razuprotafib subcutaneous (EYP-2301 SC) / EyePoint Pharma - LARVOL DELTA

Inhibition of VE-PTP rejuvenates Schlemm's canal in aged mice and acts via Tie2. (PubMed, PLoS One) - "Interference with VE-PTP function improves SC function in a strictly Tie2 dependent way and pharmacologic inhibition of VE-PTP with AKB9778 is a promising approach for improving SC function in the aged eye."

Journal • Preclinical • Glaucoma • Ophthalmology • CDH5

The In Vivo Disposition of Subcutaneous Injected C-Razuprotafib (C-AKB-9778), a Sulfamic Acid Phosphatase Inhibitor, in Nonclinical Species and Human. (PubMed, Xenobiotica) - "Radioactivity is distributed greater to human plasma than whole blood (B:P = 0.36).In pigmented rats, radioactivity distributes to whole-body tissues rapidly and, within 24 hr, is localised to elimination pathway end organs and injection site.Overall recovery of radioactivity across species is >93%, with the majority recovered within 24-48 hr, and >80% in faeces.The CYP2C8 enzyme contributes significantly to razuprotafib metabolism.A hydrolysis product of razuprotafib (m/z 380) is the main component in rat plasma at 2 hr (49% peak area radioactivity) while razuprotafib (m/z 585) is the main component in plasma for dog (58%), monkey (99.3%) and human (100%).Razuprotafib is present in dog, monkey and human faeces, with the greatest percentage of radioactivity as metabolites. The major metabolite (>25%) in monkey and human, m/z 633, is an S-methylated oxidised derivative of razuprotafib and is localised in faeces.Overall disposition of C-razuprotafib in human is..."

Journal • Preclinical • CYP2C8

RESCUE: A Study to Evaluate the Safety and Efficacy of Razuprotafib, a Novel Tie 2 Activator, in Hospitalized Subjects With Moderate to Severe Coronavirus Disease 2019 (COVID-19) (clinicaltrials.gov) - P2; N=31; Terminated; Sponsor: Aerpio Therapeutics; N=180 ➔ 31; Recruiting ➔ Terminated; After completion of Step 1 Part 1, the Sponsor discontinued the study based on challenges associated with recruiting and monitoring patients in the current pandemic environment.

Enrollment change • Trial termination • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Quantum Leap Healthcare Collaborative Discontinues Testing of Aerpio Pharmaceutical’s Razuprotafib in I-SPY COVID Trial (GlobeNewswire) - P2, N=1500; I-SPY_COVID (NCT04488081); "The sponsor halted testing of Aerpio’s razuprotafib in the I-SPY COVID Trial because it was challenging to administer in the setting of COVID-19, with 30% of patients discontinuing the agent due to disease-related hypotension, including protocol-mandated stopping rules....At the conclusion of two safety lead-in cohorts, it was determined there was a small but not clinically significant decline in systolic blood pressure and mean arterial blood pressure by approximately 4–5 mm Hg....Data Monitoring Committee recommended that razuprotafib not be advanced after the second safety lead-in....Dr. Carolyn Calfee...and principal investigator for the I-SPY COVID Trial, added, 'While we were disappointed to not to be able to continue with razuprotafib in this trial, we are continuing to press onward in our search for new treatments that may help us treat patients who become severely ill with COVID-19.'"

Discontinued • DSMB • Media quote • P2 data • Infectious Disease • Novel Coronavirus Disease

A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure. (PubMed, Invest Ophthalmol Vis Sci) - "This is the first report of IOP lowering in humans with a Tie2 activator and functional demonstration of its action in remodeling SC to increase outflow facility and lower IOP in fully developed mice. Based on these studies, a phase II clinical trial is in progress to advance topical ocular AKB-9778 as a first in class, Tie2 activator for treatment for ocular hypertension and glaucoma."

Journal • Diabetic Retinopathy • Glaucoma • Hypertension • Ocular Infections • Ophthalmology • Retinal Disorders • EGF

RESCUE: A Study to Evaluate the Safety and Efficacy of Razuprotafib, a Novel Tie 2 Activator, in Hospitalized Subjects With Moderate to Severe Coronavirus Disease 2019 (COVID-19) (clinicaltrials.gov) - P2; N=180; Recruiting; Sponsor: Aerpio Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Phase 2 clinical trial to examine the effects of razuprotafib on COVID-19 patients (News-Medical) - "Researchers at the University of Cincinnati and UC Health will host a Phase 2 clinical trial (NCT04511650) to examine the effects of a drug that targets blood vessel inflammation and injury in patients with COVID-19. They will study the effects of razuprotafib, an investigational drug that activates a key pathway for stabilizing blood vessels in the lung and other organs in patients with moderate to severe cases..."

New P2 trial • Infectious Disease • Novel Coronavirus Disease

Aerpio Pharmaceuticals Inc. and Quantum Leap Reports the Dosing of the First Patient with Razuprotafib in the I-SPY COVID Trial (BioPharma Journal) - "According to the I-SPY programs founder, Laura Esserman razuprotafib was identified because of its ability to reverse the lung damage. This was accomplished through the activation of Tie2 and the stabilization of the leaky blood vessels, which more often cause the damage....Even though pharmaceuticals are working on multiple vaccines, Esserman has emphasized on the need to find an effective therapeutic agent. She also outlined the promising nature of razuprotafib in preventing death and the improvement of recovery time."

Media quote

Aerpio Pharmaceuticals Inc. [ARPO] Stock trading around $1.27 per share: What’s Next? - "'Finding an effective therapeutic agent to treat patients who get critically ill in response to the COVID 19 infection is of utmost importance regardless of whether we have a vaccine,' said Laura Esserman...'Our group is focused on screening promising agents and quickly identifying therapies that work. Razuprotafib was selected because of its potential to reverse the lung damage by activating Tie2 and stabilizing the leaky blood vessels that cause some of the damage. This has the potential to prevent death and improve time to recovery, which is what we need for this pandemic and any other that comes along in the future.'"

Media quote

Aerpio and Quantum Leap Announce First Patients Dosed with Razuprotafib in the I-SPY COVID Trial to Treat ARDS in Critically-ill COVID-19 Patients (GlobeNewswire) - "Aerpio Pharmaceuticals, Inc....announced today dosing of the first patient with razuprotafib in the I-SPY COVID Trial....The goal of the trial is to rapidly screen, in parallel, multiple promising agents in order to identify drugs that will have a high impact on reducing mortality, and avoid or reduce the duration of mechanical ventilation for critically-ill COVID-19 patients. This study arm will evaluate razuprotafib's potential to sufficiently stabilize the pulmonary vasculature, in order to slow or prevent the progression of COVID-19 associated pulmonary pathology, decrease the need for ventilator support, and reduce mortality....'Finding an effective therapeutic agent to treat patients who get critically ill in response to the COVID-19 infection is of utmost importance regardless of whether we have a vaccine,' Laura Esserman...said in a company news release."

Media quote • Trial status • Infectious Disease • Novel Coronavirus Disease

Aerpio Pharmaceuticals, Inc. and Quantum Leap Healthcare Collaborative Announce the Selection of Razuprotafib for Evaluation in the I-SPY COVID Trial for the Treatment of Acute Respiratory Distress Syndrome in COVID-19 Patients (GlobeNewswire, Aerpio Pharmaceuticals, Inc.) - "Aerpio Pharmaceuticals, Inc....and Quantum Leap Healthcare Collaborative™ (Quantum Leap) announced today an agreement has been reached to evaluate razuprotafib in a new randomized, investigational treatment arm in the I-SPY COVID Trial for the treatment of acute respiratory distress syndrome (ARDS) in adult patients with moderate to severe COVID-19....The goal of the I-SPY COVID Trial is to rapidly screen multiple promising agents, in the setting of an adaptive platform trial, for the treatment of critically ill COVID-19 patients to identify agents that will have a high impact on reducing mortality, and the need for as well as duration of, mechanical ventilation....Aerpio has already produced subcutaneous razuprotafib to support the rapid start-up of this arm of the trial."

Licensing / partnership • New trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

RESCUE: A Study to Evaluate the Safety and Efficacy of Razuprotafib, a Novel Tie 2 Activator, in Hospitalized Subjects With Moderate to Severe Coronavirus Disease 2019 (COVID-19) (clinicaltrials.gov) - P2; N=180; Not yet recruiting; Sponsor: Aerpio Therapeutics

Clinical • New P2 trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Aerpio Pharmaceuticals, Inc. Announces a Second Clinical Trial with Funding from MTEC to Evaluate Razuprotafib for the Prevention and Treatment of ARDS in Patients with Moderate to Severe COVID-19 (GlobeNewswire) - "Aerpio Pharmaceuticals, Inc....announced today that an agreement has been reached to evaluate razuprotafib in a new randomized, investigational trial for the prevention and treatment of Acute Respiratory Distress Syndrome (ARDS) in adult patients with moderate to severe COVID-19 as part of MTEC-20-09-COVID-19 Treatment Military Infectious Disease Research Program (MIDRP)....MTEC will provide up to $5.1 million in funding toward the clinical trial. Aerpio will support the trial with 'in kind' spending in the amount of $2.8 million....The partnership between Aerpio and MTEC will provide resources to support a second COVID-19 Phase 2 clinical trial with razuprotafib..."

Financing • Licensing / partnership • New P2 trial • Infectious Disease • Novel Coronavirus Disease