REDWOOD CITY, Calif., September 10, 2020 — Ashvattha Therapeutics, a biotech company focused on developing novel hydroxyl dendrimer therapeutics (HDTs) to treat unmet medical needs in oncology, ocular, and inflammatory diseases, today announced that Jeffrey Cleland, Ph.D., chairman, chief executive officer and president, will present at the virtual H.C. Wainwright 22nd Annual Global Investment Conference.
The presentation by Dr. Cleland will include an overview of the company and provide an update on its HDT development programs. The HDT pipeline consists of preclinical assets in oncology and a pre-IND compound, D-4517, that is a potential first in class home administered product for wet age-related macular degeneration (AMD). Last month, Ashvattha’s wholly owned subsidiary, Orpheris, announced enrollment of the first patients in its multicenter Phase 2 PRANA clinical study of the HDT, OP-101, to treat hospitalized adults with severe COVID-19. Initial data is expected at the end of the fourth quarter of 2020.
To register for the live webcast event, please visit: https://hcwevents.com/.
Event: H.C. Wainwright 22nd Annual Global Investment Conference
Date: Monday, September 14
Presentation Time (EDT): 9:30 to 9:50AM
About Oncology HDTs
HDTs selectively target tumor associated macrophages (TAMs). In pre-clinical models, a single dose of HDTs is selectively taken up by ~60% of the M2 TAMs. M2 TAMs cause suppression of immune response to tumors and facilitate tumor metastases. Ashvattha’s HDTs have been constructed with novel compounds that enable phenotype switching of macrophages from M2 to M1 facilitating phagocytosis of tumor cells. The ability of HDTs to cross the blood brain barrier in several species including dogs and monkeys indicate the potential for HDTs to treat brain metastases and tumors. Ashvattha is currently synthesizing a library of proprietary HDTs to treat a range of cancers.
Neovascular (wet) age-related macular degeneration (wet AMD) currently requires frequent intravitreal injections (every 4-8 weeks) with an anti-VEGF agent to prevent loss of central vision and blindness. Intravitreal and other ocular injections are administered by retinal ophthalmologists. With over 10 M intravitreal injections in the past year alone, both retinal ophthalmologists and wet AMD patients have a substantial treatment burden.
Past attempts to develop systemic therapy for wet AMD have failed due to off target toxicity and lack of blood retinal barrier penetration. The HDT, D-4517, selectively targets reactive macrophage, microglia and retinal pigment epithelial cells in the neovascular regions of the eye. D-4517 inhibits tyrosine kinases of receptors responsible for angiogenesis (VEGFR, PDGFR). A subcutaneous dose of D-4517 is equally effective to an intravitreal dose of aflibercept (Eylea®) in a mouse model of laser induced choroidal neovascularization (CNV) at 14 days after a single administration. HDTs have been demonstrated to persist in the reactive cells in the CNV lesions for up to 30 days after a single systemic dose. Initial nonclinical toxicology studies indicate at least an 80-fold safety factor for the effective human subcutaneous dose. HDTs have been demonstrated to cross the blood retinal barrier in mice, rats, and monkeys. D-4517 has the potential to become the first up to once per month home administered subcutaneous treatment for wet AMD and other neovascular eye diseases.
OP-101, an investigational compound created by the conjugation of N-acetyl cysteine to the hydroxyl dendrimer, is the only clinical-stage therapeutic with the ability to shut down multiple pathways causing hyperinflammation. OP-101 selectively targets reactive macrophages, which are responsible for hyperinflammation, lung injury and multi-organ failure caused by viral or bacterial infections. Through this unique targeting mechanism of action, OP-101 increases the probability of effectiveness in stopping hyperinflammation while potentially avoiding side effects and non-specific immune suppression.
OP-101 has been shown to arrest hyperinflammation by normalizing reactive macrophages, reducing the pro-inflammatory cytokine storm, and reducing oxidative stress after a single dose in multiple animal models of inflammation. Once inside the macrophage, OP-101 inhibits IƘƘβ and NFƘβ, blocking the expression of pro-inflammatory cytokines such as IL-6 and IL-1β, and inhibits the JAK/STAT/MAPK pathway.
Results from a Phase 1 study of a single IV dose of OP-101 (20 or 40 mg/kg) in healthy volunteers demonstrated that it was well tolerated based on an assessment of clinical and laboratory adverse events. A Phase 1 study of a single subcutaneous (SC) dose of OP-101 (4 or 8 mg/kg) in healthy volunteers demonstrated that it was well tolerated, with only mild transient injection site reactions and no other adverse events. Preclinical studies have demonstrated that OP-101 persists for up to one month at the site of inflammation and is systemically cleared within two days, potentially enabling once per month SC dosing.
About Ashvattha Therapeutics
Ashvattha Therapeutics, a clinical stage biopharmaceutical company, is developing novel therapeutics that target and alter specific cells in areas of diseased tissues. The Company’s targeted platform technology, hydroxyl dendrimers (HD), is exclusively licensed from Johns Hopkins University. HDs chemically conjugated to disease modifying drugs create novel proprietary HD therapeutics (HDTs). Ashvattha has initiated multiple programs with HDTs focused on hyperinflammation in diseases such as COVID-19, age-related macular degeneration, or AMD, neuroinflammatory diseases such as ALS and Alzheimer’s disease, and immune oncology.
Orpheris is a clinical-stage company wholly owned by Ashvattha Therapeutics.