acetylcysteine zidrimer (OP-101) / Ashvattha Therap - LARVOL DELTA

Journey from lab to clinic: Design, preclinical, and clinical development of systemic, targeted dendrimer-N-acetylcysteine (D-NAC) nanomedicines. (PubMed, Adv Pharmacol) - "This chapter, we delve into the journey of the hydroxyl PAMAM dendrimer-N-acetylcysteine (NAC) OP-101 formulation from the laboratory to the clinic. It will specifically focus on the design, synthesis, preclinical, and clinical development of OP-101, highlighting the potential it holds for the future of medicine and the positive Phase 2a results for treating severe COVID-19."

Journal • Preclinical • Review • CNS Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Vascular Neurology

PRANA: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients (clinicaltrials.gov) - P2 | N=28 | Terminated | Sponsor: Ashvattha Therapeutics, Inc. | N=284 ➔ 28 | Active, not recruiting ➔ Terminated; Lack of enrollment

Enrollment change • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP • IL6 • NEFL

Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial. (PubMed, Sci Transl Med) - "OP-101, a hydroxyl-polyamidoamine dendrimer-N-acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19."

Clinical • Journal • P2a data • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • GFAP

PRANA: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients (clinicaltrials.gov) - P2 | N=284 | Active, not recruiting | Sponsor: Ashvattha Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP • IL6

PRANA: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients (clinicaltrials.gov) - P2 | N=284 | Recruiting | Sponsor: Ashvattha Therapeutics, Inc. | Active, not recruiting ➔ Recruiting | N=24 ➔ 284

Enrollment change • Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP • IL6

PRANA: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients (clinicaltrials.gov) - P2; N=24; Active, not recruiting; Sponsor: Orpheris, Inc.; Trial completion date: May 2021 ➔ Jun 2022; Trial primary completion date: May 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP • IL6

Ashvattha Therapeutics Announces Positive Interim Data from Ongoing Phase 2 PRANA Clinical Study of OP-101 in Severe COVID-19 Patients (Businesswire) - P2, N=24; "Ashvattha Therapeutics...announced positive interim results from its ongoing multicenter Phase 2 PRANA clinical study of the HDT, OP-101...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...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...'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.'"

Biomarker • P2 data • Infectious Disease • Novel Coronavirus Disease

PRANA: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients (clinicaltrials.gov) - P2; N=24; Active, not recruiting; Sponsor: Orpheris, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP • IL6

PRANA: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients (clinicaltrials.gov) - P2; N=24; Recruiting; Sponsor: Orpheris, Inc.; Trial primary completion date: Oct 2020 ➔ Jan 2021

Clinical • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Neurologists test novel compound for lung and brain injury in severe COVID-19 patients (Newswise) - "Neurologists are researching whether a novel immunomodulatory treatment, OP-101, can dampen lung and brain injury in hospitalized COVID-19 patients through a clinical trial at The University of Texas Health Science Center at Houston (UTHealth)....The Phase II trial, called PRANA, is taking place at Memorial Hermann-Southwest and Memorial Hermann-Memorial City, along with several other sites across the country....At the Houston site, seven patients have been enrolled so far, and researchers are seeking two to four more. The national study will enroll approximately 24 patients."

Enrollment status • Infectious Disease • Novel Coronavirus Disease

1a/1b Study of OPT101 (clinicaltrials.gov) - P1a/1b; N=15; Not yet recruiting; Sponsor: Op-T LLC

Clinical • New P1 trial

Ashvattha Therapeutics Subsidiary Orpheris Enrolls First Patients in Phase 2 PRANA Clinical Study Evaluating OP-101 for Severe COVID-19 (Businesswire) - "Orpheris...today announced enrollment of the first patients in its multicenter Phase 2 PRANA clinical study of the HDT, OP-101....The study will be conducted by investigators at leading U.S. academic medical centers, including Johns Hopkins Hospital, Emory University, Loma Linda University Health and The University of Texas Health Science Center at Houston (UTHealth)....Initial data from the Phase 2 proof-of-concept study is expected to be reported in the fourth quarter of 2020. An expansion into a double-blind, placebo-controlled COVID-19 trial has been discussed with the U.S. Food and Drug Administration (FDA), which is anticipated to include up to 20 sites after the results from the ongoing stage are evaluated."

Clinical protocol • Enrollment status • P2 data • Infectious Disease • Novel Coronavirus Disease

[VIRTUAL] Selective targeting of Plaque Associated Microglia through systemic dendrimer administration in an Alzheimers disease model (AAIC 2020) - "To test whether we could alter plaque associated microglia phenotypes via peripheral drug administration, we next injected 5xFAD mice intraperitoneally with hydroxyl dendrimers conjugated to N-acetyl cysteine, OP-101, which has demonstrated ability to cause normalization of reactive microglia in several animal models... These data provide evidence that hydroxyl dendrimers are specifically taken up by reactive microglia rather than other central nervous system cells. This study demonstrated that systemic administration of hydroxyl dendrimers is a sufficient tool to target plaque associated microglia, demonstrating the potential for hydroxyl dendrimer-based therapeutics in AD."

Alzheimer's Disease • CNS Disorders • Immunology • Solid Tumor

PRANA: A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients (clinicaltrials.gov) - P2; N=24; Recruiting; Sponsor: Orpheris, Inc.

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease

A Clinical Study to Measure the Effect of OP-101 After Being Administered Subcutaneous in Healthy Volunteers (clinicaltrials.gov) - P1; N=8; Completed; Sponsor: Orpheris, Inc.; Not yet recruiting ➔ Completed

Clinical • Trial completion

Ashvattha Therapeutics subsidiary Orpheris announces FDA agreement to initiate phase 2 study evaluating OP-101 in severe Covid-19 patients (Businesswire) - "Orpheris...today announced the U.S. Food and Drug Administration (FDA) has agreed to a Phase 2 clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of OP-101 in patients with severe COVID-19....The Phase 2 clinical trial is a randomized, double-blind, placebo-controlled evaluation....An evaluation of reduction in pro-inflammatory markers (CRP, ferritin, and IL-6) after treatment with OP-101 is also included in the study....A single IV dose Phase 1 study of OP-101 (20 or 40 mg/kg) in normal healthy volunteers demonstrated that OP-101 is generally well tolerated in healthy subjects..."

Cytokine storm • FDA event • New P2 trial • P1 data • Infectious Disease • Novel Coronavirus Disease