SoftOx Biofilm Eradicator – Development of an antimicrobial drug composition for eradication of biofilm in chronic wounds

The development of chronic wounds has become a major and serious problem and it is projected that up to 2% of the population in developing countries is estimated to have chronic wounds. Antimicrobial resistance and biofilm infections are important reasons for this. SoftOx's technology is tailored to eliminate microbes in wounds, including those in biofilms. In addition, it does not contribute to the development of resistance, as today's antibiotics do. During the time period, SoftOx has had two development projects dealing within the wound area: 1. SoftOx Wound Irrigation Solutions (SWIS), classified as medical device, for acute wounds 2. SoftOx Biofilm Eradicator (SBE), classified as drugs, for chronic wounds For the SWIS project, the company has tested a less concentrated solutions in acute wounds. SWIS will be classified as a class III medical device and has the potential to become a valuable wound cleanser with attractive properties. The clinical studies of SWIS (SWIS-01 and SWIS-02) were successfully completed and have been published. The study, SWIS-02, which was conducted at Bispebjerg University Hospital in Copenhagen, was a confirmatory clinical investigation documenting the safety and performance of SoftOx Wound Irrigation Solution (SWIS) compared to Normal Saline (NS) in a human wound model. The study showed both a significant improvement in wound healing and a reduction in bacterial load compared to normal saline (NS), which positions the product as superior to today's market leaders. For the SBE project, the company succeeded in 2021 in submitting, obtaining approval and starting the clinical study SBE-01 phase I study. The SBE solutions were manufactured in accordance with Good Manufacturing Practice (GMP), and the study site was launched in June. Due to a prolonged nationwide nurses' strike in Denmark and Covid in 2021, recruitment of patients to the study was significantly delayed. The study was completed in September 2022, and data from the top line results show that SBE was safe and well tolerated. There were no statistically significant differences in the evaluation of pain during and after the wound debridement procedure comparing SBE with placebo. Treatment with all SBE formulations consistently reduced the absolute number of bacteria (bacterial load) in the wound compared to pretreatment (baseline). A dose-dependent reduction in wound size was also observed in the multiple-dose SBE treatment groups. The SoftOx technology platform is highly versatile, a new generation antimicrobial agent with the potential to treat various types of wounds, from infections in acute surgical or non-surgical wounds to infection clearance in wounds typically associated with biofilm such as chronic leg ulcers and traumatic penetrating injuries. Clinical data from both the SWIS study supports the connection between the use of SoftOx technology and improved wound healing in acute wounds. This, together with the results from the SBE-01 study of antimicrobial effects in chronic leg ulcers, provides a "proof of concept" for SoftOx's wound treatment technology platform for a number of potential acute and chronic wound treatment indications.

Outcomes and impacts Outcomes The project has together with its partners generated new knowledge on the SoftOx technology. SINTEF, Costerton Biofilm Center (Copenhagen University) and Bispebjerg University Hospital (Copenhagen) have become experts in testing active chlorine solutions in terms of analytics/measurements, degradation, minimal inhibitory / bactericidal concentrations, biofilm effects, resistance, mm. The tech transfer of the manufacturing line from SoftOx facilities to a GMP facility (Solural Pharma) resulted in significant learnings and knowledge for future commercial production of SoftOx wound products. Also, the R&D efforts on new formulations have been important for PhD work at SoftOx. The most important outcomes for SoftOx and its technology are related to the wide range of results that have been delivered. New product knowledge on stability and degradables, production, primary packaging is crucial to provide a product with adequate properties. The project has also been essential for understanding the composition and formulation of wound products and their effect on microorganisms. Animal and human studies have collectively given important results on the tolerability, safety and efficacy of the tested solutions. Altogether, the research performed under the BIA project has facilitated the early stages of product development both for a safe wound irrigation solution (SWIS) and SoftOx Biofilm Eradicator (SBE), providing a good basis for further development and increased likelihood for market approval. Impact The results and knowledge generated will impact future scientific research on how to counteract microbial infections and other threats . The healthcare community needs new antimicrobial solutions with improved properties (environmentally friendly, tolerable and safe, non-alcohol, non-antibiotic, non-allergic, skin friendly, strong antimicrobial / antibiofilm activity, favourable wound healing, etc.) to prevent emergence and further spread of antibiotic resistance and to facilitate chronic wound healing through preventing and eliminating wound infections. provide hope to reduce the prevalence of chronic wounds.

SoftOx Solutions AS (SoftOx) aims to develop a drug composition for topical use that can rapidly and effectively eradicate biofilm infections in chronic wounds, and subsequently lead to a more rapid wound healing, which reduces the costs of treatment and improves patient quality of life. The objective of SoftOx is to become the first company to have a range of clinically proven wound care products that prevent and eradicate biofilm infections. This will provide the company with a unique position in the growing wound care market. Our partners, SINTEF and the Costerton Biofilm Center at the University of Copenhagen are among the world leaders in biofilm research, and the Copenhagen Wound Healing Center at Bispebjerg Rigshospital, is in the front of clinical excellence with respect to treating patients with chronic wounds. Catapult Life Science will help developing a GMP compliant manufacture process. The SoftOx Biofilm Eradicator (BE), is estimated to be ready for regulatory evaluation in 2023-2024 as a medicinal product. SoftOx BE has the potential to be the first biofilm eradicator with approval from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). With successful R&D results, SoftOx will need additional 15-20 employees in Norway, and 5-10 employees abroad, to be able to commercialize the product(s) properly. For safety reasons, the project has carefully tested various wound treatment solutions clinically, in small steps. First, based on successful preclinical studies, we have tested product candidates in healthy volunteers (intact and compromised skin). Thereafter we have progressed to further testing in superficial, acute wounds. Positive results from this study has now finally allowed us to move into patients with more severe, chronic wounds (phase Ia/Ib trial). Thus, we have performed more clinical studies than originally planned, with the advantage of a safe development program and risk reduction. The main challenge with this R&D project is ultimately to provide medical evidence that the SoftOx drug lead delivers on the primary endpoint of the clinical trials. Positive results will lead SoftOx to conduct a large multicentre therapeutic confirmatory (phase III) study, in accordance with regulatory requirements.