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.

Pictured: Blue and white Pfizer sign on building/c cbies - stock.adobe.com The company’s aztreonam-avibactam matched the cure rate of a meropenem-based regimen in patients with drug-resistant infections. Pictured: Blue and white Pfizer sign on building/cbies/Adobe Stock Data from the Phase III REVISIT and ASSEMBLE studies showed that Pfizer ’s investigational antibiotic combination aztreonam-avibactam could safely cure infections caused by Gram-negative bacteria , the company announced Thursday. Pfizer and AbbVie are jointly developing aztreonam-avibactam (ATM-AVI), which is supported by public-private partnerships between Pfizer and the Biomedical Advanced Research and Development Authority. Pfizer holds global commercial rights to ATM-AVI, while AbbVie owns these rights in the U.S. and Canada. These findings from REVISIT and ASSEMBLE position ATM-AVI as an “important treatment option for patients with life-threatening bacterial infections that are resistant to almost all currently available antibiotics,” James Rusnak, senior vice president and chief development officer, Internal Medicine, Anti-Infectives and Hospital, Pfizer, said in a statement. Enrolling from regions with suspected multi-drug resistant pathogens and with endemic or emerging carbapenem resistance, REVISIT enrolled 422 adults hospitalized for complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). ATM-AVI was administered with or without metronidazole. The ATM-AVI regimen had a cure rate of 76.4% for cIAI patients compared to 74.0% in those treated with meropenem with or without colistin. For HAP and VAP, the ATM-AVI and meropenem regimens had corresponding cure rates of 45.9% and 41.7%, respectively. ATM-AVI showed better cure rates in both cases, but its treatment effect did not reach statistical significance. Regarding safety, REVISIT found ATM-AVI to be well tolerated, and serious adverse events were balanced between the treatment and control groups. Its side effects were consistent with what had previously been established for aztreonam alone. No serious toxicities were attributed to the study treatment. ASSEMBLE further confirmed these findings, which enrolled patients hospitalized for metallo-β-lactamases-producing Gram-negative bacteria. The ATM-AVI regimen cured 41.7% of treated patients, while none of those on the best available therapy were cured. With data from REVISIT and ASSEMBLE, Pfizer will make a regulatory filing with the FDA in the second half of 2023. The company will also submit complete findings and analyses of these studies for scientific publication. Biopharma Stands Against AMR Antimicrobial resistance (AMR) is among the world’s most pressing global health threats , according to the World Health Organization. While resistance is a natural phenomenon, the misuse and overuse of these drugs have accelerated this process, rendering more and more antibiotics ineffective. At the World Vaccine Congress last April 2023, industry leaders pointed to vaccination as a potential solution to the AMR problem. “Vaccines can prevent or reduce life-threatening diseases and decrease health care costs,” AMR specialist Francesca Micoli, director of Innovation Academy for Global Health, GSK, told BioSpace after a panel at the World Vaccine Congress. Immunization can also ease residual health consequences following an infection. Beyond vaccines, Micoli said that the fight against AMR should include a holistic strategy, including new interventions to target multi-drug resistant pathogens. In July 2022, three European companies banded together with the same goal. Boehringer Ingelheim, Evotec SE and bioMérieux created a new company, Aurobac Therapeutics SAS, to advance the next generation of antimicrobial agents and create diagnostic products for more appropriate medication. With the backing of these three companies, Aurobac launched with around $40.7 million to develop a precision approach against AMR. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com .