The California Institute for Medical Research (CIMR) and Riptide Bioscience, Inc. announce the publication of a research study demonstrating remarkable efficacy for Riptide’s drug candidate RP557 in recurrent vaginal fungal infections. The study, entitled “Designed Antimicrobial Peptides for Recurrent Vulvovaginal Candidiasis Treatment,” appears in the August 2019 issue of Antimicrobial Agents and Chemotherapy, a publication of the American Society for Microbiology (https://aac.asm.org).
Surveys show that about 75% of women develop vaginal candidiasis at some point in their lifetime, and recurrent vulvovaginal candidiasis (RVVC), characterized by four or more infections per year, afflicts an estimated 6% of all women every year.
“This is an indication with great unmet need,” explained Dr. David A. Stevens, President of CIMR in San Jose, Professor Emeritus at Stanford Medical School, and senior author of the study report. “There are no therapeutics currently approved for the treatment of RVVC. The over-the-counter and prescription topical drugs commonly used, such as miconazole, are ineffective against resistant fungi, which are a rapidly growing source of these infections. An oral drug, fluconazole, is sometimes prescribed, but two-thirds of patients still have their infections recur. Also, the FDA has noted a risk of oral fluconazole inducing birth defects in pregnancy. Since most RVVC patients are of childbearing potential, that’s a real concern.” Dr. Hasan Nazik of CIMR also collaborated in this study.
In a series of tests on common strains of resistant fungi, including C. albicans, C. krusei and C. tropicalis, Riptide’s drug candidates inhibited fungal growth at lower concentrations than fluconazole. In animal models, the lead candidate RP557 performed equally well to topical miconazole; oral fluconazole was shown to be completely ineffective. “Those are important results given that RP557 is much less susceptible to the development of bacterial resistance,” explained the study’s first author, Dr. Kathryn Woodburn, Vice President of Riptide. “Almost 60% of infections by the most common pathogen C. albicans are already miconazole-resistant, and that figure will likely continue to increase.”
“Another key advantage of this approach is its effectiveness against biofilm,” commented Dr. L. Edward Clemens, study co-author and Riptide Principal Scientist. “Pathogenic fungi, like many strains of bacteria, excrete a protective film which shields them from the effects of antibiotics. It’s been shown in this study that these drug candidates readily penetrate biofilm, and in fact also retard its formation.”
The drug candidates evaluated in the study are the culmination of several decades of rational design and iteration by Riptide co-author and Chief Science Officer Dr. Jesse Jaynes, of Tuskegee University, Alabama. Jaynes commented, “These drugs are engineered analogues of peptides synthesized by horseshoe crab, a “living fossil” that is among the most ancient animals still extant. These organisms have been fighting off infections for hundreds of millions of years and have gotten pretty good at it.”
The publication of this research study, in the major scholarly journal devoted to antimicrobials, was an international collaborative effort, involving not only Vallejo, Stanford and San Jose, California, and
Tuskegee, Alabama, but also researchers in electron microscopy, under Prof. Lydia Joubert, at Stellenbosch University in South Africa.
Woodburn concluded, “We’re extremely excited that RP557, in particular, has extraordinary efficacy with very low toxicity for host tissues, as demonstrated in the study, and should be a logical candidate to advance to clinical trials. In an indication with extreme need and few current therapeutic solutions, we think there is potential to make dramatic steps forward in clinical treatment.”