Manchester University NHS Foundation Trust

Invizius estimates that about 20% of dialysis patients may have "angry blood," where an overzealous inflammatory response can lead to serious complications. Invizius has completed a first-in-human study of its approach to taming the immune system’s overreaction to dialysis—with the goal of addressing the complications that can come with “angry blood.” While you would normally want a zealous white blood cell to attack any newcomers to the body, to protect it against infections and the like, heightened inflammation can take its toll during hemodialysis.  As the living blood makes its way through the machine, every surface is a surface that triggers the foreign-body response: From the cells' point of view, none of it should be there. Enter Invizius’ H-Guard priming solution, which is run through the machine before each procedure. It coats the insides with a layer of proteins that effectively camouflage the dialysis hardware from the immune system—stealing a trick from certain bacteria that are capable of evading white blood cells, without triggering the cascading inflammatory reactions known as the complement system. Late last month, the Scotland-based company—and former Fierce 15 winner—announced that its first eight patients had been successfully treated in a phase 1 study. Analyses before and after dialysis showed that the blood filtration process worked as expected. Its next step will be to perform a phase 2b trial of hospitalized patients with acute kidney injuries, looking to see if H-Guard can lower the amount of time spent in the ICU or reduce renal damage from the immune system’s reactions to dialysis. “This is an important milestone for H-Guard and Invizius, allowing us to progress into a larger efficacy study showing the clinical benefits of controlling complement activation in [continuous renal replacement therapy] and a number of extracorporeal systems,” CEO Magnus Nicolson said in a statement. The priming solution is also being studied preclinically for use during heart bypass procedures and in other life support systems. A previous biomarker analysis study by the company screened blood samples from over 350 participants that undergo routine hemodialysis and found that patients can be categorized by their immune reactions to the procedure.  While chronic, low-grade inflammation is common among dialysis patients, those with the strongest responses can carry higher risks of developing serious complications—such as blood clots, organ damage or a wide range of other conditions—and may benefit the most from the addition of a product like H-Guard.  Dubbed “angry blood,” Invizius estimates that about one-in-five dialysis patients may be susceptible to the overreactions, out of the more than 3 million people worldwide who undergo the procedure multiple times per week. According to Invizius, the results of the biomarker study won “best abstract” last month at the annual meeting of the European Renal Association in Stockholm, as presented by Duha Ilyas, a clinical research fellow at the Manchester Royal Infirmary, part of the Manchester University NHS Foundation Trust and the site of the first-in-human trial. “This is the largest kinetic analysis of complement activation in routine haemodialysis (HD) ever undertaken in [the U.K.],” said study leader Sandip Mitra, a professor of renal medicine at the Manchester NHS trust. “Our results indicate patient-specific complement activation associated with inflammatory response during routine haemodialysis. Reduction in complement activation in HD may yield significant clinical outcome benefits.” The company previously raised £5.3 million in a 2021 series A round, joined by Mercia, Downing Ventures, Old College Capital, Scottish Enterprise, Solvay Ventures and Calculus Capital.

As per the findings of the research, up to 25% of post-menopausal women at high risk of developing breast cancer will not benefit from taking the medication MFT scientists developed a hormone blood test which can determine the effectiveness of anastrozole. (Credit: Nappy on Unsplash) Scientists at Manchester University NHS Foundation Trust (MFT) have developed a new highly sensitive hormone blood test to assess the efficacy of the preventative breast cancer drug, anastrozole. Anastrozole is currently the recommended preventative therapy for women in the post-menopausal stage who are at high risk of developing breast cancer. MFT published the findings of the research in the Lancet Oncology journal. The research demonstrated that up to 25% of these post-menopausal women will not benefit from taking the medication. It also showed that clinicians will be able to provide these patients with a customised treatment plan if they conduct routine hormone testing. This will prevent thousands of women from experiencing negative effects of the drug, the NHS trust said. According to the study, anastrozole would have little to no effect on a woman’s risk of breast cancer if her oestradiol levels were low. As a result, these women might have avoided the medication’s potential five-year adverse effects, which frequently include hot flushes, pains, and low mood. MFT medical genetics and cancer epidemiology consultant D Gareth Evans said: “These results indicate the importance of incorporating serum oestrogen levels into risk models, so women can be reassured despite other risk factors if their levels are low, and likewise, higher levels may make more women eligible for anastrozole.” In postmenopausal women, anastrozozole reduces oestrogen levels, which would otherwise promote the growth of breast cancer cells. The once daily 1mg tablet of the hormone therapy medication known to be an aromatase inhibitor is administered over five years. It can only be taken by women who have gone through menopause as the medication cannot reduce oestrogen in women whose ovaries are still functioning. Anastrozole has been suggested as a preventive treatment by the National Institute for Health and Care Excellence (NICE) since 2017. The Medicines and Healthcare Products Regulatory Agency (MHRA) granted the medication a licence for use on the NHS in November 2023. It was based on results from an earlier study from the IBIS-II preventive trial, which was funded by MFT researchers. The trial revealed that anastrozole lowers the incidence of breast cancer in postmenopausal women who are at increased risk by 49%.

First patients treated with H-Guard® at the National Institute for Health and Care Research Manchester Clinical Research Facility MHRA approves continuation of Invizius's first-in-human clinical study following a prearranged two-patient safety and performance review Study is investigating safety and tolerability of H-Guard®, a second generation complement regulator, to address serious immune system-driven complications of dialysis GLASGOW, Scotland, Feb. 7, 2024 /PRNewswire/ -- Invizius Limited ("Invizius"), a biotechnology company developing breakthrough treatments for patients on dialysis, is pleased to announce that the first two patients have been treated at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) with lead product, H-Guard® Priming Solution, in the Company's first-in-human Phase 1 clinical study. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved continuation of the study, following the submission of safety and performance data from the first two patients. Up to eight more patients will be recruited to the CRF, the only UK site to participate in the study. The study is being conducted at the NIHR Manchester CRF at the Manchester Royal Infirmary (MRI), part of the Manchester University NHS Foundation Trust, and is led by Professor Sandip Mitra and Co-investigators, Dr Leonard Ebah and Dr Duha Ilyas. The study is investigating the safety and tolerability of lead product, H-Guard, in patients undergoing haemodialysis (HD) who are vulnerable to dialysis-induced immune activation. Immune activation occurs when a patient's blood comes into contact with foreign surfaces in the dialysis circuit, which can result in excessive inflammation, coagulation, vascular and organ damage and other adverse consequences. H-Guard is flushed through the dialysis machine prior to commencing treatment and aims to prevent serious complications by attenuating the patient's immune response to the dialysis procedure. Richard Boyd, Chief Executive Officer of Invizius, said: "The treatment of the first patients with our lead product, H-Guard, is a major milestone for Invizius as we enter clinical development with our first-in-human Phase 1 study at the Manchester Clinical Research Facility. We are pleased to have received MHRA approval to continue the study after a prearranged, two-patient safety and performance review, and we are excited by the potential of H-Guard to improve the treatment paradigm of patients on dialysis." Professor Sandip Mitra, Consultant Nephrologist and Professor of Renal Medicine at Manchester University NHS Foundation Trust, commented: "Our aim is to improve the outcomes of patients on dialysis. We are continuing this study to seek more safety and performance data necessary to demonstrate H-Guard's potential and to direct future clinical applications and testing." H-Guard is a potent anti-inflammatory and anti-coagulatory, second generation, complement regulator which coats the dialysis filter and tubing during the priming process. This is designed to suppress complement activation on the extracorporeal circuit's surfaces by recruiting and enhancing the patient's own, natural complement modulator, Factor H, whilst still allowing effective infection control. About Invizius Invizius is developing second generation complement therapies to treat inflammatory, fibrotic and autoimmune disorders. Invizius' proprietary approach was born out of over ten years of research by Dr Andy Herbert into how pathogenic microbes evade the human complement system. The novel mechanism of action enhances the activity of the body's own complement regulators to effectively downregulate immune responses while maintaining antimicrobial protection. The lead product, H-Guard, addresses serious complement-driven complications of dialysis, and enables additional indications in other extra-corporeal treatments (ECMO, cardiopulmonary bypass). A second product is being developed to extend the period that patients can sustain home-based, peritoneal dialysis. The company is working with Key Opinion Leaders from Manchester University NHS Foundation Trust, Karolinska Institutet, University of Heidelberg, University Medical Centre Groeningen, and University of Strathclyde. It is backed by Mercia, Downing, Calculus, and Syensqo, a corporate VC. Other investors include University of Edinburgh's Old College Capital fund, Scottish Enterprise, and well-known life science investor, Dr Jonathan Milner. For more information on Invizius, please visit: SOURCE Invizius