The Ultupharma programmes
Ultupharma’s current antibiotics programmes now has focus on ULT2 and ULT3. Antibiotics in these programmes have activity against a wide range of bacterial pathogens in the WHO and CDC priority lists (Table 1, click table to enlarge).
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ULT2
Experience from developing antiviral drugs has given a deep knowledge in nucleotide chemistry and biochemistry and animal models is the basis for the ULT2 programme. ULT2A, B, C and D are active against a large number of multi-resistant Gram-negative and Gram-positive bacteria such as 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, Haemophilus influenza, S. aureus, S. epidermis, Streptococcus pneumoniae, Micrococcus luteus, and Bacillus anthracis (Table 2, click table to enlarge).
ULT2A treatments give potent antibacterial effects in mice with peritonitis/sepsis and urinary tract E. coli infections, with no toxicity and at doses expected to be safe in humans. The therapeutic effects of ULT2 combinations are expected to be more than ten time more potent in humans than in mice as mice have exceptionally high thymidine concentrations counteracting the effect of ULT2 combinations. Humans have very low thymidine levels in blood and urine. ULT2A and ULT2C are likely to inhibit H. pylori at concentrations safe for humans offering promising use as cancer prophylaxis and to reduce development of Alzheimer's and Parkinson. Further possibilities for ULT2A and ULT2C are topical use against several skin infections. This has the advantage of obtaining inhibitory concentrations at the site of infection without effect on the normal bacterial flora at other sites. ULT2C has very potent effect against S. aureus resistant to many antibiotics such as methicillin and mupirosin and resistance to these antibiotics is increasing and a serious problem for patients with diabetic foot infections. ULT2A might also have effect on leishmaniasis as the protozoan causing this disease is inhibited by AZT, which is a component of ULT2A, and the bacteria underlying disease severity are inhibited by ULT2A. The first paper describing ULT2 combinations was recently published in Journal of Antimicrobial Chemotherapy.
Patents have been granted in Sweden (SE540411), the USA (US10828316 and US10828317), Japan (JP6895435), Europe (EP/NL/IE/GB/FR/DE/CH/BE3407898), Hong Kong (HK40000701), China (ZL201780004884.X), Australia (AU2017212224), and Canada (CA3007831).
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ULT3
New ways to isolate bacteria producing novel antibiotic compounds have been developed by Ultupharma in collaboration with the research group at SLU, as described in the recent key-publication in Frontiers in Microbiology: Selective isolation of multidrug-resistant Pedobacter spp., producers of novel antibacterial peptides. A result from this is the ULT3-programme, which has 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. These antibiotic peptides are described in a recent publication in ACS Chemical Biology: Isopedopeptins A–H: Cationic Cyclic Lipodepsipeptides from Pedobacter cryoconitis UP508 Targeting WHO Top-Priority Carbapenem-Resistant Bacteria. ULT3 (isopedopeptin B) at sub MIC concentrations can reactivate old antibiotics with resisance problems, indlucing resistance to colistin. A local application of ULT3 in combination with systemic use of old antibiotics offers an interesting possibility to use in surgery.
Patents have been granted in Sweden (SE543054), the USA (US11981759), China (ZL201980056367.6), Japan (JP7492503), Australia (AU2019329130), South Korea (10-2021-7007592), Canada (CA3110143), Europe (PCT/SE2019/050789) and Hong Kong (HK62021035624.7).
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