Torezolid phosphate is being developed for multiple gram-negative infections, including ABSSSI.

Bayer is paying Trius Therapeutics $25 million up front as part of an exclusive agreement to develop and commercialize the latter’s Phase III-stage oxazolidinone antibiotic, torezolid phosphate, in China, Japan, and all other countries in Asia, Africa, Latin America, and the Middle East, excluding North and South Korea. Under terms of the deal Trius could receive another $69 million on the achievement of specified development, regulatory, and commercial milestones, plus double-digit royalties on Bayer’s sales of the drug in its designated territories. Trius retains rights to develop the drug in all other markets including the U.S. and Europe.

The German firm will in addition contribute about 25% of future costs associated with global development for torezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and pneumonia.

Torezolid is antibiotics firm Trius’ lead candidate and is currently in Phase III studies for the ABSSSI indication. The drug has in addition completed Phase II stage trials for the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), and Phase I trials against bacteraemia. Torezolid is an intravenous and orally administered second generation oxazolidinone for the treatment of serious gram positive infections including MRSA. The firm claims its candidate is chemically distinct from first generation oxazolidinones, and has been designed to demonstrate improved potency and spectrum of activity, with lower resistance issues. Trius notes that the only first-generation oxazolidinone to have achieved regulatory approval to date is Pfizer’s linezolid (Zyvox). Linezolid made global sales of nearly $1.2 billion in 2010.

Trius’ preclinical pipeline includes a GyrB/ParE program that is fully funded under an NIAID contract worth up to $27.7 million. The project is focused on identifying and developing antibacterials targeting the GyrA and GyrB epitopes on the bacterial DNA gyrase enzyme, and ParC and ParE on Topoisomerase IV. The firm states that while fluoroquinolone antibiotics such as ciprofloxacin target GyrA and ParC, and novobiocin targets GyrB, there are currently no antibiotics that inhibit both GyrB and ParE.  

The NIAID sponsored research aims to develop agents against gram-negative spectrum that include bacteria important for biodefense purposes. However, Trius notes, antibiotics against these biodefense targets often have cross activity against clinically important gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli. As a result it expects that compounds developed under the NIAID contract will have applications against respiratory tract, urinary tract, and intra-abdominal infections.

Trius’ second preclinical program, focused on marine natural products, is fully funded under a potentially $29.5 million contract with the Defense Threat Reduction Agency, and is exploiting the firm’s antisense screening technology and structure-based drug design platform to screen chemical libraries created from marine microorganisms. The aim is to develop antibiotics with broad spectrum activity against both gram-negative and gram-bacterial pathogens, including multiple biodefense-related infections.

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