Omnicin Therapeutics is an early-stage pharmaceutical company based in the Netherlands. The company is engaged in developing therapeutic solutions to overcome antimicrobial resistance, mainly in resistant Gram-negative pathogens. Omnicin is developing OTX003, a dry-powder inhalation formulation of low-dose colloidal bismuth subcitrate that potentiates existing antibiotics to effectively treat lung infections caused by resistant P. aeruginosa.
Pseudomonas aeruginosa is a Gram-negative bacterium, listed in the World Health Organization's Top 3, responsible for severe acute and chronic lung infections affecting large patient populations worldwide, with high mortality. Although Pseudomonas aeruginosa may cause severe infections in other organs and tissues, Omnicin Therapeutics is primarily focusing on pulmonary infections, spanning a huge group of patients.
Year after year, it is becoming more difficult to treat these lung infections successfully, due to:
To solve the hard-to-treat P. aeruginosa pulmonary infections problem, Omnicin is developing OTX003, a dry-powder inhalation formulation of low-dose colloidal bismuth subcitrate that potentiates existing antibiotics to effectively treat lung infections caused by resistant P. aeruginosa.
High-dose colloidal bismuth subcitrate is already known for its oral use in Helicobacter pylori gastric infections. It is widely used and has shown to be safe. Omnicin has IP on a low-dose inhalation formulation in a specific inhalation device for the treatment of P. aeruginosa in lung infections.
Inhaled OTX003, when given in combination with an existing antibiotic, effectively eradicates multi-resistant P. aeruginosa. In addition, OTX003 prevents resistance development and prevents the formation of harsh biofilms, whereas the antibiotic alone, or OTX003 alone, has very limited or no effect.
Since colloidal bismuth subcitrate is a repurposed drug with an excellent safety profile after oral use, and GMP material is available at low prices, the non-clinical and clinical development of OTX003 is greatly simplified compared to a new chemical entity, which is reflected in lower cost, shorter lead times and an overall lower development risk.
OTX003 has superior efficacy in resistant strains of P. aeruginosa. Mice that were infected with resistant strains of P. aeruginosa and treated with OTX003 combined with a relevant antibiotic, largely survived, whereas mice treated with the antibiotic alone or with bismuth alone had a poor prognosis to survive. OTX003 overcomes the development of resistance of susceptible strains while counteracting the evolution of antibiotic resistance. For the antibiotic alone, the MIC is doubled already after 1 day, whereas in the presence of OTX003, the MIC is doubled only after 17 days. OTX003 overcomes harsh biofilm formation in the affected lung. At sub-MIC concentrations of antibiotics, addition of OTX003 leads to dramatic killing efficacy of biofilm-associated bacteria
Colloidal bismuth subcitrate is a registered drug for combination therapy of Helicobacter pylori in stomach infections. The registered and allowed dose for oral use is up to 480 mg per day. OTX003 for inhalation has a much lower calculated daily dose and therefore the systemic exposure is also much lower. It was demonstrated that high-dose OTX003 exposed to the lungs is well tolerated. High doses of OTX003 had no significant effects on viability of human lung endothelial cells, to the lungs in life animals and did not show changes in lung histopathology.
