Appendix 4C Quarterly Activity Report
July 29 2022 - 7:05AM
Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in
allogeneic cellular medicines for inflammatory diseases, today
provided an activity report for the fourth quarter ended June 30,
2022.
Financial highlights
- Net cash usage for operating
activities in the quarter was reduced by 33%, or US$6.8 million, to
US$13.9 million compared with US$20.7 million in the comparative
quarter last year.1
- Net cash usage for operating
activities for the 12 months ended June 2022 were reduced by 38%,
or US$40.9 million, to US$68.7 million compared with US$106.7
million in the comparative 12 months.1
- Cash on hand at the end of the
quarter was US$60.4 million, with up to an additional US$40 million
available to be drawn down from existing financing facilities
subject to certain milestones.
- Revenues2 in the quarter were US$2.2
million, including US$2.1 million from TEMCELL® HS Inj.3 royalties
on sales for SR-aGvHD in Japan, an increase of 12% on the
comparative quarter last year.
- Revenues2 for the 12 months ended
June 2022 increased 37%, compared with the comparative 12-month
period, to US$10.2 million primarily due to increased royalties on
sales of TEMCELL® HS Inj. royalties on sales for SR-aGvHD in Japan
and other milestone revenue.
Key updates on remestemcel-L
Biologics License Application (BLA) resubmission to the US Food
and Drug Administration (FDA) for the treatment of children with
steroid-refractory graft versus host disease (SR-aGVHD)
- In response to FDA guidance,
Mesoblast has optimized a potency assay that was in place at the
time of the 54-patient Phase 3 trial in children with
SR-aGVHD.
- Mesoblast believes that the proposed
potency assay measuring remestemcel-L’s in vitro anti-inflammatory
and immunomodulatory activity helps establish a clear understanding
of remestemcel-L’s mechanism of action in SR-aGVHD.
- The potency assay from the Phase 3
trial demonstrates a relationship between the product’s activity in
vitro and its effects on survival in the Phase 3 trial, with the
strongest correlation to survival in those patients at highest
mortality risk as measured by clinical severity or high biomarker
levels of inflammation.
- Additionally, Mesoblast has now
generated data from the expanded access program (EAP 275) of 241
children which confirm the ability of the in-vitro potency assay to
measure product activity relevant to survival outcomes.
- In preparation for the expected FDA
review, during the period Mesoblast completed a successful mock
pre-approval inspection of its GMP manufacturing facility and
process comprising both on-site and virtual inspections by
external auditors.
- Mesoblast will provide these new data to FDA and address all
chemistry, manufacturing and controls (CMC) outstanding items as
required for the planned BLA resubmission in the current quarter.
If the resubmission is accepted, CBER will consider the adequacy of
the clinical data in the context of the related CMC issues.
COVID-19 acute respiratory distress syndrome (ARDS)
- Mesoblast provided a 12-month update
on survival outcomes from the randomized controlled trial of
remestemcel-L in ventilator-dependent COVID-19 patients with
moderate/severe acute ARDS. Through the initial 90 days,
remestemcel-L reduced mortality by 48% compared to controls in a
pre-specified analysis of 123 patients below age 65 (26% vs 44%,
p=0.038),4,5 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).4,5 These early survival outcomes in the
remestemcel-L 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).4,5
- Mesoblast has entered into a non-binding Memorandum of
Understanding (MOU) with Vanderbilt University Medical Center,
which coordinates and works closely with clinical investigators at
over 40 sites across the United States focused on studying ARDS and
other critical illnesses. The MOU proposes a collaboration toward
the design and execution of a second COVID-19 trial for
remestemcel-L; to jointly develop a trial protocol and seek FDA
approval for the trial, the results from which Mesoblast may use to
support regulatory filings (such as seeking Emergency Use
Authorization from FDA); and to negotiate a written, cooperative
agreement and proceeding with the trial upon receipt of FDA
approval.
Inflammatory Bowel Disease (IBD) – ulcerative colitis (UC) and
Crohn’s colitis
- Results from the first patient
cohort in the randomized, controlled study of remestemcel-L by
direct endoscopic delivery to areas of inflammation in patients
with medically refractory Crohn’s colitis were published in the
peer-reviewed journal British Journal of Surgery.6
- Strategically, Mesoblast views UC and Crohn’s colitis as a
potentially important label extension for remestemcel-L given the
gastrointestinal involvement common to acute graft versus host
disease and inflammatory bowel disease. Gastrointestinal damage is
the major driver of aGVHD mortality and is linked to systemic
inflammation in aGVHD. Biomarkers that predict high mortality in
aGVHD, such as blood levels of soluble suppression of
tumorigenicity 2 (ST2),7,8 have shown to be significantly reduced
in patients treated with remestemcel-L.9 ST2 has also been shown to
be associated with active IBD (UC & Crohn’s).
Key updates on rexlemestrocel-L:
Chronic Heart Failure
- Results from the DREAM-HF Phase 3
trial of rexlemestrocel-L in patients with chronic heart failure
and reduced ejection fraction (HFrEF) were highlighted at a heart
failure panel discussion titled “Late-Stage Advancements in Heart
Failure Therapeutics and Management.”
- Treatment with rexlemestrocel-L
resulted in greater improvement in the pre-specified analysis of
left ventricular ejection fraction (LVEF) at 12 months relative to
controls, after a single intervention in the 565-patient randomized
controlled trial in New York Heart Association (NYHA) class II/III
chronic heart failure. 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. Effects on LVEF and MACE outcomes were even more pronounced
in 301 HFrEF patients with high baseline levels of inflammation as
measured by hsCRP. LVEF improvement at 12 months may be an
appropriate early surrogate endpoint for long-term reduction in
MACE.
- 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 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.
Chronic Low Back Pain
- Mesoblast hosted a webinar for
analysts and investors focused on the current treatment landscape
and unmet medical need for patients with chronic low back pain
(CLBP) due to degenerative disc disease (DDD), a condition
associated with local inflammation in the disc. The webinar
featured presentations from Key Opinion Leaders (KOLs) Douglas P.
Beall, MD, FIPP, FSIR, DAAPM (Clinical Radiology Oklahoma) and Hyun
W. Bae, MD (Spine-Center at Cedars-Sinai Medical Center). The KOLs
focused on Mesoblast’s Phase 3 program for rexlemestrocel-L and
where it may fit in the paradigm of the patient journey.
- Mesoblast received feedback in
December 2021 from FDA on the Phase 3 program for CLBP and plans to
conduct an additional US Phase 3 trial which may support
submissions for potential approval in both the US and EU. Following
review of the completed Phase 3 trial data, FDA agreed with
Mesoblast’s proposal for pain reduction at 12 months as the primary
endpoint of the next trial, with functional improvement and
reduction in opioid use as secondary endpoints.
Other:
Salary payments to full-time Executive Directors were US$337,605
and fees to Non-Executive Directors were US$192,798, detailed in
Item 6 of the Appendix 4C cash flow report for the quarter.10
A copy of the Appendix 4C – Quarterly Cash Flow Report for the
fourth quarter FY2022 is available on the investor page of the
company’s website www.mesoblast.com.
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
References / Footnotes
- Accounting policy change resulted in a US$1.8 million benefit
in the June 2022 quarter and a US$6.1m benefit for the 12 months
ended 30 June 2022
- Unaudited
- TEMCELL® HS Inj. is a registered trademark of JCR
Pharmaceuticals Co. Ltd.
- All p-values are descriptive and not adjusted for
multiplicity
- Hazard Ratios calculated using Cox regression proportional
hazards model without adjustment; p-value from log rank test
- Lightner AL., et al. Remestemcel-L allogeneic bone
marrow-derived mesenchymal stem cell product to treat medically
refractory Crohn’s colitis: preliminary phase IB/IIA study. British
J Surgery 2022; 1-3. https://doi.org/10.1093/bjs/znac078
- Reichenbach DK et al. Blood. 2015 May 14;125(20):3183-92.
- Vander Lugt MT et al. New Engl J Med. 2013 Aug 8
369:529-39.
- Kurtzberg J., 62nd annual meeting of the American Society of
Hematology (ASH) on December 6, 2020
- As required by ASX listing rule 4.7 and reported in Item 6 of
the Appendix 4C, reported are the aggregated total payments to
related parties being Executive Directors and Non-Executive
Directors
Forward-Looking StatementsThis 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 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 (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 |
Media |
Paul Hughes |
Sumit Media |
T: +61 3 9639 6036 |
Grant Titmus |
E: investors@mesoblast.com |
T: +61 419 388 161 |
|
E: grant@sumitmedia.com.au |
|
|
|
Rubenstein |
|
Tali Mackay |
|
E: tmackay@rubenstein.com |
Mesoblast (NASDAQ:MESO)
Historical Stock Chart
From Mar 2024 to Apr 2024
Mesoblast (NASDAQ:MESO)
Historical Stock Chart
From Apr 2023 to Apr 2024