S-MGBs for Antibacterials

S-MGBs are bactericidal that act primarily on Gram-positive pathogens and work in synergy with existing antibiotics

The technology

As anti-bacterials, second-generation molecules have potency in vitro at least equivalent to first-generation (< 1 mg/mL), but with reduced toxicity and therefore improved therapeutic index. An earlier first-generation molecule was out-licensed in 2009 and is now 'Phase-3-ready' for the treatment of C diff.

S-MGBs are bactericidal and act primarily on Gram-positive pathogens, including the 'ESKAPE' S. aureus and E faecalis. 

Although current molecules are less effective on Gram-negatives, due to reduced accumulation, an ongoing development program will improve efficacy in Gram-negatives by enhanced accumulation. In vitro, S-MGBs work well in synergy with existing antibiotics (for example ceftazidime) to which many clinical pathogens are already resistant.

SMGBs bind to DNA but do not modify it and therefore are not mutagenic. Mechanism of Action studies are consistent with multiple binding sites on the pathogen’s DNA, which interferes with various key metabolic processes causing rapid cell death. Significantly, due to the multiplicity of binding sites, mutation to drug resistance has never been observed. This bodes well for the continued efficacy of S-MGBs when used in the clinic.

Please see the links below for more information: 

Background

Rostra Therapeutics is a spinout from the University of Strathclyde. It was incorporated in February 2022 to undertake clinical development of a family of small molecules, invented at Strathclyde using a platform technology, and known collectively as ‘Strathclyde Minor Groove Binders’ (S-MGBs). We've agreed to an exclusive license with Rostra to exploit second-generation S-MGBs as anti-infectives.