3K3A-APC

Name: 3K3A-APC Name (English): 3K3A-APC

Description: 3K3A-APC is a genetically engineered variant of activated protein C (APC). APC is a naturally occurring human protein with anticoagulant and cytoprotective properties. 3K3A-APC is modified to significantly reduce its anticoagulant activity while retaining its cytoprotective effects, including anti-apoptotic, anti-inflammatory, and endothelial barrier stabilization properties.

Mechanism of Action: 3K3A-APC's cytoprotective effects are believed to be mediated through the activation of protease-activated receptor 1 (PAR-1). This activation leads to alterations in gene expression profiles, promoting cell survival and reducing inflammation.

Clinical Development:

• Acute Ischemic Stroke: 3K3A-APC has been the primary focus of clinical development for the treatment of acute ischemic stroke. A Phase 2 clinical trial (RHAPSODY) evaluated its safety and tolerability in this population. Exploratory analyses suggested a potential reduction in intracranial hemorrhage rates. However, concerns regarding increased early mortality and potential research misconduct were raised by whistleblowers regarding this trial in November 2023. A Phase 3 trial is reportedly underway.
• Amyotrophic Lateral Sclerosis (ALS): A Phase 2 open-label trial is ongoing to assess the safety and potential efficacy of 3K3A-APC in patients with ALS. The study aims to determine if 3K3A-APC can reduce pathological changes associated with ALS, including microglial activation.
• Alzheimer's Disease: Preclinical studies in mouse models of Alzheimer's disease suggest that 3K3A-APC may have beneficial effects by inhibiting the BACE1 amyloidogenic pathway, reducing amyloid-beta deposits, and improving cognitive and cerebrovascular function.
• Traumatic Brain Injury: Animal studies have shown that 3K3A-APC can reduce lesion volume and improve behavior in a mouse model of traumatic brain injury.