inflammatory cells. By measuring the extent of [18F]OP-801 uptake in the brain, we will be able select patients with HD uptake based on PET signal. These patients will then be treated with the same HD chemically linked to a drug to treat the disease. Ultimately, this means that we will be able to provide physicians insight on how much drug will get to the diseased part of the patient’s brain before the treatment. No other non-invasive approach can achieve this key de-risking of neurological therapy.” Key highlights from the presentation include: At 3.75 months of age, [18F]OP-801 yielded a 3-fold higher PET signal in diseased mice compared to healthy mice demonstrating the superior selectivity of the tracer towards activated macrophages and microglia.No significant differences were observed between healthy and diseased mice in PET images using [18F]GE180.Images from brains of diseased mice at 5 months of age showed significantly greater uptake of [18F]OP-801 when compared to healthy mice in the same age group across the entirety of the brain and especially in regions commonly associated with Alzheimer's disease Chronic activation of macrophages and microglia plays a critical role in the onset and progression of many neurological diseases. While PET imaging has the potential to non-invasively visualize and quantify innate immune responses in vivo, most available PET tracers are not specific for macrophages/microglia. To address this need, Ashvattha is developing a HD-based PET tracer, [18F]OP-801, as a companion biomarker to pair with its HD therapeutics to treat neuroinflammation. About [18F]OP-801 [18F]OP-801 is a hydroxyl dendrimer-based neuroimaging agent being developed as a companion biomarker and a pharmacodynamic tool for therapeutics to treat neuroinflammation due to neurodegenerative diseases including Alzheimer’s and amyotrophic lateral sclerosis (ALS). This imaging agent was designed to cross the blood-brain barrier — a highly selective membrane that prevents most molecules from reaching the brain and spinal cord — in the presence of inflammation and to enter active microglial cells so they can be seen on images. [18F]-OP801 has been shown to be selectively (>95%) taken up by reactive macrophages/microglia.1 [18F]OP-801 shows promise for visualizing the progression of neuroinflammation with high specificity and sensitivity, warranting clinical investigation. A Phase 1/2 clinical trial of [18F]OP-801 is currently underway in healthy volunteers and ALS patients. About Ashvattha Therapeutics Ashvattha Therapeutics is a clinical-stage biotech company developing novel hydroxyl dendrimer therapeutics (HDTs) targeting unmet medical needs in ophthalmology, neurology, inflammatory diseases and neuro-oncology. The therapies are based on hydroxyl dendrimers (HDs), a targeted platform technology exclusively licensed from our founders, Kannan Rangaramanujam and Sujatha Kannan at Johns Hopkins University. HDs chemically conjugated to disease-modifying drugs create novel proprietary HD therapeutics (HDTs) selectively targeting reactive inflammatory cells in disease tissue with localized sustained effects. Ashvattha has initiated multiple programs with HDTs focused on neurology, ocular neovascular disease including neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME), and hyperinflammation in diseases. For more information, visit: www.avttx.com. Media Contact Jordyn Temperato LifeSci Communicationsjtemperato@lifescicomms.com 1 Henningfield, C.M., Cleland, J.L., Sharma, R., Green, K.N.Selective targeting of plaque-associated microglia through systemic dendrimer administration in an Alzheimer’s disease model. Alzheimer's & Dementia. 2020; Volume 16. Issue S2. https://doi.org/10.1002/alz.040661