The CDC has identified Neisseria gonorrhoeae as a pathogen of the highest threat level ("Urgent Threat") tothe US public health. Currently there is only a single recommended agent remaining on the CDC treatmentguidelines, an intramuscular injection of the extended spectrum cephalosporin, ceftriaxone. However, in thepast decade, reports of resistance to ceftriaxone have appeared across the globe. If one of these strains wereto disseminate widely, we would be facing an era of untreatable gonorrhea. Untreated infections can causeserious and life-threatening sequelae. Thus, developing new antibiotics without cross-resistance to the currenttherapeutics is of critical importance to public health. Between 20 and 40% of individuals infected with N.gonorrhoeae are co-infected with Chlamydia trachomatis, a predominantly asymptomatic infection that canhave devastating long-term effects on reproductive health and fertility if not treated. Ceftriaxone is not activeagainst C. trachomatis and the clinical signs and symptoms of gonorrhea and chlamydia are indistinguishablefrom one another. Therefore, unless chlamydia can be excluded by a laboratory diagnosis, empiric treatmentfor gonorrhea typically involves administration of two different classes of antibiotics in order to cover bothpathogens. A single oral antibiotic effective against both infections would change the current treatmentparadigm, improving adherence to treatment as well as reducing the impact that dual antibiotic therapy canhave on promoting resistance in co-infecting pathogens and commensal organisms. Furthermore, as an oralantibiotic, it would provide a much-needed treatment option to patients and physicians and allow for expeditedpartner therapy. AimMax Therapeutics has discovered a novel antibiotic with activity against N. gonorrhoeaethat is comparable to ceftriaxone. It has demonstrated potent activity against multidrug- and pan-resistant N.gonorrhoeae isolates, including isolates resistant to ceftriaxone, with no evidence of cross-resistance toexisting classes. The overall goal of this proposed FastTrack SBIR application is to develop a novel oralantibiotic for the treatment of gonorrhea as the top priority, and if suitable, for the treatment of chlamydia also,the two most common bacterial sexually transmitted infections in the US. The studies proposed herein willconfirm the suitability of this new class of antibiotic for the treatment of gonorrhea and chlamydia, identify aformulation that delivers optimal oral bioavailability and plasma exposure to provide effective treatment, andadvance development towards filing of an IND. Rising antibiotic resistance combined with ease oftransmission, risks for outbreaks, and lack of second-line treatment options, all point to the critical need toidentify new antibiotics for the treatment of gonorrhea and expeditiously advance their development to theclinic.
Public Health Relevance Statement: PROJECT NARRATIVE
The emergence of multidrug resistant Neisseria gonorrhoeae, including strains resistant to the injectable
antibiotic ceftriaxone, the only remaining treatment recommended by the CDC, represents a serious and
urgent threat to US public health. With more than 600,000 new cases of gonorrhea in the US each year, the
spread of an untreatable strain would have devastating consequences, highlighting the need for prompt action
to identify and develop new classes of antibiotics to treat this disease. We aim to develop a novel oral antibiotic
for the treatment of drug-resistant N. gonorrhoeae to address the urgent threat of untreatable gonorrhea.
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