Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - NANOSEPSIS (Rapid Magnetic Blood Filtration for the Treatment of Sepsis: a Feasibility Study)

Teaser

Sepsis is one of the leading causes of death in the world, exerting a huge human and economic toll with more than 900K cases in Europe and 1M cases in the US. Globally over 6M newborns and children are affected annually with over 20M total cases. Despite decades of research to...

Summary

Sepsis is one of the leading causes of death in the world, exerting a huge human and economic toll with more than 900K cases in Europe and 1M cases in the US. Globally over 6M newborns and children are affected annually with over 20M total cases. Despite decades of research to improve treatment, with reported mortality rates upwards of 30%, there is a clear need for better treatments especially as the current antibiotic therapies are increasingly vulnerable to antimicrobial resistance (AMR).
Sepsis is caused by pathogens from an infection which can elicit a dysregulated immune response that can escalate to septic shock. The challenge in sepsis is that both the pathogens (typically bacteria) and the body’s own response contribute to the disease. The destruction of bacteria by the immune system or antibiotics creates large quantities of endotoxins (LPS), which are found in the membrane of gram-negative bacteria), which in turn aggravate the immune response and cause the cascade towards septic shock and death. The key need is a treatment capable of rapidly removing both the pathogens and the endotoxins, particularly in AMR cases.
MediSieve’s technology is similar to dialysis: we circulate a patient’s blood through an external blood loop to remove disease causing targets. While dialysis relies on non-specific size based filtration, MediSieve’s uses magnetic particles coated with antibodies to target specific components and magnetic forces to extract them. Our approach enables us to provide a platform technology to treat blood-borne medical conditions.
In sepsis, our particles target bacteria and LPS, rapidly reducing their levels in the blood. Used in combination with anti-biotics, it could help eliminate the infection, and prevent escalation to septic shock. Endotoxin levels correlate with clinical outcomes, and their removal would be beneficial in helping to treat the disease. Since magnetic filtration is a purely physical method, can also target and remove pathogens which are resistant to antibiotics. It could therefore reduce the chances of treatment failure and escalation to full septic shock.
The objectives of this project were to:
1. Particle development lab studies
2. Regulatory and route to market strategy
3. Perform Market analysis and healthcare economics
4. Commercialisation strategy and business planning

Work performed

1. Particle development and lab studies
The lab studies were focussed on the manufacture of the magnetic particles, which need to be “conjugated” to the antibodies which can bind to LPS and bacteria. The core magnetic particle can have several different coatings to enable the antibody to conjugate correctly to the particle. These tests validated the manufacturing procedure and enabled us to define the precise characteristics of the particle and its coating. The particles were also passed through MediSieve’s magnetic filter, which was developed as part of our separate malaria R&D project.
2. Regulatory and route to market strategy
A full regulatory analysis was performed to establish the regulatory strategy for the particles in both the EU (CE mark) and US (FDA approval). By identifying the data that the regulatory bodies will require, we have defined a precise, fully costed development plan that will generate the pre-clinical data required to progress to clinical trials and commercialisation. This was completed by a clinical trials plan establishing a full route to market strategy. The intellectual property landscape was also reviewed alongside an internal review of our IP strategy.
3. Perform Market analysis and healthcare economics
Market research helped to define the primary patient segment and initial total addressable market. Competitor analysis helped better define the unique selling points of MediSieve’s approach – rapid removal of several targets – and show current market prices. The healthcare economics enabled a detailed analysis of the potential beneficial economic impact. Sepsis is expensive to treat, so preventing disease escalation can lead to significant cost savings. We analysed costs in the UK, Germany, France, Spain and the US. At a price point of £1500, with conservative assumptions of 20% reduction in average length of stay, all countries except France showed a net savings to the healthcare system.
4. Exploitation and dissemination
The project is continuing and MediSieve is currently seeking both equity and grant funding. This will enable further development and pre-clinical validation of the full MediSieve sepsis system, with a product ready for clinical trials. The results will be published in a suitable journal.

Final results

This project has advanced the area of clinical magnetic blood filtration by providing further evidence of the potential of the technology to be a platform that can be used to treat a range of blood-borne diseases. The project supported the achievement of significant proof of concept milestones, namely the successful conjugation of antibodies to the magnetic particles, and their subsequent high efficiency capture using the MediSieve magnetic filter. The investigated particles were the first to be manufactured and tested specifically for use with the filter, supporting the idea that different antibodies could be used in order to develop several “families” of particles that bind to a wide range of different disease-relevant targets in blood, moving closer towards providing doctors with a tool to enable them to “clean” blood to treat blood-borne diseases.
This project will continue for several years before a product reaches the market. Pre-clinical testing showing safety and efficacy, first in vitro and then in vivo, will be conducted. Approvals from regulatory bodies will be required to perform clinical trials. These will start with Phase 1 First in Man safety trials before progressing to sepsis patients, with the primary objective of proving the reduction in endotoxins and/or pathogens. This will be followed by a larger Phase 3 Efficacy Trial looking at mortality and length of stay reduction.
There is significant potential human and socio-economic impact, as demonstrated by the healthcare economics analysis. In the EU and US, there are an estimated 430,000 deaths per annum and 410,000 ICU cases; widespread adoption of magnetic blood filtration to treat these patients could save thousands of lives and lead directly to economic benefits through QALY savings. Sepsis is a very expensive medical condition, accounting for 5% of total healthcare spending in the US, so reducing costs by reducing average time in hospital would have a significant economic benefit, saving the US healthcare system over $500M/yr with 30% of patients reached. With increasing AMR, having magnetic blood filtration available as a non-drug treatment option could bring further clinical benefits and save more lives in the future.
If successful in commercialising the technology, MediSieve expects to enter a market worth £1.8B in 2022, with the project directly contributing to the creation of tens of new jobs in the EU.

Website & more info

More info: http://www.medisieve.com.