Periodic Reporting for period 2 - Phagediag (Fast, easy diagnostics for personalised phage therapy)
Okres sprawozdawczy: 2024-02-01 do 2025-10-31
Phage therapy (using bacteriophages to treat bacterial infections) is among the most promising solutions for the antimicrobial resistance (AMR) crisis. Attempts with unspecific, pre-defined phage cocktails developed as classical medicinal products have failed to demonstrate efficacy in clinical trials (only 20-30% efficiency). In contrast, case reports with a personalized, specific approach using magistral preparations based on pre-manufactured phage API's provided effective treatment (> 85% success rate) allowing for a targeted and flexible approach. Therefore, personalized phage therapy using magistral preparations of phages is among the most promising solutions to fight AMR. But to implement this approach a rapid diagnostic susceptibility test identifying the phages active against the specific infection is required. Actual classical lab techniques for phage susceptibility testing are time consuming and labour intensive to use as standard technique in a hospital microbiology lab. Additionally, they are difficult to interpret and are not multiplexed. This is not feasible with current laboratory techniques for in vitro phage susceptibility testing, which are slow, difficult to interpret, requiring excessive labour and expertise in phage biology (rare to find in clinical laboratories). Inteliphage has developed the “Phagogram”, the 1st automated in-vitro diagnostic tool that enables a fast determination of bacteriophages suitable for treating a particular bacterial infection. It consists of a basic test kit (a disposable well plate with a collection of fixed phages and a set of reagents), a high-performance luminometer and a dedicated software that proposes the best matching phage cocktail to treat the patient. Compared to current diagnostic methodologies, which take up to 3 – 4 days, the Phagogram compares the activity of up to 25 phages on a bacterial culture within 3 – 4 hours, making phage susceptibility testing accessible for hospital microbiology labs and enabling personalized therapy on a routine basis.
The concept of the automated phagogram was developed during the period 2019 – 2022 to a point where a working prototype was demonstrated. During the last year, the industrial production development of the prototype was planned and tested. This further development was performed using a rigid schedule guided by the European Regulation for developing, manufacturing and testing of In Vitro Diagnostic tests. Simultaneously with the dossier for the test equipment and material, a 2nd workplan was completed developing the software necessary to manage and run the test system. March 2024, the company was ready to start the validation tests on the Phagogram. This validation, amongst others, contains a clinical validation of the susceptibility test in different European hospitals which will demonstrate the performance and reliability of the test and its predictive value for composing the right bacteriophage cocktails to treat in a personalized model drug multiresistant infections. However, during the verification phase, which is preceding the validation phase and is the 1st check of the performance in a real-world situation, it appeared that main values for the sensitivity of the test were unacceptable and made the validation phase impossible. Main reason for this underperformance is the total absence of standards, norms and guidelines like they are existing in bacterial microbiology. Old fashioned unvalidated techniques had to be used as standard reference methods. A mitigation strategy was planned very precisely and comprised amongst other measures the validation of different reference techniques against each other and the phagogram and drastically increasing the sample size. In this way, Inteliphage developed its own standards. Methodology for developing the algorithm guiding the test results finally led to a performance where precision, robustness and sensitivity are more than 90% making the test now very performant. The Phagogram is now ready to take the last step and start the final validation procedure, planned Q2-Q3 - 2026 ,to be ready for final CE-marking as IVD
Personalized phage therapy is probably the most promising treatment solution for antibiotic multi-resistant (AMR) bacterial infections. The Phagediag susceptibility test is developed as diagnostic tool enabling the identification of the best phages to treat a specific resistant infection. With a high diagnostic accuracy, the Phagogram test is an effective tool to install a correct phage therapy reducing the burden and impact of an AMR infection, alleviating human suffering, decreasing economic burden to entire social security systems and reducing long-term consequences of antibiotic treatment and saving lives by providing a fast diagnostic (3-4 hours compared to actual 3-4 days). Internally, for Inteliphage, the Phagogram plays a central role in our strategy since finalizing, validating and fulfilling the regulatory pathway of the Phagogram will enable us to its final industrialization converting us in a leader position by distributing this unique diagnostic product. Additionally, this previous knowledge starting with 4 bacteria responsible for about 70% of all AMR infections will give us the expertise to expand the technology to new strains and applications. Summarizing, the Phagogram will revolutionize the market by providing a way of making personalized phage medicine possible thanks to the implementation of this accurate diagnostic step. Once personalized cocktails are made possible, most biotechnology companies working on phage therapy are expected to change their approach, to also become able to provide this type of methodology (more efficient and aligned with the trend in medicine towards adapting to the specific patient needs).