Genelabs Technologies Inc., of Redwood City, Calif., reported that it synthesized a family of DNA-binding cationic poly-heterocyclic molecules that are fungicidal toward a large number of pathogenic yeasts and molds.

At the 42nd annual Interscience Conference on Antimicrobial Agents and Chemotherapy in San Diego that began Friday and continued through Monday, Genelabs reported on examples of derivative compounds generated during optimization of GLO47296. One of these derivatives, GL663142, which demonstrated improved metabolic stability, is especially potent against certain emerging pathogens and is active against C. albicans strains resistant to flucytosine and fluconazole, Genelabs said. Another compound, GL406349, is active in vitro against several Candida species with MIC values ranging from 0.8 to 3 ug/ml. GL406349 also demonstrated in vivo efficacy in prolonging survival against C. albicans in a murine systemic candidosis model, where its efficacy was shown at 5 mg/kg (p=0.025) and 10 mg/kg (p=0.015).

In other news from ICAAC:

Acambis plc, of Cambridge, UK, presented preclinical data on its West Nile vaccine, ChimeriVax-West Nile. The vaccine was shown to be safe and induced high levels of neutralizing antibodies. Data also demonstrated the ability of ChimeriVax-West Nile to protect against challenge with wild-type West Nile virus.

Achillion Pharmaceuticals Inc.'s L-nucleoside, Beta-L-Fd4C (ACH-126,443), demonstrated "encouraging advances" in the treatment of chronic hepatitis B virus infection based on presentations by researchers at Beth Israel Deaconess Medical Center in Boston. In a blinded, placebo-controlled Phase I/II trial, the once-daily oral agent produced potent anti-HBV activity in patents chronically infected with HBV. Beta-L-Fd4C was well tolerated through the 14-day study. Achillion also reported the development of a new class of compounds that inhibits drug-resistant HIV strains by targeting a virus protein. ACH-0100703, a representative preclinical candidate, was developed to target a zinc finger-containing protein on HIV identified by Achillion, of New Haven, Conn., as a drug target.

Agouron Pharmaceuticals Inc., of La Jolla, Calif., revealed that for patients co-infected with hepatitis C and HIV, Viracept (nelfinavir mesylate) is generally well tolerated. The retrospective analysis, conducted by Agouron, a Pfizer Inc. company, examined the responses of 1,055 HCV/HIV co-infected individuals treated with more than three months of protease inhibitor therapy and compared responses of patients on Viracept, indinavir, saquinavir, ritonavir and amprenavir based upon comparisons of grade three and grade four elevations in asparatate aminotransferase and alanine aminotransferase. The study collected safety data, viral load, CD4 cell count and treatment history.

BioCryst Pharmaceuticals Inc., of Birmingham, Ala., presented in vitro data demonstrating that BCX-1777, its candidate for the treatment of T-cell malignancies, acts by increasing intracellular deoxyguanosine triphosphate, thus altering dNTP supply and resulting in characteristics of apoptosis. The data demonstrated its efficacy compared to cyclosporin in a mouse model. BioCryst's team followed the proliferation inhibition in vitro of lymphocytes treated with BCX-1777 and deoxyguanosine by measuring the levels of deoxynucleotides. The results showed that BCX-1777's efficacy was comparable to treatment with cyclosporin in a severe combined immunodeficient murine model in which xenogenetic graft-vs.-host disease was induced by transplantation of human lymphocytes.

Cubist Pharmaceuticals Inc., of Lexington, Mass., presented data on the new "superbug" strain known as vancomycin-resistant Staphylococcus aureus. Michael Rybak of Wayne State University presented data comparing the activity of Cubist's daptomycin, linezolid, quinupristin/dalfopristin and vancomycin against the VRSA strain and its presumptive parent strain of methicillin-resistant S. aureus in an in vitro model with simulated endocardial vegetations. After 24 hours, vancomycin exhibited no effect on the strain, while daptomycin achieved close to a 6.0 log¹⁰ reduction in bacterial density. Cubist's stock (NASDAQ:CBST) rose 68 cents, or 15.4 percent, Monday to close at $5.11.

Enanta Pharmaceuticals Inc., of Watertown, Mass., presented initial findings of its macrolide antibiotic research program to identify classes of macrolides with improved antimicrobial and pharmacologic properties. Enanta uses chemistry techniques to modify existing macrolide natural products to overcome resistance mechanisms in Gram-positive pathogens such as Streptococcus pneumoniae. Enanta scientists have converted 16-membered ring macrolide antibiotics into 14-membered ring structures that provide the basis for new therapeutics to combat the emergence of bacterial resistance.

ID Biomedical Corp., of Vancouver, British Columbia, presented Phase I trial results of the FluINsure flu vaccine, demonstrating that the vaccine is a trivalent product and was strongly immunogenic. Statistically significant increases in both serum hemagglutination-inhibiting antibody and in virus-specific secretory IgA antibodies in the nose were shown for all types of influenza viruses represented in the vaccine.

Microbia Inc., of Cambridge, Mass., identified a gene required by Staphylococcus aureus to mediate antibiotic resistance when forming biofilm colonies. The company said the study is the first to find a link between the resistance mechanisms of biofilm bacteria and those present in methicillin-resistant S. aureus. Microbia also reported the discovery of a new class of small-molecule compounds that increase the antibiotic sensitivity of S. aureus biofilms.

Mymetics Corp., of Annapolis, Md., presented data on two gp41-derived peptide candidates that demonstrated potent inhibition of HIV in vitro. Both peptides were developed to disrupt a phenomenon Mymetics discovered called molecular mimicry, which describes an inter-reaction between the virus and the host cell that contributes to disease progression.

SciClone Pharmaceuticals Inc., of San Mateo, Calif., reported that SCV-07, a compound designed to enhance the immune system, demonstrated the capability to significantly increase the rate at which treated tuberculosis patients become noncontagious. In Phase II trials, 80 percent of tuberculosis patients undergoing standard anti-TB chemotherapy were no longer contagious (as measured by sputum cultures) three months after receiving a five-day regimen of parenteral SCV-07. Additionally, all of the patients receiving SCV-07 reported an improvement in symptoms, including fever and cough, and there was a significant decrease in the number of patients with lung damage. Like SciClone's lead product, Zadaxin, SCV-07 promotes differentiation of T cells into the T-helper subset.

Serono SA, of Rockland, Mass., reported 24-week results from a completed clinical trial of Serostim [somatropin (rDNA origin) for injection] evaluating the treatment of an HIV-related metabolic complication. The results from the STARS trial at that point were consistent with 12-week results that showed a reduction in abnormal adipose tissue accumulation, as well as cardiovascular risk factors, such as a reduction in total and non-HDL cholesterol.

The Medivir Group, of Huddinge, Sweden, said its antiviral MIV-210 is active against HIV and hepatitis B virus. Medivir presented Phase I trial results that MIV-210 administered to healthy volunteers has oral bioavailability and achieves high blood plasma levels. Phase I clinical trials with repeat dosing will now be finalized and evaluated. When evaluated in woodchucks, MIV-210 reduced the amount of hepatitis virus in the blood to less than one ten-millionth of the pretreatment levels. It is also active against HIV, both in cell culture and in in vivo models.

Trimeris Inc., of Durham, N.C., and Hoffmann-La Roche Inc., of Nutley, N.J., reported new data from a Phase III pivotal study demonstrating that regardless of patient demographics or treatment history, Fuzeon, formerly known as T-20, in combination with other antiretrovirals provided benefit to treatment-experienced HIV patients at 24 weeks. The companies also presented data on the long-term tolerability of Fuzeon in Phase II trials, and Phase I/II results for T-1249, the second-generation fusion inhibitor. Trimeris and Roche said in mid-September that they submitted a new drug application for Fuzeon to the FDA. (See BioWorld Today, Sept. 18, 2002.)

Versicor Inc., of Fremont, Calif., said its compound, VRC-4887, was shown to be effective in preclinical studies against serious upper respiratory pathogens, including S. pneumonia, M. catarrhalis and H. influenzae, including drug-resistant strains. VRC-4887 belongs to a new antibiotic class for the community-based market - peptide deformylase inhibitors, and is being developed under Versicor's ongoing research collaboration with Novartis AG. PDF inhibitors target an enzyme that is essential to bacteria but not required in human cells.