ZZ Biotech Announces Preliminary Phase 2 Stroke Trial Results with 3K3A-APC

HOUSTON, January 26, 2018—ZZ Biotech today announced that preliminary results of RHAPSODY, the company’s Phase 2 clinical trial in acute ischemic stroke patients, were presented at the 2018 International Stroke Conference in Los Angeles.

The placebo-controlled dose-escalation trial was designed to establish a maximally tolerated dose (MTD) of 3K3A-APC in patients with acute ischemic stroke treated with intravenous tPA, intra-arterial thrombectomy, or both. A secondary endpoint was to evaluate the effect of 3K3A-APC on cerebral hemorrhage in this patient population. Study participants, aged 18-90, were followed for 90 days.

The experimental drug 3K3A-APC is a genetically engineered variant of the naturally occurring activated Protein C, which plays a role in the regulation of blood clotting and inflammation. In animal models of stroke, 3K3A-APC has helped prevent bleeding caused by tPA, the only drug currently indicated for the treatment of acute ischemic stroke.

Patrick Lyden, MD, chair of the Department of Neurology at Cedars-Sinai, presented the results. Between January 2015 and July 2017, 110 patients were enrolled in the study. Demographics resembled those expected for a stroke population. Four dose levels were evaluated: 120, 240, 360, and 540 µg/kg, and a continual reassessment method was used to establish dosing throughout the study. All doses were deemed safe and well-tolerated, yielding an MTD of 540 µg/kg, the highest dose studied.

Total hemorrhage volume and hemorrhage incidence were both substantially reduced in 3K3A-APC treated patients. The incidence of any hemorrhage was reduced from 86.5% in placebo-treated patients to 67.4% in the combined treatment arms (p=0.046). Total hemorrhage volume was likewise reduced from an average of 2.1±5.8 mL on placebo to 0.8±2.1 mL in the combined treatment arms (p=0.066).

“The observed trend toward lower hemorrhage rates is consistent with our expectations based on the drug’s mechanism of action and activity in animal studies,” said Lyden. “These results should be confirmed in a larger clinical trial.”

The NIH National Institute of Neurological Disorders and Stroke (NINDS) sponsored RHAPSODY through a clinical trial grant to Cedars-Sinai (Dr. Lyden, Principal Investigator) and a NeuroNEXT Infrastructure Resource Access award to ZZ Biotech. Kent Pryor, PhD, the company’s chief operating officer, was the principal investigator for that grant, under which NINDS had a cooperative research and development agreement with the company.

“We appreciate the support of NINDS on this study, and we are pleased to have had such a productive collaboration with Dr. Lyden and the NeuroNEXT project team,” said Pryor.“Acute stroke studies are not easy to conduct, either from a recruitment or an operational standpoint. The study team did an excellent job successfully completing the study.”

The new drug originated in the laboratory of John Griffin, PhD, professor in the Department of Molecular and Experimental Medicine at The Scripps Research Institute, which licensed development rights to ZZ Biotech.

NIH-funded preclinical development of the drug for stroke and other neurological indications was carried out in the laboratory of Berislav Zlokovic, MD, PhD, director of the Zilkha Neurogenetic Institute and professor and chair of the Department of Physiology and Neuroscience at Keck School of Medicine of the University of Southern California. Zlokovic, who was scientific founder of ZZ Biotech, was also a co-investigator on the Phase 2 study.

Joseph Romano, ZZ Biotech CEO, said: “We are delighted by the safety window for our drug established in this study, and the strong trend toward reduced bleeding is very promising. We are excited by the prospects for 3K3A-APC, and we look forward to continuing its development in ischemic stroke and in other indications.”

About ZZ Biotech

ZZ Biotech, LLC is a clinical stage company developing innovative biologic treatments for ischemic stroke and other neurological diseases and wound healing applications including the treatment of diabetic foot ulcers.  Headquartered in Houston, ZZ Biotech is developing a genetically engineered variant of recombinant human activated protein C (APC), named 3K3A-APC, that has reduced anticoagulant activity, but preserved cell-protective and anti-inflammatory activities compared to wild-type APC. ZZ Biotech has completed a Phase 2 study in acute ischemic stroke patients.

About 3K3A-APC

ZZ Biotech’s 3K3A-APC is a genetically engineered variant of the naturally occurring activated protein C, which plays a role in the regulation of blood clotting and inflammation. APC has cell-protecting, anti-inflammatory and anti-coagulant properties; 3K3A-APC has reduced anti-coagulant ability, which minimizes the risk of bleeding induced by unmodified APC. In animal models of stroke, amyotrophic lateral sclerosis (ALS), neurotrauma, and sepsis, 3K3A-APC therapy has shown an advantage over recombinant APC in enhanced efficacy and reduced risk for bleeding. The protective effect of 3K3A-APC on the lining of blood vessels in the brain further helps prevent bleeding sometimes caused by tissue plasminogen activator, or tPA, the only drug currently indicated for the treatment of acute ischemic stroke.

CONTACT: Dr. Kent E. Pryor, Chief Operating Officer at (619) 574-0820 or kpryor@zzbiotech.com.

###

Phase 2 Study Title

ZZ-3K3A-201, NN104, RHAPSODY: A multi-center, Phase 2 study using a continual reassessment method to determine the safety and tolerability of 3K3A-APC, a Recombinant Variant of Human Activated Protein C (APC), in combination with tissue plasminogen activator (tPA), mechanical thrombectomy or both in moderate to severe acute ischemic stroke.

Stem cell therapy heals injured mouse brain

NIH

Animal study examines method for restoring brain cells killed by stroke or other neurological diseasesPR Brain

Scientists and clinicians have long dreamed of helping the injured brain repair itself by creating new neurons, and an innovative NIH-funded study published today in Nature Medicine may bring this goal much closer to reality. A team of researchers has developed a therapeutic technique that dramatically increases the production of nerve cells in mice with stroke-induced brain damage.

Read More

ZZ Biotech’s regenerative bio drugs manufactured in Brisbane with support of Biopharmaceuticals Australia

ZZ Biotech was awarded a $250,000 grant by BPA to support clinical development of its lead drug product, 3K3A-APC. The drug was manufactured at Patheon’s state-of-the-art contract manufacturing located in Brisbane, and will be used in animal studies and Phase 2 clinical trials targeting ischemic stroke and diabetic foot ulcers.

Read More

ZZ Biotech Acquires Bioatrix

In December 2015, US company ZZ Biotech LLC completed the acquisition of Bioatrix Pty Ltd. Based in Houston, ZZ Biotech is in a Phase 2 trial with 3K3A-Activated Protein C (‘3K3A-APC’) in acute ischemic stroke patients, supported by a grant from the National Institute for Neurological Disease and Stroke.

ZZ Biotech’s Australian subsidiary is presently manufacturing 3K3A-APC at Patheon Biologics in Brisbane and it has secured Queensland Government grant funding to facilitate the manufacture.

The Australian subsidiary will pursue a Phase 2 trial with 3K3A-APC in chronic wounds in 2016, and ZZ Biotech will undertake further trials of 3K3A-APC in stroke.

$8 Million NIH Grant Will Fund Multicenter Clinical Trial of Stroke Intervention Drug

Award to Cedars-Sinai Stroke Intervention Researchers Supports Collaborative Study Involving National Institute of Neurological Disorders and Stroke

LOS ANGELES (April 22, 2014) – Cedars-Sinai stroke intervention researchers have been informed that the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, will award an $8 million grant to fund a multicenter Phase II clinical trial of an experimental drug for stroke.

Read More

ZZ Biotech Announces Phase 2 Trial with 3K3A-APC in Stroke

ZZ Biotech Announces Phase 2 Trial with 3K3A-APC in Stroke; Funds Will Be Provided by NIH and Broadview Ventures

HOUSTON, April 22, 2014—ZZ Biotech today announced that the National Institutes of Health will support a multicenter Phase 2 clinical trial of its experimental drug, 3K3A-APC, in patients suffering from acute ischemic stroke.

The Phase 2 study will evaluate safety, tolerability and activity of ZZ Biotech’s 3K3A-APC when given after tissue plasminogen activator, or tPA, in patients who have experienced moderately severe ischemic stroke. The drug will be given intravenously as a 15-minute infusion every 12 hours for up to five treatments, and four dose levels will be evaluated. About 100 participants, ages 18 to 80, will be followed for 90 days.

Read More

Experimental stroke therapeutic developed at Keck Medicine of USC also shows promise for people with Lou Gehrig’s disease (ALS)

New research finds vascular damage in mice with ALS contributes to early development of the neurodegenerative disease, while repairing damage delays disease progression

LOS ANGELES, March 3, 2014Keck School of Medicine of USC neuroscientists have unlocked a piece of the puzzle in the fight against Lou Gehrig’s disease, a debilitating neurological disorder that robs people of their motor skills. Their findings appear in the March 3, 2014, online edition of the Proceedings of the National Academy of Sciences of the United States of America, the official scientific journal of the U.S. National Academy of Sciences.

Read More

Experimental drug reduces brain damage, eliminates brain hemorrhaging in rodents afflicted by stroke

Multi-site phase 2 clinical trials anticipated to begin recruiting patients in 2014

LOS ANGELES, October 24, 2013 — An experimental drug called 3K3A-APC appears to reduce brain damage, eliminate brain hemorrhaging and improve motor skills in older stroke-afflicted mice and stroke-afflicted rats with comorbid conditions such as hypertension, according to a new study from Keck Medicine of the University of Southern California (USC).

Read More

Clinical Trials Start for Stroke Drug Developed by Scripps Research Institute, USC, and ZZ Biotech

Experimental drug may extend window for effective stroke treatment

LA JOLLA, CA, August 8, 2012 — Clinical trials start this week for a stroke drug initially created by a team led by scientists at The Scripps Research Institute and the University of Southern California (USC) and further developed by biotech company ZZ Biotech.

The clinical trials will test the safety in humans of the experimental drug 3K3A-APC, which has been shown in animal models to reduce brain damage and improve motor skills after stroke when given in conjunction with a federally approved clot-busting therapy.

Read More
1 2