Dimerix Limited advised that 662 patients have now been recruited into the feasibility/Phase 3 ACE2 renin angiotensin system (RAS) modulation study domain in patients with COVID-19 pneumonia, which incorporates DMX-200. Of those 662 subjects, 485 have been recruited in sites across the UK, and represents a 39% increase since 23 November 2021. DMX-200 has regulatory and ethics approval in both the UK and the Netherlands and is available at sites for administration to patients randomised to the DMX-200 treatment arm. Additional sites in other European countries are anticipated in the coming months, including Italy and France. A planned, routine review of the ACE2 RAS modulation REMAP-CAP study domain in Europe by an independent REMAP-CAP DSMB has been completed and "the DSMB did not note any significant or concerning safety issues. The DSMB recommendation is to continue enrolling within the study overall and within the [ACE2 RAS] domain". A review by an independent DSMB is consistent with good clinical practice in clinical trials. The primary responsibilities of the DSMB are to review and evaluate the available study data for participant safety, study conduct and progress, and to make recommendations concerning the continuation, modification, or termination of the trial. The company's approach is based on a clear scientific rationale, is unique and potentially complementary to others being investigated globally, and importantly if effective in this study, would likely be effective against any strain as well as potentially other pneumonias with a common mechanism of action. Antiviral medications are typically effective at preventing damage caused by a virus when administered within 3-5 days of infection (when many are asymptomatic), as the treatment aims to minimise viral replication. 3 Further, antivirals are usually very specific for a virus and sometimes even the particular strain of the virus. In contrast, DMX-200 does not rely on early inhibition of viral replication but aims to prevent the damaging immune response and lung flooding regardless of vaccination or antiviral treatment. As such, DMX-200 may be beneficial for patients with a wide range of respiratory diseases in addition to the various COVID-19 variants. COVID-19 Epidemiology - During the week 29 November to 5 December, the WHO reported COVID-19 deaths increased by 10% globally, with over 52,500 new deaths reported during that week alone. 4 The African Region reported the largest increase in new weekly cases (111% increase compared to the previous week) and a corresponding 82% increase in hospital admissions due to COVID-19 during the same period. However, Europe continues to report the highest incidence of COVID-19, with 65% of new cases of COVID-19 and 55% of COVID-19 deaths globally during the week ending 5th December 2021.4 As of 5 December, nearly 265 million confirmed cases and over 5.2 million deaths have been reported globally. On 13th December, the World Health Organization's (WHO) provided an update on the variants of concern. In particular, the WHO determined that the overall risk related to the new variant of concern Omicron remains very high, as there was still limited data on the clinical severity of Omicron and the high transmission rates could lead to further surges with severe consequences. ACE2 RAS Modulation Domain Design In the REMAP-CAP approved ACE2 RAS study domain, participants who meet platform entry criteria will be randomised to receive one RAS blockade treatment arm or a control: ARB in combination with DMX-200; Angiotensin receptor blocker (ARB); Angiotensin converting enzyme (ACE) inhibitor; No RAS inhibitor (no placebo). The feasibility/Phase 3 study is a multi-centre, randomised, standard of care vs multi-active comparators platform study in patients with COVID-19. The overarching REMAP-CAP study incorporating DMX-200 is funded by the European Union through the H2020 Project called "Rapid European COVID-19 Emergency Research response," which uses the acronym "RECOVER". REMAP-CAP: DMX-200 is included in the investigator-led feasibility/Phase 3 study in patients with COVID-19 pneumonia, driven by a consortium of global trialists, clinicians and experts through the study sponsor, REMAP-CAP. The study, endorsed by the World Health Organization (WHO), has initiated a master protocol across over 300 clinical sites across eight global regions. REMAP-CAP has investigated 48 active treatments for COVID-19, mostly repurposed and novel medicines, including for registration purposes. The study has now recruited over 7,000 patients with suspected or proven COVID-19 overall.6 Two Phase 3 Clinical Studies in Respiratory Complications Associated with COVID-19 Dimerix lead drug candidate, DMX-200, is being studied as part of two different investigator-led feasibility/Phase 3 studies in COVID-19 patients with respiratory complications, both of which are actively recruiting. As announced on 3 September 2020, for one of these studies Dimerix was awarded $1 million from MTPConnect's Biomedical Translation Bridge (BTB) program provided by the Australian Government's Medical Research Future Fund, with support from UniQuest. Dimerix proactively supports both studies driven by the REMAP-CAP and CLARITY 2.0 teams in providing them information for the regulatory submissions and in supplying DMX-200 to the study sites. Dimerix looks forward to reporting on progress and as key milestones are met. Dimerix continues to progress the Phase 3 pivotal program in FSGS, a rare kidney disorder without an approved pharmacologic treatment that often leads to end-stage kidney failure, as well as assess the next study design in diabetic kidney disease patients and finally advance the COPD program towards the clinical stage of development.