iron sucrose/Tin protoporphyrin (RBT-1) / Renibus Therap - LARVOL DELTA

Cardio-renal disease targeting biopharma Renibus Therapeutics has raised $47 million from the initial closings of a Series B financing round. (Longevity.Technology) - "The funding will be used to advance its lead program (RBT-1) through a pivotal Phase 3 trial...The Phase 3 trial, expected to commence in Q3 2023, will evaluate RBT-1 for its lead indication of reducing the risk of post-operative complications following cardiothoracic surgery...RBT-1 was granted Breakthrough Therapy designation status from the US FDA for this indication in June."

Breakthrough therapy • Financing • New P3 trial • Cardiovascular

Candida albicans releases a peptide from the Rbt1 protein to promote its invasion into the gut epithelium. (PubMed, Gut Microbes) - "Here, we show that, during the first steps of the infection process, C. albicans releases a peptide from the Repressed by Tup1 protein 1 (Rbt1), which disorganizes the cell‒cell adhesion junctions in Caco-2 intestinal epithelial cells by notably downregulating constitutive proteins of the tight junction complex (i.e. ZO-1). This is the first report to show that a peptide of a human pathogenic fungus promotes fungal invasion into the gut epithelium by disorganizing the protective epithelial barrier."

Journal • Candidiasis • Infectious Disease • TJP1

An Evaluation of Patient Reported Outcomes and Clinical Outcomes (clinicaltrials.gov) - P=N/A | N=379 | Active, not recruiting | Sponsor: Renibus Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Clinical protocol • Enrollment closed • Cardiovascular

Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery (clinicaltrials.gov) - P3 | N=454 | Completed | Sponsor: Renibus Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular

A Study of RBT-1 in Healthy Volunteers and Subjects With Stage 3/4 Chronic Kidney Disease (clinicaltrials.gov) - P1 | N=54 | Completed | Sponsor: Renibus Therapeutics, Inc. | Phase classification: P1b ➔ P1

Phase classification • Chronic Kidney Disease • Nephrology • Renal Disease

Integrated metabolomics and transcriptomics unravel the biosynthZaesis mechanism of anthocyanin in postharvest red raspberry (Rubus idaeus L.). (PubMed, Front Plant Sci) - "This study used metabolomic and transcriptomic analyses to explore anthocyanin biosynthesis in postharvest raspberries at various color stages: white (RBT-1), white-to-pink (RBT-2), pink (RBT-3), red (RBT-4), and deep red (RBT-5)...This study explored the regulatory mechanisms of MYB, WRKY, bHLH, and NAC transcription factors, as well as structural genes and phytohormone-related genes, in modulating anthocyanin metabolism during postharvest color changes in raspberries. The findings provide valuable insights for optimizing postharvest fruit storage conditions and enhancing fruit quality."

Journal

Clinical and Economic Impact of RBT-1 on Post-Operative Complications and Costs of Cardiac Surgery (ISPOR 2025) - P2 | "Cardiac surgery complications are common. Multiple complications increase costs exponentially. Phase 2 trial results support a protective effect of RBT-1 that lowers complication rates/expected costs across different surgery types."

Clinical • HEOR • Surgery • Cardiovascular

Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery (clinicaltrials.gov) - P3 | N=454 | Active, not recruiting | Sponsor: Renibus Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular

Molecular mechanism of PP2A/B55α phosphatase inhibition by IER5. (PubMed, Cell Chem Biol) - "Using structural bioinformatics, we identify homology of IER5-N50 with SERTA (SEI-1, RBT-1, and TARA) domain containing proteins. These studies define the molecular basis of PP2A/B55α nuclear inhibition by IER5 and suggest a roadmap for selective pharmacologic modulation of PP2A/B55α complexes."

Journal • ARPP19 • KRT1 • PPP2R2A

RBT-1, a "preconditioning" agent, mitigates syndecan-1 shedding in patients undergoing "on pump" cardiac surgery and following experimental AKI. (PubMed, Physiol Rep) - "RBT-1 preconditioning diminishes SDC-1 release and upregulates vascular ferritin and Nrf2. Hence, RBT-1 preconditioning can confer select vasoprotective effects."

Clinical • Journal • Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease • IL6 • KIM1 • SDC1

RBT-1 reduces blood product utilization in patients undergoing nonemergency coronary artery bypass grafting and/or valve surgery. (PubMed, JTCVS Open) - No abstract available

Journal

RBT-1 Reduces the Number of Post-Operative Complications Associated with Cardiac Surgery (ACS-CLINCON 2024) - "RBT-1 significantly reduces the number of post-operative complications in patients undergoing cardiac surgery. A confirmatory Phase 3 study has commenced. RBT-1 has received Breakthrough Therapy designation by the FDA."

Surgery • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Nephrology • Renal Disease

Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. (PubMed, EClinicalMedicine) - P2 | "A phase 3 trial is planned. Renibus Therapeutics, Inc."

Biomarker • Journal • P2 data • Surgery • Acute Kidney Injury • Cardiovascular • Nephrology • HMOX1 • IL10

An Evaluation of Patient Reported Outcomes and Clinical Outcomes (clinicaltrials.gov) - P=N/A | N=400 | Recruiting | Sponsor: Renibus Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Clinical protocol • Enrollment open • Patient reported outcomes • Surgery • Cardiovascular

Association Between AKI and Biomarkers KIM-1, Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), and Cystatin C in Patients Undergoing Cardiac Surgery (KIDNEY WEEK 2023) - "We investigated the association between these biomarkers and AKI in patients undergoing elective coronary artery bypass graft (CABG) and/or valve surgery on CPB. Urine and plasma samples were collected from 121 adult patients who participated in a Phase 2 study designed to test the ability of an investigational drug (RBT-1) to induce an organ preconditioning response and prevent post-operative complications... Urinary KIM-1, NGAL, and CysC did not correlate with AKI in this cohort of adults undergoing cardiac surgery. Plasma KIM-1, NGAL, CysC levels may hold greater promise and should be studied further."

Biomarker • Clinical • Surgery • Acute Kidney Injury • Cardiovascular • Nephrology • CST3 • KIM1 • LCN2

Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Renibus Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Surgery • Cardiovascular

An Evaluation of Patient Reported Outcomes and Clinical Outcomes (clinicaltrials.gov) - P=N/A | N=400 | Not yet recruiting | Sponsor: Renibus Therapeutics, Inc.

Clinical protocol • New trial • Patient reported outcomes • Surgery • Cardiovascular

Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Renibus Therapeutics, Inc.

New P3 trial • Surgery • Cardiovascular

START: Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery (clinicaltrials.gov) - P2 | N=135 | Completed | Sponsor: Renibus Therapeutics, Inc. | Recruiting ➔ Completed

Biomarker • Surgery • Trial completion • HMOX1 • IL10 • KIM1

Phase 2 Study Interim Results of RBT-1 Effect on Postoperative Course in Elective CABG/Valve Surgery (SCCM 2023) - "The improvements in renal complications, hospital course, and readmission rates are expected given the broad organ protective mechanism of RBT-1. Final results of this study are expected in 2023."

P2 data • Surgery • Acute Kidney Injury • Cardiovascular • Nephrology

Interim Results of a Phase 2 Study With RBT-1 Evaluating Postoperative Course in Patients Undergoing Elective CABG/Valve Surgery on Cardiopulmonary Bypass (AHA 2022) - "RBT-1 is a novel drug with cytoprotective preconditioning activity. In subjects undergoing CABG/valve surgery on CPB, interim results suggest that RBT-1 protects against postoperative complications. The observed improvements in renal complications, hospital course, and readmission rates are expected given the broad organ protective mechanism of RBT-1."

Clinical • P2 data • Acute Kidney Injury • Nephrology • HMOX1 • IL10

FS.02. New Insights - Cardiac Surgery (AHA 2022) - "This featured surgery session takes us on a journey through 4 clinical trials including use of septal reduction therapy (SRT) and mavacamten (VALOR-HCM), partial oral treatment in patients with infectious endocarditis, to the VISION cardiac surgery study looking at ECG changes after surgery and 30 day mortality, and the START study, looking at the effect of RBT-1 preconditioning response on biomarkers and post op complications in persons undergoing CABG/cardiac valve surgery."

Cardiovascular

Oxidant- induced preconditioning: A pharmacologic approach for triggering renal 'self defense'. (PubMed, Physiol Rep) - "Furthermore, interim data analyses revealed statistically significant improvements in several clinical parameters. The goals of this review are to: (i) briefly discuss the historical background of renal "preconditioning"; (ii) present the experimental data that support the concept of FeS/SnPP- induced organ protection; and (iii) discuss the initial results of clinical trials that suggest the potential clinical utility of an 'oxidant preconditioning' strategy."

Journal • Review • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Disease • IL10

START: Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: Renibus Therapeutics, Inc. | Trial primary completion date: Jun 2022 ➔ Sep 2022

Biomarker • Trial primary completion date • HMOX1 • IL10 • KIM1

A Study of RBT-1 in Healthy Volunteers and Subjects With Stage 3-4 Chronic Kidney Disease (clinicaltrials.gov) - P1b; N=54; Completed; Sponsor: Renibus Therapeutics, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Acute Kidney Injury • Chronic Kidney Disease • Nephrology • Renal Disease