The ULT1, ULT2 and ULT3-programmes
ULT1, ULT2 and ULT3 are Ultupharma’s current antibiotics programmes. Antibiotics in these programmes have activity against a wide range of bacterial pathogens in the WHO and CDC priority lists (Table 1 and 2), including carbapenem resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae. ULT3 peptides have also activity against colistin resistant Escherichia coli, A. baumannii and Klebsiella pneumoniae.
The ULT1-programme is based on new antibacterial compounds discovered in cultures of Gram-negative soil bacteria, which have shown potent effect against Staphylococcus aureus strains MRSA, MRSE, MSSE, MSSA and VRE and strains resistant to mupirocin, vancomycin, etc. (Bjerketorp et al, J. Nat. Prod., 2017, 80, 2997-3002; Swedish patent granted October 3, 2017). Several active analogues have been synthesized and more are planned.
A deep knowledge in nucleoside chemistry and biochemistry has resulted in the ULT2-programme (Swedish patent granted October 11, 2018) containing several treatments active against a large number of multi-resistant Gram-negative and Gram-positive bacteria such as S. aureus, S. epidermis, Streptococcus pneumoniae, Micrococcus luteus, Bacillus anthracis, A. baumannii, E. coli, K. pneumoniae, K. oxytoca, Enterobacter cloacae, E. aerogenes, Serratia marcescens, P. aeruginosa, Proteus mirabilis, Salmonella typhimurium, Shigella sonnei, S. flexneri, Helicobacter pylori, Yersinia pestis and Haemophilus influenza. ULT2 treatments have given potent antibacterial effects in mice with peritonitis/sepsis and urinary tract E. coli infections, with no toxicity and at doses likely to be safe in humans. Further development is ongoing with the aim to reach clinical studies, targeting both Gram-negative and Gram-positive bacterial infections not responding to treatment with present antibiotics on the market.
The ongoing analysis of metabolites from microorganisms is efficiently resulting in a rapidly growing number of new compounds with promising antibiotic properties. New ways to induce production of antibacterial metabolites in microorganisms have also been developed. One result from these developments is the ULT3-programme (Swedish patent application filed August 28, 2018), which is a series of bacterial peptides with potent activity against Gram-negative bacteria, including carbapenem-resistant E. coli, A. baumannii and P. aeruginosa, and colistin resistant E. coli, A. baumannii and K. pneumoniae, along with acceptable toxicity and haemolysis properties.
"+" indicates potent activity, whereas blank indicates poor/no activity or not thoroughly tested.