Ashvattha Therapeutics Announces Preclinical Data on Hydroxyl Dendrimer Based PET Tracer [18F]OP-801 Presented at the 2022 World Molecular Imaging Congress

– Data demonstrated [18F]OP-801 is a promising tracer for imaging activated macrophages/microglia with high sensitivity in the lumbar spine of a murine model of multiple sclerosis (MS) – – Treatment of MS model mice with a hydroxyl dendrimer CSF1R inhibitor demonstrated selective killing of reactive microglia and lower uptake of the investigative PET tracer compared to untreated mice – – Showed a reliable, high-yielding synthetic route to producing [18F]OP-801 enabling its use in humans – REDWOOD CITY, Calif., Sept. 29, 2022 (GLOBE NEWSWIRE) — Ashvattha Therapeutics (“Ashvattha”), a clinical-stage company developing novel hydroxyl dendrimer therapeutics, today announced preclinical data presented by collaborators from Stanford University demonstrating that its hydroxyl dendrimer (HD)-based PET tracer, [18F]OP-801, can detect activated macrophages and microglia with high sensitivity and specificity in an experimental autoimmune encephalomyelitis (EAE) murine model of multiple sclerosis (MS), in addition to being reproducibly synthesized and suitable for human use. The data were presented at the World Molecular Imaging Congress being held September 28th – October 1st, 2022, at the Miami Beach Convention Center in Miami, FL. “Even though there are several immunomodulatory therapies available to treat MS, selection and monitoring of interventions has been hindered by a lack of specific in vivo imaging biomarkers,” stated Michelle James, PhD, an assistant professor of radiology and neurology at Stanford University. “We are encouraged by the promising data demonstrating Ashvattha’s hydroxyl dendrimer-based PET tracer’s ability to detect aberrant immune activation in an animal model of disease with high sensitivity and specificity and look forward to further investigating which cell subtypes take up this tracer in different neuroinflammatory models.” The presentation entitled “Specific detection of pathogenic myeloid cells in a mouse model of multiple sclerosis using [18F]OP-801 before and after treatment with a CSF1R inhibitor,” was based on a study evaluating [18F]OP-801 for its ability to detect pathogenic myeloid cells in an EAE murine model of MS at both pre-symptomatic and symptomatic disease stages. Key highlights from the presentation include: Quantification of PET images revealed a significantly higher signal in spinal cord of diseased mice, even prior to symptom development, compared to healthy mice.[18F]OP-801 accurately detected treatment response in EAE mice given daily HD-CSF1R inhibitor, used to deplete microglia and macrophages. Notably, there was significantly lower uptake in spinal cord PET images of successfully treated EAE mice compared to untreated EAE mice by post-hoc analysis.PET imaging data was corroborated by autoradiography images, showing significantly higher signal in the lumbar spinal cord of untreated compared to treated EAE mice.Importantly, [18F]OP-801 signal in treated mice corresponded with a dramatic reduction in CD68 immunostaining of spinal cord tissue compared to untreated mice.Taken together, there was no significant difference in [18F]OP-801 binding in peripheral tissues in diseased mice, further confirming the specificity of [18F]OP-801 for activated microglia/macrophages. The presentation entitled “Streamlined Production of [18F]OP-801 and Radiation Dosimetry to Enable Clinical Translation for Imaging Neuroinflammation,” describes the automated, high-yield radiosynthesis and quality control (QC) analyses of [18F]OP-801 for routine clinical production, in addition to analysis of its stability in human plasma, and human dosimetry estimates. Key highlights from the presentation include: [18F]OP-801 was reproducibly synthesized in suitable yield and greater than 99% radiochemical purity.Standard quality control tests confirmed that [18F]OP-801 is suitable for injection and human use.[18F]OP-801 was shown to be stable in vitro in formulation and human plasma, with >99% tracer intact after 90 minutes.Human dosimetry estimates based on mouse imaging data are conducive to translation and clinical imaging of [18F]OP-801. Chronic activation of macrophages and microglia play a major role in the onset and progression of many neurological diseases, such as ALS, Alzheimer’s disease and MS. While PET imaging has the potential to detect activated cells in the aforementioned diseases, most current PET tracers for imaging neuroinflammation are not entirely specific for macrophages/microglia. To address this need, Ashvattha is developing a Hydroxyl dendrimer-based PET tracer, [18F]OP-801, as a companion biomarker to pair with its HD therapeutics to treat neuroinflammation.    Jeffrey Cleland, Ph.D., Chairman & CEO of Ashvattha Therapeutics, added, “This data builds on previous studies demonstrating our HD-based PET tracer’s potential to be an effective imaging agent that could play a critical role in the selection and monitoring of interventions in patients with neurodegenerative diseases characterized by neuroinflammation. We are conducting a Phase 1/2 clinical trial of [18F]OP-801 in healthy volunteers and ALS patients and anticipate sharing preliminary data in the first half of 2023.” About [18F]OP-801[18F]OP-801 is a hydroxyl dendrimer (HD) imaging agent that provides information on uptake of HDs across tissue barriers including the blood-brain barrier. [18F]-OP-801 selectively targets by reactive microglia in regions of neuroinflammation in neurodegenerative diseases. [18F]OP-801 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, inflammation and neuro-oncology. Hydroxyl dendrimers (HDs) are a targeted nanomedicine 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 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  Sky StriarLifeSci Communications [email protected] _________________________________________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