Mesoblast Limited presented 90-day survival outcomes from the 222-patient randomized controlled trial of remestemcel-L in ventilator-dependent COVID-19 patients with moderate/severe acute respiratory distress syndrome (ARDS) at an invited presentation on July 17 to the International Society for Cell & Gene Therapy (ISCT) Scientific Signatures Series on Cell and Gene Therapies in Lung Diseases and Critical Illnesses. The results showed that two doses of remestemcel-L at days 3-5 conferred durable survival benefit through at least 90 days in the pre-specified subgroup of patients under age 65. Key presentation findings were: Remestemcel-L significantly reduced mortality by 48% at 90 days compared to controls in a pre-specified analysis of 123 treated patients under 65 years old, 26% versus 44%, Hazard Ratio (HR) 0.52, 95% CI (0.277, 0.964), p=0.038.1,2 This compares favourably with the 46% mortality reduction reported at 60 days (p=0.048)1,2 and indicates a durable treatment benefit in this patient population.; Remestemcel-L was even more effective when evaluated in an exploratory analysis in patients on dexamethasone as part of their standard of care, with 90-day mortality being reduced by 77% compared to controls under 65 who received dexamethasone, 14% versus 48%, HR 0.23, 95% CI (0.080, 0.681), p=0.00371,2; These survival benefits were accompanied by significant improvements relative to controls in pre-specified secondary endpoints of ventilator-free days, respiratory function as assessed by ARDS severity, and overall clinical improvement on a 7-point ordinal scale.; Despite a treatment-related improvement in respiratory function at day 7, there was no mortality reduction in the 97 treated patients over age 65, suggesting the need for more prolonged or higher dosing of anti-inflammatory therapy in these patients who may have a more exuberant inflammatory response associated with defective immune-mediated viral clearance mechanisms. Recently published guidance to industry by the U.S. Food and Drug Administration (FDA)3 has recommended demonstration of mortality benefit for at least 60 days in critically ill patients. Mesoblast will be meeting shortly with the FDA to discuss the durable mortality reduction seen in patients under 65 years old who received remestemcel-L in this randomized controlled trial, and the regulatory pathway for remestemcel-L in this patient population. Mesoblast entered into a license and collaboration agreement with Novartis for the development, manufacture, and commercialization of remestemcel-L, with an initial focus on the treatment of acute respiratory distress syndrome (ARDS), including that associated with COVID-19. The agreement remains subject to certain closing conditions, including time to analyze the results from this COVID-19 ARDS trial. About the Trial of Remestemcel-L in Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. The trial enrolled 222 mechanically ventilated COVID-19 patients with moderate/severe ARDS across the US, of whom 217 were randomized 1:1 and received either standard of care alone or standard of care plus 2 intravenous infusions of remestemcel-L at a dose of 2 million cells/kg 3-5 days apart. This was the same remestemcel-L dosing regimen used in the earlier compassionate use program where 11 of 12 patients were younger than 65 and 75% successfully came off ventilatory support. Tha trial was halted in December 2020 after the Data Safety Monitoring Board (DSMB) performed a third interim analysis on the trial's first 180 patients, noting that the trial was not likely to meet the 30-day mortality reduction endpoint at the planned 300 patient enrolment. The trial was powered to achieve a primary endpoint of 43% reduction in mortality at 30 days for treatment with remestemcel-L on top of maximal care. The DSMB recommended that the trial complete with the enrolled 222 patients, and that all be followed-up as planned. At follow-up through day 60, remestemcel-L showed a positive but non-significant trend in overall mortality reduction across the entire population of treated patients (n=217). In the pre-specified population of patients under age 65 (n=123), remestemcel-L reduced mortality through day 60 by 46%, but not in patients 65 or older (n=94). In an exploratory analysis through day 60, remestemcel-L reduced mortality by 75% and increased days alive off mechanical ventilation in patients under age 65 when combined with dexamethasone, in comparison with controls on dexamethasone.