AlloCure is pioneering innovative treatments for kidney disease. AlloCure's clinical stage program, AC607, is a novel biologic therapy for the treatment of acute kidney injury (AKI). AC607 comprises allogeneic adult bone marrow-derived mesenchymal stem cells (MSC). In the setting of AKI, AC607 homes to the injured kidney where it mediates anti-inflammatory and organ repair processes. Importantly, AC607 avoids recognition by the immune system, enabling administration in an "off-the-shelf" paradigm without the need for tissue typing or immunosuppression.
In AlloCure's preclinical studies, MSC effectively prevented and treated AKI when administered either prior to injury or after the onset of AKI. The AC607 phase 1 study conducted in cardiac surgery subjects demonstrated that the adverse event profile observed was consistent with that expected for this subject population and no serious adverse events were attributed to AC607. Additionally, results suggested that AC607 may reduce the incidence of AKI, hospital readmission rates, and hospital length of stay when compared to a cohort of historical controls.
AC607 is derived and expanded from bone marrow obtained from healthy adult donors using a proprietary and mature state-of-the-art manufacturing process. AC607 possesses unique characteristics that enhance its potential to treat a broad population of patients, including:
- Immune privileged - avoids detection by the patient's immune system
- No donor matching - administered as an off-the-shelf product, obviating the need for blood or tissue typing
- Genetically stable - not transformed or induced
AlloCure has conducted extensive preclinical studies demonstrating that the administration of allogeneic MSC prior to or after the development of AKI effectively enhances kidney repair and improves survival. In the setting of AKI, the damaged kidney expresses increased levels of stromal-cell derived factor 1 (SDF-1), whereas SDF-1 levels decrease in the bone marrow. This reversal of the normal SDF-1 gradient promotes MSC homing to the site of injury. Blockade of CXCR4, the receptor for SDF-1 expressed on MSC, significantly reduces MSC migration and homing.
After reaching the injured kidney, AC607 mediates anti-inflammatory and organ repair processes via the secretion of beneficial paracrine factors, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factor 1 (IGF-1) and others, which instruct the local damaged kidney cells to divide and survive rather than undergo apoptosis and subsequent fibrosis. Notably, the MSC are in residence in the injured kidney only transiently, and do not differentiate and repopulate the injured organ. The paracrine mediators produced by MSC act to preserve and restore kidney function following AKI via several mechanism, including:
Due to these unique qualities, AC607 represents a promising approach to effectively treat AKI.
Adapted from Humphreys and Bonventre. Ann. Rev. Med. 2008. 59:325-39.
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