Dimerix Limited announced positive results in a Phase 2 clinical trial in individuals with diabetic kidney disease to support further development of its DMX-200 drug candidate. The Phase 2 study was a double-blind, randomised, placebo-controlled, crossover study designed to evaluate the safety and efficacy of DMX-200 in patients with diabetic kidney disease who are receiving a stable dose of standard of care, irbesartan. Patients must have been receiving irbesartan for at least 12 weeks prior to being included in the trial. Each participant in the study received 12 weeks DMX-200 preceded or followed by 12 weeks placebo, separated by a 6-week washout period. Unlike some other investigational drugs currently in development for kidney diseases, patients stayed on the standard of care angiotensin receptor blockade throughout the study. As a result, the reduction in albuminuria observed from DMX-200 is in addition to any reduction in albuminuria expected from background therapy that would have occurred prior to starting on DMX-200. A total of 45 patients were enrolled in the study, with 40 patients meeting all pre-defined criteria required for inclusion in the final analysis in accordance with the protocol. The study administered 240mg of oral DMX-200 to patients with diabetic kidney disease already taking a stable 300 mg dose of the angiotensin receptor blocker irbesartan. The primary endpoint was the percent change from baseline in 24-hour albuminuria after 12 weeks of treatment with DMX-200 as compared to placebo. Although a statistically significant difference in reduction of albuminuria for the primary endpoint was not seen, with overall analysis showing no conclusive benefit of DMX-200 compared to placebo across the entire cohort of diabetic kidney disease patients (2% difference), analysis showed statistically and clinically significant variation in treatment response for patients with higher levels of albuminuria at study baseline. A statistically significant trend was observed between treatment effect in patients that entered the study with a baseline albuminuria value above 57mg/mmol (500mg/g), a recognised clinically relevant threshold for treatment of kidney disease, compared to those with lower baseline levels of albuminuria below 57mg/mmol (study inclusion criteria was 30mg/mmol, which is also a recognised threshold for treatment). Analysis across this population demonstrated that those with a starting level of higher than 57mg/mmol demonstrated an average 18% reduction in albuminuria on DMX-200 versus placebo (p= .03; n=26). Although all prior studies also had the 30mg/mmol inclusion criteria, this is the first exploratory study that enrolled diabetic patients with baseline albuminuria below 100mg/mmol. This top line disease burden-specific treatment effect is consistent with the recent Phase 2a study in patients with focal segmental glomerulosclerosis (FSGS), where all patients had a starting baseline albuminuria of over 179mg/mmol who showed a 29% fall in proteinuria against placebo, and the previous Phase 2a study completed in 2017 data in chronic kidney disease study that showed a 36% fall in albuminuria in a group of patients with diabetic kidney disease against baseline and who also all had a starting baseline over 100mg/mmol. In the sub-group above 57mg/mmol starting albuminuria there was a compelling 64% of patients with a reduction in albuminuria level and 56% achieving a greater than 25% reduction in albuminuria versus placebo. Top line data of all patients on study suggests that 25% demonstrated a greater than 30% reduction in albuminuria on treatment with DMX-200 versus placebo. The safety findings show DMX-200 was safe and well-tolerated, with no notable variation in the incidence or severity of adverse events between treatment with DMX-200 or placebo. There were three patient withdrawals from the study (none related to the study drug) and there were no serious adverse events related to the drug reported. The safety data findings are entirely consistent with existing safety data on DMX-200. Further investigation is underway exploring the relationship between treatment effect in this study and other patient factors, including inflammatory biomarkers, concomitant medications or legacy effect, and these data will be published in due course. Findings from this in-depth analysis of the study data will be used to inform the design of future clinical studies of DMX-200 in kidney diseases, including diabetic kidney disease. A legacy effect implies continued additional benefit after a trial participant has ceased taking active drug and can be an indicator that the drug may be having a lasting effect on the function of the kidney, thereby modifying the disease. As with previous studies, these data suggest that DMX-200 does provide benefit to patients that have progressed in kidney disease severity, and thus have a higher inflammatory response within the kidney. This is also consistent with the proposed mechanism of action of DMX-200 whereby patients with higher baseline levels of albuminuria, and so inflammatory processes, responded to treatment with larger magnitudes than those with lower initial levels of these inflammatory drivers. The study has delivered data that is consistent with prior data, and which adds to the growing body of evidence to support development of DMX-200 in indications where activation of CCR2, the receptor targeted by DMX-200, is driving inflammatory processes and disease progression. In parallel to the results announced now, Dimerix continues to undertake planning for its proposed Phase 3 pivotal program in FSGS, a rare kidney disorder without an approved pharmacologic treatment that often leads to end-stage kidney failure for which Dimerix announced positive clinical study results in July 2020. This mechanism of increased treatment effect at higher levels of inflammatory disease burden is also consistent with the planned use of DMX-200 for the treatment of Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19 where high concentration of MCP-1 in lung fluid is correlated with poor patient outcomes and where DMX-200 may have the maximum effect. In the meantime, multiple patients from both the FSGS and the diabetic kidney disease study, as well as the previous Phase 2 study in 2017, continue on treatment with DMX-200 through the TGA's Special Access Scheme following respective study completion. In addition to the diabetic kidney disease and FSGS renal programs, Dimerix continues to work on a study in patients with Acute Respiratory Distress Syndrome associated with COVID-19, and DMX-700 in Chronic Obstructive Pulmonary Disease.