St George Street Capital (“SGSC”) and Excalibur Medicines Limited (“EML”) are pleased to provide an update on the positive outcome of The Arcadia COVID-19 therapy Trial

Further analysis of data from the ARCADIA clinical study confirms that the addition of AZD1656 treatment to standard care resulted in fewer deaths and earlier hospital discharge in COVID-19 patients than did placebo treatment.

The ARCADIA Phase II multi-centre study was undertaken in over 150 diabetic patients hospitalised due to moderate to severe COVID-19 infection. Patients received either AZD1656 or placebo daily for up to 21 days in addition to standard care and antidiabetic medications. To be clear, all patients in the trial received standard of care treatment (over 70% in both groups received dexamethasone) with those in the drug group receiving AZD 1656 in addition. No deaths occurred in those receiving AZD1656 in the first week of treatment, whereas six deaths occurred in the placebo group. All-cause mortality rates within 28 days of admission favoured the AZD1656 patients, with only four deaths occurring, versus nine deaths in the placebo group.

Thirty patients in the AZD1656 group (38%) were discharged from hospital within seven days of admission, but only 18 patients (25%) receiving placebo treatment. AZD1656 treatment was shown to be safe and well-tolerated.

In addition to the clinical benefit observed in this high-risk patient group, the immunological data gathered from the trial strongly supports SGSC’s rationale for the ARCADIA study by confirming that AZD1656 is an immunomodulator which damps down the inflammatory response characteristic of COVID-19 infection, while enhancing the virus-specific immune response.

Thus far, only a small number of repurposed or repositioned drugs have demonstrated benefits in treating COVID-19 infection in early clinical study¹. SGSC believes that AZD1656 has the potential to become a valuable addition to the very small number of available COVID-19 drug treatments, offering a safer and more effective alternative to immunomodulatory treatments such as dexamethasone and other steroids, infused anti-cytokines (such as tocilizumab) and Janus kinase inhibitors².

AZD1656 has an important advantage over small molecule and antibody antiviral agents in that due to its immodulatory effect, efficacy is unlikely to be compromised in treating disease caused by new coronavirus variants. The highly infectious Omicron variant appears to be associated with milder disease symptoms and lower hospitalisation rates, but we may not be so fortunate with future variants. “Variant agnostic”, readily stockpiled, transported and easily administered treatments such as AZD1656 are essential for future pandemic preparedness.

¹ COVID-19 early treatment: real-time analysis of 1,489 studies. https://c19early.com. Accessed 3rd Match 2022

² NIH Covid-19 Treatment Guidelines. Table 4f. Characteristics of Immunomodulators. https://tinyurl.com/3jbeucyh Accessed 3rd March 2022

SGSC is actively engaged in commercial discussions with appropriate global and regional pharmaceutical companies, with the objective of outright sale, partnership in future development or securing funding for the additional clinical studies necessary to get this to market. Ideally AZD1656 would be evaluated in broader non-diabetic patient populations, both hospitalised patients and those at higher risk of hospitalisation due to underlying health conditions. Despite the unknowns around the evolution of the pandemic, SGSC believes that AZD1656 has the potential to generate significant long-term revenue.

The COVID-19 pandemic has been truly global, and SGSC believes that AZD1656 could be particularly valuable in countries where limited hospital resources, low vaccine uptake and a high prevalence of vulnerable individuals have conspired to push up hospitalisation and death rates.

About AZD1656

AZD1656 was originally developed by AstraZeneca as a diabetes treatment and has an extensive record of safety in clinical studies involving more than one thousand subjects. Preclinical data suggested a likely immune mode of action, leading SGSC to secure a licence to the agent as a therapy for inflammatory conditions.

In addition to the ARCADIA study supported by EML, the Mubadala Sovereign Wealth Fund, Chlodwig Enterprises and UKRI / Innovate UK, SGSC has actively built on the scope of AZD1656 through patent filing (COVID-19 combination treatment) and intends to exploit the beneficial immunomodulatory effect in immune dysfunction applications.

Clinical Study Report On Therapy To Treat Covid-19 Patients Completed (Issued on behalf of St George Street Capital and Excalibur Medicines Ltd)

St George Street Capital, a UK-based biomedical charity, and Excalibur Medicines Ltd., a biotechnology investment company, are pleased to announce the completion of the Clinical Study Report from the ARCADIA Phase ll clinical trial which was conducted to assess a therapy that could treat diabetic patients suffering from COVID-19.

St George Street Capital and Excalibur are now undertaking commercial discussions with potential licensees and partners, and examining options for the next stage of the development and approval process. Further analysis to determine the precise nature of the biological effects of AZD1656 that explain the observed clinical outcomes will also be conducted.

The finalisation of the CSR formally marks the end of the ARCADIA trial. The trial data has shown the following:

Efficacy: A strong trend towards reduced mortality in patients receiving AZD1656. The strong trend to improved mortality for patients on AZD1656 was observed on top of patients receiving other medication, including dexamethasone, as part of standard of care.

Safety and tolerability: AZD1656 was shown to be well-tolerated in this patient population with no serious adverse reactions (SARs) occurring. Overall, no safety concerns were identified regarding the use of AZD1656 in this patient population.

Diabetes, whether type 1 or 2, has been the leading single cause of co-morbidity during the pandemic and one in three of all deaths with COVID-19 in hospital in England have been associated with diabetes.

Professor John Martin of UCL, Chairman of St George Street Capital and PI on the Innovate UK grant awarded said: “The completion of the Clinical Study Report is a major milestone and we are encouraged by the trial findings which indicate that AZD1656, a simple oral tablet, has the potential to become a new treatment for COVID-19 – independent of viral mutations – initiating a new wave of therapies for clinicians in meeting this global challenge.”

Professor Sir Chris Evans, chairman and CEO of Excalibur Healthcare Services, the parent company of Excalibur Medicines Ltd., said: “We are delighted to have played our part arranging this trial and this report confirms the great potential of AZD1656 to help people who remain vulnerable to COVID-19.”

Notes to editors:

About the ARCADIA Trial

AZD1656 was identified by St George Street Capital as a potential treatment for people with diabetes infected with COVID-19.

The objectives of the ARCADIA clinical trial were to assess the safety and tolerability of a glucose kinase activator, AZD1656, and to determine the effect of the therapy on clinical improvement and mortality in people with diabetes hospitalised with COVID-19. The trial also explored whether AZD1656 benefits COVID-19 patients via its effects on immune function.

ARCADIA was a randomised, double-blind, placebo-controlled Phase II clinical trial involving 153 patients. ARCADIA was funded by international investment through Excalibur Medicines Ltd, including the Mubadala Sovereign Wealth Fund and an HM Government grant through the UKRI/Innovate UK programme.

About St George Street Capital

St George Street is a biomedical research charity on a mission to fast-track clinical trials so we can get new treatments as quickly as possible to the people who need them. We apply bold new thinking to unlock the therapeutic potential of therapies and science currently sitting on the shelf in pharma. We are a new type of charity, sourcing investment to accelerate clinical trials, where new science shows great potential and where patients and clinicians are calling out for treatments. St George Street was established in 2017 and brings together a powerful mix of expertise, from investors and business managers to clinic.

About Excalibur Medicines Ltd

Excalibur Medicines Ltd (EML) is a subsidiary of Excalibur Healthcare Services, founded by leading scientific entrepreneur, Professor Sir Chris Evans, OBE. EML brought together the scientific intellectual property, international funding and a world leading team to take forward the ARCADIA trial. Professor Evans and the Excalibur team sourced investment from Mubadala of Abu Dhabi, one of the world’s leading sovereign wealth funds, Excalibur itself, Chlodwig Enterprises, an international ESG investment company with a particular focus on life sciences and positive impact investments and several high net worth individuals.

Further information: Excalibur Medicines Ltd: Ramsay Smith, Media House International. 07788414856 ramsay@mediahouse.co.uk

Covid-19 Trial Update - 09/09/2021
Results from ARCADIA Phase II Clinical Trial of A Potential Therapy for COVID-19

St George Street Capital, the UK-based biomedical charity, is pleased to announce the receipt of the final data from the ARCADIA Phase II clinical trial which was conducted to assess a therapy to treat diabetic patients suffering from COVID-19.

In light of the encouraging trial results, St George Street Capital will immediately start to undertake commercial discussions with potential licensees and/or fundraise for further clinical trials to investigate AZD1656 in a larger study. Further analysis to determine the precise nature of the biological effects of AZD1656 that explain the observed clinical outcomes will also be conducted. The trial data has shown the following:

Efficacy: A strong trend towards reduced mortality in patients receiving AZD1656. This was noted in both mortality on treatment and all-cause mortality, which were lower in the AZD1656 group compared to the placebo group. The strong trend to improved mortality for patients on AZD1656 was observed on top of patients receiving other medication, including dexamethasone, as part of standard of care. Certain clinically and biochemically defined subsets of patients appeared to benefit most from treatment with AZD1656. The data from ARCADIA supports continued investigation of AZD1656 for the treatment of patients with COVID-19, with or without diabetes, in future clinical trials.

Safety and tolerability: AZD1656 was shown to be well-tolerated in this patient population with no serious adverse reactions (SARs) occurring. The degree of glycaemic control, as measured by the need to increase baseline medication requirements or the need to add additional diabetic medications, was no different between the AZD1656 group and the placebo group. The proportion of Serious Adverse Events (SAEs) was numerically lower in the AZD1656 group compared with the placebo group. The proportion of Treatment Emergent Adverse Events (TEAE) was also no different between the groups. Overall no safety concerns were identified regarding the use of AZD1656 in this patient population.

About the ARCADIA Trial
AZD1656 was identified by St George Street Capital as a potential treatment for people with diabetes infected with COVID-19.

The objectives of the ARCADIA clinical trial were to assess the safety and tolerability of a glucose kinase activator, AZD1656, and to determine the effect of the therapy on clinical improvement and mortality in people with diabetes hospitalised with COVID-19. The trial also explored whether AZD1656 benefits COVID-19 patients via its effects on immune function.

ARCADIA was a randomised, double-blind, placebo-controlled Phase II clinical trial involving 153 patients. ARCADIA was funded by international investment through Excalibur Medicines Ltd and an HM Government grant through the UKRI/Innovate UK programme.

Professor John Martin of UCL, Chairman of SGSC and PI on the Innovate UK grant awarded said: “The completion of ARCADIA marks a significant milestone in the history of the charity St George Street Capital. We have demonstrated our ability to rapidly deliver a clinical trial in an area of unmet clinical need, thus fulfilling our mission to accelerate the development of new treatments for people who need them. The promising results from this trial indicate that AZD1656, a simple oral tablet, has the potential to become a new treatment for COVID-19 – independent of viral mutations – initiating a new wave of therapies for clinicians in meeting this global challenge.”

Professor Sir Chris Evans, chairman and CEO of Excalibur Healthcare Services, the parent company of Excalibur Medicines Ltd., said: “We are hugely encouraged by this data and are delighted to have played our part arranging this trial. I am particularly grateful to His Royal Highness, the Crown Prince of Abu Dhabi, the Mubadala Sovereign Wealth Fund and our own government in supporting this project. We are looking forward to the next chapter in this exciting journey which could ultimately help people who remain vulnerable to COVID-19.”

TRIAL INITIATED TO TEST POTENTIAL NEW COVID-19 TREATMENT FUNDED BY UKRI GRANT AND EML

A new therapy that could treat people with diabetes suffering from COVID-19 is to undergo an advanced clinical trial in the UK.

The Medicines and Healthcare products Agency (MHRA) has approved the trial following new preclinical research that suggests a glucose kinase activator (AZD1656) could help diabetes sufferers infected with coronavirus by dampening the overactive response of the immune system typically acute in those patients with raised blood glucose levels. The trial will involve hospitalised patients with mild to moderate COVID-19 symptoms and if successful the compound could ultimately be prescribed by a GP for people with diabetes presenting with early COVID symptoms.

People living with diabetes face a significantly higher risk of dying with COVID-19. One in three of all deaths with COVID-19 in hospital in England have been associated with diabetes. Diabetes, whether type 1 or 2, has been the leading single cause of co-morbidity during this pandemic. People living with type 1 diabetes are at three and a half times the risk, and people living with type 2 diabetes are at double the risk of dying in hospital with the virus compared to people without diabetes. Learn more.

This exciting new development, believed to be unique among the hundreds of COVID-related research projects around the world today, was arranged and structured by Professor Sir Chris Evans, Chairman and CEO of Excalibur Healthcare Services, through a new vehicle, Excalibur Medicines Ltd, which brought together the scientific intellectual property, international funding and a world leading team to drive the project forward. The idea of investigating AZD1656 in this setting was conceived by Professor John Martin and his team at St George Street, a UK-based biomedical research charity. The drug was originally developed for another indication by Astra Zeneca, who have agreed to provide the drug substance for the trial, while St George Street will lead the clinical trial.

The trial, named ARCADIA, will commence with Professor Evans and the Excalibur team having sourced investment from Mubadala of Abu Dhabi, one of the world’s leading sovereign wealth funds, Excalibur itself and several high net worth individuals. This is in addition to funding secured from the UK Government through the UKRI / Innovate UK programme. This enables the trial to go ahead at speed in 150 patients over a 4 month timeframe at multiple sites in the UK.

Professor Evans said: “All of us supporting this trial recognise this drug has the potential to make a huge difference to people with diabetes who are unfortunate enough to contract coronavirus and we foresee a significant impact on the level of fatalities in the future. Treatments such as this could be vital as we are likely to be living with this horrific virus for some time to come.”

David Tapolczay, CEO St George Street, said: “Given the current crisis, we have paused all our current research programmes to focus totally on this clinical trial and evaluate this potentially life-saving new drug. Our charity was set up to accelerate the delivery of treatments to patients and this ethos is needed now more than ever before. We want to do everything in our power to ensure patients recover from this terrible virus.”

Professor John Martin, Chairman of the charity and Principal Investigator on the grant awarded by UKRI, said: “Novel research thinking in an interdisciplinary group combined with the drive of the charity and the excellent relationship we have with Astra Zeneca have produced the potential for a great therapeutic leap. This also has potential for non-diabetic patients with COVD-19.”