Transcription factor decoy candidates are designed to prevent expression of resistance genes.
U.K.-based antibacterials firm Procarta Biosystems received investments totaling £730,000 (about $1.2 miillion) from Morningside Venture Investments and its existing investors Rainbow Seed Fund and Iceni Seedcorn Fund. The financing round could be boosted up to a total of £1.25 million (about $2 million), Procarta notes.
The firm aims to use the funds to progress its lead anti-MRSA candidate and build a pipeline of transcription factor decoy (TFDs) drugs designed to target and prevent the development of antibiotic resistance.
Procarta is developing TFDs that control gene expression in pathogenic bacteria by interfering with the key DNA-protein interactions that determine gene activity. The candidates work by flooding the cells with an excess of copies of the transcription factor’s binding site. These decoys essentially compete with the protein’s natural genomic binding site and block expression of the resistance gene. The firm claims resistance is less likely to arise against TFDs as this would require the pathogen to acquire two complementary mutations simultaneously; i.e., changing the binding specificity of the transcription factor and altering the DNA-binding site to match.
When used in combination with antibiotics, the TFDs are expected to restore their clinical efficacy and protect the use of future antibiotics. The firm says it can identify TFD sequences irrespective of whether the resistance genes have been mapped, which will enable a range of resistance mechanisms to be targeted.
Procarta’s first product is a TFD in development for use in combination with vancomycin, to help combat resistance to both this antibiotic and other glycopeptide drugs. The firm is, in addition, developing a broad TFD pipeline, with a particular emphasis on drugs against gram-negative strains, including Pseudomonas aeruginosa. Procarta says it aims to partner its programs through strategic agreements with industry.