A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery

The purpose of this study is to evaluate the effect of RBT-1 on reducing the risk of post-operative complications in subjects undergoing cardiac surgery on cardiopulmonary bypass (CPB). A sub-study will also be conducted to evaluate the pharmacokinetic (PK) profile of a single administration of RBT-1 by means of a popPK approach in subjects scheduled to undergo cardiac surgery.

Start Date17 Oct 2023

Sponsor / Collaborator

Renibus Therapeutics, Inc.Startup

NCT06092970 / RecruitingNot Applicable

Clinical Protocol REN-007E - Extension Study: An Evaluation of Patient Reported Outcomes and Clinical Outcomes Through 12 Months Post-Cardiac Surgery in Patients Enrolled in Study REN-007

This extension study is being conducted to assess the following objectives through 12 months post-cardiac surgery:
Patient reported outcomes (PRO), using the EQ-5D questionnaire
Clinical outcomes

Start Date16 Oct 2023

Sponsor / Collaborator

Renibus Therapeutics, Inc.Startup

NCT04564833 / CompletedPhase 2

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing Coronary Artery Bypass Graft (CABG) and/or Cardiac Valve Surgery (The START Study)

The purpose of this study is to evaluate the effect of RBT-1 (stannous protoporphyrin [SnPP]/iron sucrose [FeS]) on preconditioning response biomarkers in subjects who are at risk for AKI following cardiac surgery.

Start Date04 Aug 2021

Sponsor / Collaborator

Renibus Therapeutics, Inc.Startup

100 Clinical Results associated with Iron Sucrose/Tin Protoporphyrin

100 Translational Medicine associated with Iron Sucrose/Tin Protoporphyrin

100 Patents (Medical) associated with Iron Sucrose/Tin Protoporphyrin

Literatures (Medical) associated with Iron Sucrose/Tin Protoporphyrin

01 May 2020·Clinical journal of the American Society of Nephrology : CJASNQ1 · MEDICINE

A Pharmacologic “Stress Test” for Assessing Select Antioxidant Defenses in Patients with CKD

Q1 · MEDICINE

Article

Author: Keyser, Jeff ; Zager, Richard A ; Johnson, Ali C M ; Guillem, Alvaro ; Singh, Bhupinder

Background and objectives:

Oxidative stress is a hallmark and mediator of CKD. Diminished antioxidant defenses are thought to be partly responsible. However, there is currently no way to prospectively assess antioxidant defenses in humans. Tin protoporphyrin (SnPP) induces mild, transient oxidant stress in mice, triggering increased expression of select antioxidant proteins (e.g., heme oxygenase 1 [HO-1], NAD[P]H dehydrogenase [quinone] 1 [NQO1], ferritin, p21). Hence, we tested the hypothesis that SnPP can also variably increase these proteins in humans and can thus serve as a pharmacologic “stress test” for gauging gene responsiveness and antioxidant reserves.

Design, setting, participants, & measurements:

A total of 18 healthy volunteers and 24 participants with stage 3 CKD (n=12; eGFR 30–59 ml/min per 1.73 m2) or stage 4 CKD (n=12; eGFR 15–29 ml/min per 1.73 m2) were injected once with SnPP (9, 27, or 90 mg). Plasma and/or urinary antioxidant proteins were measured at baseline and for up to 4 days post-SnPP dosing. Kidney safety was gauged by serial measurements of BUN, creatinine, eGFR, albuminuria, and four urinary AKI biomarkers (kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, cystatin C, and N-acetyl glucosaminidase).

Results:

Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (r=−0.85 to −0.95). All four proteins manifested statistically significant dose- and time-dependent elevations after SnPP injection. However, marked intersubject differences were observed. p21 responses to high-dose SnPP and HO-1 responses to low-dose SnPP were significantly suppressed in participants with CKD versus healthy volunteers. SnPP was well tolerated by all participants, and no evidence of nephrotoxicity was observed.

Conclusions:

SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.

Clinical Trial registry name and registration number:

A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3–4 Chronic Kidney Disease, NCT0363002 and NCT03893799

01 Oct 1996·The American journal of physiology

Effect of nitric oxide on heme metabolism in pulmonary artery endothelial cells

Article

Author: Pitt, B. R. ; Yee, E. L. ; Kim, Y. M. ; Billiar, T. R.

Primary intracellular targets for nitric oxide (NO) include nonheme iron-containing enzymes and protein-bound iron. Because NO is an important effector molecule in lung inflammation and endothelial cell-associated iron is critical to numerous forms of oxidant-mediated lung injury, we studied the effects of the NO donor S-nitrosoacetylpenicillamine (SNAP) on heme and iron metabolism in cultured sheep pulmonary artery endothelial cells. SNAP (300 microM) caused a transient increase in heme oxygenase-1 (HO-1) mRNA associated with a fivefold increase in HO activity that was completely blocked by the competitive HO inhibitor, tin protoporphyrin IX (SnPP). SNAP-induced activation of HO caused SnPP-sensitive reduction of activity of the hemoprotein catalase and decrease in heme iron. SNAP caused increases in iron-responsive gene products, ferritin and mitochondrial aconitase, secondary to the release of iron from heme stores via HO induction, since these changes were also sensitive to SNPP. The NO-induced increase in nonheme iron was apparent via electron paramagnetic resonance, where an enhanced SNAP-induced (300 microM for 4 h) g = 2.04 signal (e.g., dinitrosyl-iron-sulfur complex) was noted after exposure to a dose of SNAP (200 microM for 14 h) that in itself did not produce a detectable signal. These data show that exposure of pulmonary endothelial cells to NO results in profound changes in intracellular heme- and nonheme-iron homeostasis and that HO plays a central role in affecting this balance.

01 Mar 1996·Molecular medicine (Cambridge, Mass.)Q2 · MEDICINE

Inhibition of Hemozoin Formation in Plasmodium falciparum Trophozoite Extracts by Heme Analogs: Possible Implication in the Resistance to Malaria Conferred by the β-Thalassemia Trait

Q2 · MEDICINE

ArticleOA

Author: Andrew F. G. Slater ; James A. Martiney ; Anthony Cerami

BACKGROUND:

Human falciparum malaria, caused by the intracellular protozoa Plasmodium falciparum, results in 1-2 million deaths per year. P. falciparum digests host erythrocyte hemoglobin within its food vacuole, resulting in the release of potentially toxic free heme. A parasite-specific heme polymerization activity detoxifies the free heme by cross-linking the heme monomers to form hemozoin or malaria pigment. This biochemical process is the target of the widely successful antimalarial drug chloroquine, which is rapidly losing its effectiveness due to the spread of chloroquine resistance. We have shown that chloroquine resistance is not due to changes in the overall catalytic activity of heme polymerization or its chloroquine sensitivity. Therefore, the heme polymerization activity remains a potential target for novel antimalarials. In this study, we investigated the ability of heme analogs to inhibit heme polymerization and parasite growth in erythrocytes.

MATERIALS AND METHODS:

Incorporation of radioactive hemin substrate into an insoluble hemozoin pellet was used to determine heme polymerization. Incorporation of radioactive hypoxanthine into the nucleic acid of dividing parasites was used to determine the effects of heme analogs on parasite growth. Microscopic and biochemical measurements were made to determine the extent of heme analog entry into infected erythrocytes.

RESULTS:

The heme analogs tin protoporphyrin IX (SnPP), zinc protoporphyrin IX (ZnPP), and zinc deuteroporphyrin IX, 2,4 bisglycol (ZnBG) inhibited polymerization at micromolar concentrations (ZnPP << SnPP < ZnBG). However, they did not inhibit parasite growth since they failed to gain access to the site of polymerization, the parasite's food vacuole. Finally, we observed high ZnPP levels in erythrocytes from two patients with beta-thalassemia trait, which may inhibit heme polymerization.

CONCLUSIONS:

The heme analogs tested were able to inhibit hemozoin formation in Plasmodium falciparum trophozite extracts. The increased ZnPP levels found in thalassemic erythrocytes suggest that these may contribute, at least in part, to the observed antimalarial protection conferred by the beta-thalassemia trait. This finding may lead to the development of new forms of antimalarial therapy.

News (Medical) associated with Iron Sucrose/Tin Protoporphyrin

26 Apr 2024

·www.prnewswire.com

Renibus Therapeutics Announces Oral Presentations on RBT-1 at AATS and SCA Medical Conferences

SOUTHLAKE, Texas, April 26, 2024 /PRNewswire/ -- Renibus Therapeutics® ("Renibus"), a clinical-stage biopharmaceutical company focusing on the prevention and treatment of cardio, renal and metabolic diseases, today announced its participation at two prestigious medical conferences: the American Association for Thoracic Surgery (AATS) 104th Annual Meeting and the Society of Cardiovascular Anesthesiologists (SCA) 46th Annual Meeting, both taking place in Toronto, Canada, April 27-30, 2024. "We are pleased to present additional clinical data on RBT-1 at the AATS and SCA meetings in collaboration with key opinion leaders in our field, Drs. Charles Mack and Andrew Shaw," stated Jeffrey Keyser, RPh, JD, PhD, President and CEO of Renibus. "These presentations are critical to advancing the understanding of our preconditioning approach with RBT-1, and we thank the meeting organizers and principal investigators for their partnership. Our Phase 3 PROTECT study is enrolling well and we remain on track to report top-line data in the third quarter of 2025." RBT-1 (stannic protoporfin / iron sucrose) is a single dose, multi-organ, preconditioning agent that is administered intravenously 24-48 hours prior to patients undergoing cardiac surgery.Renibus Therapeutics is actively enrolling its PROTECT Phase 3 pivotal trial evaluating RBT-1's potential to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. RBT-1 has received both FDA Breakthrough and Fast Track Designations. Details of the oral presentations at AATS: Title: RBT-1 Reduces Incidence of Blood Product Utilization in Patients Undergoing Non-Emergent Coronary Artery Bypass Grafting and/or Valve Surgery Date and Time: Sunday, April 28th at 9:44 am ET Location: Room 714 Presenter: Charles A. Mack, MD, FACS, Associate Professor of Cardiothoracic Surgery, New York-Presbyterian Hospital, Weill Cornell Medicine Title: RBT-1 Reduces the Number of Post-Operative Complications Associated with Cardiac Surgery Date and Time: Sunday, April 28th at 4:03 pm ET Location: Theater 2, Exhibit Hall Presenter: Bhupinder Singh, MD, Chief Medical Officer, Renibus Details of the oral presentation at SCA: Title: RBT-1 Improves Clinical Outcomes in Patients Requiring Prolonged Intensive Care Unit Stay Following Non-Emergent Cardiac Surgery Date and Time: Sunday, April 28th at 3:00 pm ET Session: Best of Meeting Oral Presenter: Andrew Shaw, MD, FRCA, FCCM, FFICM, Professor and Chair, Department of Intensive Care and Resuscitation, Cleveland Clinic About RBT-1 RBT-1 (stannic protoporfin/iron sucrose) is a potent inducer of anti-inflammatory andantioxidant pathways currently in Phase 3 [NCT # 06021457] for its lead indication to reduce post-operative complications following cardiothoracic surgery. Renibus completed the Phase 2 study of RBT-1 (NCT04564833) in February 2023 and announced positive final results from this study in May 2023. In October 2023, Renibus initiated enrollment and administration of RBT-1 in its PROTECT Phase 3 pivotal study. RBT-1 was granted Breakthrough Therapy designation status from the U.S. FDA to reduce the risk of complications in patients undergoing cardiothoracic surgery. About Renibus Therapeutics Renibus is a clinical stage biopharmaceutical company dedicated to treating, improving, and extending patients' lives by developing products to prevent disease progression, improve outcomes and protect against organ damage associated with cardio, renal and metabolic diseases. Renibus' first-in-a-new class lead program is RBT-1 (stannic protoporfin / iron sucrose), a single dose IV drug that is given over 1-2 hours, 24-48 hours prior to patients undergoing elective cardiac and/or valve surgery. It is in a Phase 3 pivotal trial to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. The drug has received FDA Breakthrough and Fast Track Designations. Veverimer is an oral, non-absorbed hydrochloric acid binder that was acquired from Tricida. We are currently evaluating veverimer in preclinical models and analyzing historical data to further our understanding of its clinical profile with a goal of identifying an indication for evaluation in clinical trials. Renibus has three additional assets at earlier stages of development. For more information, please visit the Company's website at and engage with us on LinkedIn. Investor and Media Contact: Amy Conrad Juniper Point [email protected] 858-914-1962 Business Development Contact Jamie Donadio CFO, Renibus [email protected] SOURCE Renibus Therapeutics

Phase 3Fast TrackPhase 2Breakthrough Therapy

18 Apr 2024

·www.prnewswire.com

Renibus Therapeutics Announces Oral Presentation on RBT-1 at the European Association for Cardio-Thoracic Surgery (EACTS) 2nd Innovation Summit

SOUTHLAKE, Texas, April 18, 2024 /PRNewswire/ -- Renibus Therapeutics® ("Renibus"), a clinical-stage biopharmaceutical company focusing on the prevention and treatment of cardio, renal and metabolic diseases, today announced an oral presentation on RBT-1 at the prestigious, invitation only, European Association for Cardio-Thoracic Surgery (EACTS) 2nd Innovation Summit, taking place in Paris, France, April 18-20, 2024. Charles A. Mack, MD, FACS, Associate Professor of Cardiothoracic Surgery and Vice Chairman of Quality and Patient Safety, New York-Presbyterian Hospital, Weill Cornell Medicine, will be presenting on behalf of Renibus. RBT-1 (stannic protoporfin / iron sucrose) is a single dose, multi-organ, preconditioning agent that is administered intravenously 24-48 hours prior to patients undergoing elective cardiac surgery. RBT-1 is actively enrolling in a Phase 3 pivotal trial to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. RBT-1 has received FDA Breakthrough and Fast Track Designations. "Presenting at EACTS enables Renibus to share our promising RBT-1 results with the global cardiothoracic surgery community," stated Jeffrey Keyser, RPh, JD, PhD, President and CEO of Renibus. "In a completed Phase 2 clinical trial, RBT-1 demonstrated the potential to improve outcomes in the post-cardiac surgery setting, including reductions in 30-day hospital readmission rates, time in the ICU, as well as time on ventilator. We continue to advance RBT-1 through the Phase 3 PROTECT study, with top-line data expected in the third quarter of 2025." Charles A. Mack, MD, FACS, Associate Professor of Cardiothoracic Surgery, New York-Presbyterian Hospital, Weill Cornell Medicine, added, "RBT-1 is an exciting pre-conditioning agent and I am honored to showcase its results at EACTS. While RBT-1 has demonstrated its potential benefit across multiple cardiac surgery types in its Phase 2 clinical trial, I look forward to presenting data demonstrating RBT-1's potential to have a greater impact on patients undergoing more complex procedures combining both CABG and valve surgeries where the risk of post-operative complications is greatest." Details of the oral presentation at EACTS 2nd Innovation Summit: Title: RBT-1: A Pharmacologic Approach to Reducing the Risk of Post-Operative Complications in Patients Workshop Group: Future of Extracorporeal circulation. Hypothermia in CT surgery Date and Time: Friday, April 19, 2024, 15:55 Presenter: Charles A. Mack, MD, FACS, Associate Professor of Cardiothoracic Surgery, New York-Presbyterian Hospital, Weill Cornell Medicine About RBT-1 RBT-1 (stannic protoporfin/iron sucrose) is a potent inducer of anti-inflammatory and antioxidant pathways currently in Phase 3 [NCT # 06021457] for its lead indication to reduce post-operative complications following cardiothoracic surgery. Renibus completed the Phase 2 study of RBT-1 (NCT04564833) in February 2023 and announced positive final results from this study in May 2023. In October 2023, Renibus initiated enrollment and administration of RBT-1 in its PROTECT Phase 3 pivotal study. RBT-1 was granted Breakthrough Therapy designation status from the U.S. FDA to reduce the risk of complications in patients undergoing cardiothoracic surgery. About Renibus Therapeutics Renibus is a clinical stage biopharmaceutical company dedicated to treating, improving, and extending patients' lives by developing products to prevent disease progression, improve outcomes and protect against organ damage associated with cardio, renal and metabolic diseases. Renibus' first-in-a-new class lead program is RBT-1 (stannic protoporfin / iron sucrose), a single dose IV drug that is given over 1-2 hours, 24-48 hours prior to patients undergoing elective cardiac and/or valve surgery. It is in a Phase 3 pivotal trial to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. The drug has received FDA Breakthrough and Fast Track Designations. Veverimer is an oral, non-absorbed hydrochloric acid binder that was acquired from Tricida. We are currently evaluating veverimer in preclinical models and analyzing historical data to further our understanding of its clinical profile with a goal of identifying an indication for evaluation in clinical trials. Renibus has three additional assets at earlier stages of development. For more information, please visit the Company's website at and engage with us on LinkedIn. Investor and Media Contact: Amy Conrad Juniper Point [email protected] 858-914-1962 Business Development Contact Jamie Donadio CFO, Renibus [email protected] SOURCE Renibus Therapeutics

Phase 2Phase 3Fast TrackBreakthrough Therapy

02 Apr 2024

·www.prnewswire.com

Renibus Announces Participation at the 23rd Annual Needham Virtual Healthcare Conference

SOUTHLAKE, Texas, April 2, 2024 /PRNewswire/ -- Renibus Therapeutics® ("Renibus"), a clinical-stage biopharmaceutical company focusing on the prevention and treatment of cardio-renal and metabolic diseases, today announced its participation in the 23rd Annual Needham Virtual Healthcare Conference, being held in a virtual format, April 8-11, 2024. Company management will meet with investors in one-on-one meetings during the conference. About Renibus Therapeutics Renibus is a clinical stage biopharmaceutical company dedicated to treating, improving, and extending patients' lives by developing products to prevent disease progression, improve outcomes and protect against organ damage associated with cardio, renal and metabolic diseases. Renibus' first-in-a-new class lead program is RBT-1 (stannic protoporfin / iron sucrose), a single dose IV drug that is given over 1-2 hours, 24-48 hours prior to patients undergoing elective cardiac and/or valve surgery. It is in a Phase 3 pivotal trial to reduce the risk of post operative complications and improve outcomes following cardiothoracic surgery. The drug has received FDA Breakthrough and Fast Track Designations. Veverimer is an oral, non-absorbed hydrochloric acid binder that was acquired from Tricida. We are currently evaluating veverimer in preclinical models and analyzing historical data to further our understanding of its clinical profile with a goal of identifying an indication for evaluation in clinical trials. Renibus has three additional assets at earlier stages of development. For more information, please visit the Company's website at and engage with us on LinkedIn. Investor and Media Contact: Amy Conrad Juniper Point [email protected] 858-914-1962 Business Development Contact Jamie Donadio CFO, Renibus [email protected] SOURCE Renibus Therapeutics

Phase 3Fast Track

100 Deals associated with Iron Sucrose/Tin Protoporphyrin

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Postoperative Complications	Phase 3	US	Renibus Therapeutics, Inc.Startup	17 Oct 2023
Postoperative Complications	Phase 3	CA	Renibus Therapeutics, Inc.Startup	17 Oct 2023
Acute Kidney Injury	Phase 2	US	Renibus Therapeutics, Inc.Startup	04 Aug 2021
Acute Kidney Injury	Phase 2	AU	Renibus Therapeutics, Inc.Startup	04 Aug 2021
Acute Kidney Injury	Phase 2	CA	Renibus Therapeutics, Inc.Startup	04 Aug 2021
Chronic Kidney Diseases	Phase 1	-	Renibus Therapeutics, Inc.Startup	15 Sep 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04564833 (CTgov)	Phase 2	Acute Kidney Injury	152	High Dose RBT-1 (High Dose RBT-1)	wvopdgezmy(cfvxgiorcz) = merprjpvrq xropwguvgg (aeokdhxpcn, ytbyugparj - gizhowsvns) View more	-	16 Jan 2024
				Low Dose RBT-1 (Low Dose RBT-1)	wvopdgezmy(cfvxgiorcz) = qeblqfwead xropwguvgg (aeokdhxpcn, xzoxhcnswe - dfpztftlvf) View more
NCT04564833 (GlobeNewswire) Manual	Phase 2	Heart Valve Diseases	60	RBT-1	vxfxsjzobo(qshntcyxfc): P-Value = <0.0001 View more	Positive	15 Jun 2022
				Placebo
RBT-1 (ASN2021)	Phase 1	Chronic Kidney Diseases heme oxygenase-1 \| interleukin-10 \| ferritin	54	RBT-1 (stannous protoporphyrin [SnPP] with iron sucrose [FeS])	bbkvsuygol(iirgatqwpv) = Photosensitivity was transient and generally mild in intensity. No serious adverse events were reported. uscnmfotcp (jqdgvbnuuz )	Positive	27 Oct 2021
				Placebo

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