Sanguinate (PEGylated Carboxyhemoglobin bovine) / Prolong Pharma - LARVOL DELTA

HEMERA-1: CarboxyHEMoglobin OxygEn delivery for Revascularization in Acute Stroke: A Multi-Step clinical study of safety, efficacy and Pharmacokinetics. (ISC 2025) - P1 | "Overall, the drug product has exhibited good safety and tolerability across all three treatment parts similar to previously completed PP-007 clinical trials. The improvement of NIHSS and mRS outcomes were limited in sample size but encouraging in this Ph1 setting compared to placebo rate (~48% 90-day mRs 0-2) shown in LVO MT trials metanalysis. PK data showed similar results to prior studies with high drug levels through first 24 hrs."

Clinical • Late-breaking abstract • PK/PD data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Prolong Pharmaceuticals to Present Preliminary Phase 1 Data from HEMERA-1 for PP-007 in Acute Ischemic Stroke (AIS) at the 2025 International Stroke Conference (ISC) (Businesswire) - "Prolong Pharmaceuticals, LLC...announced that it will present new clinical data from HEMERA-1 (Phase 1 clinical trial in AIS), at the International Stroke Conference (ISC) on February 5-7th, 2025, in Los Angeles, California. The Company’s poster presentation will provide updates on their lead asset PP-007, a PEGylated carboxyhemoglobin bovine product, in AIS. Prolong recently completed enrollment for Part 3 of the Phase 1 trial, marking a key milestone for the program."

P1 data • Cardiovascular • Ischemic stroke

U.S. Food and Drug Administration (FDA) Grants Prolong Pharmaceuticals FDA Fast Track Designation for Novel Stroke Therapy (PP-007) in HEMERA-1 Clinical Study (Businesswire) - "Prolong Pharmaceuticals, LLC, a clinical-stage biopharmaceutical company, announced today that its investigational therapy, PP-007 (PEGylated carboxyhemoglobin, bovine), has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of acute ischemic stroke (AIS). PP-007 is currently being evaluated for safety and efficacy in an ongoing U.S.-based clinical trial, HEMERA-1."

Fast track • Cardiovascular • Ischemic stroke

Flow augmentation therapies preserve brain network integrity and hemodynamics in a canine permanent occlusion model. (PubMed, Sci Rep) - "In this study, we investigated the effects of two such therapies, NEH (a combination of norepinephrine and hydralazine) and Sanguinate (pegylated bovine carboxyhemoglobin), on resting-state functional connectivity, global mean signal (GMS), and blood oxygen level-dependent (BOLD) time lag in a pre-clinical canine model of stroke via permanent occlusion of the middle cerebral artery (total of n = 40 IACUC-approved mongrel canines randomly split into control/natural history and two treatment groups). The correlation of BOLD time-lag variations with neuroimaging functional biomarkers highlighted the impact of stroke and the efficacy of early therapeutic interventions. Our study supports the further study of flow augmentation therapies such as NEH and Sanguinate in stroke treatment protocols and suggests flow augmentation therapies should be further explored in an effort to improve patient outcomes."

Journal • Cardiovascular • Ischemic stroke

HEMERA-1: Safety Study of PP-007 in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Prolong Pharmaceuticals | Completed ➔ Recruiting | N=16 ➔ 24 | Trial completion date: Mar 2023 ➔ Feb 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2024

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Varying Effects Of Organ Toxicity With Multiple Artificial Oxygen Carriers: Structure/activity/biochemical Relationships (ASA 2023) - "Variables are shown in the Table. Trends were noted in heme loss from higher to lower as HBOCs were developed from small cross-linked molecules of lower MW to larger, polymerized ones; with the exception of Sanguinate, which is discontinued. Of the three available HBOCs, Hemopure and Oxyglobin appear safer, while Hemarina was not tested."

Inflammation • CAT

HEMERA-1: Safety Study of PP-007 in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Prolong Pharmaceuticals | Trial completion date: Sep 2022 ➔ Mar 2023 | Trial primary completion date: Sep 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Hemoglobin-Based Oxygen Carriers: Where Are We Now in 2023? (PubMed, Medicina (Kaunas)) - "OxyVita and Sanguinate are still undergoing active clinical studies. The field of oxygen therapeutics seems to be entering a phase of rapid growth in the coming 10-20 years."

Journal • Review • Transplantation

Promising Cerebral Blood Flow Enhancers in Acute Ischemic Stroke. (PubMed, Transl Stroke Res) - "We identified heme-free soluble guanylate cyclase activators; Sanguinate, remote ischemic perconditioning; Fasudil, S1P agonists; and stimulation of the sphenopalatine ganglion as promising potential CBF-enhancing therapeutics requiring further investigation. Additionally, we outline and discuss the critical steps required to advance research strategies for clinically translatable CBF-enhancing agents in the context of acute ischemic stroke models."

Journal • Review • Cardiovascular • Ischemic stroke

HEMERA-1: Safety Study of PP-007 in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Prolong Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Cardiovascular • Ischemic stroke

Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis. (PubMed, Exp Mol Med) - "Finally, we show that PP-007 does not compromise the clearance of PA in the setting of chronic airway infection. Overall, we reveal the mechanism of action of PP-007 responsible for the immunomodulatory function observed in clinical trials for a wide range of diseases and demonstrate the potential use of PP-007 in controlling neutrophilic pulmonary inflammation by promoting the expression of HO-1 in monocytes/macrophages."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • HMOX1 • MYD88

HEMERA-1: Safety Study of PP-007 in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Prolong Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2021 ➔ Dec 2022 | Trial primary completion date: Aug 2021 ➔ Sep 2022

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion. (PubMed, J Neurointerv Surg) - "Preliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration."

Journal • Cardiovascular • Ischemic stroke • MRI

Tangential Flow Filtration Facilitated Fractionation and PEGylation of Low and High Molecular Weight Polymerized Hemoglobins and Their Biophysical Properties. (PubMed, Biotechnol Bioeng) - "Several commercial PEGylated Hbs (MP4®, Sanguinate®, Euro-PEG-Hb) have been developed for clinical use with longer circulatory half-life and improved safety compared to Hb...Both T- and R-state PEG-PolybHb exhibited significantly lower haptoglobin binding rates than the precursor PolybHb, indicating potentially reduced clearance by CD163+ monocytes and macrophages. Thus, PEG-PolybHb is expected to function as a promising HBOC due to its low oxygen affinity and enhanced stealth properties afforded by the PEG hydration shell."

Journal • Hypertension • CD163 • HP

[VIRTUAL] Carbon monoxide–based therapy primes macrophages to express HO-1 and to resolve lung hyper-inflammation in cystic fibrosis (NACFC-I 2021) - "Treatment with PP-007, which strongly induces HO-1, counteracts the defective HO-1 expression in CF monocytes and MΦs and helps resolve lung inflammation in CF mice. PP-007 may be a new therapeutic intervention to ameliorate lung hyperinflammation without increasing infection risk for patients with CF."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • AKT1 • HMOX1 • IL17A • IL6 • MYD88 • TNFA

Early Experiences With PEGylated Carboxyhemoglobin Bovine in Anemic Jehovah's Witnesses: A Case Series and Review of the Literature. (PubMed, J Pharm Pract) - "We report 3 cases in which the HBOC, PEGylated carboxyhemoglobin bovine (Sanguinate®), was requested under emergent circumstances for severely anemic (hemoglobin <5 g/dL) JW patients who refused blood transfusions...The other patient's hemoglobin recovered and she was discharged in stable condition. This series demonstrates the complex nature of the critically anemic JW population and highlights the clinical considerations of using HBOCs in clinical practice and the critical need for further research before they can be broadly recommended."

Clinical • Journal • Review • Hematological Disorders

HEMERA-1: Safety Study of PP-007 in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: Prolong Pharmaceuticals; Initiation date: Dec 2020 ➔ Mar 2021

Clinical • Trial initiation date • Cardiovascular • Ischemic stroke

HEMERA-1: Safety Study of PP-007 in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: Prolong Pharmaceuticals

Clinical • New P1 trial • Cardiovascular • Ischemic stroke

[VIRTUAL] Surgical Pearls for Graft and Suture Technique (ASDS 2020) - "The sanguinated surgical defect/wound bed is covered by a 4”x4” woven gauze sponge...The running horizontal mattress with alternating simple running loops technique offers all of the benefits of the vertical mattress sutures without the difficulty of removal. Simplifying the suture removal process improves patient’s comfort and minimizes the suture removal encounter time."

Mood Disorders

The effect of SANGUINATE (PEGylated carboxyhemoglobin bovine) on cardiopulmonary bypass functionality using a bovine whole blood model of normovolemic hemodilution. (PubMed, Perfusion) - "SANGUINATE does not impact the performance of the cardiopulmonary bypass circuit in a bovine whole blood model. The results support further evaluation of SANGUINATE in the setting of normovolemic hemodilution and cardiopulmonary bypass."

Journal • Cardiovascular • Hepatology

Alternatives to Transfusion. (PubMed, Am J Clin Pathol) - "We find that artificial oxygen carriers are an attractive field of research because of the practical limitations and the multitude of potential complications that surround human blood transfusions."

Journal

Pharmacotherapy in Acutely Anemic Jehovah's Witnesses: An Evidence-Based Review. (PubMed, Ann Pharmacother) - "There are currently not enough data to make definitive recommendations on the use of pharmacological agents to treat severe anemia in the JW population. Further evidence utilizing EPO and HBOCs will be beneficial to guide therapy."

Journal

Bovine Hemoglobin-Based Oxygen Carrier Treatment in a Severely Anemic Jehovah's Witness Patient After Cystoprostatectomy and Nephrectomy: A Case Report. (PubMed, A A Pract) - "We present the case of a 77-year-old male Jehovah's Witness who underwent a cystoprostatectomy and radical nephrectomy with a postoperative Hb nadir of 4.5 g/dL. He received an Hb-based oxygen carrier, PEGylated carboxyhemoglobin bovine (Sanguinate), with gradual improvement in anemia symptoms and eventual discharge to a short-term rehabilitation facility."

Clinical • Journal

Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats. (PubMed, J Cereb Blood Flow Metab) - "Limited collateral flow in SHR during MCAO is consistent with small penumbra and large infarction. The ability to increase collateral flow in SHR with SG suggests that this compound may be useful as an adjunct to endovascular therapy and extend the time window for treatment."

Journal • Preclinical

Targeting the HO-1/CO Pathway with Sanguinate: Toward Development of a Novel Anti-inflammatory Therapy for Cystic Fibrosis (CF) Lung Disease (ATS 2019) - "Abstract embargoed at this time."