You might say Zengen Inc. is looking to do twice the work in one shot.
The Woodland Hills, Calif.-based company is developing peptides designed to control inflammation and fight infection, suggesting that its small molecules might be a more complete therapeutic option than steroids or antibiotics. Zengen believes its peptides, based on the larger melanocortin peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), have applications as anti-inflammatory and anti-infective drugs.
Hypothetically linking the use of its peptides to treating a car accident victim with multiple injuries and infections, Chief Scientific Officer James Lipton summed up the potential of Zengen's drugs.
"Why not treat yourself with a single medication rather than running out three or four drugs," he told BioWorld Today. "We see this as a major value for treatment prospects."
The peptides, originally researched in efforts to control fevers without the gastrointestinal side effects of acetaminophen, also displayed activity in anti-inflammatory conditions. Recent journal publications point to the company's laboratory success.
Findings published in the Feb. 20, 2003, issue of the Journal of Medicinal Chemistry showed that Zengen's peptide kills Candida albicans, with one peptide killing 99.7 percent of Candida cells over repeated experiments.
Zengen already has been at work to confirm in humans its early findings. The company has begun a 20-patient Phase I/II trial to study an intravaginal gel formulation of CZEN 002 in treating vulvovaginal candidiasis (vaginal yeast infection). The study, for which patient enrollment has begun at three U.S. sites, is scheduled to conclude by June.
In addition to data demonstrating the efficacy of CZEN 002, Zengen said recently completed Chinese clinical trials show that the molecule treats yeast infections. Trial data, which was incorporated into Zengen's investigational new drug application filed in October with the FDA, demonstrated that CZEN 002 directly inhibits or kills C. albicans, the major cause of all vaginal yeast infections. CZEN 002 also relieved the clinical symptoms of vulvovaginal candidiasis without any noticeable side effects.
"Our strategy has us going for certain soft targets now because of its antimicrobial and anti-inflammatory properties," President and CEO Rob Davidson told BioWorld Today, adding that CZEN 002 is designed to overcome bacterial resistance associated with azole class drugs as well as other antibiotics. "Our goal is to start researching those avenues, bring the technology to a certain level and look for partnering out, co-development and licensing deals."
Zengen is involved in a pair of overseas co-development deals for CZEN 002 for vulvovaginal candidiasis. In Italy the company has partnered with Pisa-based Abiogen Pharma SpA, while Hong Kong-based Lee's Pharmaceuticals Holdings Ltd. is its partner for China.
In preclinical and clinical studies, CZEN 002 has been shown to directly kill pathological fungi in addition to C. albicans, including Gram-negative and Gram-positive bacteria, and to inhibit replication of HIV-1. While HIV work is not in Zengen's near-term picture, the company has developed additional molecules based on CZEN 002 it hopes to advance down the road.
"We have several novel molecules that we have developed to increase our pipeline pretty effectively over the past two years," Davidson said. "Hopefully we eventually can gather more support in the industry through co-development deals to enable us to attack some larger indications."
Other recent publications point to the multiple applications of the peptide technologies.
Data published in the Feb. 20, 2003, issue of NeuroImmunoModulation showed that a synthetic form of alpha-MSH has an anti-inflammatory effect in celiac mucosa. Separate findings published in the Dec. 15, 2002, issue of Transplantation pointed to an approach to reduce organ rejection based on alpha-MSH.
The company, which employs 16 on its U.S. staff, also maintains a staff in Italy that continues research on derivatives of CZEN 002 for such applications, though it plans to prove its principle through the ongoing antimicrobial work before more capital-intensive work begins elsewhere.
"Quite frankly, Zengen is not going to be in a financial position to take that very far along despite the fact that it has great potential," Lipton said. "We are going to put our dollars into soft targets, many of which will be dermal, and then after we build this drug up, we will be in a better position to tackle larger enterprises."
Zengen was incorporated in 1999 following a merger between two privately held companies in which Davidson and Lipton were principals. Davidson worked at Woodland Hills, Calif.-based Bio-Delivery Technologies Inc., a company focused on drug delivery through gels and topicals, while Lipton developed the peptide technology for Abitis Pharmaceuticals LLC while a professor at the University of Texas Southwestern's medical school in Dallas.
Soon after the merger, Zengen raised $12.5 million in April 1999 primarily through private financings with companies in Taiwan.
The company also earns revenue from over-the-counter sales of products that contains its first molecule, a tri-peptide called CZEN 001.