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.

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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.