Disorders of the Urogenital Tract
Commensal bacteria, primarily certain Lactobacillus species present in the vaginal tract, play an important role in protecting from infection. Disruption of the Lactobacillus-dominated vaginal microbiota often leads to overgrowth of disease-causing microbes which are associated with Bacterial Vaginosis (BV), and an increased incidence of Urinary Tract Infection (UTI) and recurrent UTI (rUTI).
Epidemiological studies suggest that a healthy vaginal microbial ecosystem may play a critical role in reducing the risk of urogenital infections and dysbioses. Based on these observations, Osel has developed a proprietary Live Biotherapeutic Product (LBP), called LACTIN-V. LACTIN-V, Osel’s leading drug candidate, produces substances that protect and maintain a healthy microbiome. LACTIN-V also adheres to vaginal epithelial cells and antagonizes bacteria associated with BV and uropathogenic E. coli, which is responsible for most UTIs. In clinical studies, LACTIN-V has demonstrated the ability to reduce the number of recurrent UTIs in women by about half compared to a placebo.
Urinary Tract Infection
UTIs account for almost 11 million physician visits each year in the US, and an equal number in Europe. Up to 33% of women with UTIs develop recurrent infections (>2 per year). While a routine UTI is easily treated with a short course of oral antibiotics, treatment of recurrent UTI (rUTI) with multiple courses of antibiotics may lead to resistant strains, diarrhea, and vaginal yeast infections. There are currently no therapies available to prevent UTI recurrence other than prophylactic antibiotics. Thus, there is significant interest amongst women who suffer from rUTI for novel non-antibiotic therapies.
BV is a common condition in women that accounts for up to 25% of visits to gynecologic clinics in the U.S. and afflicts over 16 million women every year worldwide. BV is characterized as a disorder of the vaginal microbiome, i.e. normally dominant Lactobacillus species are depleted and replaced with largely anaerobic organisms that can cause an unpleasant “fishy” odor. BV is also a risk factor for pre-term labor, post-caesarean section infections, and HIV infection. BV is treated with oral or topical antibiotics, typically metronidazole, but up to 50% of women will experience one or more recurrent infections because antibiotics do not treat the underlying cause of the disorder, i.e. the disrupted vaginal microbiome. It is expected that LACTIN-V will treat and prevent recurrences of both UTI and BV. There are no therapies available to prevent BV recurrence.
Women worldwide continue to be infected with HIV at an alarming rate, and young women are disproportionately represented among those newly infected. The majority of HIV infections occur by the mucosal route during unprotected vaginal sexual intercourse. Several commensal Lactobacillus species generally dominate the vaginal microbiota of healthy women of childbearing age and are associated with vaginal health and a reduced risk of bacterial vaginosis (BV), human immunodeficiency virus (HIV), and other sexually transmitted infections (STIs), including herpes simplex virus-2 (HSV-2), and Neisseria gonorrhoeae (gonorrhea). These lactobacilli produce lactic acid that contributes to the maintenance of a low vaginal pH (4.0-4.5) and hydrogen peroxide that inhibits genital pathogens, including HIV. Osel has bioengineered vaginal lactobacilli to secrete potent HIV inhibitors. These bacteria can persist on the mucosal surfaces where HIV is transmitted and represent an ideal platform for the development of novel woman-controlled and coital-independent microbicides (see: MucoCept).
How is a woman's microbiome unique?
The microbiome of the vagina is unlike the microbiome of any other region of the human body. During reproductive years, the vaginal microbiota of most women is relatively simple with low diversity and mainly made up of species of Lactobacillus. The vaginal strains of Lactobacillus are adapted to the vaginal environment and different from those found elsewhere. These bacteria produce lactic acid, keeping vaginal pH low, and protect women against the proliferation of undesirable bacteria or pathogenic infections. During pregnancy, the levels of these beneficial bacteria can increase further to protect the fetus. Low levels of vaginal Lactobacillus, particularly hydrogen peroxide producing strains, are associated with recurrent urinary tract infections, bacterial vaginosis, and sexually transmitted infections.