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CBST... zwar schon etwas her, aber noch zur Calixa-Übernahme

Das dabei erworbene CXA-201 könnte recht aussichtsreich sein... zumindenst waren die Gründer von Calixa zuvor mit Antibiotika bereits sehr erfolgreich.


http://www.pharmacychoice.com/news/article.cfm?Article_ID=36…

3/30/09 - Calixa Pushes Anti-Pseudomonal Antibiotic Toward Phase II for UTI

With $30 million of Series A financing in its coffers, Calixa Therapeutics Inc. is gearing up for a Phase II trial of CXA-101, a broad-spectrum cephalosporin antibiotic that has shown potent anti-pseudomonal activity.

San Diego-based Calixa was founded in late 2007 by antibiotic expert James Ge and serial entrepreneur Eckard Weber. The two have a long history of working together at antibiotic firms funded by Domain Associates, where Weber serves as a partner.

In the early part of the decade, Ge and Weber teamed up at Peninsula Pharmaceuticals Inc., where Ge headed drug development and Weber served as chairman. Peninsula was acquired by Johnson & Johnson in 2005 for $245 million, giving the big pharma control of Peninsula's broad-spectrum carbapenem antibiotic Doribax (doripenem). (See BioWorld Today, April 20, 2005.)

Doribax gained approval for complicated intra-abdominal and urinary tract infections although, like many antibiotics, it has hit regulatory hurdles in hospital-acquired pneumonia. (See BioWorld Today, July 18, 2008.)

While J&J focused on Doribax, the Peninsula team spun out Cerexa Inc. to develop the Phase I broad-spectrum cephalosporin antibiotic ceftaroline, which was licensed from Takeda Chemical Industries Ltd. Again, Ge headed drug development and Weber served as chairman until Cerexa was acquired by Forest Laboratories Inc. in late 2006 for $480 million. (See BioWorld Today, Dec. 15, 2006.)

While Forest moved ceftaroline through Phase III, Ge and Weber had their sights on FR264205, a preclinical broad-spectrum cephalosporin antibiotic in development at Tokyo-based Astellas Pharma Inc. Cerexa had done "extensive due diligence" on the compound, but it hadn't been licensed prior to the Forest acquisition, and Forest wasn't interested in pursuing such an early-stage program, Ge said.

So Ge and Weber founded Calixa, raised $30 million and licensed FR264205 - now known as CXA-101.

The Series A round came from Domain as well as Canaan Partners and Frazier Healthcare Ventures. The money should carry Calixa "into 2010," Ge told BioWorld Today.

What differentiates CXA-101 from other antibiotics on the market or in development is its potent activity against Pseudomonas aeruginosa, Ge explained.

The bacteria ranks alongside Escherichia coli and Streptococcus pneumoniae as one of the most common causes of hospital-acquired infections and can lead to hospital-acquired pneumonia, urinary tract infections, wound infections and sepsis.


P. aeruginosa infections commonly are treated with broad-spectrum antibiotics such as the cephalosporin antibiotics ceftazidime or cefepime, or the carbapenem antibiotic imipenem.

In a paper published in the March 2007 issue of Antimicrobial Agents and Chemotherapy, Astellas' researchers demonstrated that the concentration of CXA-101 needed to inhibit 90 percent of 193 P. aeruginosa isolates was eight times to 16 times lower than that needed for ceftazidime, cefepime or imipenem. CXA-101 also demonstrated activity against strains resistant to the existing drugs and showed evidence that it may be less prone to resistance.

In murine models, CXA-101 showed superior or comparable efficacy to ceftazidime and imipenem.

Calixa filed an investigational new drug application for CXA-101 in mid-2008 and completed two Phase I studies.

CXA-101 was well tolerated with no dose-limiting toxicities and a safety profile similar to that of marketed cephalosporin antibiotics.

With Phase I data in hand, Calixa is now gearing up for a Phase II trial, slated to start in the second quarter. Ge said the double-blind study will compare intravenous CXA-101 to an existing antibiotic for complicated urinary tract infections. Data are expected within a year.

Behind CXA-101, Calixa is developing CXA-201, which combines CXA-101 with a beta-lactamase inhibitor to provide even broader activity. If the data with CXA-201 pan out, Ge said Calixa will focus all of its resources on that program rather than CXA-101.

A similar approach is being pursued by Paris-based Novexel SA, which is conducting a Phase II trial combining its broad-spectrum beta lactamase inhibitor, NXL 104, with ceftazidime for complicated intra-abdominal infections. But Ge noted that CXA-101 has shown better anti-pseudomonal activity than ceftazidime.

He added that CXA-101 has the potential to be "best-in-class" as far as its anti-pseudomonal activity, based on in vitro and in vivo data.

Calixa also is developing an inhaled form of CXA-101 for P. aeruginosa infections in cystic fibrosis patients. The program, dubbed CXA-301, is in preclinical, with formulation work under way.

As of now, the only inhaled antibiotic for CF infections is TOBI (tobramycin solution for inhalation, Novartis AG), but Gilead Sciences Inc. is in regulatory discussions with the FDA regarding its inhaled aztreonam, and Phase II programs include Bayer AG's ciprofloxacin inhaled powder, Aradigm Corp.'s inhaled liposomal ciprofloxacin, Transave Inc.'s Arikace (liposomal amikacin for inhalation) and Mpex Pharmaceuticals Inc.'s MP-376, an aerosol formulation of levofloxacin.

Preclinical data have shown CXA-101 to be more potent than tobramycin and aztreonam, Ge noted


mfg ipollit
 
aus der Diskussion: Biotech Depot 2010
Autor (Datum des Eintrages): ipollit  (21.01.10 23:12:29)
Beitrag: 64 von 334 (ID:38786997)
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