Mesoblast Ltd 6-K, filed Jan 19, 2021
Mesoblast Ltd (MESO)
About this 6-K
Mesoblast Ltd filed this 6-K on January 19, 2021.
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UNITED STATES |
Washington, D.C. 20549
Form 6-K
Report of Foreign Private Issuer
Pursuant to Rule 13a-16 or 15d-16 under the Securities Exchange Act of 1934
For the month of January 2021
Commission File Number 001-37626
Mesoblast Limited
(Exact name of Registrant as specified in its charter)
Not Applicable
(Translation of Registrant’s name into English)
Australia
(Jurisdiction of incorporation or organization)
Silviu Itescu
Chief Executive Officer and Executive Director
Level 38
55 Collins Street
Melbourne 3000
Australia
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover Form 20-F or Form 40-F:
Form 20-F ☑ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):
Yes ☐ No ☑
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):
Yes ☐ No ☑
INFORMATION CONTAINED ON THIS REPORT ON FORM 6-K
On January 11, 2021, Mesoblast Limited filed with the Australian Securities Exchange a new release announcement, which is attached hereto as Exhibit 99.1, and is incorporated herein by reference.
On January 12, 2021, Mesoblast Limited filed with the Australian Securities Exchange a new release announcement and investor presentation, which are attached hereto as Exhibit 99.2 and Exhibit 99.3, and are incorporated herein by reference.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly organized.
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Mesoblast Limited |
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/s/ Niva Sivakumar |
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Niva Sivakumar |
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Company Secretary
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Dated: January 19, 2021
INDEX TO EXHIBITS
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99.1 |
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Press release of Mesoblast Ltd, dated January 11, 2021. |
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99.2 |
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Press release of Mesoblast Ltd, dated January 12, 2021. |
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99.3 |
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Investor presentation of Mesoblast Ltd, dated January 12, 2021. |
Exhibit 99.1
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SINGLE DOSE OF REXLEMESTROCEL-L PROVIDES SUBSTANTIAL AND DURABLE REDUCTION IN HEART ATTACKS, STROKES AND CARDIAC DEATH IN PATIENTS WITH CHRONIC HEART FAILURE
Melbourne, Australia; January 11, and New York, USA; January 10, 2021: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced additional results from the landmark DREAM-HF randomized controlled Phase 3 trial in 537 treated patients with chronic heart failure with reduced left ventricular ejection fraction (HFrEF) who received rexlemestrocel-L (REVASCOR®) or control sham. A single dose of rexlemestrocel-L resulted in substantial and durable reductions in heart attacks, strokes, and cardiac deaths. Since existing therapies have only minimal or no benefit on these endpoints, these notable outcomes may signal a breakthrough in addressing the principal unmet needs in patients with chronic heart failure. The results of this trial identify New York Heart Association (NYHA) class II HFrEF patients as the optimal target population for greatest rexlemestrocel-L treatment effect, and therefore a focus for registration and commercialization of rexlemestrocel-L in the largest market in heart failure.
The incidence of heart attacks and strokes were reduced by 60% over a median follow-up period of 30 months following a single dose of rexlemestrocel-L in the population of 537 patients with New York Heart Association (NYHA) class II or III chronic heart failure (5% vs 13%, p=0.002). Patients who received rexlemestrocel-L had a 68% reduction in the rate of recurrent hospitalizations from non-fatal heart attacks or strokes compared with controls, with a hospitalization rate of 1.90 per 100 patient-years of follow-up in the rexlemestrocel-L arm versus 5.95 per 100 patient-years of follow-up in the control arm (p=0.0002).
The incidence of death from cardiovascular causes was reduced by 60% following a single dose of rexlemestrocel-L in the 206 patients with NYHA class II disease (8% vs 20%, p=0.037), a significant reduction which was evident in both ischemic and non-ischemic subgroups as well as diabetic and non-diabetic patients. Whereas NYHA class II controls progressed to cardiac death rates of NYHA class III patients after a period of approximately 20 months of disease stability, NYHA class II patients treated with a single dose of rexlemestrocel-L did not show such cardiac death progression (p=0.004 compared to Class II control patients).
The combination of the three pre-specified outcomes of cardiac death, heart attack or stroke into a single composite outcome - called the three-point Major Adverse Cardiovascular Event (MACE) is a well-established endpoint used by the United States Food and Drug Administration (FDA) to determine cardiovascular risk. Rexlemestrocel-L significantly reduced this three-point MACE by 30% compared to controls across the population of 537 patients (20.6% vs 30%, p=0.027). In the NYHA class II subgroup of 206 patients, rexlemestrocel-L reduced the three-point MACE by 55% compared to controls (13% vs 29%, p=0.009).
The ability of rexlemestrocel-L to significantly impact cardiac death, heart attacks and strokes on top of maximal HFrEF therapy reflects the unique mechanisms of action of this allogeneic cellular therapy on reduction of inflammation and improved microvasculature. The unchecked intra-cardiac inflammation in HFrEF patients causes progressive loss of heart muscle, replacement with scar tissue, and death. Persistent inflammation in the blood circulation also results in accelerated atherosclerosis with plaque progression and instability resulting in plaque rupture and potential blockage of major arteries. The net result is high rates of heart attacks and strokes in chronic HFrEF patients. Rexlemestrocel-L reduces inflammatory cytokine production by immune cells and generates an improved local network of blood vessels in the damaged heart that has the potential protect against heart muscle cell death and replacement by scar tissue. Reduction in inflammation is the likely explanation for the observed reduction in incidence of heart attacks and strokes in patients who received rexlemestrocel-L.
Based on the observed reduction in mortality and morbidity in this Phase 3 trial, Mesoblast intends to meet with the FDA to discuss a potential approval pathway.
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Mesoblast Limited
www.mesoblast.com |
Corporate Headquarters Level 38 55 Collins Street Melbourne 3000 Victoria Australia
T +61 3 9639 6036 F +61 3 9639 6030 |
United States Operations 505 Fifth Avenue Third Floor New York, NY 10017 USA
T +1 212 880 2060 F +1 212 880 2061 |
Asia 21 Biopolis Road #01-22 Nucleos (South Tower) SINGAPORE 138567
T +65 6570 0635 F +65 6570 0176 |
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About Chronic Heart Failure
Heart failure affects approximately 6.5 million people in the US and 26 million people globally, with increasing prevalence and incidence. Chronic heart failure is a progressive disease associated with cardiac and systemic inflammation and a high mortality rate that approaches 50% at 5 years as patients progress beyond NYHA class II disease. In addition, these patients are at high risk of recurrent heart attacks and strokes, reflecting the high degree of systemic inflammation and progressive atherosclerosis associated with chronic heart failure. The high rate of cardiac death, heart attacks and strokes accompanying disease progression continues to be the most significant unmet need in this patient population since new therapies that have reduced recurrent hospitalizations due to cardiac decompensation have not materially impacted these MACE outcomes.
About the DREAM HF Phase 3 Trial
Clinical outcomes were evaluated in 537 treated advanced HFEF patients (206 with NYHA class II disease and 331 with NYHA class III disease) randomized 1:1 to either a sham-control procedure or a transendocardial injection by catheter of rexlemestrocel-L (150 million cells). Inclusion criteria enriched the trial for patients with advanced disease by requiring a prior heart failure hospitalization over the past one-to-nine months and/or a N-terminal pro–B-type natriuretic peptide (NT-proBNP) level of at least 1000 pg/ml (at least 1200 pg/mL in patients with atrial fibrillation). All patients were continued on maximal oral agents for heart failure and were followed for at least twelve months post the index cath lab-procedure. At the end of the trial, vital status (alive or dead) was established in 100% of the randomized patients.
Baseline characteristics for the 537 treated patient population showed that patient groups with baseline NYHA class II or NYHA class III clinical grades had advanced disease, but those with NYHA class III disease had significantly greater severity (mean NT-proBNP 2390 pg/ml for NYHA class III vs 1809 pg/ml for NYHA class II; p=0.001).
Recurrent non-fatal decompensated heart failure hospitalization events, incidence of heart attacks, strokes, and death from cardiac causes, and recurrent hospitalizations from these outcomes were evaluated for the 537 HFrEF patients over a median follow-up period of approximately 30 months.
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 commercial products and 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.
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. Mesoblast has completed Phase 3 trials of rexlemestrocel-L 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
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. All statements other than statements of historical fact, including our intention to discuss potential pathways to potential approval with the FDA, are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “likely,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions and variations thereof. 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
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Mesoblast Limited
www.mesoblast.com |
Corporate Headquarters Level 38 55 Collins Street Melbourne 3000 Victoria Australia
T +61 3 9639 6036 F +61 3 9639 6030 |
United States Operations 505 Fifth Avenue Third Floor New York, NY 10017 USA
T +1 212 880 2060 F +1 212 880 2061 |
Asia 21 Biopolis Road #01-22 Nucleos (South Tower) SINGAPORE 138567
T +65 6570 0635 F +65 6570 0176 |
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results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. The risks, uncertainties and other factors that may impact our forward-looking statements include, but are not limited to: the timing, progress and results of Mesoblast’s preclinical and clinical studies; Mesoblast’s ability to advance product candidates into, enroll and successfully complete, clinical studies; the timing or likelihood of regulatory filings and approvals; whether the FDA agrees to a potential approval pathway; and the pricing and reimbursement of Mesoblast’s product candidates, if approved; 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. 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. Unless required by law, 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.
Release authorized by the Chief Executive.
For more information, please contact:
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Corporate Communications / Investors Schond Greenway T: +212 880 2060 E: schond.greenway@mesoblast.com |
Paul Hughes T: +61 3 9639 6036 E: paul.hughes@mesoblast.com |
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Media Kristen Bothwell T: +1 917 613 5434 E:kbothwell@rubenstein.com |
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Mesoblast Limited
www.mesoblast.com |
Corporate Headquarters Level 38 55 Collins Street Melbourne 3000 Victoria Australia
T +61 3 9639 6036 F +61 3 9639 6030 |
United States Operations 505 Fifth Avenue Third Floor New York, NY 10017 USA
T +1 212 880 2060 F +1 212 880 2061 |
Asia 21 Biopolis Road #01-22 Nucleos (South Tower) SINGAPORE 138567
T +65 6570 0635 F +65 6570 0176 |
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Exhibit 99.2
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MESOBLAST PRESENTS HEART FAILURE PHASE 3 TRIAL RESULTS AT INVESTOR HEALTHCARE CONFERENCE
Melbourne, Australia; January 12, and New York, USA; January 11, 2021: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, announced that its Chief Executive Officer, Dr Silviu Itescu, today presented additional data from the landmark DREAM-HF Phase 3 trial in patients with chronic heart failure. The presentation materials have been lodged with the ASX, and Mesoblast’s presentation at the H.C. Wainwright Virtual BioConnect 2021 Conference can be accessed at https://journey.ct.events/view/f353f7fd-772e-43aa-aab0-e959da38254d. An archived webcast of the conference presentation will be available for 90 days on the Company’s website at www.mesoblast.com.
The randomized controlled Phase 3 trial compared clinical outcomes between rexlemestrocel-L and sham control in 537 treated patients with chronic heart failure and reduced left ventricular ejection fraction (HFrEF).
Key Conclusions of the Presentation
Rexlemestrocel-L may provide a major breakthrough in reducing heart failure progression and mortality when used early (New York Heart Association, NYHA, class II disease), and may provide durable protection from heart attacks or strokes in high-risk patients. The specific data supporting these conclusions include:
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60% reduction in incidence of Major Adverse Cardiac Events (MACE) due to heart attacks or strokes across entire 537 patient study population, irrespective of NYHA class II or III, ischemic or non-ischemic etiology (p=0.002); |
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68% reduction in the rate of recurrent hospitalizations from non-fatal heart attacks or strokes, with a hospitalization rate of 1.90 per 100 patient-years of follow-up in the rexlemestrocel-L arm versus 5.95 per 100 patient-years of follow-up in the control arm (p=0.0002); |
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60% reduction in cardiac death in NYHA class II patients (p=0.037) and prevention of progression to NYHA class III rate of cardiac death (p=0.004); |
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Covariate regression analyses showed that elevated baseline levels of CRP, an important biomarker of systemic inflammation, predicted rexlemestrocel-L treatment effect on both MACE in all patients and cardiac death in NYHA class II patients, consistent with the proposed anti-inflammatory mechanism of action of the agent; |
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30% reduction in incidence of three-point MACE (cardiac death, heart attack or stroke) across entire 537 patient study population (p=0.027); and |
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55% reduction in incidence of three-point MACE (cardiac death, heart attack or stroke) in NYHA class II patients (n=206) (p=0.009). |
Based on the observed reduction in mortality and morbidity in this Phase 3 trial, Mesoblast intends to meet with the United States Food and Drug Administration (FDA) to discuss a potential approval pathway.
About Chronic Heart Failure
Heart failure affects approximately 6.5 million people in the US and 26 million people globally, with increasing prevalence and incidence. Chronic heart failure is a progressive disease associated with cardiac and systemic inflammation and a high mortality rate that approaches 50% at 5 years as patients progress beyond NYHA class II disease. In addition, these patients are at high risk of recurrent heart attacks and strokes, reflecting the high degree of systemic inflammation and progressive atherosclerosis associated with chronic heart failure. The high rate of cardiac death, heart attacks and strokes accompanying disease progression continues to be the most significant unmet need in this patient population since new therapies that have reduced recurrent hospitalizations due to cardiac decompensation have not materially impacted these MACE outcomes.
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Mesoblast Limited
www.mesoblast.com |
Corporate Headquarters Level 38 55 Collins Street Melbourne 3000 Victoria Australia
T +61 3 9639 6036 F +61 3 9639 6030 |
United States Operations 505 Fifth Avenue Third Floor New York, NY 10017 USA
T +1 212 880 2060 F +1 212 880 2061 |
Asia 21 Biopolis Road #01-22 Nucleos (South Tower) SINGAPORE 138567
T +65 6570 0635 F +65 6570 0176 |
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About the DREAM HF Phase 3 Trial
Clinical outcomes were evaluated in 537 treated advanced HFEF patients (206 with NYHA class II disease and 331 with NYHA class III disease) randomized 1:1 to either a sham-control procedure or a transendocardial injection by catheter of rexlemestrocel-L (150 million cells). Inclusion criteria enriched the trial for patients with advanced disease by requiring a prior heart failure hospitalization over the past one-to-nine months and/or a N-terminal pro–B-type natriuretic peptide (NT-proBNP) level of at least 1000 pg/ml (at least 1200 pg/mL in patients with atrial fibrillation). All patients were continued on maximal oral agents for heart failure and were followed for at least twelve months post the index cath lab-procedure. At the end of the trial, vital status (alive or dead) was established in 100% of the randomized patients.
Baseline characteristics for the 537 treated patient population showed that patient groups with baseline NYHA class II or NYHA class III clinical grades had advanced disease, but those with NYHA class III disease had significantly greater severity (mean NT-proBNP 2390 pg/ml for NYHA class III vs 1809 pg/ml for NYHA class II; p=0.001).
Recurrent non-fatal decompensated heart failure hospitalization events, incidence of heart attacks, strokes, and death from cardiac causes, and recurrent hospitalizations from these outcomes were evaluated for the 537 HFrEF patients over a median follow-up period of approximately 30 months.
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.
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. Mesoblast has completed Phase 3 trials of rexlemestrocel-L 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
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. All statements other than statements of historical fact, including our intention to discuss potential pathways to potential approval with the FDA, are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “likely,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions and variations thereof. 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. The risks, uncertainties and other factors that may impact our forward-looking statements include, but are not limited to: the timing, progress and results of Mesoblast’s preclinical and clinical studies; Mesoblast’s ability to advance product candidates into, enroll and successfully complete, clinical studies; the timing or likelihood of regulatory filings and approvals; whether the FDA agrees to a potential approval pathway; and the pricing and reimbursement of Mesoblast’s product candidates, if approved; 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. 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-
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Mesoblast Limited
www.mesoblast.com |
Corporate Headquarters Level 38 55 Collins Street Melbourne 3000 Victoria Australia
T +61 3 9639 6036 F +61 3 9639 6030 |
United States Operations 505 Fifth Avenue Third Floor New York, NY 10017 USA
T +1 212 880 2060 F +1 212 880 2061 |
Asia 21 Biopolis Road #01-22 Nucleos (South Tower) SINGAPORE 138567
T +65 6570 0635 F +65 6570 0176 |
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looking statements. Unless required by law, 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.
Release authorized by the Chief Executive.
For more information, please contact:
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Corporate Communications / Investors Schond Greenway T: +212 880 2060 E: schond.greenway@mesoblast.com |
Paul Hughes T: +61 3 9639 6036 E: paul.hughes@mesoblast.com |
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Media Kristen Bothwell T: +1 917 613 5434 E:kbothwell@rubenstein.com |
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Mesoblast Limited
www.mesoblast.com |
Corporate Headquarters Level 38 55 Collins Street Melbourne 3000 Victoria Australia
T +61 3 9639 6036 F +61 3 9639 6030 |
United States Operations 505 Fifth Avenue Third Floor New York, NY 10017 USA
T +1 212 880 2060 F +1 212 880 2061 |
Asia 21 Biopolis Road #01-22 Nucleos (South Tower) SINGAPORE 138567
T +65 6570 0635 F +65 6570 0176 |
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ASX: MSB; Nasdaq: MESO Rexlemestrocel-L for Cardiovascular Diseases Heart Failure Phase 3 Trial Top Line Results January 2021 Exhibit 99.3
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This presentation 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. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Words such as, but not limited to, “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “targets,” “likely,” “will,” “would,” “could,” and similar expressions or phrases identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and future events , recent changes in regulatory laws, and financial trends that we believe may affect our financial condition, results of operation, business strategy and financial needs. These statements may relate to, but are not limited to: expectations regarding the safety or efficacy of, or potential applications for, Mesoblast's adult stem cell technologies; expectations regarding the strength of Mesoblast's intellectual property, the timeline for Mesoblast's regulatory approval process, and the scalability and efficiency of manufacturing processes; expectations about Mesoblast's ability to grow its business and statements regarding its relationships with current and potential future business partners and future benefits of those relationships; statements concerning Mesoblast's share price or potential market capitalization; and statements concerning Mesoblast's capital requirements and ability to raise future capital, among others. 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. You should read this presentation together with our financial statements and the notes related thereto, as well as the 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, include, without limitation: risks inherent in the development and commercialization of potential products; uncertainty of clinical trial results or regulatory approvals or clearances; government regulation; the need for future capital; dependence upon collaborators; and protection of our intellectual property rights, among others. 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. | 2
Our Mission Mesoblast is committed to bringing to market innovative cellular medicines to treat serious and life-threatening illnesses | 3
Product Pipeline This chart is figurative and does not purport to show individual trial progress within a clinical program Mesoblast has the right to use data generated by JCR Pharmaceuticals Co Ltd in Japan to support its development and commercialization plans for remestemcel-L in the US and other major healthcare markets, including for GVHD, Hypoxic Ischemic Encephalopathy and Epidermolysis Bullosa | 4 Remestemcel-L (RYONCILTM) Acute GVHD - Adult Pediatric & adult systemic inflammatory diseases Rexlemestrocel-L Localized inflammatory diseases Advanced Heart Failure Chronic Low Back Pain End-Stage Ischemic Heart Failure PRODUCT CANDIDATE THERAPEUTIC AREA PHASE 1/2 PHASE 3 REGISTRATION MESOBLAST COMMERCIAL RIGHTS Global ex-Japan Global ex-China Global ex-EUR, LATAM Acute GVHD - Pediatric COMMERCIAL PARTNERS Acute Respiratory Distress Syndrome COVID-19, Influenza, Other Causes Global Collaboration Refractory Inflammatory Bowel Disease * # The closing of the license agreement is subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and certain other conditions #
Platform Technology – Mechanism of Action | 5 Our mesenchymal precursor/stromal cells respond to and are activated by multiple inflammatory cytokines through surface receptors, resulting in orchestration of an anti-inflammatory cascade Source: data on file IL-6
Extensive patent portfolio with protection extending through 2040 in all major markets Over 1,100 patents and patent applications (82 patent families) across all major jurisdictions Covers composition of matter, manufacturing, and therapeutic applications of mesenchymal lineage cells Provides strong global protection in areas of our core commercial focus against cell-based competitor products When outside our core commercial areas, may consider granting rights to third parties who require access to our patent portfolio to commercialize their products Mesoblast receives royalty income from its patent licensee TiGenix, S.A.U., a wholly owned subsidiary of Takeda, on its worldwide sales of its product Alofisel® for the treatment of complex perianal fistulas in adult patients with Crohn’s disease, as well as milestone payments Global IP Estate Provides Substantial Competitive Advantage Alofisel® is a registered trademark of TiGenix, S.A.U. | 6
Scalable allogeneic “off-the-shelf” cellular platforms Manufacturing meets stringent criteria of international regulatory agencies Robust quality assurance processes ensure final product with batch-to-batch consistency and reproducibility Projected increase in capacity requirements for maturing pipeline Commercial Scale Manufacturing Capability | 7 Proprietary xeno-free technologies will increase yields and output Moving to 3D bioreactors will reduce labor and improve manufacturing efficiencies These innovations will significantly reduce cost of goods Manufacturing Remestemcel-L © Lonza, reproduced with permission
Worldwide license and collaboration agreement with Novartis for the development, manufacture and commercialization of remestemcel-L* Initial focus is on the treatment of acute respiratory distress syndrome (ARDS) and other respiratory conditions Novartis intends to initiate a Phase 3 study in non-COVID-19-related ARDS after the anticipated closing of the license agreement and outcome of the current COVID-19 ARDS study Mesoblast will retain full rights and economics for remestemcel-L for graft versus host disease (GVHD), and Novartis has an option to, if exercised, become the commercial distributor outside of Japan For most non-respiratory indications, the parties may co-fund development and commercialization on a 50:50 profit-share basis | 8 Overview of Collaboration with Novartis for Remestemcel-L * The closing of the license agreement is subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and certain other conditions
On August 13 2020, results from 309 children with steroid refractory acute graft versus host disease (SR-aGVHD) treated with remestemcel-L were presented to the Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) The ODAC panel voted 9:1 that the available data support the efficacy of remestemcel-L in pediatric patients with SR-aGVHD* Despite the overwhelming ODAC vote, on September 30, the FDA provided Mesoblast with a Complete Response Letter Mesoblast intends to meet with the FDA during Q1 CY2021 through a well-established process for continuing discussions on the potential for accelerated approval with a post-approval commitment to conduct an additional randomized controlled study | 9 SR-aGVHD Regulatory & Commercial Update * This vote includes a change to the original vote by one of the ODAC panel members after electronic voting closed
MPC-06-ID for Chronic Low Back Pain Phase 3 trial of MPC-06-ID for chronic low back pain in 404 patients: Final study visits for all patients have been completed Ongoing quality review of all data is being completed at the study sites Data readout expected shortly Continued operational progress in strategic partnership for chronic lower back pain with Grünenthal in Europe to complete clinical protocol design, obtain regulatory input, and receive clearance from European regulatory authorities to begin European Phase 3 trial Results from the Phase 3 trials will be considered pivotal to support regulatory approval in the US, as well as in Europe | 10
DREAM HF Phase 3 Trial in Chronic Heart Failure Rexlemestrocel-L Mechanism of Action
Chronic Heart Failure: Rising Incidence & High Mortality Cardiovascular disease (CVD) remains the leading cause of death in the United States1 Heart failure affects 6.5 million patients in the US and 26 million patients globally. As populations age, the prevalence is increasing2 Chronic heart failure is a progressive disease with a high mortality that approaches 50% at 5 years2,3, and at least 75% after an initial hospitalization4 Patients with heart failure are also at high risk of recurrent major adverse cardiac events involving large vessels (heart attacks / strokes) New therapies for chronic heart failure reduce recurrent hospitalizations due to cardiac decompensation, however they do not materially improve cardiac mortality or major ischemic events (heart attacks/strokes) | 12 1. Muntner BEJ, et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. Feb 19, 2019. 2. United States Food & Drug Administration. Treatment for Heart Failure: Endpoints for Drug Development. Draft Guidance. June 2019. 3. Taylor CJ, et al. Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study. BMJ. 2019;364:I223. 4. Shah KS, et al. Heart Failure with Preserve, Borderline, and Reduced Ejection Fraction; 5-Year Outcomes. JACC. 2017;Nov12.
Myocardial Infarction & Stroke in Chronic Heart Failure: Current Unmet Needs Each year in the United States approx. 805,000 people suffer from a myocardial infarction (heart attack) and approx. 795,000 people experience a new or recurrent stroke1 A major consequence of a heart attack is chronic heart failure, and patients with chronic heart failure are at higher risk of recurrent heart attacks and strokes2 Atherosclerosis is a chronic inflammatory condition associated with endothelial dysfunction3 Cardiovascular complications associated with atherosclerosis in chronic heart failure patients may respond to potent anti-inflammatory therapeutic approaches | 13 1. Virani ss, et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. Jan 29, 2020 2. Kim W, Kim EJ. Heart Failure as a Risk Factor for Stroke. J Stroke. 2018 Jan;20(1):33-45. 3. Frostegard J. Immunity, atherosclerosis and Cardiovascular Disease. BMC Med. 2103;11:117.
Proposed Mechanism of Action of Intra-Cardiac MPC Administration in Treatment of both Heart Failure & Large Vessel Atherosclerosis Mesenchymal precursor cells (MPC) key mechanisms of action thought to beneficially impact the heart and the systemic vasculature: Reduction in cardiac and systemic inflammation Reversal of endothelial dysfunction Induction of microvascular network within viable heart muscle Reduction in heart muscle death Borow KM, Yaroshinsky A, Greenberg B, Perin E. Phase 3 DREAM-HF Trial of Mesenchymal Precursor Cells in Chronic Heart Failure: A Review of Biological Plausibility and Implementation of Flexible Clinical Trial Design. Circ Res. 2019;125:265-281 | 14
GlobalData-PharmaPoint Heart Failure (2016); McMurray et al., 2012;Yancy et al., 2013, 2016 ACC/AHAHFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Early ACEI or ARB Statins Beta blockers Re-vascularization or valvular surgery Pharmacological Add-on Diuretics for fluid retention Aldosterone antagonists Hydralazine / isosorbide dinitrate Digitalis Treatment Algorithm in Progressive Heart Failure Mesoblast Target Market Chronic Heart Failure1 ↓ Cardiac Death / Heart Attack / Stroke Rexlemestrocel-L for Chronic Heart Failure Progressive Vascular (Endothelial) Dysfunction and Heart Failure Class I Class IV | 15 Class II Class III New Oral Therapies for Class II ↓ Decompensated Hospitalization Events sacubitril / valsartan SGLT2 inhibitors
DREAM HF Phase 3 Trial in Chronic Heart Failure Rexlemestrocel-L vs Sham Clinical Outcomes
DREAM HF: Overview of Phase 3 Trial Mesoblast’s allogeneic cell therapy rexlemestrocel-L has a dual mechanism of action that involves immunomodulation and improvement in blood vessel integrity/function DREAM-HF Phase 3 trial was designed to evaluate whether rexlemestrocel-L could improve morbidity and mortality in advanced chronic heart failure patients Trial design: 1:1 randomized, controlled, double blinded; conducted over 55 sites across North America using 150 million cell dose vs control in 565 patients Primary endpoint: reduction in recurrent heart failure-related hospitalizations Additional pre-specified key clinical endpoints: Reduction in ischemic cardiovascular events (heart attack / stroke) Reduction in recurrent hospitalizations due to ischemic events (heart attack / stroke) Reduction in death due to cardiac causes Major Adverse Cardiac Events (MACE: heart attack, stroke or cardiac death) | 17
28 randomized but not treated 18 randomized to MPCs 10 randomized to Control 565 patients randomized 283 to MPCs 282 to Control 276 randomized and treated without receiving any MPCs Intent-to-Treat (ITT) Randomized Patient Population N = 565 Pts. Full Analysis Set (FAS) Actual Treatment Patient Population N = 537 Pts. 1,167 patients assessed for eligibility 261 randomized and treated with at least 1 injection of MPCs | 18 DREAM HF: Patient Flow
DREAM HF: Baseline FAS Summary Data by NYHA CLASS II or III | 19
DREAM HF: Baseline FAS Summary Data by NYHA CLASS II or III | 20
DREAM HF Recurrent Decompensated Heart Failure Hospitalization Events Non-Fatal Ischemic MACE (Heart attacks or Strokes)
Rexlemestrocel-L Did Not Reduce Non-Fatal Heart Failure MACE (Recurrent Decompensated Heart Failure Events or High-Grade Arrhythmias) All Patients (n=537) HR: 1.2 p=0.4 | 22
Rexlemestrocel-L Significantly Reduced Incidence of Ischemic MACE (MI, Stroke) by 60% Relative to Controls (n=537 Patients) | 23 All Patients (n=537) REX 5% vs Controls 13%, p=0.002 REX Effect Size: ↓60%
Myocardial Infarction or Cerebrovascular Accident Elevated Baseline CRP Levels Predict Rexlemestrocel-L Benefit on Incident Heart Attacks or Strokes … Consistent with Anti-Inflammatory MOA | 24
Rexlemestrocel-L Significantly Reduced Incidence of Ischemic MACE (MI, Stroke) by 57% & 67% Relative to Controls In NYHA Class II & III, respectively | 25 NYHA II REX 6% vs Controls 14%, p=0.05 REX Effect Size: ↓ 57% NYHA III REX 4% vs Controls 12%, p=0.014 REX Effect Size: ↓ 67%
Rate Ratio: 0.29 REX Effect Size = ↓71% p=0.0085 Hospitalization Rate per 100 patient-years of follow-up Rate Ratio: 0.32 REX Effect Size = ↓68% p=0.0002 Rate Ratio: 0.32 REX Effect Size = ↓68% p=0.0049 Rexlemestrocel-L Significantly Reduced Hospitalization Rates from Non-Fatal MI or Stroke in All Patients, with Similar Effect Size in NYHA Class II and Class III Patients REX vs CONTROL (N=537) REX vs CONTROL NYHA CLASS II (N=206) REX vs CONTROL NYHA CLASS III (N=331) | 26
DREAM HF Death From Cardiac Causes (CV Death)
High Baseline CRP and NT-proBNP are Significant Predictors of Rexlemestrocel-L Treatment Benefit on Cardiac Death Cardiac Death | 28 * Multi-variate regression analysis using COX proportional hazards
Rexlemestrocel-L Reduced Cardiac Death by 60% in NYHA Class II Patients | 29 NYHA II (n=206) REX 8% vs Controls 20%, p=0.037 REX Effect Size: ↓60%
DREAM HF Three-Point MACE (CV Death, MI or Stroke)
Rexlemestrocel-L Significantly Reduced 3-Point Composite MACE (CV Death, MI or Stroke) Compared to Controls Across All 537 Patients | 31 All Patients (n=537) REX 20.6% vs Controls 30%, p=0.027 REX effect size: ↓30%
Rexlemestrocel-L Significantly Reduced 3-Point Composite MACE (CV Death, MI or Stroke) in 206 NYHA Class II Patients | 32 NYHA II (n=206) REX 13% vs Controls 29%, p=0.009 REX effect size: ↓ 55%
GlobalData-PharmaPoint Heart Failure (2016); McMurray et al., 2012;Yancy et al., 2013, 2016 ACC/AHAHFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Early ACEI or ARB Statins Beta blockers Re-vascularization or valvular surgery Pharmacological Add-on Diuretics for fluid retention Aldosterone antagonists Hydralazine / isosorbide dinitrate Digitalis Treatment Algorithm in Progressive Heart Failure Mesoblast Target Market Chronic Heart Failure1 ↓ Cardiac Death / Heart Attack / Stroke Rexlemestrocel-L for Chronic Heart Failure Progressive Vascular (Endothelial) Dysfunction and Heart Failure Class I Class IV | 33 Class II Class III New Oral Therapies for Class II ↓ Decompensated Hospitalization Events sacubitril / valsartan SGLT2 inhibitors
Rexlemestrocel-L Phase 3 Trial Conclusions | 34 Rexlemestrocel-L may provide a major breakthrough in reducing heart failure progression and mortality when used early (class II disease), and may provide durable protection from heart attacks or strokes in high-risk patients 60% reduction in incidence of ischemic MACE (heart attack or stroke) across entire 537 patient study population, irrespective of NYHA class II or III, ischemic or non-ischemic etiology (p=0.002) 30% reduction in incidence of three-point MACE (cardiac death, heart attack or stroke) across entire 537 patient study population (p=0.027) 55% reduction in incidence of three-point MACE (cardiac death, heart attack or stroke) in NYHA class II patients (n=206) (p=0.009) 60% reduction in cardiac death in NYHA class II patients (p=0.037) and prevention of progression to NYHA class III rate of cardiac death Based on observed reduction in mortality and morbidity in this Phase 3 trial, Mesoblast intends to meet with the United States Food and Drug Administration (FDA) to discuss potential approval pathways
