LJPC-30Sa and LJPC-30Sb

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.

About Gentamicin and Aminoglycoside Antibiotics

Gentamicin is an FDA-approved aminoglycoside antibiotic that is commonly used in infections in pregnancy and end-stage renal disease, urinary tract infections, endocarditis, serious Staphylococcus infections, and a wide range of other infections. Aminoglycosides are a broad-spectrum class of Gram-negative antibiotics that are a mainstay in the hospital setting. They are also used to potentiate the activity of certain classes of Gram-positive antibiotics. The use of the aminoglycoside class has increased over the last 10 years due to its broad spectrum activity against resistant bacteria, concentration-dependent killing, and prolonged duration of action, but its usage has been limited by dose-dependent and cumulative kidney toxicity and ototoxicity, which is toxicity to the ear. Current prescription data for aminoglycosides as antimicrobial agents represent over a $500 million market opportunity in the U.S., adjusted for branded pricing of comparable hospital antimicrobials.

A product manufactured through fermentation, gentamicin consists of a mixture of distinct but closely related chemical entities. While these distinct chemical entities appear to all retain antimicrobial activity, they may contribute differentially to toxicity. In particular, gentamicin’s kidney toxicity appears to be associated with some but not all of its constituent chemical entities. A gentamicin derivative that retains antimicrobial activity but had reduced kidney toxicity would represent a major advance for patients.

Gentamicin’s ability to induce a lack of fidelity in gene transcription, intrinsic to its antimicrobial mechanism of action, can 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 currently marketed gentamicin as a chronic treatment for these genetic diseases has been limited by its toxicity profile.