HEMERA 1: CarboxyHEMoglobin oxygEn delivery for Revascularization in Acute Stroke: a Prospective, Randomized Phase 1 Clinical Trial of PP-007: A First-in-Class Neuroprotective Agent Moves into Phase 3 Stroke Trial

A novel investigational compound, PP-007 (PEGylated carboxyhemoglobin), is advancing to a global Phase 3 clinical trial as a potential breakthrough in the treatment of acute ischemic stroke. Led by Italo Linfante MD, FAHA Director of Interventional Neuroradiology at Miami Neuroscience Institute, part of Baptist Health South Florida, the trial investigates this synthetic hemoglobin-based therapy as a fundamentally new approach to neuroprotection, designed to preserve brain tissue in the crucial window before and during reperfusion.

Italo Linfante MD, FAHA

While mechanical thrombectomy has revolutionized the treatment of large-vessel occlusions, achieving successful revascularization in more than 90% of patients, only about 40% regain full functional independence. The gap reflects a core limitation of thrombectomy – it cannot reverse neuronal death that occurs before blood flow is restored. As Dr. Linfante notes, “For every minute a stroke goes untreated, nearly two million neurons are lost. We need tools that don’t just restore blood flow, we need to protect the brain while we’re working on recanalizing the occluded artery.”

PP-007 is a nanoparticle-sized, polymer-bound hemoglobin molecule that exerts its effects via three complementary mechanisms. First, it delivers oxygen more efficiently than native red blood cells. Second, it carries small, physiologically relevant amounts of carbon monoxide, acting as a potent vasodilator to improve microcirculatory flow. Third, it expands plasma volume, thereby enhancing cerebral perfusion during the ischemic period. Critically, the compound remains active for up to 24 hours, a duration that spans the entire treatment window from first response to definitive reperfusion.

Guilherme Dabus

In preclinical rodent models of cerebral ischemia, PP-007 significantly reduced infarct size and improved perfusion of penumbral tissue. The results included data on Spontaneously Hypertensive Rats (SHR) that are genetically modified to develop high blood pressure at 40-60 weeks of age. Even in SHR, PP-007 improved collateral blood flow and reduced infarct size. Dr Linfante lead the experimental design and was an author in the study that was published in the Journal of Cerebral Blood Flow and Metabolism. These results led to HEMERA 1 CarboxyHEMoglobin oxygEn delivery for Revascularization in Acute Stroke: a Prospective, Randomized Phase 1 Clinical Trial first-in-human Phase 1 trial, conducted at Miami Neuroscience Institute under Dr. Linfante’s leadership. The trial demonstrated that PP-007 was safe, with no adverse effects on cardiac, pulmonary, renal, or hepatic systems. A mild but beneficial rise in systemic blood pressure was also observed at the time of the bolus of PP-007, likely contributing to enhanced cerebral perfusion. Some of the data from HEMERA 1 were published in the Journal of the Society of Vascular Interventional Neurology, a journal of the American Heart Association. Based on these results, the FDA granted PP-007 fast-track status to expedite development.

The next step is a 700-patient, multicenter, randomized Phase 3 trial with adaptive design and progressive enrichment comparing PP-007 to placebo in acute stroke patients undergoing mechanical thrombectomy (MT). The study will assess neurological recovery, imaging biomarkers, and functional outcomes. Enrollment sites are expected across the U.S., Europe, and South America. Dr. Guilherme Dabus will serve as the local Principal Investigator (PI) for the study at Miami Neuroscience Institute, one of the highest-enrolling centers during Phase 1, which will continue to play a leading role in the nationwide clinical trial.

Although some of the final Phase 1 outcome data at the present time remain under embargo, Dr. Linfante shared encouraging early findings from a propensity-score analysis of 35 acute stroke patients treated with MT and PP-007 against 70 patients matched for stroke severity and other parameters from the University of Pennsylvania Medical Center (UPMC) Database . “We’re seeing outcomes that truly exceeded expectations, including full recovery in older patients who would typically have poor prognoses,” he said. “One 91-year-old patient treated with PP-007 had no visible stroke on MRI. That kind of result is remarkable.”

Beyond its primary stroke indication, PP-007 has the potential to address other acute ischemic and hypoxic events, such as myocardial infarction, traumatic brain injury, and perioperative cardiac complications. And unlike thrombectomy, which requires advanced infrastructure and specialty teams, PP-007 is administered intravenously, making it a viable option in prehospital or rural settings where timely stroke intervention is often unavailable.

The HEMERA 2 trial was awarded Fast-Track designation from the FDA and is expected to launch within the year. Dr. Linfante and global co-PIs presented some of the data from the propensity score analysis at LINNC 2025 meeting in Paris. The data was also accepted as a late breaking trial abstract at the annual meeting of the Society of Neuro Interventional Surgery and was submitted to be presented at the International Stroke Conference in New Orleans, and the World Stroke Organization Congress in Barcelona.

If HEMERA 2 is proven effective, PP-007 could mark the beginning of a new therapeutic era, one in which clinicians can use pharmacological agents protect the brain of acute stroke patients while undergoing mechanical thrombectomy (MT).