encoberminogene rezmadenovec (XC001) / XyloCor - LARVOL DELTA

EXACT-CABG: Epicardial Delivery of XC001 Gene Therapy to Promote Angiogenesis in CAD Patients Undergoing Treatment With CABG (clinicaltrials.gov) - P2 | N=116 | Not yet recruiting | Sponsor: XyloCor Therapeutics, Inc.

New P2 trial • Cardiovascular • Coronary Artery Disease • Gene Therapies • Heart Failure

Discovery of Two New Neuroprotective Isocoumarin Dimers From the Dendrobium huoshanense-derived Streptomyces sp. AHMU XC001. (PubMed, Chem Biodivers) - "Notably, compounds 1-4 effectively inhibited Aβ1-42-induced reduction in cell viability and alleviated cytotoxicity in the human neuroblastoma SH-SY5Y cell line. These findings pave the way for further investigation of compounds 1-4 as potential lead molecules for the development of neuroprotective agents targeting Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • Neuroblastoma • Oncology • Solid Tumor

EXACT 2: An Investigational Trial to Evaluate the Effects of the Drug XC001 Delivered Via an Endocardial Delivery Catheter in Subjects With Chronic Angina Caused by Coronary Artery Disease (clinicaltrials.gov) - P2 | N=106 | Recruiting | Sponsor: XyloCor Therapeutics, Inc.

New P2 trial • Cardiovascular • Coronary Artery Disease • Gene Therapies

A VEGF gene therapy approach for the treatment of patients with coronary artery disease and refractory angina: assessment of clinical development. (PubMed, Expert Opin Investig Drugs) - "In initial trials, intramyocardial XC001 has been shown to be safe with signals for efficacy in decreasing myocardial perfusion defects, improving exercise duration, and anginal complaints in patients with RA. A Phase 2 trial using a novel percutaneous delivery catheter for endomyocardial delivery of XC001 is currently underway and has potential benefits in multiple other conditions, including as an adjunct therapy in patients undergoing CABG treatment at risk for incomplete revascularization, patients with coronary microvascular dysfunction, and others with peripheral arterial disease."

Journal • Review • Cardiovascular • Coronary Artery Disease • Gene Therapies • Myocardial Ischemia • Peripheral Arterial Disease

XyloCor Therapeutics Raises $67.5 Million in Series B Financing to Advance Clinical Development of Novel Gene Therapy in Cardiovascular Disease (Businesswire) - "XyloCor Therapeutics, Inc...announced the completion of a $67.5 million Series B financing. New investment will support a randomized, double-blind Phase 2b clinical trial (EXACT-2) of XC001 (encoberminogene rezmadenovec), in refractory angina, using a new non-surgical method of endocardial administration via a novel injection catheter. The financing will also fund a second randomized, double-blind Phase 2 trial of XC001 as an adjunctive treatment to coronary artery bypass graft surgery (CABG)....XyloCor plans to launch a randomized, double-blind Phase 2b in refractory angina in 2025 to further build upon the clinically-meaningful evidence generated to-date....XyloCor also aims to initiate a second Phase 2 trial of XC001 in 2025 as an adjunctive therapy to augment the effectiveness of CABG: a procedure used to treat coronary artery disease....XyloCor plans to dose the first patient in the Phase 2 study by year end 2025."

Financing • New P2 trial • New P2b trial • Cardiovascular • Coronary Artery Disease

XC001 gene therapy for the treatment of refractory angina: 6‐month efficacy and safety from the phase 1/2 first‐in‐human study (EXACT Trial) (ESGCT 2023) - "Mean (SD) change in angina episodes at 6 months showed a reduction of 6.7 (8.1) episodes (p < 0.001) over a 2-week period prior to each visit while at the same time nitroglycerin use decreased (-3.8 (6.9), p = 0.008). No serious adverse events (SAEs) were considered related to XC001 and SAEs related to the administration procedure (38%) were expected and occurred within 2 weeks of dosing. In summary, multiple EXACT study efficacy endpoints demonstrated that intramyocardial administration of XC001 was associated with improvements in angina symptoms and exercise capacity in RA subjects while cardiac imaging measured by PET provided supportive evidence of a biologic effect."

Clinical • Gene therapy • P1/2 data • Cardiovascular • Coronary Artery Disease • Gene Therapies

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial. (PubMed, Circ Cardiovasc Interv) - P1/2 | "XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis...Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732."

Gene therapy • Journal • P2 data • Cardiovascular • Coronary Artery Disease • Gene Therapies

Angiogenic gene therapy for refractory angina: results of the epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (EXACT) phase 2 trial (ESC 2023) - "Angina frequency and nitroglycerin use measured during a two-week diary decreased by 6.6 episodes (95% CI, 3.5–9.7) and 4.1 doses (95% CI, 1.3–6.9), respectively. Improvements in objective and subjective measures including total exercise time, myocardial perfusion, angina frequency and quality of life support a clinically meaningful biologic effect . This therapy warrants study in larger randomized studies."

Gene therapy • P2 data • Cardiovascular • Myocardial Ischemia

Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases. (PubMed, Gene Ther) - "XC001 DNA was not detected in blood at any time but was present at Day 8 around the site of injection and to a much lesser extent in the spleen, liver, and lungs, persisting at low levels in the heart and spleen until at least Day 91. These findings demonstrate that intramyocardial injection of XC001 is supported for use in human studies."

Gene therapy • Journal • Preclinical • Cardiovascular • Gene Therapies • Inflammation • TNNI3

EXACT Trial: Results of the Phase 1 Dose-Escalation Study. (PubMed, Circ Cardiovasc Interv) - P1/2 | "Epicardial delivery of encoberminogene rezmadenovec via minithoracotomy is feasible, and up to 1×10 viral particle appears well tolerated. A dose response was observed across 4 dosing cohorts in total exercise duration, myocardial perfusion deficit, and angina class. The highest dose (1×10 viral particle) was carried forward into phase 2."

Journal • P1 data • Cardiovascular • Coronary Artery Disease • Gene Therapies

Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial) (clinicaltrials.gov) - P1/2 | N=41 | Completed | Sponsor: XyloCor Therapeutics, Inc. | Active, not recruiting ➔ Completed

Gene therapy • Trial completion • Cardiovascular • Coronary Artery Disease • Gene Therapies • Heart Failure

Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial) (clinicaltrials.gov) - P1/2 | N=41 | Active, not recruiting | Sponsor: XyloCor Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2022 ➔ Jul 2023 | Trial primary completion date: Jan 2022 ➔ Jan 2023

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Coronary Artery Disease • Gene Therapies • Heart Failure

XyloCor Therapeutics (BIO 2022) - "Our lead product candidate, XC001, is in clinical development for patients with refractory angina for which there are no treatment options. XyloCor also has a secondary product, XC002, in discovery stage, for patients with cardiac tissue damage from heart attacks."

Cardiovascular • Coronary Artery Disease • Gene Therapies • Myocardial Infarction

Preliminary Safety, Tolerability and Efficacy of Direct Epicardial Administration of Encoberminogene Rezmadenovec to Ischemic Myocardium in Patients with Refractory Angina: Six Month Phase 1 Data (ASGCT 2022) - P1/2 | "Encoberminogene rezmadenovec (XC001) is a replication-deficient adenoviral serotype 5 (Ad5) vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) including isoforms -121, -165 and -189... In the Phase 1 portion of this Phase 1/2 Study treating refractory angina, direct epicardial administration of encoberminogene rezmadenovec appears to be well-tolerated and safe at all tested doses. Preliminary efficacy evaluation in a small sample size suggests a possible dose-response and therapeutic potential with this therapy. Based on observed safety, tolerability, and preliminary efficacy with 1x1011 viral particle dose, continued investigation of the direct epicardial approach at this dose in the Phase 2 expansion portion of this trial has begun."

Clinical • Late-breaking abstract • P1 data • Cardiovascular • Fatigue • Gene Therapies

Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial): Rationale, Design, and Clinical Considerations. (PubMed, Am Heart J) - P1/2 | "The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation."

Clinical • Journal • Cardiovascular • CNS Disorders • Depression • Gene Therapies • Psychiatry

[VIRTUAL] XyloCor Theraputics (BIO 2021) - "Our lead product candidate, XC001, is in clinical development for patients with refractory angina for which there are no treatment options. XyloCor also has a secondary product, XC002, in discovery stage, for patients with cardiac tissue damage from heart attacks."

Cardiovascular • Coronary Artery Disease • Gene Therapies • Myocardial Infarction

[VIRTUAL] Evaluation of Human Cardiomyocytes for Use in a Potency Assay for XC001, an Adenoviral Gene Therapy Vector for Treatment of Refractory Angina (ASGCT 2021) - "Three candidate human cardiomyocyte cell lines were evaluated, and all showed significant levels of vector-derived VEGF secretion over background after transduction with XC001, using an ELISA for VEGF protein quantitation. A clear dose response was demonstrated across a three-log range of multiplicities of infection (MOI) for the two most promising cell lines. Using a western blot, both cell lines showed the expected pattern of VEGF isoforms."

Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Gene Therapies • Infectious Disease • Myocardial Ischemia • Pain

Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial) (clinicaltrials.gov) - P1/2; N=44; Recruiting; Sponsor: XyloCor Therapeutics, Inc.; N=33 ➔ 44

Clinical • Enrollment change • Cardiovascular • Coronary Artery Disease • Gene Therapies • Heart Failure • Hepatology

Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial) (clinicaltrials.gov) - P1/2; N=33; Recruiting; Sponsor: XyloCor Therapeutics, Inc.; Trial completion date: Sep 2021 ➔ Jul 2022; Trial primary completion date: Mar 2021 ➔ Jan 2022

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • Coronary Artery Disease • Gene Therapies • Heart Failure • Hepatology

Administration of AdVEGF-All6A+ to Myocardium of Individuals With Diffuse CAD Via Minimally Invasive Surgery (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: Weill Medical College of Cornell University; N=41 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Cardiovascular • Coronary Artery Disease • MRI

Enhancement of sphingolipids synthesis improves osmotic tolerance of Saccharomyces cerevisiae. (PubMed, Appl Environ Microbiol) - "To enhance the growth performance of Saccharomyces cerevisiae under osmotic stress, mutant XCG001, which tolerates up to 1.5 M NaCl, was isolated through adaptive laboratory evolution (ALE)...Elo2, a sphingolipid acyl chain elongase, was related to osmotic tolerance, through transcriptome analysis of the wild-type strain and an osmotic tolerant strain generated from ALE. Overexpression of ELO2 increased the content of complex sphingolipid with longer acyl chain, thus membrane integrity and osmotic tolerance improved."

Journal

Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial) (clinicaltrials.gov) - P1/2; N=29; Recruiting; Sponsor: XyloCor Therapeutics, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open