When Prabhavathi Fernandes started Cempra Pharmaceuticals Inc. in January, she knew the company needed to build a foundation by in-licensing new technology.
Cempra recently signed on with Optimer Pharmaceuticals Inc. for an exclusive license to a preclinical antibacterial program. The Morrisville, N.C.-based company now has worldwide rights, except for in the Association of Southeast Asian Nations (ASEAN), to discover, develop and commercialize drugs based on the class of compounds called macrolides and ketolides.
"It's not just one compound, it's a whole program," Fernandes, Cempra's president and CEO, told BioWorld Today. If the company had started from scratch, "it would have taken us several years to get to this stage."
As part of the agreement, San Diego-based Optimer will receive an equity position in Cempra, in addition to royalties and milestone payments from any drug candidates developed or co-developed by Cempra. The companies will jointly conduct discovery and development activities of several preclinical compounds included in the license. The compounds have been shown to have potent activity against multidrug-resistant Streptococcus pneumoniae and Streptococcus pyogenes, and a lead candidate administered once-a-day to animal models has demonstrated oral activity and efficacy.
Macrolides, such as Biaxin (clarithromycin, from Abbott Laboratories) and Zithromax (azithromycin, from Pfizer Inc.), are on the market today for use in upper and lower respiratory tract infections where the primary pathogens could be S. pneumoniae, S. aureus, S. pyogenes, H. influenzae, M. catarrhalis and Legionella pneumophila. The drugs also are used to treat Helicobacter pylori gastritis, but many pathogens have become resistant to the available macrolides.
"Our compound, the first one from Optimer's license, has activity against macrolide-resistant strains and also against ketolide-resistant strains," Fernandes said. "So it's one more step above these compounds."
Ketek (telithromycin, from Sanofi-Aventis Group) became the first ketolide approved in the U.S. in April 2004, but Cempra's licensed compounds are expected to address even streptococci that are resistant to telithromycin. The approved drug does have activity against some macrolide-resistant strains, but it also appears to have more liver toxicity than azithromycin or clarithromycin, Fernandes said.
Cempra initially intends to develop the lead candidate for respiratory tract infections in adults and children, including sinusitis, pharyngitis and community-acquired mild to moderate pneumonia. It plans to file an investigational new drug application in March 2007 to take the lead agent into clinical testing.
About 40 percent to 45 percent of all S. pneumoniae and S. pyogenes are resistant to the current macrolides, Fernandes said.
"So even though you have up to $5 billion of sales of Zithromax and Biaxin today, a large number are resistant," she added. "We hope to be able to get that market."
Ketek is expected to have sales of more than $200 million in the U.S., and ketolides in general could take a significant portion of the macrolide market.
Fernandes learned of the Optimer antibacterial program through her work on the company's scientific advisory board. She also was the leading microbiologist for clarithromycin development at Abbott. Since then and before founding Cempra, she worked as an executive vice president in drug discovery at New York-based Bristol-Myers Squibb Co.; co-founded Small Molecule Therapeutics Inc., which later merged and became part of Morphochem AG, of Munich, Germany; served as CEO of Ricerca Biosciences LLC, of Concord, Ohio; and joined DarPharma Inc., of Chapel Hill, N.C., in July 2003 as CEO.
By starting Cempra, she found a way to return to her roots in antibacterial research. The company started operations in January with some angel money, but is seeking investors to participate in a Series A round, which should be complete sometime this year, she said.
The name "Cempra" is an acronym representing the four people from the company's original team. PRA stands for Prabha Fernandes, while C and E stand for Cindy Ingram, the company's director of business operations, and E. Cali Downs, its director of scientific operations. The M was for Michael Dombeck, a founder and adviser who is employed elsewhere.
It's too early to say at what stage Cempra will look to partner, but the company intends to take the compounds "forward as far as possible," Fernandes said, perhaps through the completion of Phase III trials.
Optimer's anti-infective compounds are different from older-generation antibiotics, which mostly are derived from natural products, because they have key sugar components that contribute to their antibacterial properties. The company has applied its sugar chemistry technology to modify regions of macrolides and ketolides, offering new hope of developing effective antibiotics against drug-resistant bacteria.
"Their chemistry has opened up a structure of the macrolide ring, which up to now has never been addressed," Fernandes said.