Edesa Biotech, Inc. (NASDAQ:EDSA), a clinical-stage biopharmaceutical company developing host-directed therapeutics for immuno-inflammatory diseases, today reported favorable exploratory data for paridiprubart, its first-in-class anti-TLR4 monoclonal antibody, in patients with acute kidney injury (AKI) and respiratory distress.

The data, which expand upon previously reported Phase 3 clinical results through new exploratory analyses, will be presented today in a scientific oral presentation at the 63rd European Renal Association (ERA) Congress in Glasgow, Scotland. These new analyses are based on exploratory evaluations from the company's completed clinical studies in hospitalized patients with acute respiratory distress syndrome (ARDS).

Because TLR4-mediated inflammation plays a central role in both lung and kidney injury, Edesa conducted additional analyses to evaluate paridiprubart's effect in patients with concurrent AKI, a high-mortality complication that currently lacks approved, targeted pharmacological therapies. Patients with AKI and ARDS represent a high-risk population, with substantially elevated mortality relative to patients without renal dysfunction. Among the findings, paridiprubart plus standard of care treatments (SOC) was associated with a 32% relative reduction in mortality in these AKI patients at 28 days. The observed reductions in mortality were supported by concordant improvements in kidney-specific outcomes, including the MAKE30 composite endpoint.

"These exploratory findings in a high-risk subgroup provide an important clinical perspective on how paridiprubart's mechanism of action may translate beyond the lungs. Acute kidney injury shares many of the same inflammatory pathways seen in severe respiratory illness, and the consistency we're observing across these larger analyses helps reinforce the biological rationale for further evaluation in AKI patients," said Par Nijhawan, MD, Chief Executive Officer of Edesa Biotech.

Key Findings*

The AKI findings reported here expand on previously reported exploratory results in 48 AKI patients from the Phase 3 ITT population by incorporating additional patients from the Phase 2 study and the broader 278-patient treatment population, for a combined AKI cohort of 101 patients. The AKI subgroup included all patients with AKI present at baseline, and outcomes were analyzed using the same multivariate methodology prespecified in the Phase 3 statistical analysis plan for ARDS.

Patients in this AKI cohort were severely ill, with approximately 90% having moderate-to-severe ARDS at baseline and approximately 50% requiring invasive mechanical ventilation or ECMO, consistent with a population at high risk of mortality. Mean age was 58 years.

28-Day Mortality

Paridiprubart + SOC reduced adjusted 28-day mortality to 33% (95% CI: 28%–39%) from 49% (95% CI: 41%–57%) with placebo + SOC, a 32% relative reduction in the risk of death (nominal p<0.005).

MAKE30 (Major Adverse Kidney Events at 30 days)

Using the same multivariate logistic regression methodology, paridiprubart + SOC reduced the adjusted incidence of MAKE30 at Day 30 to 41% (95% CI: 36%–46%) from 53% (95% CI: 47%–60%) with placebo + SOC, a 23% relative reduction in MAKE30 incidence (nominal p<0.005). MAKE30 is a composite endpoint comprising all-cause mortality, initiation of renal replacement therapy, or persistent renal dysfunction through Day 30.

Safety and Tolerability

Paridiprubart was well tolerated in the AKI subpopulation. Overall rates of adverse events, serious adverse events, and infections were low and showed no significant differences between the paridiprubart and placebo groups. The safety profile was consistent with more than 400 patients treated across clinical studies to date.

These exploratory findings are consistent with the hypothesis that modulation of TLR4-mediated inflammation may influence multi-organ dysfunction in critically ill patients, and are directionally consistent with the previously reported Phase 3 results. Since AKI represents a high-mortality subgroup within ARDS, the company believes the consistency of benefit observed here reinforces the rationale for paridiprubart's ongoing development in ARDS. In addition, the company believes these data support further evaluation of paridiprubart in prospective studies specifically targeting patients with AKI and may inform the design of future clinical trials in this high-unmet need population.

* Estimated using multivariate logistic regression-derived risk differences (95% confidence intervals). Nominal p-values, not adjusted for multiplicity. These analyses are exploratory in nature and were not prespecified. Results should be interpreted with caution and are intended to generate hypotheses for further clinical evaluation. Confirmatory studies would be required to establish efficacy in AKI.

Presentation

Edesa's abstract was selected for oral presentation at the ERA Congress. The presentation, titled "Exploratory Analysis of Paridiprubart, an Anti-TLR4 Antibody, in Patients with Acute Kidney Injury and Respiratory Distress," is scheduled today at approximately 4:30 pm BST. The presentation will be available in the Events section of the Edesa Biotech website.

About Paridiprubart