exeporfinium chloride (XF-73) / Destiny Pharma, Cystic Fibrosis Foundation - LARVOL DELTA

Exeporfinium chloride (XF-73) nasal gel significantly reduces Staphylococcus aureus nasal carriage in cardiac surgery patients throughout surgery and the early recovery period: results from a randomized placebo-controlled Phase 2 study. (PubMed, Infect Control Hosp Epidemiol) - "aureus burden rapidly decreased after 2 doses (-2.2log10 CFU/mL; placebo -0.01log10 CFU/mL) and was maintained to 6 days post-surgery. Among XF-73 patients, 46.5% received post-operative anti-staphylococcal antibiotics versus 70% in placebo (P = 0.045)."

Journal • P2 data • Surgery • Cardiovascular • Infectious Disease

Screening of the novel antimicrobial drug, XF-73, against 2,527 Staphylococcus species clinical isolates. (PubMed, Front Cell Infect Microbiol) - "XF-73 was found to be equally effective against antibiotic resistant isolates as antibiotic sensitive isolates, with no impact of pre-existing antibiotic resistance mechanisms to cell wall synthesis inhibitors (β-lactams, carbapenems, glycopeptides and cephalosporins), protein synthesis inhibitors (oxazolidinones, macrolides and tetracyclines), DNA synthesis inhibitors (fluoroquinolones) and a folate synthesis inhibitor. This dataset expands the knowledge of the breadth of activity of this novel antibacterial against a wide range of global S. aureus isolates and supports the potential utility of XF-73 for the treatment of patients who are S. aureus nasal carriers. Similar results were also obtained for multidrug-resistant isolates of other Staphylococcus species included in the study and collectively support the continued clinical development of XF-73 as an effective anti-staphylococcal drug."

Journal • Infectious Disease

Antimicrobial effects of XF drugs against Candida albicans and its biofilms. (PubMed, Front Fungal Biol) - "Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by C. albicans. Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70."

Journal • Infectious Disease

Efficacy of a Novel Antibacterial Agent Exeporfinium Chloride, (XF-73), Against Antibiotic-Resistant Bacteria in Mouse Superficial Skin Infection Models. (PubMed, Infect Drug Resist) - "The in vitro antibacterial activity of XF-73 and comparator antibacterial drugs, (mupirocin, fusidine, retapamulin, vancomycin, erythromycin, linezolid and daptomycin), against S. aureus (both antibiotic sensitive and resistant strains) was assessed using a broth microdilution method. SEM analysis demonstrated that this cell wall and cell membrane disruption did not lead to disintegration of the plasma membrane, and did not cause bacterial cell lysis. Therefore, XF-73 may be an effective drug alternative to combat multi-drug-resistant skin infections in the clinical setting."

Journal • Preclinical • Dermatology • Infectious Disease

Exeporfinium chloride (XF-73) nasal gel dosed over 24 hours prior to surgery significantly reduced Staphylococcus aureus nasal carriage in cardiac surgery patients: Safety and efficacy results from a randomized placebo-controlled phase 2 study. (PubMed, Infect Control Hosp Epidemiol) - "We studied 83 cardiac-surgery patients with nasal S. aureus carriage who received 4 intranasal administrations of XF-73 nasal gel or placebo <24 hours before surgery. One hour before surgery, patients exhibited a S. aureus nasal carriage reduction of 2.5 log with XF-73 compared to 0.4 log CFU/mL for those who received placebo (95% CI, -2.7 to -1.5; P < .0001)."

Journal • P2 data • Surgery • Cardiovascular

Antibacterial and Antibiofilm Potency of XF Drugs, Impact of Photodynamic Activation and Synergy With Antibiotics. (PubMed, Front Cell Infect Microbiol) - "XF-73 and XF-70 exhibited synergy with ertapenem against a methicillin resistant Staphylococcus aureus (MRSA) strain (± PD) and XF-73 with polymyxin B (± PD) against Pseudomonas aeruginosa. XF drugs exhibited significant antimicrobial activity against Gram-positive bacteria, with PD enhancement of bacterial susceptibility. Additionally, XF drugs displayed synergy with conventional antibiotics and demonstrated antibiofilm effects."

Journal • Infectious Disease

Destiny Pharma receives award from the Cystic Fibrosis Foundation (PharmiWeb) - "Destiny Pharma...today announces it has received an award from the Cystic Fibrosis Foundation. The research project will establish the potential of the Company’s proprietary XF-73 drug as a novel treatment for cystic fibrosis patients infected with methicillin-resistant Staphylococcus aureus (MRSA)."

Financing • Cystic Fibrosis • Infectious Disease

Destiny Pharma plc (BIO 2022) - "It has two late-stage clinical assets which it is preparing for Phase 3 studies - NTCD-M3 for prevention of recurrence of C. difficile infection; and XF-73 for prevention of post-surgical S. aureus infections...Beyond this, it has a pipeline related to its proprietary and patent protected XF platform; and separately a preclinical stage collaboration focused on COVID-19. Destiny is also open to collaborations involving its earlier programmes and expanding its pipeline of microbiome assets."

Infectious Disease • Novel Coronavirus Disease

Antibacterial efficacy of XF-73 via two mechanisms of action against Gram-positive microorganisms in biofilm mode of growth (ECCMID 2022) - No abstract available

Clinical • Infectious Disease

"Our client @DestinyPharma has noted a Phase 4 study presented during @IDWeek2021 which provides strong support for the potential of their XF-73 nasal product as an alternative to mupirocin. #AMR #biotech #IDWeek2021 #DEST #microbiome" (@OptimumComms)

P4 data • Infectious Disease

[VIRTUAL] Repeated doses of exeporfinium chloride (XF-73) nasal gel over 24 hours significantly reduced the burden of Staphylococcus aureus nasal carriage in at-risk surgical patients: preliminary results from a phase II study (ECCMID 2021) - No abstract available

Clinical • Late-breaking abstract • P2 data

[VIRTUAL] Antimicrobial efficacy of XF-73 and antibiotic comparators against clinically relevant Gram-positive microorganisms in biofilm mode of growth (ECCMID 2021) - No abstract available

Clinical • Infectious Disease

Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection (clinicaltrials.gov) - P2; N=124; Completed; Sponsor: Destiny Pharma Plc; Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • PCR

Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection (clinicaltrials.gov) - P2; N=125; Active, not recruiting; Sponsor: Destiny Pharma Plc; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • PCR

Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection (clinicaltrials.gov) - P2; N=125; Recruiting; Sponsor: Destiny Pharma Plc; N=200 ➔ 125

Clinical • Enrollment change • Infectious Disease

Assessing the Potential for Staphylococcus aureus to Evolve Resistance to XF-73. (PubMed, Trends Microbiol) - No abstract available

Journal

Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S. Aureus in Patients at Risk of Post-op Staphylococcal Infection (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Destiny Pharma Plc; Trial completion date: Jul 2020 ➔ Mar 2021; Trial primary completion date: Apr 2020 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date • PCR

Staphylococcus aureus nasal decolonization strategies: a review. (PubMed, Expert Rev Anti Infect Ther) - "Areas covered: Mupirocin nasal ointment has been used for the nasal decolonization and prevention of staphylococcal infections in various settings like surgeries...Some old approved antiseptics (chlorhexidine, povidone-iodine) or antibiotics (rifampicin, bacitracin) have been investigated for their efficacy in this indication. Other new agents (tea tree oil, retapamulin, LTX-109, XF-73, phages, lysostaphin, squalamine analogues, etc.) are being studied. Some of them are still in preclinical phases, and others have reached clinical trials, but further research is needed. Special interest should be given to single dose decolonization strategies and to molecules that do not select resistant strains."

Journal

Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S. Aureus in Patients at Risk of Post-op Staphylococcal Infection (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Destiny Pharma Plc; Trial completion date: Dec 2019 ➔ Jul 2020; Trial primary completion date: Nov 2019 ➔ Apr 2020

Clinical • Trial completion date • Trial primary completion date • PCR

A two-part phase I study to establish and compare the safety and local tolerability of two nasal formulations of XF-73 for decolonization of Staphylococcus aureus: A previously investigated 0.5 mg/g viscosified gel formulation versus a modified formulation. (PubMed, J Glob Antimicrob Resist) - "XF-73 was found to be safe and was tolerated with minimal side effects at doses of 0.5 mg/g 2% gel and 2 mg/g 2% gel in healthy volunteers. These findings support moving on to Phase 2 trials to further evaluate the efficacy of XF-73."

Clinical • Journal • P1 data

Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S. Aureus in Patients at Risk of Post-op Staphylococcal Infection (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Destiny Pharma Plc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open