Appendix 4C Quarterly Activity Report

NEW YORK, July 29, 2021 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today provided an update on its pipeline of late-stage product candidates, and an activity report for the fourth quarter ended June 30, 2021.

“During the quarter we made significant progress in both regulatory and clinical outcomes for our lead product candidate, remestemcel-L. FDA’s CBER has recently recommended the next steps in the potential approval pathway for remestemcel-L in the treatment of steroid-refractory acute graft versus host disease in children,” said Silviu Itescu, Chief Executive of Mesoblast. “Additionally, as COVID infections continue to surge, the 90-day survival outcomes from the remestemcel-L trial in adults with COVID ARDS demonstrated the potential for durable benefit of this therapy in certain segments experiencing the most extreme complication of this disease.”

Key operational highlights:

• Mesoblast met with the United States Food & Drug Administration (FDA) on potential pathways to regulatory approval of its lead technology platform product remestemcel-L for steroid refractory acute graft versus host disease (SR-aGVHD) in children and acute respiratory distress syndrome (ARDS) in adults with COVID-19
• Regarding SR-aGVHD, FDA’s Center for Biologics Evaluation and Research (CBER) recommended that Mesoblast as a next step discuss with CBER’s review team at the Office of Tissue and Advanced Therapies (OTAT) our approach to address certain outstanding chemistry, manufacturing and controls (CMC) items, including potency assays, which could support a resubmission of the current Biologic License Application (BLA) with a six-month review period
• Regarding COVID ARDS, Mesoblast met with the FDA this week to determine the registration pathway for approval of remestemcel-L in this indication, with formal minutes expected in coming weeks
• Results from the randomized controlled trial of remestemcel-L in 222 ventilator-dependent COVID-19 patients with moderate/severe acute respiratory distress syndrome (ARDS) were recently highlighted at the biennial Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases conference hosted by the University of Vermont, Burlington, VT, and at the International Society for Cell & Gene Therapy (ISCT) Scientific Signatures Series event on Cell and Gene-Based Therapies in Lung Diseases and Critical Illnesses
• The presented data included improved respiratory function in patients treated with remestemcel-L, as well as 90-day survival outcomes showing 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
• Mesoblast has 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
• Mesoblast filed requests and expects to hold meetings with the FDA during the next two quarters to discuss the pathways to US regulatory approvals for its second technology platform rexlemestrocel-L following the recently completed Phase 3 trials in patients with chronic heart failure and chronic inflammatory back pain due to degenerative disc disease
• Mesoblast and its partner in Europe and Latin America, Grünenthal, amended their collaboration agreement in line with a strategy to achieve regulatory harmonization, cost efficiencies and streamlined timelines aiming to leverage the results from a planned US trial in support of potential product approvals in both US and EU

Cash Flow Report for the Fourth Quarter FY2021

Cash on hand at the end of the quarter was US$136.4 million.

Total Operating Activities resulted in net cash usage of US$20.7 million in the quarter ended June 30, 2021. This included an investment of US$10.8 million associated with remestemcel-L for SR-aGVHD and COVID-19 ARDS. Specifically:

• Sales of TEMCELL^® HS Inj.¹ in Japan for the treatment of aGVHD continue to recover from the effects of the temporary shutdown in production during mid-2020 which was undertaken in order to increase capacity to meet growing demand for the product
• Revenues from TEMCELL^® royalties for the quarter ended June 30, 2021 were US$1.9 million compared to US$0.7 million in the quarter ended June 30, 2020. Royalty receipts for the quarter were US$1.9 million, reflecting revenues recognized in the prior quarter
• Research and Development payments were US$5.9 million for the current quarter. This comprises payments for the recently completed trials in COVID-19 ARDS, CHF and CLBP, as well as potency assay work in support of these programs
• Product manufacturing & operating costs and manufacturing commercialization payments were US$8.1 million for the current quarter, the majority being for commercial manufacturing and inventory build in anticipation for product launch of remestemcel-L
• Payments to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter, comprise approximately US$643,000 in Non-Executive Director fees and Executive Director’s salary
  

A copy of the Appendix 4C – Quarterly Cash Flow Report for the fourth quarter FY2021 is available on the investor page of the company’s website www.mesoblast.com.

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.

The 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 reduced overall mortality by 14% across the entire population of treated patients (n=217), and by 46% in the pre-specified population of patients under age 65 (n=123). 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.

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 2040 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 has completed Phase 3 trials of rexlemestrocel-L for advanced chronic heart failure and chronic low back pain. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease and moderate to severe acute respiratory distress syndrome. 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

References / Footnotes

1. TEMCELL^® HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.
   

Forward-Looking Statements
This announcement includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of Mesoblast’s preclinical and clinical studies, and Mesoblast’s research and development programs; Mesoblast’s ability to advance product candidates into, enroll and successfully complete, clinical studies, including multi-national clinical trials; Mesoblast’s ability to advance its manufacturing capabilities; the timing or likelihood of regulatory filings and approvals, manufacturing activities and product marketing activities, if any; the commercialization of Mesoblast’s product candidates, if approved; regulatory or public perceptions and market acceptance surrounding the use of stem-cell based therapies; the potential for Mesoblast’s product candidates, if any are approved, to be withdrawn from the market due to patient adverse events or deaths; the potential benefits of strategic collaboration agreements and Mesoblast’s ability to enter into and maintain established strategic collaborations; Mesoblast’s ability to establish and maintain intellectual property on its product candidates and Mesoblast’s ability to successfully defend these in cases of alleged infringement; the scope of protection Mesoblast is able to establish and maintain for intellectual property rights covering its product candidates and technology; estimates of Mesoblast’s expenses, future revenues, capital requirements and its needs for additional financing; Mesoblast’s financial performance; developments relating to Mesoblast’s competitors and industry; and the pricing and reimbursement of Mesoblast’s product candidates, if approved. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast’s actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

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