Colistin Sulfate

Bactericidal activity demonstrated in vitro and in vivo against broad range of Gram-negative bacteria, including multidrug-resistant strains Basilea Pharmaceutica Ltd, Allschwil (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today that it has entered into an asset purchase agreement with Spexis AG (SIX: SPEX) for a preclinical program of antibiotics from a novel class, targeting Gram-negative bacteria, including multidrug-resistant strains.1 Dr. Laurenz Kellenberger, Chief Scientific Officer of Basilea, said: “The acquired antibiotics are of a novel class, targeting the lipopolysaccharide transport in Gram-negative bacteria, which have been highlighted by the World Health Organization as priority pathogens against which new antibiotics are urgently needed. The convincing potent and rapid bactericidal activity against bacteria such as Escherichia coli or Klebsiella pneumoniae, including multidrug-resistant species, and the activity in infection models, is very encouraging. We are excited by the addition of this new program to our growing pipeline and to continue the development of this targeted antibiotics class, which has the potential to address an unmet medical need in the treatment of severe bacterial infections in the hospital.” The antibiotics were developed within Spexis’ Outer Membrane Protein Targeting Antibiotics (OMPTA) program and selectively disrupt the lipopolysaccharide transport bridge, an essential structure in Gram-negative bacteria. This results in a loss of the integrity of the outer cell membrane, intracellular accumulation of lipopolysaccharides and killing of the bacteria. Activity has been shown in vitro and in vivo against Enterobacteriaceae such as E. coli and K. pneumoniae, including strains resistant to beta-lactams and colistin, an antibiotic regarded as last-resort therapy. The program was funded in part by CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator).2 This underscores the potential of this novel class of antibiotics. CARB-X is a global non-profit partnership dedicated to supporting early-stage antibacterial research and development, to address the rising threat of drug-resistant bacteria. Basilea is acquiring all program compounds, know-how and intellectual property and is paying Spexis up to a total of CHF 2 million, which consists of an upfront payment, a payment related to the transfer of the assets to Basilea, and a potential final milestone payment related to the availability of near-term external funding for the further development of the program. In addition, Basilea assumes the rights and obligations of Spexis, including potential low single-digit percentage royalties on sales, under licensing agreements. The transaction is subject to the approval by the Western District Court of the Canton Basel-Landschaft. Infections by multidrug-resistant Gram-negative bacteria (GNB) are a major challenge for healthcare professionals. Due to an additional outer cell membrane compared to Gram-positive bacteria, it is more difficult for antibiotics to get into the cell. In addition, this outer membrane carries lipopolysaccharides/endotoxins which induce inflammation and play an important amplifying role in the pathogenesis of infections by GNB and are therefore considered an important virulence factor. Moreover, GNB can acquire resistance to several classes of antibiotics such as carbapenems, fluoroquinolones, tetracyclines and earlier-generation cephalosporins, making infections with GNBs particularly difficult to treat. In 2017, the World Health Organization published a list of 12 classes of priority bacterial pathogens that pose the greatest threat to human health, of which nine classes are Gram-negative.3 Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the needs of patients with severe bacterial and fungal infections. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of bacterial infections. In addition, we have preclinical and clinical anti-infective assets in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com. References M. Schuster, E. Brabet, K. K. Oi et al. Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug-resistant Enterobacteriaceae. Science Advances 2023 (9), eadg3683 Research reported in this press release is supported by CARB-X. CARB-X’s funding for this project is provided in part with federal funds from the US Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; under agreement number 75A50122C00028; and by awards from Wellcome (WT224842) and Germany’s Federal Ministry of Education and Research (BMBF). The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders. https://www-who-int.libproxy1.nus.edu.sg/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed (Accessed: January 14, 2024) The content above comes from the network. if any infringement, please contact us to modify.

Adam Zamecnik @a_zamecnik Credit: Kateryna Kon via Shutterstock. On 17 April, a US Food and Drug Administration (FDA) Advisory Committee (AdCom) has unanimously voted in favour of the potential approval of Entasis Therapeutics’ sulbactam-durlobactam for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex. Members of the FDA’s Antimicrobial Drugs AdCom voted 12-0 for the drug’s potential approval based on a positive benefit-risk assessment. The agency accepted the drug’s new drug application (NDA) for priority review in November 2022. The application’s PDUFA date was set to 29 May 2023. Entasis is a subsidiary of Innoviva . Also known as SUL-DUR, sulbactam-durlobactam is a targeted antibiotic that combines the β-lactamase inhibitors sulbactam and durlobactam. Acinetobacter is a major cause of hospital-acquired infections, said Dr. David Paterson, professor at National University of Singapore’s Saw Swee Hock School of Public Health, who presented at the meeting . There is no clear standard of care for these infections, said Paterson. The World Health Organization (WHO) designated carbapenem-resistant Acinetobacter baumannii as a priority pathogen for new antibiotic development in 2017. Carbapenems are a class of antibiotics. New treatment needed but postmarket surveillance is important There is a clear clinical need for an effective treatment against an extremely drug-resistant organism, said Dr. Michael Green, professor of paediatrics, surgery, and clinical and translational science at the University of Pittsburgh’s School of Medicine. Specifically, the committee voted on whether the overall benefit-risk assessment was favourable for the use of the drug in the patients prespecified in the NDA. The NDA submission features data from the Phase III ATTACK trial, which studied the treatment’s safety and efficacy in comparison to the antibiotic colistin, based on a November 2022 press release. Also called polymyxin E, colistin is used as a “last-resort” treatment for bacterial infections caused by susceptible Gram-negative bacteria. According to the trial’s results, sulbactam-durlobactam was reported to be statistically non-inferior against colistin in the primary endpoint of the 28-day all-cause mortality. The drug had a favourable safety profile, including a statistically significant reduction in nephrotoxicity, based on the press release. However, there are some concerns with the relatively small size of the studied population, which impacts the understanding of the drug’s safety profile, said Green. While the number of patients is small, this disease process is difficult to study, said panel member Dr. Richard Murphy, chief of infectious diseases at the Veterans Affairs White River Junction Medical Center. It is also unlikely that the efficacy would be lower than the antibiotic colistin, which is less safe, he added. Overall, sulbactam-durlobactam appears “friendlier” to the patient’s kidneys than colistin, noted Dr. George Siberry, medical officer at the Adult Clinical Branch of the Office of HIV/AIDS at the United States Agency for International Development’s Bureau of Global Health. According to Siberry, the high risk of death that comes with these infections was the reason for his positive vote. He adds that due to limited available data, there should be enhanced surveillance when it comes to the safety profile.