Supporting Invizius on Their First-in-Human Hemodialysis Trial

Nonclinical collaboration secures MHRA approval of H-Guard^® Solution

Imagine a world where millions of people suffering from kidney failure can undergo hemodialysis without triggering harmful inflammation and blood clotting. This is Invizius’ vision, a biotech company that developed a groundbreaking solution to prevent Complement activation, a key driver of these complications. In this exclusive interview, we spoke with Dr. Magnus Nicolson, the Chief Operating Officer at Invizius, about their journey of innovation and collaboration.

Congratulations on receiving MHRA approval for the First-in-Human (FIH) clinical study for H-Guard^® Priming Solution. Can you share how this achievement aligns with Invizius’ long-term goals and vision for addressing Complement-driven inflammatory disorders?

Invizius was co-founded by Dr Andy Herbert, formerly at the University of Edinburgh, an international expert in Complement; a key component of the innate immune system. H-Guard^® is designed to prevent Complement activation as blood passes over any Hemodialysis filter surface. The H-Guard^® control of Complement is localized to the dialysis membrane surface which is coated with H-Guard^® and is not the systemic suppression of Complement in patients. So, with H-Guard^® and all other Invizius’ products, we intend to control Complement responses to treat a condition or disease, not to eliminate Complement responses. That’s why we call ourselves a Second Generation Complement Company. The FIH study is the first step in our journey to verify the efficacy of H-Guard^® in the context of hemodialysis.

H-Guard's^® anti-inflammatory and anti-coagulant properties are impressive. Could you please explain the strategic importance of balancing these properties with extracorporeal systems like hemodialysis? How does this differentiation give H-Guard^® a competitive advantage?

Andy Herbert often describes H-Guard^® as an “invisibility cloak” for extracorporeal systems. As you rightly say the Complement system is directly linked to the coagulation system and as well as reducing inflammation we expect to see a reduction in coagulation in any extracorporeal system where H-Guard^® is used. We currently believe that H-Guard^® can be coated onto any extracorporeal membrane just prior to use and will potentially have short-, medium- and longer-term benefits on patient health and mortality. We believe this ease of application to multiple systems, and targeted application rather than systemic inhibition is likely to be of value and look forward to our clinical trial program demonstrating the health benefits for dialysis and other patients.

I presume that the journey from preclinical to MHRA approval was a long and challenging one. How did the partnership with Charles River help inform your strategic decisions and resource allocation, which were essential to achieving this significant milestone?

I used Charles River and worked with Pete Gaskin on multiple successful projects during my career and I have confidence designing my pre-clinical packages with their guidance.  When you trust a contractor, making management decisions about timelines and costs as well as getting Board agreement is a lot easier. From there, the Pre-Clinical package must be reviewed and agreed in principle by the relevant regulatory authority: in our case the UK MHRA, before committing to proceed.

Can you please provide specific examples of how the collaboration between Invizius and Charles River helped overcome regulatory hurdles, if any?

Due to species specificity restrictions, we used a transgenic mouse strain for some of our pre-clinical studies. The support Lynne Maciorowski and her team at ICM in the USA provided was outstanding. A big part of our project was developing analytical methods for extremely low levels of H-Guard^® in difficult matrixes. Katie Sime and her team were obsessed with getting my assays to work and did a fantastic job. We are also very grateful to Laura Mackie for effectively coordinating all the subprojects in the USA, Hungary, and the UK as well as expediting the issuance of Final Reports to enable us to meet our company submission deadlines. I always feel that the Charles River team is committed to me and my projects and not just providing a generic service.

Looking ahead, what are the company's plans for advancing H-Guard's^® development beyond the clinical study? Are there other products or therapies in the pipeline that you're particularly excited about?

The H-Guard^® FIH study will provide the safety data for Hemodialysis (HD) but also all other extracorporeal applications. Our next project is Peritoneal Dialysis (PD) using a related approach. We won major grant funding for this project and are currently working with a University Hospital in Germany. Immune activation on the peritoneal membrane drives fibrosis through TGF-beta as well as mesothelial to mesenchymal cell transitions which are pivotal to mechanical changes resulting in PD losing its ability to work after several years. PD is often a great alternative to HD especially in children, so extending the time patients can remain on PD is what we hope to achieve.

What are the long-term safety and efficacy outcomes that you are hoping to achieve with H-Guard®?

Hemodialysis (HD) is a temporary fix that in some patients is made to last a lifetime when transplants are not available. Survival rates have not increased significantly in over 20 years. We believe that the chronic release of Complement-driven inflammatory molecules contributes to the development of cardiovascular problems which are the major cause of mortality in this patient group. Life expectancy on HD is dramatically shorter than if the patient had not required dialysis. There are high risk groups of patients with existing conditions that may be even more impacted by Complement driven inflammatory responses. We are currently looking for patients with high Complement reactivity who we term as having “Angry Blood”. This significant patient group (~20%) was first identified by University of Groningen Medical Centre who we have worked with. We are currently looking at how Complement activation affects HD patients during each three hour session. In the largest kinetic biomarker study of HD patients ever performed to our knowledge with the University of Manchester Hospital Trust. We believe H-Guard^® coated HD filters could have a significant impact on various Acute and Chronic HD applications ranging from improvements in Quality of Life to reduced mortality.  We are currently designing our next Clinical trials with these and other clinically relevant end points in mind. 

How will H-Guard^® be made available to patients once it is approved for clinical use?

Richard Boyd our CEO is responsible for all partnering activities for H-Guard^®, and we fully expect to have secured a partner(s) in every major market by the time of Marketing Authorization based on our future clinical trial results.

Concluding thoughts:

H-Guard^® Priming Solution has the potential to make a significant difference in the lives of patients by preventing Complement activation and inflammation during hemodialysis and other medical procedures. Dr. Magnus Nicolson, the Chief Operating Officer at Invizius, shared some of his insights into the development and approval this novel product that aims to prevent Complement activation and inflammation in hemodialysis patients. We learned about the scientific rationale, the clinical trial design, and the future plans of Invizius, as well as the role of Charles River experts in supporting their innovation journey.

If you are interested in learning more about how Charles River can help you with your drug development needs, please request a consultation with one of our experts here. 

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