BioWorld International Correspondent

PARIS - Novexel SA and Forest Laboratories Holdings Ltd., a wholly owned subsidiary of Forest Laboratories Inc. signed an agreement allowing the U.S. company to develop, manufacture and commercialize Novexel's novel intravenous beta lactamase inhibitor, NXL104, in combination with Forest's ceftaroline.

NXL104 is designed to be co-administered with certain antibiotics to enhance their spectrum of activity, and the license that Paris-based Novexel has granted Forest Laboratories, of New York, gives it exclusive rights to administer NXL104 in conjunction with ceftaroline as a combination product in North America.

Under the terms of the agreement, Forest will pay Novexel an up-front license fee of €75 million (US$109.6 million) and fund the development and commercialization of the ceftaroline/NXL104 combination. Novexel could be eligible for additional milestone payments of up to €75 million if the combination product is developed successfully. In addition, if the product obtains regulatory marketing approval, Forest will pay Novexel low double-digit royalties on product sales throughout North America.

NXL104 inhibits bacterial enzymes called beta-lactamases that break down beta-lactam antibiotics (in particular penicillins and cephalosporins). Beta-lactamase inhibition is a mechanism for counteracting resistance and enhancing broad-spectrum activity of beta-lactam antibiotics.

Ceftaroline is a bactericidal, injectable, broad-spectrum cephalosporin being developed as a therapeutic agent for the treatment of gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant Streptococcus pneumoniae (MDRSP), as well as common gram-negative organisms. The drug currently is being tested as a monotherapy in Phase III clinical trials for complicated skin and skin structure infections and community-acquired pneumonia.

Forest intends to initiate a Phase I trial of the ceftaroline/NXL104 combination in its next fiscal year. Novexel has filed a composition-of-matter patent covering the ceftaroline/NXL104 combination product, which would provide protection until 2022 at least.

The agreement also gives Forest first negotiation rights in North America for a combination of NXL104 with ceftazidime, a cephalosporin antibiotic with a different spectrum of activity from ceftaroline. That combination is being studied in Phase I clinical trials conducted by Novexel, and as the company's CEO, Iain Buchanan, pointed out, "the significant funding which Novexel will receive under this agreement [with Forest] will enable the company to devote the appropriate resources to the parallel and independent Phase II development of NXL104 in combination with ceftazidime."

Novexel is developing a range of novel anti-infective and antifungal drugs to treat hospital-acquired infections. It has two other compounds in Phase I clinical trials besides NXL 104. They are NXL103, an oral streptogramin being developed as a treatment for bacterial respiratory infections, and NXL201 (aminocandin), which is being developed as an injectable antifungal agent for use as a first-line treatment against various fungal infections.