Fast-Track proposals will be accepted Direct-to-Phase II proposals will be accepted Number of anticipated awards: 2-3 Budget (total costs): Phase I: $300,000 for up to one year; Phase II: $1,500,000 for up to 3 years Background Injectable benzathine penicillin (BPG) is currently the only CDC-recommended first line therapy for treatment of infection with Treponema pallidum (syphilis) in all populations, including pregnant persons and infants. There are several barriers that limit use of BPG: • BPG is not available orally. • Only a limited number of facilities in a single country currently manufacture the raw active pharmaceutical ingredient which means the supply chain can easily be disrupted and shortages of BPG are common in the US and globally. Page 119 • BPG may sometimes not be administered at lower-level facilities or by non-physician medical staff out of fear of anaphylactic reactions that might require referral to a tertiary care center. Alternative therapies to BPG that address some of these barriers are urgently needed, as acquired and congenital syphilis rates are increasing rapidly. WHO estimates over six million persons per year are infected with syphilis, and many more are treated presumptively for syphilis. Clinicians and health systems are eager for BPG alternatives. Recent advances in the ability to culture T. pallidum mean that identification of alternatives to BPG is now more feasible than has been possible in the past.