Pipeline

IgA Nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. This serious, progressive autoimmune disease can lead to significant kidney damage, with 20–40% of patients requiring renal replacement therapy. Dysregulated activation of the alternative complement pathway is a key factor in the progression of complement-mediated kidney diseases, such as IgAN. ADX-038 is an siRNA-based therapeutic candidate that targets CFB mRNA to selectively and durably inhibit the alternative complement pathway, and is expected to reduce immune-mediated kidney injury. A Phase 2 clinical trial will evaluate the safety and efficacy of ADX-038 in patients with complement-mediated kidney diseases including IgAN.

Geographic Atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD), a leading cause of blindness affecting over five million people worldwide. Patients with GA experience progressive vision loss due to the degeneration of light-sensitive photoreceptors in the retina. Genetic studies have implicated CFB in AMD progression, and underscore the promise of targeting this pathway. ADX-038 is an siRNA-based therapeutic candidate that targets CFB mRNA to selectively and durably inhibit the alternative complement pathway, with the goal to slow or halt vision loss associated with GA. A Phase 2 clinical trial will evaluate the safety and efficacy of ADX-038 in patients with GA.

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and severe disease characterized by uncontrolled activation of the complement system, leading to the destruction of red blood cells and severe anemia. The destruction of red blood cells within the blood vessels (intravascular hemolysis) and the destruction by immune cells outside the blood vessels (extravascular hemolysis) both contribute to disease severity. ADX-038 is an siRNA-based therapeutic candidate that targets CFB mRNA to selectively and durably inhibit the alternative complement pathway, and is expected to prevent both forms of hemolysis. A Phase 2 clinical trial will evaluate the safety and efficacy of ADX-038 in patients with PNH.

Hereditary Angioedema (HAE) is a rare genetic disorder caused by dysregulation of the plasma kallikrein pathway, leading to unpredictable and potentially dangerous swelling attacks. ADX-324, an siRNA-based therapeutic candidate, is designed to selectively and durably silence the mRNA encoding PKK, a critical protein in the plasma kallikrein pathway which regulates the production of bradykinin, and to prevent the debilitating swelling attacks associated with HAE. A Phase 3 clinical trial will evaluate the efficacy and safety of ADX-324 in patients with HAE.

Uncontrolled hypertension is a leading contributor to stroke, heart attack, kidney disease and vision loss. Angiotensinogen (AGT) is the principal component of the renin-angiotensin-aldosterone system (RAAS), which is a key regulator of blood pressure. ADX-850 is an siRNA-based therapeutic candidate designed to selectively and durably inhibit AGT production in the liver while sparing the reno protective AGT production in the kidney, to provide effective and convenient blood pressure control. A Phase 1 clinical trial is on-going to evaluate the safety and efficacy of ADX-850 in patients with hypertension.

Factor XI plays a critical role in the intrinsic pathway of the coagulation cascade, which contributes to blood clot formation. Targeting Factor XI to inhibit its activity is a promising approach for reducing clot formation without significantly increasing the risk of bleeding. ADX-626 is an siRNA-based therapeutic candidate designed to selectively and durably inhibit Factor XI, and to provide effective thrombosis prevention while minimizing bleeding complications in several diseases such as deep venous thrombosis, atrial fibrillation, stroke and acute coronary syndrome. A Phase 1 clinical trial will evaluate the safety and pharmacodynamic activity of ADX-626.