SURVIVAL OUTCOMES IN COVID-19 ARDS PATIENTS TREATED WITH REMESTEMCEL-L

Melbourne, Australia; May 31 and New York, USA; May 30, 2022: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today provided an update on survival outcomes from the randomized controlled trial of remestemcel-L in ventilator-dependent COVID-19 patients with moderate/severe acute respiratory distress syndrome (ARDS) and plans for a pivotal trial with collaborative investigators. 

Through the initial 90 days, remestemcel-L reduced mortality by 48% compared to controls in a prespecified analysis of 123 patients below age 65 (26% vs 44%, p=0.038),(1,2) but not in 97 patients over age 65, as previously reported. In an exploratory analysis in patients under age 65 who also received dexamethasone as part of their standard of care, remestemcel-L reduced 90-day mortality by 77% compared to controls (14% vs 48%, p=0.0037).1,2 These early survival outcomes in the remestemcelL group relative to controls were maintained at later timepoints in those under age 65, with a 42% reduction in mortality through 12 months and with continued observed synergy with dexamethasone (p<0.05). (1,2) 

The Phase 2/3 trial in COVID ARDS randomized 1:1 to either standard of care alone or standard of care plus two doses of remestemcel-L 2 million cells/kg 3-5 days apart. This two-dose regimen of remestemcel-L was the same as in the earlier compassionate use program where 11 of 12 patients were younger than 65 and 75% successfully came off ventilatory support. These pilot study results were recently published in the peer-reviewed journal Cytotherapy. In contrast, remestemcel-L is used at an eight-dose regimen of 2 million cells/kg over four weeks in patients with steroid-refractory acute graft versus host disease (SR-aGVHD). The established extended dosing regimen in SR-aGVHD, another severe inflammatory condition, provides a rationale for exploring an extended course of remestemcel-L in older patients with COVID ARDS who have higher levels of inflammation. 

ARDS remains a major cause of mortality for COVID-19 patients who are immunocompromised, unvaccinated, or with comorbidities, as well as those with seasonal influenza and other pathogens. Mesoblast is working together with investigators from a clinical trial network focused on acute lung injury at over 40 sites across the United States affiliated with Vanderbilt University Medical Center to design and implement a pivotal trial of remestemcel-L to reduce mortality in high-risk patients with ARDS.

About remestemcel-L

 
Remestemcel-L, is an investigational therapy comprising of culture-expanded mesenchymal stromal cells (also known as mesenchymal stem cells) derived from the bone marrow of an unrelated donor (4). Remestemcel-L is thought to have immunomodulatory properties to counteract the cytokine storms that are implicated in various inflammatory conditions by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues (4). In the Phase III study in COVID-19-related ARDS, remestemcel-L is administered as two infusions of 2x106 MSC/kg given three to four days apart.3 The administration of remestemcel-L for the treatment of all-cause ARDS could be the subject of further exploration.

About Mesoblast 

Mesoblast is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of late-stage product candidates which respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process. 

Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide. 

Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease, biologic-resistant inflammatory bowel disease, and acute respiratory distress syndrome. Rexlemestrocel-L is in development for advanced chronic heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.

Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast 

Reference / Footnotes 

1. All p-values are descriptive and not adjusted for multiplicity 

2. Hazard Ratios calculated using Cox regression proportional hazards model without adjustment; pvalue from log rank test 

3. Whittaker Brown S., et al. Mesenchymal Stromal Cell Therapy for Acute Respiratory Distress Syndrome due to COVID-19. Cytotherapy, April 2022, https://doi.org/10.1016/j.jcyt.2022.03.006

4. National Health Service - National Institute for Health Research. Remestemcel-L (Prochymal) for steroid refractory acute graft versus host disease – second line.; 2015 http://www.io.nihr.ac.uk/wp-content/uploads/migrated/Remestemcel-L-July2015.pdf

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