A prospective, open, randomized controlled clinical study of colistimethate sodium aerosol inhalation in the treatment of hospital-acquired pneumonia infected with carbapenem-resistant Acinetobacter baumannii

Start Date15 Oct 2024

Sponsor / Collaborator-

NCT06488794 / Not yet recruitingPhase 2/3IIT

Inhaled Colistin to Prevent Pediatric Ventilator-associated Pneumonia: A Double Blind Multicenter Randomized Controlled Trial Protocol

The goal of this clinical trial is to learn if nebulized colistin can prevent pneumonia in ventilated children. The main question it aims to answer is:
• Does nebulized colistin lower the number of times participants develop ventilation associated pneumonia? Researchers will compare nebulized colistin to a placebo (a look-alike substance that contains no drug) to see if nebulized colistin works to prevent ventilation associated pneumonia in children.
Participants will:
* Take nebulized Colistin or a placebo twice a day for 3 days.
* Will be followed to check for pneumonia occurrence while they are on mechanical ventilation.

Start Date01 Oct 2024

Sponsor / Collaborator

University Hospital Fattouma Bourguiba

ChiCTR2400083557 / RecruitingNot ApplicableIIT

Effectiveness and Safety of Intravenous and Nebulized Colistin Methanesulfonate in the Treatment of Carbapenem-Resistant Gram-Negative Bacterial Pulmonary Infections: A Multicenter, Retrospective Study

Start Date30 Apr 2024

Sponsor / Collaborator

Peking University People's Hospital

100 Clinical Results associated with Colistimethate Sodium

100 Translational Medicine associated with Colistimethate Sodium

100 Patents (Medical) associated with Colistimethate Sodium

1,252

Literatures (Medical) associated with Colistimethate Sodium

01 Dec 2024·Applied microbiology and biotechnology

Sensing chemical-induced DNA damage using CRISPR/Cas9-mediated gene-deletion yeast-reporter strains

Article

Author: Eki, Toshihiko ; Hirose, Yuu ; Matsunobu, Shogo ; Yamamoto, Kosuke ; Miura, Yuuki ; Tochikawa, Shintaro

Abstract:

Microorganism-based genotoxicity assessments are vital for evaluating potential chemical-induced DNA damage. In this study, we developed both chromosomally integrated and single-copy plasmid–based reporter assays in budding yeast using a RNR3 promoter–driven luciferase gene. These assays were designed to compare the response to genotoxic chemicals with a pre-established multicopy plasmid–based assay. Despite exhibiting the lowest luciferase activity, the chromosomally integrated reporter assay showed the highest fold induction (i.e., the ratio of luciferase activity in the presence and absence of the chemical) compared with the established plasmid-based assay. Using CRISPR/Cas9 technology, we generated mutants with single- or double-gene deletions, affecting major DNA repair pathways or cell permeability. This enabled us to evaluate reporter gene responses to genotoxicants in a single-copy plasmid–based assay. Elevated background activities were observed in several mutants, such as mag1Δ cells, even without exposure to chemicals. However, substantial luciferase induction was detected in single-deletion mutants following exposure to specific chemicals, including mag1Δ, mms2Δ, and rad59Δ cells treated with methyl methanesulfonate; rad59Δ cells exposed to camptothecin; and mms2Δ and rad10Δ cells treated with mitomycin C (MMC) and cisplatin (CDDP). Notably, mms2Δ/rad10Δ cells treated with MMC or CDDP exhibited significantly enhanced luciferase induction compared with the parent single-deletion mutants, suggesting that postreplication and for nucleotide excision repair processes predominantly contribute to repairing DNA crosslinks. Overall, our findings demonstrate the utility of yeast-based reporter assays employing strains with multiple-deletion mutations in DNA repair genes. These assays serve as valuable tools for investigating DNA repair mechanisms and assessing chemical-induced DNA damage.

Key points:

• Responses to genotoxic chemicals were investigated in three types of reporter yeast.• Yeast strains with single- and double-deletions of DNA repair genes were tested.• Two DNA repair pathways predominantly contributed to DNA crosslink repair in yeast.

01 Dec 2024·APPLIED RADIATION AND ISOTOPES

Radiolabeling and preclinical evaluation of technetium-99m labeled colistin

Article

Author: Shanbhag#, Nagesh C ; Chaudhari, Pradip ; Sasidharan, Gopalakrishnan M ; Shanbhag, Nagesh ; Thakur, Riptee ; Gopalakrishnan, M.S. ; Mohanty, Bhabani ; Kumar, Pardeep ; Shanbhag, Nagesh C

INTRODUCTION:

Antibiotic resistance is a burden on the healthcare system. In present study, we have labeled an antibiotic named Colistimethate sodium (CMS) with technetium-99m (^99mTc) to develop a SPECT based imaging tracer.

METHODS:

We standardised the labeling using 0.5-2 mg of CMS (in water) using stannous chloride dihydrate as a reducing agent followed by addition of 370 ± 74 MBq of ^99mTc. A group of mice were injected intravenously (in tail vein) with 4-6 MBq of [^99mTc]Tc-CMS diluted with saline and euthanized at various time intervals. microSPECT Imaging (ϒ-eye) was acquired to study the biodistribution in the healthy mice.

RESULTS:

We standardised the labeling using 0.5 mg of colistin in 0.5 ml of saline with addition of 30 μg stannous chloride dihydrate. The retention factor value was 0.1-0.3 as compared to 0.9-1.0 for free ^99mTc by TLC and retention time was found to be 14.2 ± 1.3 min as evaluated by HPLC. The biodistribution data showed uptake in lungs, spleen, and liver at 30 min but the uptake decreased in lung at 60 min. The imaging data corroborated with the biodistribution data.

CONCLUSIONS:

We could successfully label [^99mTc]Tc-CMS ^99mTc and we could study its biodistribution in healthy mice.

01 Nov 2024·ANALYTICA CHIMICA ACTA

Ultrasensitive mass spectrometric quantitation of apurinic/apyrimidinic sites in genomic DNA of mammalian cell lines exposed to genotoxic reagents

Article

Author: Liu, Ying ; Xue, Chen-Yu ; Liu, Ya-Hong ; Zhang, Xin-Xiang ; Yu, Yue ; Zhou, Ying-Lin

The apurinic/apyrimidinic (AP) site is an important intermediate in the DNA base excision repair (BER) pathway, having the potential of being a biomarker for DNA damage. AP sites could lead to the stalling of polymerases, the misincorporation of bases and DNA strand breaks, which might affect physiological function of cells. However, the abundance of AP sites in genomic DNA is very low (less than 2 AP sites/10⁶ nts), which requires a sensitive and accurate method to meet its detection requirements. Here, we described an ultrasensitive quantification method based on a hydrazine-s-triazine reagent (i-Pr₂N) labeling for AP sites combining with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The limit of detection reached an ultralow level (40 amol), realizing the most sensitive MS-based quantification for the AP site. To guarantee the accuracy of the quantitative results, the labeling reaction was carried out directly on DNA strands instead of labeling after DNA enzymatic digestion to reduce artifacts that might be produced during the enzymatic process of DNA strands. And selective detection was realized by MS to avoid introducing the false-positive signals from other aldehyde species, which could also react with i-Pr₂N. Genomic DNA samples from different mammalian cell lines were successfully analyzed using this method. There were 0.4-0.8 AP sites per 10⁶ nucleotides, and the values would increase 16.1 and 2.75 times when cells were treated with genotoxic substances methyl methanesulfonate and 5-fluorouracil, respectively. This method has good potential in the analysis of a small number of cell samples and clinical samples, is expected to be useful for evaluating the damage level of DNA bases, the genotoxicity of compounds and the drug resistance of cancer cells, and provides a new tool for cell function research and clinical precise treatment.

News (Medical) associated with Colistimethate Sodium

12 Sep 2024

·www.prnewswire.com

Zambon Announces Publication of Phase 3 PROMIS I and II Study Results in The Lancet Respiratory Medicine Showing Efficacy Results of CMS I-neb in Patients with Non-Cystic Fibrosis Bronchiectasis Colonized with P. aeruginosa

Inhalation of colistimethate sodium via the I-neb® Adaptive Aerosol Delivery System (CMS I-neb) significantly reduced pulmonary exacerbations and improved quality of life in non-cystic fibrosis bronchiectasis (NCFB) patients colonized with P. aeruginosa Both trials showed that CMS I-neb was generally well tolerated, with no major safety concerns, and bronchospasm occurred in fewer than 5% of patients Zambon is continuing to work with regulatory authorities with the goal of making colistimethate sodium delivered via a customized inhalation device available to patients with bronchiectasis and P. aeruginosa chronic infection MILAN and MORRISTOWN, N.J., Sept. 12, 2024 /PRNewswire/ -- Zambon, a multinational pharmaceutical company focused on innovating cure and care to improve people's health and the quality of patients' lives, today announced the online publication of its Phase 3 PROMIS-I and PROMIS-II studies in The Lancet Respiratory Medicine journal. The PROMIS studies assessed the efficacy and safety of inhaled colistimethate sodium administered via the I-neb® Adaptive Aerosol Delivery System ("CMS I-neb") as a treatment to reduce the frequency of pulmonary exacerbations in patients with Non-Cystic Fibrosis Bronchiectasis (NCFB) chronically colonized with P. aeruginosa over 12 months, compared to placebo. "The publication of these pivotal data in The Lancet Respiratory Medicine represents an important milestone in our commitment to developing innovative therapies for patients with severe respiratory diseases," said Paola Castellani, Chief Medical Officer and R&D Head at Zambon. "For patients with NCFB, a condition with no approved treatment options, the results from the PROMIS program highlight the potential of CMS I-neb to improve outcomes and quality of life. We look forward to working with regulatory authorities on a path to making this important treatment available to patients as quickly as possible." Chronic infection with P. aeruginosa is associated with more severe disease, accelerated lung function decline, increased exacerbations, hospitalizations and a higher mortality rate.i The PROMIS trials represent the first large-scale, double-blind, placebo-controlled studies of inhaled colistimethate sodium, a widely used antibiotic in Europe for NCFB. The published study results are based upon the two global Phase 3, multicenter, randomized, double-blind, placebo-controlled PROMIS-I and PROMIS-II trials in adult patients with bronchiectasis chronically colonized with P. aeruginosa with a history of at least two exacerbations requiring oral antibiotics or one requiring intravenous antibiotics in the previous year. Patients were randomized (377 in PROMIS-I and 287 in PROMIS-II) to receive inhaled colistimethate sodium or placebo via the I-neb device twice daily for up to 12 months. The primary efficacy endpoint was the annual pulmonary exacerbation rate. Key secondary efficacy endpoints were time to first exacerbation, quality of life, change in P. aeruginosa density, severe exacerbation rate, and time to first severe exacerbation. Key Findings from PROMIS-I and PROMIS-II: In the PROMIS-I trial, the primary endpoint of a significant reduction in annual pulmonary exacerbation rate was achieved, with a 39% reduction in exacerbations (rate ratio 0.61; 95% CI 0.46–0.82; p=0.0010) compared with placebo. Severe exacerbations were reduced by 59%, and patients treated with CMS I-neb experienced a clinically importantii improvement in quality of life, as measured by the St. George's Respiratory Questionnaire, and a reduction of P. aeruginosa density. The PROMIS-II study had to be stopped prematurely due to the COVID-19 pandemic and the results were not satisfactory. However, when a sub analysis of the PROMIS-II pre-pandemic period was done, the results were consistent with those obtained in the PROMIS-I trial. Both trials reported good tolerability, with no major safety issues identified. Bronchospasm was rare, occurring in less than 5% of patients. "The results of the PROMIS program represent an important breakthrough for patients with NCFB, a population that has long suffered from chronic respiratory infections without any approved treatments. For the first time, we have robust evidence showing that CMS I-neb can significantly reduce exacerbations and improve quality of life in patients with NCFB and chronic P. aeruginosa infection, offering hope where there were previously limited options," said Dr. Charles Haworth, Respiratory Physician at the Cambridge Centre for Lung Infection at Royal Papworth Hospital, and PROMIS trials Chief Investigator. "These findings underscore the importance of inhaled antibiotics, such as CMS I-neb, in reducing exacerbations and improving outcomes in patients with NCFB chronically infected with P. aeruginosa. Chronic bronchial infection plays a key role in driving inflammation and airway damage in bronchiectasis, and reducing exacerbations has been linked to better prognosis, quality of life and lung function," said Professor James Chalmers, Professor of Respiratory Research at the University of Dundee and PROMIS Investigator. The PROMIS clinical program has received FDA Qualified Infectious Disease Product (QIDP), Fast Track and Breakthrough designations for the reduction in the incidence of pulmonary exacerbations in adult NCFB patients colonized with P. aeruginosa. About the PROMIS Development Program The PROMIS-I and PROMIS-II are multicenter, randomized, double-blind, placebo-controlled trials investigating the efficacy and safety of inhaled colistimethate sodium administered via the I neb® Adaptive Aerosol Delivery System (CMS I-neb®) in adults with non-cystic fibrosis bronchiectasis chronically infected with P. aeruginosa. The primary objective of both trials was to investigate the annual rate of pulmonary exacerbations in patients receiving CMS I-neb® administered twice daily versus placebo. Secondary endpoints included the time to first pulmonary exacerbation, the annual rate of severe pulmonary exacerbations, the time to first severe pulmonary exacerbation, quality of life measured by the St. George's Respiratory Questionnaire and the Quality of Life Questionnaire-Bronchiectasis (QOL-B), the number of exacerbation-free days, P. aeruginosa density and susceptibility, any developing resistance, and overall safety and tolerability. The PROMIS-I trial enrolled 377 patients in 12 countries, including Australia, Belgium, Germany, Greece, Israel, Italy, Netherlands, New Zealand, Portugal, Spain, Switzerland, and the United Kingdom. The PROMIS-II trial enrolled 287 patients in 12 countries, including Argentina, Australia, Canada, Germany, Greece, Israel, Italy, New Zealand, Poland, Portugal, France, and the United States. About NCFB Non-cystic fibrosis bronchiectasis (NCFB) is a chronic lung disease characterized by recurrent infection, inflammation, persistent cough, and production of sputum, and its prevalence is increasing worldwide. NCFB has a progressive course primarily determined by the rate of exacerbations, many of which are related to Pseudomonas aeruginosa. Consequently, research efforts directed to treat infection by P. aeruginosa and its associated acute exacerbations remain a clinical priority.iii The objectives of treatment in bronchiectasis are to prevent exacerbations, reduce symptoms, improve quality of life, and stop disease progression. Cough and sputum production, along with breathlessness, are the most frequent symptoms, but rhinosinusitis, fatigue, hemoptysis, and thoracic pain are also common. Over the last decade, the prevalence of NCFB has increased by 40% and is now estimated to be up to 566 per 100,000 people, making it the third most common chronic airways disease.iv The incidence of NCFB appears to be rising too, particularly in women and older individuals. About Colistimethate sodium (CMS) Colistimethate sodium (CMS) is a pro-drug (the form used for inhalation therapy) of the antibiotic colistin. Colistin is a polymyxin antibiotic derived from Bacillus polymyxa var. colistinus. Polymyxin antibiotics are surface active agents that act by binding to and changing the permeability of the bacterial cell membrane, causing bacterial cell death. Colistin is an active agent against aerobic Gram-negative pathogens that can cause life-threatening infections, such as P. aeruginosa. Colistin remains one of the few active antimicrobial agents against multi-drug-resistant Gram-negative bacteria. It is currently considered one of the last therapeutic options for infections such as carbapenem-resistant P. aeruginosa. About Zambon SpA Zambon SpA is a multinational pharmaceutical company established in 1906 in Vicenza, whose history is founded on the values of an Italian family committed to innovating cure & care to improve patients' lives. It employs more than 2,500 people worldwide, is present in 23 countries in Europe, America and Asia, and has production facilities in Italy, Switzerland, China and Brazil. Thanks to its innovative, quality products commercialized in 87 countries, Zambon Spa reported a revenue of 843 million euros in 2023. Alongside the three historical therapeutic areas - diseases of the respiratory system, urinary tract infections and pain treatment – Zambon is focused on developing treatments for neurodegenerative diseases such as Parkinson's or rare diseases such as cystic fibrosis, BOS, to which is linked the major 2019 acquisition of Breath Therapeutics, and NCFB. For further information on Zambon please visit . For more information, please contact: [email protected] Elixir Health Public Relations Lindsay Rocco +1 862-596-1304 [email protected] i Finch S, McDonnell MJ, Abo-Leyah H, Aliberti S, Chalmers JD. A Comprehensive Analysis of the Impact of Pseudomonas aeruginosa Colonization on Prognosis in Adult Bronchiectasis. Ann Am Thorac Soc Vol 12, No 11, pp 1602–1611, Nov 2015 ii McLeese RH, Spinou A, Alfahl Z, et al. Psychometrics of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis. Eur Respir J 2021; 58: 2100025. iii Severiche-Bueno D, Gamboa E, Reyes LF, Chotirmall SH. Hot topics and current controversies in non-cystic fibrosis bronchiectasis. Breathe 2019; 15: 286–295 iv Thornton, Christina S., Somayaji, Ranjani, Lim, Rachel K. Assessment of factors and interventions towards therapeutic adherence among persons with non-cystic fibrosis bronchiectasis. ERJ Open Research. 2022; 2022-10-01, 00340-2022. 10.1183/23120541.00340-2022. SOURCE Zambon S.p.A. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Clinical ResultFast TrackAcquisitionQualified Infectious Disease Product

08 Jan 2024

·www.biospace.com

Essential Pharma acquires European rights to Colobreathe®(colistimethate sodium) from Teva

Essential Pharma acquires European rights to Colobreathe®(colistimethate sodium) from Teva Colobreathe® is an inhaled antibiotic for the management of chronic Pseudomonas aeruginosainfections in cystic fibrosis patients The acquisition will help ensure continued access to an important medicine for this vulnerable patient population First rare disease medicine to be added to the Essential Pharma product portfolio Zug, Switzerland and Egham, UK – 8 January 2024 – Essential Pharma, an international specialty pharma group focused on ensuring that patients have sustainable access to low volume, clinically well-established pharmaceutical products across key therapeutic areas, announces that it has completed the acquisition of European rights to Colobreathe® from Teva Laboratories UK Limited. Colobreathe® is indicated for the management of chronic pulmonary infections due to Pseudomonas aeruginosa (PsA) in patients with cystic fibrosis aged 6 years and older. Bacterial lung infection with PsA is frequent in cystic fibrosis patients due to the accumulation of mucus in the lungs which allows bacteria to grow more easily causing infections, lung damage and breathing problems.1 There are two elements to Colobreathe®, a capsule containing the active pharmaceutical ingredient and a Turbospin inhaler to deliver the drug. Under the terms of the acquisition, Essential Pharma has acquired the rights to Colobreathe® across European markets; the product is currently marketed across more than 20 countries in Europe, including the UK. The acquisition represents the first rare disease product acquisition for the group and further establishes Essential Pharma as a leading specialty pharma business ensuring the continual supply of niche medicines of high clinical importance to patients, healthcare providers and carers. Emma Johnson, CEO of Essential Pharma, commented: “Our singular focus is on ensuring patients can maintain sustainable access to vital medicines. Colobreathe® is an important treatment for a serious complication that arises frequently among cystic fibrosis patients. Our acquisition of the European rights to this medicine, which will become our first product indicated for treatment in a rare disease, will help ensure that cystic fibrosis patients in Europe have continued access.” About Essential Pharma Essential Pharma is an international specialty pharmaceutical group dedicated to maintaining access to well-established, at-risk products essential to patients across multiple therapeutic areas. The group has been an important and valued partner to healthcare providers for over 20 years by giving patients access to medicines that otherwise might not be available. Essential Pharma operates globally in more than 70 countries, supplying a portfolio of over 300 products across multiple therapeutic areas. Essential Pharma's growth strategy is based on identifying and acquiring mature, at-risk products from larger pharmaceutical groups looking to streamline their product portfolios. It is a trusted partner to multiple pharma companies of all sizes, with a proven history of integrating assets and managing complex technology transfers seamlessly while ensuring continuous and sustainable supply to patients. Essential Pharma's growth strategy is backed by Gyrus Capital, an investment firm dedicated to transformational investments in sectors with long-term sustainable growth, including healthcare. For more information, please visit essentialpharmagroup.com CONTACTS Essential Pharma Emma Johnson, CEO Tel: +44(0)1784 477 167 Email: info@essentialpharmaceuticals.com ICR Consilium Mary-Jane Elliott/Tracy Cheung/Chris Welsh Tel: +44 (0) 20 3709 5700 Email: Essentialpharma@consilium-comms.com Job code: EP/Consilium/2023/12/001 January 2024 1

AcquisitionDrug Approval

29 Sep 2023

·www.globenewswire.com

Spexis provides business update and announces financial results for the first half of 2023

Ad hoc announcement pursuant to Art. 53 LR Balixafortide, a potent CXCR4 inhibitor, to be evaluated for the treatment of pancreatic ductal adenocarcinoma (PDAC)Spexis closed capital commitments totaling USD $7.5 million supporting Phase 3 ColiFin® program in cystic fibrosis (CF) infectionsCOPILOT study expected to initiate in fourth quarter 2023Appointed Gonçalo Bernardes, PhD, as acting Head of Chemical BiologyAnnounced strong safety and pharmacokinetics results from first-in-human study with inhaled murepavadin, a novel macrocycle compoundEngaged Maxim Group LLC as M&A advisor to evaluate strategic transactions of which Spexis would be the surviving companyBusiness update conference call to be held in October ALLSCHWIL, Switzerland, Sept. 28, 2023 (GLOBE NEWSWIRE) -- Spexis AG (SIX: SPEX), a clinical-stage biopharmaceutical company focused on macrocycle therapeutics for rare diseases and oncology, today announced its financial results for the first half of 2023 and provided a strategic business update. “Spexis remains on track to deliver on the potential of our robust pipeline with multiple clinical development milestones on the horizon,” said Jeff Wager, M.D., Chairman & CEO of Spexis. “We anticipate initiating our Phase 3 ColiFin® program beginning with the COPILOT study in the fourth quarter supported by our financial partner on this program, SPRIM Global Investments. In addition, we have completed our initial analysis of further indication development potential for balixafortide. Based on our analysis, we are excited to announce balixafortide’s new focus on the treatment of PDAC where patients have long faced bleak and limited treatment options. Balixafortide’s well-documented and encouraging selective antagonism of the CXCR4 chemokine receptor and the new preclinical research illustrating its potential in PDAC have encouraged the company to focus our resources on the clinical development of balixafortide in this indication. We look forward to providing additional updates as our novel macrocycle derived pipeline continues to advance.” Pipeline status and plans The plans outlined below regarding the further development of various programs are subject to Spexis raising additional funds and/or entering into partnering agreements. Lead Program, ColiFin®: Spexis is committed to progressing its lead program ColiFin®, which is currently being developed to treat chronic lung infections in cystic fibrosis patients, but which also has strong therapeutic potential in non-CF bronchiectasis (nCFBE) and chronic obstructive pulmonary disease (COPD), as these patients also suffer from chronic Pseudomonas aeruginosa (PA) lung infections. ColiFin® has been approved in the EU as an inhaled therapeutic and holds Orphan Drug and QIDP designations in the U.S. The company has worldwide rights to ColiFin® ex-Europe and is preparing a Phase 3 program in CF patients which includes the COPILOT safety and tolerability trial, and the COPA efficacy trial. COPILOT is expected to initiate prior to the end of 2023. Capital commitments from SPRIM Global Investments (SGI) and additional institutional investors totaling USD $7.5 million to-date will enable the near-term initiation of COPILOT. The company’s clinical trial partnership with SGI, which includes debt facilities, is expected to provide Spexis with up to half of the Phase 3 clinical development costs of ColiFin®. Future milestones are contingent on securing additional capital and/or partnering agreements. Balixafortide: Today Spexis announced plans to pursue the clinical development of balixafortide, the Company’s potent and selective macrocyclic CXCR4 inhibitor, in PDAC, an aggressive form of pancreatic cancer with a poor survival rate. Balixafortide has been well-studied in clinical trials and has demonstrated a promising safety profile both as a monotherapy as well as in combination with other therapies. PDAC has been traditionally resistant to immunotherapy due to a combination of tumor microenvironment features unique to PDAC, but recent preclinical studies have shown the successful modulation of these factors using anti-CXCR4 antibodies, anti-programmed cell death protein 1 antibodies (anti-PD-1) and focal adhesion kinase inhibitors (FAKi). The combination of anti-CXCR4 antibodies, anti-PD-1 antibodies and FAKi led to a significantly decreased metastatic rates in a well-validated PDAC murine liver metastasis model. These results were subsequently validated substituting anti-CXCR4 antibodies for balixafortide. The synergistic effects of targeting PDAC with this regimen represents a unique opportunity for balixafortide to address the significant unmet need that has persisted in the fight against pancreatic cancer. PDAC accounts for more than 90% of pancreatic cancer diagnoses, and its poor survival rate is due to limited treatment options and the absence of an early diagnosis in many patients. The average 5-year survival rate is less than 10%, and pancreatic cancer represents an increasing and worrying proportion of cancer deaths. In 2023, the American Cancer Society projects over 50,000 patients will die of pancreatic cancer in the United States, the third-leading cause of cancer deaths. Despite a growing patient population, treatment options have remained limited, increasing the demand for novel therapeutics and approaches. Inhaled murepavadin (iMPV): Earlier in 2023, Spexis announced safety and pharmacokinetics results from the company’s first-in-human study with inhaled murepavadin, its novel macrocycle compound. Results indicated that iMPV was well tolerated at all dose levels and no serious adverse events were reported in the Phase 1 double-blind, randomized, placebo-controlled trial. iMPV was derived from Spexis’ macrocycle platform, validating its potential to generate clinically relevant therapeutics capable of drugging specific targets across a variety of rare diseases. The study was supported by the European Innovative Medicines Initiative (IMI), with iMPV successfully targeting the outer membrane of Pseudomonas aeruginosa, showing activity against highly resistant strains of bacteria. Spexis remains committed to addressing antibiotic resistance and progressing iMPV through the clinic. Macrocycle platform: Macrocycles remain a key differentiator at Spexis as this burgeoning area of drug discovery yields additional promise. The company’s leadership in the space represents an opportunity to yield novel therapeutics and the potential to combine macrocycles with a wide variety of complementary technologies, including, but not limited to, molecular glues and degraders. Spexis possesses two distinct, highly diverse and very well characterized macrocycle libraries, together with deep data on each: PEMfinder®, which is comprised of peptidomimetic macrocycles, and MACROfinder®, which are small molecule macrocycles. Each library has distinct applications depending on the targets involved, with several pre-clinical characterized leads for various indications having already been identified and characterized. As one example of the power of Spexis’ macrocycle platform, in June of this year, Spexis announced the publication of promising results for a novel class of macrocyclic, peptidomimetic antibiotics in Science Advances demonstrating potent in vitro and in vivo antimicrobial activity against MDR and XDR Enterobacteriaceae, including carbapenem-resistant and colistin-resistant strains. The novel antibiotics were developed by Spexis in close collaboration with Professor Oliver Zerbe’s group at the University of Zurich with substantial funding by Innosuisse and CARB-X. Corporate updates Spexis announced the appointment of Gonçalo Bernardes, Ph.D., as acting Head of Chemical Biology. Dr. Bernardes is a Full Professor of Chemical Biology and a Fellow of Trinity Hall College, Cambridge. He has co-founded companies using technologies developed in his lab and has been awarded three European Research Council grants, as well as awards from the Royal Society of Chemistry, International Chemical Biology Society, European Federation of Medicinal Chemistry and The Blavatnik Family Foundation. Dr. Bernardes also serves as a Senior Fellow at Flagship Pioneering, the largest global venture incubator. He completed his Ph.D. at the University of Oxford, U.K., and his postdoctoral work at the Swiss Federal Institute of Technology (ETH) in Zürich. Multiple discoveries made in his lab have been translated into leading biopharmaceutical companies. At Spexis Dr. Bernardes will focus his efforts on the company’s leading and proprietary macrocycle platform to produce novel therapeutics for the treatment of cancer and rare diseases. The Company expects to announce specific programs already in development in collaboration with Prof. Bernardes in the coming weeks and months. Financial results In the first half of 2023, Spexis’ total loss was CHF 3.9 million, primarily driven by research and development (R&D) expenditures of CHF 2.7 million. The total cash position was CHF 0.9 million (cash and cash equivalents) as of June 30, 2023. In August, Spexis closed additional capital commitments from SPRIM Global Investments and institutional investors totaling USD $2.5 million supporting the Phase 3 ColiFin® program in cystic fibrosis (CF) infections. Key figures1 CHF million Income Statement 30.06.2023 30.06.2022Total revenue0.00.0Research and development expenses-2.7-6.8Other operating expenses2-1.6-2.8Net loss for the period-3.9-10.0 Balance Sheet30.06.202330.06.2022Cash and cash equivalents0.91.8Total assets29.730.0Total equity17.319.4Average net cash burn30.51.0Number of FTEs2028Equity ratio in %5865 1based on consolidated IFRS financial statements 2net of other income 3represents the average monthly cash used in operating and investing activities The half year report 2023 is available for download on our website: Reporting* – Spexis (spexisbio.com) Spexis business update call to take place in October Management will provide a business and financial update, followed by a Q&A session. The specific date and time of said update shall be announced shortly. About Spexis Spexis (SIX: SPEX) is a clinical-stage biopharmaceutical company based in Allschwil, Switzerland, focused on macrocycle therapeutics for rare diseases and oncology. For further information please visit: www.spexisbio.com. For further information please contact: For Investors: Hernan LevettChief Financial OfficerSpexis AG.+41 61 567 16 00IR@spexisbio.com Or Stephen Jasper Managing DirectorGilmartin Groupstephen@gilmartinir.com For Media: Dr. Stephan FeldhausFeldhaus & Partner+41 79 865 92 56feldhaus@feldhaus-partner.ch Disclaimer This press release contains forward-looking statements which are based on current assumptions and forecasts of Spexis management. Known and unknown risks, uncertainties, and other factors could lead to material differences between the forward-looking statements made here and the actual development, in particular Spexis’ results, financial situation, and performance. Readers are cautioned not to put undue reliance on forward-looking statements, which speak only of the date of this communication. Spexis disclaims any intention or obligation to update and revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Phase 1Phase 3Executive Change

100 Deals associated with Colistimethate Sodium

External Link

KEGG	Wiki	ATC	Drug Bank
D02049	Colistimethate Sodium	J01XB01 A07AA10	DB01111

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Gram-Negative Bacterial Infections	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	11 Oct 2021
Infectious Lung Disorder	EU	Essential Pharma Ltd.	13 Feb 2012
Infectious Lung Disorder	IS	Essential Pharma Ltd.	13 Feb 2012
Infectious Lung Disorder	LI	Essential Pharma Ltd.	13 Feb 2012
Infectious Lung Disorder	NO	Essential Pharma Ltd.	13 Feb 2012
Pseudomonas aeruginosa infection	EU	Essential Pharma Ltd.	13 Feb 2012
Pseudomonas aeruginosa infection	IS	Essential Pharma Ltd.	13 Feb 2012
Pseudomonas aeruginosa infection	LI	Essential Pharma Ltd.	13 Feb 2012
Pseudomonas aeruginosa infection	NO	Essential Pharma Ltd.	13 Feb 2012
Infectious Diseases	US	Endo Operations Ltd.	04 Jun 1970
Infectious enteritis	JP	Sun Pharma Japan Ltd.	22 Nov 1960

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic lung disease	Phase 3	US	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	AR	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	AU	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	CA	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	FR	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	DE	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	GR	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	IL	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	IT	Zambon SpA	29 Jan 2018
Chronic lung disease	Phase 3	NZ	Zambon SpA	29 Jan 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03460704 (PROMIS-II, CTgov)	Phase 3	Non-cystic fibrosis bronchiectasis \| Chronic lung disease	287	CMS (CMS (Colistimethate Sodium))	jvkaxprdiq(cbtgdfsjba) = mlxcezdvag gheqnseepy (agnvcivasa, gnrzniyqef - unrdeghmoh)	-	29 Dec 2023
				Placebo (Placebo)	jvkaxprdiq(cbtgdfsjba) = xqeeqpdfcw gheqnseepy (agnvcivasa, fcjzplyobh - dposzkbqsj)
NCT03093974 (PROMIS-I, CTgov)	Phase 3	Non-cystic fibrosis bronchiectasis \| Infectious Diseases	377	Placebo	eakxfcdvhd(ncwwpjpohk) = whzkydptph imknvgnlam (jpybtntyss, lirbjoyrhc - adkvgfmwux)	-	15 Nov 2023
NCT03093974 (PROMIS-I, Corporate Publications) Manual	Phase 3	Non-cystic fibrosis bronchiectasis	377	Colistimethate Sodium	fnhsmsotdy(wvgiyaelhk) = xrxoclokib ptklbrrjje (qmgdmdhvcw )	Positive	08 Sep 2021
				Placebo	fnhsmsotdy(wvgiyaelhk) = qijjdmjmnj ptklbrrjje (qmgdmdhvcw )
PROMIS-I (ERS2021)	Not Applicable	Bronchiectasis Pseudomonas aeruginosa	377	Colistimethate sodium I-neb	hyxzgjezxt(vwaqckairx) = xjimvqpynp bgjzsiqcdo (pefxyradot )	Positive	05 Sep 2021
				Placebo	hyxzgjezxt(vwaqckairx) = ddjbemhpam bgjzsiqcdo (pefxyradot )
ASN2017	Not Applicable	Acute Kidney Injury	126	Colistimethate Sodium	osicuoygfl(ighkyqvoad) = gfkfxghitt msgbjcaitx (wuzexaevmm )	Positive	31 Oct 2017
ERS2016	Not Applicable	-	-	Colistimethate sodium reconstituted with deionized water	uaovhzukkp(dcinitzeys) = mufkxxyqoh zsvcjeggdx (lmajcfacca, 97 - 101)	-	01 Sep 2016
				Colistimethate sodium reconstituted with 0.9% saline	uaovhzukkp(dcinitzeys) = mytevugoxc zsvcjeggdx (lmajcfacca, 97 - 101)
ERS2015	Not Applicable	Glutamate Monosodium Sensitivity	106	Nebulized colistimethate sodium (Promixin)	eunufdhehc(apvigtiwmk) = ncfacmihcb ziajgyutdq (wmhuvbrlys )	-	01 Sep 2015
ISRCTN49790596 (Pubmed \| Pediatrics)	Not Applicable	Pseudomonas Infections	-	Colistin	pgiqpvokdo(pbhwzhzdnr) = toxpzkksui mylgmpmxla (vtqjymopao )	Positive	15 Apr 2014
				Placebo	pgiqpvokdo(pbhwzhzdnr) = hbpbyepvqi mylgmpmxla (vtqjymopao )
AAAAI2014	Not Applicable	-	-	Colistimethate Sodium	qkwsxakipy(vldkpqukpo) = xakbtwqjen tdbwehmbyj (gwdipbnxxt )	-	01 Feb 2014
ISRCTN49790596 (ERS2013)	Not Applicable	Non-cystic fibrosis bronchiectasis Pseudomonas aeruginosa	144	Colistimethate sodium (CMS)	xatoevkzvp(qqvkwttmrt) = ohgfkaglvs jcgjkfofty (hjtdpezteg )	-	01 Sep 2013
				Placebo (0.45% saline)	xatoevkzvp(qqvkwttmrt) = pfmwqdwdpd jcgjkfofty (hjtdpezteg )

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Colistimethate Sodium

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