XyloCor Therapeutics has achieved a significant milestone in cardiovascular gene therapy by dosing the first patient in its Phase 2b EXACT-2 trial, evaluating XC001 (encoberminogene rezmadenovec) for the treatment of coronary artery disease and refractory angina. The clinical-stage biopharmaceutical company announced this development as it advances its novel one-time catheter-based treatment designed to create new blood vessels in the heart.
Novel Gene Therapy Approach
XC001 represents an innovative adenoviral vector-based gene therapy encoding for vascular endothelial growth factor (VEGF). The therapy is uniquely designed as a one-time treatment to reduce cardiac ischemia by creating new blood vessels in the heart, thereby reducing episodes of chest pain and improving patients' ability to perform everyday activities.
The percutaneous administration approach involves injecting XC001 directly into the heart muscle, allowing the therapy to achieve higher gene expression levels locally in the heart while minimizing systemic vector circulation and associated side effects. This method eliminates the need for surgical administration that was required in previous trials.
EXACT-2 Trial Design
The EXACT-2 study is a Phase 2b, multicenter, randomized, double-blind trial designed to evaluate 100 patients with refractory angina. The trial will assess the safety and efficacy of one-time gene therapy with XC001, delivered using the Extroducer® Infusion Catheter System, an endocardial delivery catheter designed to inject advanced therapies directly into the heart through a simple injection procedure in the cardiac catheterization lab.
The first patient was dosed by Timothy Henry, MD, at The Christ Hospital Health Network in Cincinnati, OH. Dr. Henry, a cardiovascular interventionist and the Lindner Family Distinguished Chair in Clinical Research and Medical Director of The Carl and Edyth Lindner Center for Research at The Christ Hospital, expressed enthusiasm about the trial participation.
"After seeing the convincing results from the EXACT-1 trial, we were eager to participate in EXACT-2," commented Dr. Henry. "We believe that XC001 delivered through the Extroducer® Infusion Catheter System will maintain the accuracy of delivery of XC001 to the heart and improve the safety over the surgical administration approach used in EXACT-1."
Promising EXACT-1 Results
The XC001 Phase 1/2 EXACT-1 trial results demonstrated the transformative, disease-modifying potential of XC001 to reduce cardiac ischemia, reduce anginal symptoms and improve quality of life for cardiac patients who have no other treatment options. The results showed that XC001 could be safely administered and achieve durable clinical improvements.
Key efficacy outcomes from EXACT-1 included increases in exercise duration, decrease in ischemic burden as measured by Positron Emission Tomography (PET) imaging, and a reduction in angina frequency. Notably, 93% of patients in the trial entered with chest pain so severe that it markedly limited daily activities, whereas at six months 43% reported no chest pain with ordinary activities.
XC001 was well tolerated in the patient population and there were no serious adverse events related to the study drug, supporting its safety profile for further development.
Addressing Unmet Medical Need
Refractory angina represents a growing problem that occurs in patients with chronic angina who are symptomatic despite optimal medical therapy and are no longer eligible for mechanical interventions like percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). These patients currently have no treatment options and are frequently highly symptomatic, which severely impacts their quality of life and may exacerbate comorbidities.
"Initiating the EXACT-2 trial is an important milestone as we continue to develop XC001 for the treatment of refractory angina in patients who have exhausted available treatment options and have a debilitating quality of life," said Albert Gianchetti, President and CEO of XyloCor. "Building on the positive results from EXACT-1, we are now focused on advancing the EXACT-2 trial to bring this potentially transformative treatment to patients as quickly as possible."
Advanced Delivery Technology
The Extroducer® Infusion Catheter System represents a first-in-class endovascular delivery device that enables direct-to-tissue drug delivery. The system addresses a significant unmet need in the field of novel therapies, enabling targeted delivery of a wide range of treatment modalities to otherwise hard-to-reach organs.
Using standard fluoroscopy equipment and routine interventional radiology approaches, the Extroducer provides access to hard-to-reach tissues by safely penetrating the vessel wall and delivering payload directly to the target location. The device received U.S. Food and Drug Administration (FDA) clearance under 510(k) in June 2022, and XyloCor entered into a licensing agreement with SmartWise, a unit of SmartCella, to deliver XC001 via this system in 2024.
Expanding Clinical Program
XyloCor is also initiating a second clinical trial this year – a double-blind Phase 2 trial of XC001 as an adjunctive treatment to coronary artery bypass graft surgery (CABG), further expanding the potential applications of this gene therapy approach in cardiovascular disease treatment.
