Key points:
• Improvement in left ventricular ejection fraction (LVEF) at 12 months was shown after a single
intervention with rexlemestrocel-L in the 565-patient randomized controlled trial in New York
Heart Association (NYHA) class II/III chronic heart failure (CHF) with reduced ejection fraction
(HFrEF)
• Increased LVEF preceded long-term reduction in major adverse cardiovascular events (MACE)
and associated recurrent hospitalizations for non-fatal heart attack or stroke
• LVEF improvement at 12 months may be an appropriate early surrogate endpoint for longterm reduction in MACE
• Effects on LVEF and MACE outcomes were even more pronounced in 301 HFrEF patients with
high baseline levels of inflammation as measured by hsCRP
• Results from three randomized controlled trials in class II/III HFrEF and in end-stage HFrEF
with left ventricular assist devices (LVADs) support the idea of a common mechanism of action
(MOA) by which rexlemestrocel-L reverses inflammation-related endothelial dysfunction and
reduces adverse clinical outcomes across the spectrum of HFrEF patients
• Rexlemestrocel-L has regenerative medicine advanced therapy (RMAT) designation from the
US Food and Drug Administration (FDA) for treatment of chronic heart failure with left
ventricular systolic dysfunction in patients with an LVAD. Mesoblast now intends to meet with
FDA under the RMAT framework to discuss the totality of the data and the evidence of a
common rexlemestrocel-L MOA across the broader HFrEF spectrum.
Melbourne, Australia; July 19, and New York, USA; July 18, 2022: Mesoblast Limited
(ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases,
today announced that treatment of HFrEF patients with rexlemestrocel-L, its allogeneic “off-the-shelf”
product candidate for the treatment of chronic heart failure with reduced ejection fraction, resulted in
greater improvement in the pre-specified analysis of left ventricular ejection fraction at 12 months
relative to controls in the DREAM-HF Phase 3 trial. Improvement in LVEF was most pronounced in the
setting of inflammation and preceded long-term reduction in the 3-point MACE of cardiovascular
death, non-fatal heart attack or stroke. These results were recently highlighted in a heart failure panel
discussion titled “Late-Stage Advancements in Heart Failure Therapeutics and Management.”
Rexlemestrocel-L is an immunomodulatory therapy developed to target the high degree of
inflammation and resultant endothelial dysfunction present across the spectrum of HFrEF, from NYHA
class II through end-stage CHF on LVADs. This MOA is postulated to improve systolic function and
LVEF in HFrEF patients and reduce the high rate of major cardiovascular events and complications,
notably 3-point MACE in NYHA class II/III patients and gastrointestinal (GI) tract ischemia, abnormal
GI blood vessels, and life-threatening GI bleeding events in LVAD patients. Rexlemestrocel-L has
already been granted FDA RMAT and Orphan Drug designations for treatment of chronic heart failure
with left ventricular systolic dysfunction in patients with an LVAD.
Results from two large placebo-controlled randomized studies in patients with HFrEF, a disease
associated with inflammation, a 565-patient trial in NYHA class II/III patients (DREAM-HF) and a 159-
patient trial in end-stage heart failure patients implanted with an LVAD, as well as in an earlier 30-
patient trial in LVAD patients, provide support for a common MOA for rexlemestrocel-L across the
spectrum of HFrEF. New data from the DREAM-HF trial shows that a single intervention with
rexlemestrocel-L resulted in improvement from baseline to 12 months in LVEF, which preceded and
correlated with long-term reduction in MACE across a mean follow up of 30 months. This suggests that
early improvement in LV systolic function, as measured by LVEF change from baseline to 12 months,
could be an appropriate surrogate endpoint predictive of adverse long-term clinical outcomes in this
patient population.
In the DREAM-HF study, among the 537 patients who were randomized and received either treatment
or sham, a single injection of rexlemestrocel-L resulted in the following: (Note1)
• 52% greater increase in LVEF from baseline to 12 months compared with controls. While both
groups had similar LVEF at baseline (28.7% and 28.6%), at 12 months least squared mean
change from baseline was 5.0 for the rexlemestrocel-L group and 3.3 for controls (p=0.021)
• 65% reduction in 2-point MACE (non-fatal heart attack or stroke) compared to controls, 4.6%
vs 13.0%, p=0.001, across a mean follow-up of 30 months
• 33% reduction in 3-point MACE compared to controls, 20.3% vs 30.1%, p=0.021, across a
mean follow-up of 30 months
• 68% reduction in the rate of recurrent hospitalizations from non-fatal heart attacks or strokes
compared with controls (p=0.0002)
Outcomes were even more pronounced in the pre-specified subgroup of 301 NYHA class II/III HFrEF
patients with detectable circulating evidence of inflammation as measured by elevated baseline hsCRP,
where a single injection of rexlemestrocel-L resulted in the following: (Note1)
• 86% greater increase in LVEF from baseline to 12 months compared with controls: while both
groups had similar LVEF at baseline (29.1% and 28.2%), at 12 months least squared mean
change from baseline was 5.6 for the rexlemestrocel-L group and 2.9 for controls (p=0.005)
• 79% reduction in 2-point MACE compared to controls, 2.6% vs 12.2%, p=0.004, across a
mean follow-up of 30 months
• 45% reduction in 3-point MACE compared to controls, 19.0% vs 32.4%, p=0.012, across a
mean follow-up of 30 months
Outcomes in a second HFrEF population with high levels of inflammation, 159 patients with end-stage
heart failure and LVAD implantation, showed that a single intervention with rexlemestrocel-L reduced
life-threatening mucosal bleeding events requiring hospitalization through 6 months (GI or epistaxis)
compared with controls, 17% vs 33%, p=0.02. These results confirmed the observed reduction in
major GI bleeding events seen in an earlier 30-patient randomized study. The FDA has indicated that
a reduction in life-threatening mucosal bleeding events is an important clinical outcome in patients
implanted with an LVAD.
These results are consistent with a postulated mechanism of action by which rexlemestrocel-L targets
inflammation and endothelial dysfunction across the spectrum of HFrEF with the potential to reduce
major adverse clinical events in HFrEF patients from NYHA class II/III through to end-stage disease
and LVADs. Mesoblast now intends to meet with FDA under the RMAT framework to discuss the
totality of the data, the evidence of a common MOA across the broad HFrEF spectrum, and how the
outcomes from each trial may support the regulatory approval pathway for rexlemestrocel-L.
About Heart Failure
Heart failure affects approximately 6.5 million people in the United States and 26 million people
globally, with increasing prevalence and incidence. The mortality rate approaches 50% at 5 years as
patients progress beyond NYHA class II disease in parallel with increasing inflammation in the heart
and in the circulation.2,3 Despite recent approvals of new therapies for HFrEF, including SGLT2
inhibitors, that have reduced hospitalizations due to reversible volume-related events, NYHA class
II/III HFrEF patients with inflammation remain at high risk for cardiac death, heart attacks and
strokes. Over 60,000 patients annually in the US progress to end-stage heart failure (NYHA class IV)
and these patients have a one-year mortality exceeding 50%. (Note 4) Use of LVADs in end-stage heart failure
patients to improve survival is gaining momentum, with approximately 5,500 LVADs implanted
annually in the US. (Notes 5-7) However, systemic inflammation associated with major life-threatening
gastrointestinal bleeding high rates of rehospitalization remain a major obstacle to greater
LVADsuse (Notes 8-9)
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
Footnotes
LVEF, 2-point MACE, and recurrent hospitalizations due to heart attack or stroke were prespecified endpoints and the 3-point MACE was a post-hoc analysis of pre-specified endpoint
components
AHA’s 2017 Heart Disease and Stroke Statistics
Ponikowski P., et al. Heart Failure: Preventing disease and death worldwide. European Society of
Cardiology. 2014; 1: 4-25
Gustafsson F, Rogers JG. Left ventricular assist device therapy in advanced heart failure: patient
selection and outcomes. European Journal of Heart Failure 2017;19:595-602.
United Network for Organ Sharing
Agency for Healthcare Research and Quality – Healthcare Cost and Utilization Project – Claims
Analysis ICD- 37.6.
Data on file
Chatterjee A, Feldmann C, Hanke JS (2018) The momentum of HeartMate 3: a novel active
magnetically levitated centrifugal left ventricular assist device (LVAD). J Thorac Dis 10 (Suppl 15):
S1790-S1793.
Mehra, MR Salerno C, Cleveland JC (2018) Health care resources use and cost implications in the
MOMENTUM 3 long-term outcome study: a randomized controlled trial of a magnetically levitated
cardiac pump in advanced heart failure.
Forward-Looking Statements
This press release 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 forwardlooking 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. Forwardlooking 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 (including BLA resubmission), 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.
Release authorized by the Chief Executive.For more information, please contact:
Corporate Communications / Investors
Paul Hughes , T: +61 3 9639 6036 , E: investors@mesoblast.com
Media
Sumit Media, Grant Titmus, T: +61 419 388 161, E: grant@sumitmedia.com.au
Rubenstein, Tali Mackay, E: tmackay@rubenstein.com
