PROJECT SUMMARY / ABSTRACT The CDC has identified Neisseria gonorrhoeae as a pathogen of the highest threat level (“Urgent Threat”) to the US public health. Currently there is only a single recommended agent remaining on the CDC treatment guidelines, an intramuscular injection of the extended spectrum cephalosporin, ceftriaxone. However, in the past decade, reports of resistance to ceftriaxone have appeared across the globe. If one of these strains were to disseminate widely, we would be facing an era of untreatable gonorrhea. Untreated infections can cause serious and life-threatening sequelae. Thus, developing new antibiotics without cross-resistance to the current therapeutics 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 can have devastating long-term effects on reproductive health and fertility if not treated. Ceftriaxone is not active against C. trachomatis and the clinical signs and symptoms of gonorrhea and chlamydia are indistinguishable from one another. Therefore, unless chlamydia can be excluded by a laboratory diagnosis, empiric treatment for gonorrhea typically involves administration of two different classes of antibiotics in order to cover both pathogens. A single oral antibiotic effective against both infections would change the current treatment paradigm, improving adherence to treatment as well as reducing the impact that dual antibiotic therapy can have on promoting resistance in co-infecting pathogens and commensal organisms. Furthermore, as an oral antibiotic, it would provide a much-needed treatment option to patients and physicians and allow for expedited partner therapy. AimMax Therapeutics has discovered a novel antibiotic with activity against N. gonorrhoeae that 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 to existing classes. The overall goal of this proposed FastTrack SBIR application is to develop a novel oral antibiotic 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 will confirm the suitability of this new class of antibiotic for the treatment of gonorrhea and chlamydia, identify a formulation that delivers optimal oral bioavailability and plasma exposure to provide effective treatment, and advance development towards filing of an IND. Rising antibiotic resistance combined with ease of transmission, risks for outbreaks, and lack of second-line treatment options, all point to the critical need to identify new antibiotics for the treatment of gonorrhea and expeditiously advance their development to the clinic.