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Ashvattha Therapeutics Announces Positive Interim Data from Ongoing Phase 2 PRANA Clinical Study of OP-101 in Severe COVID-19 Patients

REDWOOD CITY, Calif.–()–Ashvattha Therapeutics, a clinical stage biotech company focused on novel hydroxyl dendrimer therapeutics (HDTs) targeting unmet medical needs in neurology, neuro-oncology, and ophthalmology, today announced positive interim results from its ongoing multicenter Phase 2 PRANA clinical study of the HDT, OP-101, to treat hyperinflammation in hospitalized adults with severe COVID-19.

The first stage of the Phase 2 PRANA study randomized patients to a single therapeutic dose of OP-101 – 2 mg/kg (N=6), 4 mg/kg (N=6) or 8 mg/kg (N=5) – or placebo (N=7). Interim results showed that in this severe COVID-19 population, only 3 of 7 patients (42.8%) survived compared to 14 of 17 patients (82.4%) in the OP-101 treated groups with only one death at the higher two doses (caused by withdrawal of life support). A single dose of OP-101 provided a significant and sustained reduction in pro-inflammatory biomarkers (until discharge or Day 30) (p<0.01). OP-101 was more effective in reducing inflammation than corticosteroids alone, indicating that OP-101 has potent and sustained anti-inflammatory effects with just a single dose.

Patients treated with OP-101 showed a significant (p < 0.001) and sustained reduction of the neurofilament light chain (NfL) returning to levels comparable to age-matched healthy controls, indicating that OP-101 crosses the blood brain barrier. In all placebo patients, NfL increased from baseline. NfL is a well-validated biomarker to assess neurological damage to evaluate neuronal loss and the rate at which a disease is progressing (as in multiple sclerosis and amyotrophic lateral sclerosis) and has been shown to increase in critically ill COVID-19 patients. The ability of OP-101 to shut down multiple pathways that cause hyperinflammation led to decreased inflammation and neuronal injury, which is especially relevant for patients with COVID-19 who may experience neuroinflammation and potentially longer-term neurologic dysfunction as a complication of the disease.

“We are encouraged by the interim Phase 2 data demonstrating the ability of OP-101 to cross the blood brain barrier and reduce neuronal injury as well as systemic hyperinflammation. This is critically important because severe COVID-19 patients can experience long-term neuroinflammation,” said Jeffrey Cleland, Ph.D., Chairman, CEO and President of Ashvattha Therapeutics. “The next stage of our Phase 2 PRANA study will enroll additional moderate to severe COVID-19 patients sufficient for statistical significance on a survival primary endpoint. We look forward to expanding OP-101 into neuroinflammatory diseases based on the encouraging and significant NfL results.”

“These results tell us that OP-101 not only has the potential to save lives but can maintain healthy neurological function – with just a single dose that is well tolerated even in critically ill COVID patients,” says Sujatha Kannan, MD, co-founder of Ashvattha Therapeutics. Dr. Kannan is also Professor of Anesthesiology and Critical Care Medicine & Pediatrics and the Richard Traystman Endowed Chair at the Johns Hopkins University School of Medicine.

Severe COVID-19 is characterized by excessive activation of macrophages, the immune cells responsible for hyperinflammation, which can lead to life-threatening complications. Unlike single-agent approaches that address only one pathway, such as antibodies, OP-101 is designed to target and shut down all proinflammatory pathways and restore macrophages and microglia to a normal, anti-inflammatory state.

The randomized, double-blind, placebo-controlled Phase 2 PRANA (OP-101 to ArRest HyperinflAmmatioN in COVID-19 PAtients) clinical study is evaluating OP-101 in patients with severe COVID-19 as defined by the World Health Organization’s (WHO) ordinal scale. The study was conducted at five clinical centers in the United States. The first stage of the study enrolled 24 patients who, in addition to standard of care therapy, were randomized to a single intravenous (IV) infusion of OP-101 (2 mg/kg, 4 mg/kg or 8 mg/kg) or placebo. The primary endpoint was safety and tolerability. Secondary endpoints included efficacy as measured by all-cause mortality, discharge from clinic or hospital, and number of days free from a ventilator, among other measures. The study also evaluated the effect of OP-101 in reducing blood levels of pro-inflammatory biomarkers (e.g., CRP and ferritin) and a neuronal injury biomarker (NfL) after a single dose of OP-101.

For more information about the first stage of the Phase 2 PRANA study design, visit clinicaltrials.gov (NCT04458298).

About OP-101

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 demonstrated to also target reactive microglia selectively in the brain, restoring them to a normal state to reduce neuroinflammation.

OP-101 shuts down the pro-inflammatory cytokine storm and reduces 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. OP-101 may also have potential benefits in treating long term complications of COVID including neurocognitive impairments.

Results from a Phase 1 study of a single intravenous (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 assessments. 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 neuro-oncology, neurology, age-related macular degeneration (AMD), and hyperinflammation in diseases such as COVID-19. For more information, visit: www.avttx.com.

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