Chemokine-based microbicides: a pathway from a first-in-human study towards Phase 2/3 and licensure.

The chemokine analogue 5P12-RANTES is a candidate topical anti-HIV protection agent ('microbicide'). It promises to empower women and girls in developing countries to protect themselves by applying it intravaginally and intrarectally, the latter indication also being of interest to men. It is: i. among the most potent anti-HIV substances known, active against most subtypes worldwide; ii. highly effective at preventing infection of female macaques; iii. very stable (temperature, low pH, vagina l enzymes, seminal fluid); iv. readily produced in good yield and purity by a highly scalable fermentation and purification process, promising ultra-low cost, bulk production for and in the developing world; v. less likely to enter the body systemically after topical application than small-molecule antivirals, reducing the chances of complications; vi. proven to present a considerably higher barrier to the generation of resistant strains of the virus than small-molecule inhibitors, e.g. tenof ovir and maraviroc; vii. without detectable cell signaling activity in vitro or inflammatory response in tissue explants, an important safety criterion. 5P12-RANTES is nearing its first Phase 1 trial (vaginal). The proposed work will: allow a potential major backer to trial rectally; permit development of long-acting formulations; further reduce production costs for both indications. The expected results should attract other major stakeholders en route to licensure.