LJPC-501 is La Jolla’s proprietary formulation of angiotensin II. Angiotensin II, the major bioactive component of the renin-angiotensin system, serves as one of the body’s central regulators of blood pressure. La Jolla is developing LJPC-501 for the treatment of catecholamine-resistant hypotension (CRH), which is an acute, life-threatening condition in which blood pressure drops to dangerously low levels in patients who respond poorly to current treatments. Angiotensin II has been shown to raise blood pressure in a randomized, placebo-controlled clinical trial in CRH, which was recently published in the journal Critical Care, as well as in animal models of hypotension. Preclinical pharmacology studies conducted by La Jolla have demonstrated that catecholamine resistance may be in part a result of reduced endogenous production of angiotensin II. La Jolla is currently enrolling patients into its ATHOS (Angiotensin II for the Treatment of High-Output Shock) 3 trial, which is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 clinical trial of LJPC-501 in patients with CRH. The ATHOS 3 trial is being conducted under a Special Protocol Assessment with the U.S. Food and Drug Administration in which it was agreed that the primary efficacy endpoint is increase in blood pressure. Results from ATHOS 3 are expected in the first quarter of 2017
LJPC-401 is La Jolla’s novel formulation of hepcidin. Hepcidin, an endogenous peptide hormone, is the body’s naturally occurring regulator of iron absorption and distribution. Hepcidin prevents excessive iron accumulation in vital organs, such as the liver and heart, where it can cause significant damage and even result in death. La Jolla is developing LJPC-401 for the potential treatment of iron overload, which occurs as a result of diseases such as hereditary hemochromatosis (HH), beta thalassemia and sickle cell disease (SCD). HH is a disease caused by a genetic deficiency in hepcidin that results in excessive iron accumulation. HH is the most common genetic disease in Caucasians and causes liver cirrhosis, liver cancer, heart disease and/or failure, diabetes, arthritis and joint pain. Beta thalassemia and SCD are genetic diseases of the blood that can cause life-threatening anemia and usually require frequent and life-long blood transfusions. These blood transfusions cause excessive iron accumulation in the body, which is toxic to vital organs, such as the liver and heart. In addition, the underlying anemia causes excessive iron accumulation independent of blood transfusions. LJPC-401 has been shown to be effective in reducing serum iron in preclinical testing. La Jolla has initiated a Phase 1 clinical trial of LJPC-401 in patients at risk of iron overload due to conditions such as HH, beta thalassemia and SCD.
LJPC-30Sa and LJPC-30Sb are La Jolla’s next-generation gentamicin derivatives. Despite kidney toxicity, gentamicin has become one of the most commonly prescribed hospital antibiotics. Gentamicin consists primarily of a mixture of four distinct but closely related chemical entities that may contribute differentially to the product’s toxicity profile. Gentamicin’s ability to induce a lack of fidelity in gene transcription, intrinsic to its antimicrobial mechanism of action, can also be leveraged in the correction of certain human genetic mutations that lead to rare genetic disorders, such as cystic fibrosis and Duchenne muscular dystrophy. In spite of favorable short-term clinical proof-of-efficacy data in cystic fibrosis, development of gentamicin as a chronic treatment for these genetic diseases has been limited by its toxicity profile. LJPC-30Sa and LJPC-30Sb are purified components of the currently marketed gentamicin product that retain the biologic activity of gentamicin, yet appear to lack the traditional kidney toxicity associated with it. La Jolla is developing LJPC-30Sa and LJPC-30Sb for the potential treatment of serious bacterial infections and rare genetic disorders, such as cystic fibrosis and Duchenne muscular dystrophy. Following a pre-Investigational New Drug application (IND) meeting with the U.S. Food and Drug Administration, La Jolla has received guidance that it may proceed with its proposed Phase 1 clinical trial following the submission of an IND.