Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in
allogeneic cellular medicines for inflammatory diseases, today
reported operational highlights and financial results for the
fourth quarter and full-year ended June 30, 2021 (FY2021).
“During this calendar year we made significant progress in both
regulatory and clinical outcomes for our lead product candidate,
remestemcel-L, after experiencing a disappointing set-back last
year” said Silviu Itescu, Chief Executive of Mesoblast. “We are
pleased with recent recommendations by FDA’s CBER to meet with the
review team and address remaining CMC items for remestemcel-L in
the treatment of steroid-refractory acute graft versus host disease
in children. Additionally, our most recent meeting with the FDA has
provided clarity on the pathway towards an emergency use
authorization for remestemcel-L in the treatment of COVID
ARDS.”
Operational Highlights
Remestemcel-L – Outcome of recent meeting with FDA on regulatory
pathway for emergency use authorization in the treatment of
COVID-19 ARDS:
- Mesoblast met with the United States
Food & Drug Administration (FDA) in regard to potential
emergency use authorization (EUA) for remestemcel-L in the
treatment of ventilator-dependent patients with moderate or severe
acute respiratory distress syndrome (ARDS) due to COVID-19
- The FDA advised Mesoblast that an
additional clinical study in COVID ARDS would be required which, if
statistically positive, could provide a dataset in conjunction with
the recently completed 222 patient clinical study that might be
sufficient to support an EUA
- FDA provided guidance that the
existing COVID ARDS Investigational New Drug (IND) file and future
submissions for remestemcel-L in this indication may continue to
cross-reference manufacturing information in Biologics License
Application (BLA) 125706 for pediatric steroid-refractory acute
graft versus host disease (SR-aGVHD)
- FDA indicated that potency assays
must be established and agreed prior to commencement of the
proposed Phase 3 clinical trial
- FDA indicated that the potency
assays currently in development appeared to be reasonable based on
in vitro results provided in the briefing document, the in vitro
activity of the product appears to be relatively well established,
though the relationship between in vitro activity and the product’s
actual mechanism of action remains theoretical
- Mesoblast intends to meet with FDA’s
Office of Tissue and Advanced Therapies (OTAT) in Q4 CY21 to
address potency assays for remestemcel-L in relation to SR-aGvHD,
attributes which we believe to be also relevant to COVID ARDS
- 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 the COVID-19 ARDS trial
Remestemcel-L in the treatment of steroid-refractory acute graft
versus host disease (SR-aGVHD) in children:
- Mesoblast continues to be in
discussion with the FDA through a well-established regulatory
process that may include a resubmission with a six-month review
with the aim of achieving approval of remestemcel-L in the
treatment of SR-aGVHD in children
- The FDA’s Center for Biologics
Evaluation and Research (CBER) has recommended that Mesoblast as a
next step discuss with CBER’s review team at OTAT our approach to
address certain outstanding chemistry, manufacturing and controls
(CMC) items, including potency assays, which could support a
resubmission of the current BLA
- Mesoblast intends to meet with FDA’s OTAT in Q4 CY21, to
address potency assays and other outstanding CMC items
Rexlemestrocel-L in the treatment of chronic heart failure and
chronic low back pain:
- Mesoblast expects to receive
feedback from the FDA in the next quarter on the potential pathways
to US regulatory approval for its rexlemestrocel-L technology
platform following the recently completed Phase 3 trials in
patients with chronic heart failure and chronic low back pain
(CLBP) due to degenerative disc disease
- Mesoblast and its partner for CLBP 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
Manufacturing
- During fiscal year 2021, Mesoblast
continued to invest in manufacturing of remestemcel-L as part of
its readiness strategy for potential FDA approval and commercial
launch, with 92% of total manufacturing spend being for commercial
readiness and next generation, pre-launch inventory and clinical
cell supply for life cycle management
- Considerable effort has been focused
on development and validation of specific CMC items necessary for
Mesoblast’s potential resubmission of the BLA for remestemcel-L, as
well as potency assay work that will support both the aGVHD BLA
resubmission and the IND for the Phase 3 trial COVID ARDS
- Work has also continued on Mesoblast’s proprietary technology
that facilitates the increase in yields necessary for the long-term
commercial supply of its product candidates, and next generation
manufacturing processes to reduce labor, drive down cost of goods
and improve manufacturing efficiencies
Financial Highlights
- US$136.9 million cash on hand at
June 30, 2021
- Sales of TEMCELL® HS Inj.1 in Japan
by licensee JCR for the treatment of aGVHD have re-established a
steady growth trajectory after plant capacity was expanded to meet
growing demand
- Revenue from TEMCELL® royalties
increased by 10% from the prior year period to US$7.2 million in
the year ended June 30, 2021
- Mesoblast has entered into a
contractual amendment to extend the interest-only period of its
current senior debt facility through to at least January 2022 and
is in active discussions to refinance the facility
- Ongoing investment in remestemcel-L
platform to support the regulatory pathway to potential approval,
manufacturing scale up and life cycle management
- We expect to recognize the existing
US$21.9 million of remestemcel-L pre-launch inventory on the
balance sheet if we receive FDA approval
DETAILED CLINICAL ACTIVITIES FOR THE FISCAL YEAR
FY2021
Remestemcel-L
Acute Respiratory Distress Syndrome due to
COVID-19
Mesoblast recently presented results from the randomized
controlled trial of remestemcel-L in 222 ventilator-dependent
COVID-19 patients with moderate/severe acute respiratory distress
syndrome (ARDS) 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 exploratory
analysis of 123 treated patients under 65 years old. The trial had
been halted after the third interim analysis since the 30-day
primary endpoint would not be attained.
Key presentation findings were:
- Remestemcel-L reduced mortality by
48% at 90 days compared to controls in a pre-specified analysis of
123 treated patients under 65 years old, 26% vs 44%, Hazard Ratio
(HR) 0.52, 95% CI (0.277, 0.964), p=0.035.2,3 This compares
favourably with the 46% mortality reduction reported at 60 days
(p=0.048)2,3 and indicates a durable treatment benefit in this
patient population
- Remestemcel-L showed benefit in an
exploratory analysis in patients on dexamethasone as part of their
standard of care, with 90-day mortality being reduced by 77%
compared to controls under 65 who received dexamethasone, 14% vs
48%, HR 0.23, 95% CI (0.080, 0.681), p=0.00372,3
- These survival benefits were
accompanied by improvements relative to controls in pre-specified
secondary endpoints of ventilator-free days, respiratory function
as assessed by ARDS severity, and overall clinical improvement on a
7-point ordinal scale
- Despite a treatment-related improvement in respiratory function
at day 7, there was no mortality reduction in the 97 treated
patients over age 65, suggesting the potential need for more
prolonged or higher dosing of anti-inflammatory therapy in these
patients who may have a more exuberant inflammatory response
associated with defective immune-mediated viral clearance
mechanisms
Mesoblast plans to move forward with an additional Phase 3 trial
in COVID-19 ARDS with the next step being to agree with the FDA the
final protocol and potency assay.
Inflammatory Bowel Disease – Crohn’s Disease and
Ulcerative Colitis
A randomized, controlled study of remestemcel-L delivered by an
endoscope directly to areas of inflammation and tissue injury in up
to 48 patients with medically refractory Crohn’s disease and
ulcerative colitis commenced at Cleveland Clinic in October 2020.
The investigator-initiated study is the first in humans using local
cell delivery in the gut and will enable Mesoblast to compare
clinical outcomes using this delivery method with results from an
ongoing randomized, placebo-controlled trial in patients with
biologic-refractory Crohn’s disease where remestemcel-L was
administered intravenously.
Rexlemestrocel-L
Chronic Heart Failure
The results from the landmark DREAM-HF randomized controlled
trial in 537 treated patients with chronic heart failure with
reduced left ventricular ejection fraction (HFrEF) who received
rexlemestrocel-L (REVASCOR®) or control sham, demonstrated that a
single dose of rexlemestrocel-L resulted in substantial and durable
reductions in heart attacks, strokes, and cardiac deaths. The
trial’s primary endpoint of reduction in volume overload related
hospitalizations was not achieved. 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 developing
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 entire population of 537 treated
patients. The incidence of death from cardiovascular causes was
reduced by 60% in the 206 patients with NYHA class II disease, a
significant reduction which was evident in both ischemic and
non-ischemic subgroups as well as diabetic and nondiabetic
patients.
The results also show that the NYHA class II patients in the
control group, following an initial period of approximately 20
months of disease stability, progressed to cardiac death rates
in-line with NYHA class III patients. NYHA class II patients
treated with a single dose of rexlemestrocel-L did not show such
cardiac death progression.
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 events (MACE)
is a well-established endpoint used by the FDA to determine
cardiovascular risk. Rexlemestrocel-L reduced this three-point MACE
by 30% compared to controls across the entire population of 537
treated patients. In the NYHA class II subgroup of 206 patients,
rexlemestrocel-L reduced the three-point MACE by 55% compared to
controls.
Mesoblast expects feedback from the FDA in the next quarter on
the potential pathway to US regulatory approval for
rexlemestrocel-L in patients with chronic heart failure.
Chronic Low Back Pain due to Degenerative Disc
Disease
The results from the randomized controlled trial of its
allogeneic mesenchymal precursor cell (MPC) therapy
rexlemestrocel-L in 404 enrolled patients with chronic low back
pain (CLBP) due to degenerative disc disease (DDD) refractory to
conventional treatments indicate that a single injection of
rexlemestrocel-L+hyaluronic acid (HA) carrier may provide a safe,
durable, and effective opioid-sparing therapy for patients with
chronic inflammatory back pain due to degenerative disc disease,
and that greatest benefits are seen when administered earlier in
the disease process before irreversible fibrosis of the
intervertebral disc has occurred. The trial's composite outcomes of
pain reduction together with functional responses to treatment were
not met by either MPC group.
The rexlemestrocel-L+HA treatment group achieved substantial and
durable reductions in CLBP compared to control through 24 months
across the entire evaluable study population (n=391) compared with
saline controls. Greatest pain reduction was observed in the
pre-specified population with CLBP of shorter duration than the
study median of 68 months (n=194) and subjects using opioids at
baseline (n=168) with the rexlemestrocel-L+HA group having
substantially greater reduction at all time points (1, 3, 6, 12, 18
and 24 months) compared with saline controls. There was no
appreciable difference in the safety of MPC groups compared to
saline control over the 24-month period of follow-up in the entire
study population. In subjects using opioids at baseline, the MPC+HA
demonstrated a reduction in the average opioid dose over 24 months,
while saline control subjects had essentially no change.
There is a significant need for a safe, efficacious, and durable
opioid-sparing treatment in patients with chronic low back pain due
to severely inflamed degenerative disc disease. Mesoblast has filed
a request and expects to receive feedback from the FDA on the
pathway to US regulatory approval in patients with chronic low back
pain due to degenerative disc disease.
Intellectual Property
Mesoblast has an extensive patent portfolio with over 1,000
patents and patent applications across 77 patent families, and
patent terms extending through 2041. These patents cover
composition of matter, manufacturing, and therapeutic applications
of mesenchymal lineage cells, and provide strong commercial
protection for our products in all major markets, including the
United States, Europe, Japan and China. During the fiscal year
Mesoblast has significantly expanded its patent portfolio, focusing
on areas of its strategic commercial interests.
Licensing agreements with JCR, Grünenthal, Tasly and Takeda
highlight the strength of Mesoblast's extensive intellectual
property portfolio covering mesenchymal lineage cells. Mesoblast
will continue to use its patents to prosecute its commercial rights
as they relate to its core strategic product portfolio. When
consistent with the Company’s strategic objectives, it may consider
providing third parties with commercial access to its patent
portfolio.
DETAILED FINANCIAL RESULTS
Financial Results for the Year Ended June 30, 2021
(FY2021)
- Balance sheet cash
on hand of US$136.9 million at June 30, 2021.
In August we entered into a contractual amendment to extend the
interest-only period of its current senior debt facility to at
least January 2022 and as a result no loan repayments will be
required prior to January 2022. Mesoblast is in active discussions
to refinance the facility.
- Royalty revenues on
sales of TEMCELL® HS Inj. in Japan increased by 10% to US$7.2
million for the year ended June 30, 2021 compared to US$6.6 million
for the year ended June 30, 2020. Sales of TEMCELL by Mesoblast
licensee in Japan JCR for the treatment of aGVHD have
re-established a steady growth trajectory after plant capacity was
expanded to meet growing demand.
- Milestone revenue
FY2020 included US$25.0 million in rexlemestrocel-L upfront &
milestone payments from Grünenthal and Tasly, which was not
reported in FY2021
- Research and
Development expenses decreased from US$56.2 million in
FY2020 to US$53.0 million in FY2021, due to a reduction in third
party clinical trial costs; 54% (US$28.5 million) of total spend
related to remestemcel-L development, including clinical, medical
& regulatory support ($14.8 million), process development
(including potency assays & support costs) (US$9.5 million),
and COVID ARDS Phase 3 clinical trial (US$4.2 million).
- Manufacturing
expenses increased by US$7.4 million to US$32.7 million for FY2021,
compared to US$25.3 million for FY2020; 92% (US$30.2 million) of
total spend related to remestemcel-L, including: pre-launch
inventory (US$13.1 million), clinical cell supply for life cycle
management (US$3.5 million), commercial readiness and next
generation processes (US$13.6 million) to improve cost efficiencies
and yields of remestemcel-L to support long-term commercial supply
for SR-aGVHD and COVID ARDS.
We expect to recognize the existing US$21.9 million of
remestemcel-L pre-launch inventory on the balance sheet if we
receive FDA approval.
- Management and
Administration expenses increased from US$25.6 million for
FY2020 to US$30.9 million for FY2021; this increase was
predominantly due to costs associated with insurance, BLA filing,
debt refinancing and other corporate transactions.
- Finance Costs
predominantly for borrowing arrangements with Hercules and
NovaQuest were US$10.7 million for FY2021, compared to US$14.1
million for FY2020.
As a result of the above and other remeasurements on revaluation
of assets and liabilities, the loss after tax for FY2021 was
US$98.8 million compared to US$77.9 million for FY2020. The net
loss attributable to ordinary shareholders was 16.33 US cents per
share for FY2021, compared with 14.74 US cents per share for
FY2020.
Conference Call
There will be a webcast today, beginning at 7.00pm EDT (Monday,
August 30, 2021); 9.00am AEST (Tuesday, August 31). It can be
accessed
via:https://webcast.boardroom.media/mesoblast-limited/20210826/NaN61036c41df5665001c97fc67
The archived webcast will be 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 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
- 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 Kaplan-Meier log
rank statistics
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.
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 |
|
|
|
Kristen Bothwell |
|
T: +1 917 613 5434 |
|
E: kbothwell@rubenstein.com |
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