Mereo BioPharma Group plc (NASDAQ: MREO), (“Mereo” or “the
Company”), a clinical-stage biopharmaceutical company focused on
rare diseases today announced that data from the Phase 2 “ASTRAEUS”
trial of alvelestat for the treatment of Alpha-1 Antitrypsin
Deficiency-associated Lung Disease (AATD-LD), as well as post-hoc
analyses demonstrating the association between biomarker reductions
with alvelestat and improvements in SGRQ, a key Patient-Reported
Outcome (PRO) measure, were presented for the first time to the
scientific community at the 2023 American Thoracic Society
International Conference. The ASTRAEUS data were presented during
an oral abstract session on novel treatments and targets by Prof.
Robert Stockley, Lung Investigation Unit, University of Birmingham
(United Kingdom) and Chief Investigator of the ASTRAEUS trial,
while the post-hoc analyses were presented in a poster session by
Dr. Jackie Parkin, Senior Vice President and Therapeutic Head at
Mereo.
Consistent with previously reported biomarker
analyses, alvelestat demonstrated significant and consistent
reductions in all three biomarkers related to AATD-LD disease
activity: blood neutrophil elastase (NE), Aα-val360 and the elastin
breakdown product, desmosine. Low - and high-dose alvelestat
significantly suppressed NE activity compared to baseline (-83.5%
and -93.3%, p=0.023 and p<0.001 respectively) and versus placebo
(p=0.001 and p<0.001). In the high dose arm, Aα-val360 and
desmosine progressively decreased from baseline, -22.7% (p=0.004)
and -13.2% (p=0.045) respectively, with significant reductions
compared to placebo as well (p=0.001 and p=0.041). The low dose did
not generate consistent changes in Aα-val360 or desmosine.
Based on these data, Mereo is completing
preparatory work for a single pivotal Phase 3 study evaluating the
high dose of alvelestat (240mg), which, if successful, is expected
to support submissions for full regulatory approvals in both the
U.S. and EU. The planned study will have two independent primary
endpoints, based on the recommendations of the U.S. Food and Drug
Administration (FDA) and European Medicines Agency (EMA): i) a
Patient-Reported Outcome (PRO) expected to be change from baseline
in the SGRQ-Activity Domain score, as guided by the FDA, and ii)
lung density measured by CT scan, as guided by the EMA. In line
with previous guidance, Mereo is continuing to explore potential
partnerships to fund the Phase 3 development of alvelestat.
Findings from the biomarker-SGRQ post-hoc
analysis showed an association between the extent of reduction in
biomarkers and degree of improvement in the SGRQ-Activity domain in
alvelestat-treated subjects. By week 12, there was an observed
difference in improvement in SGRQ-Activity in biomarker responders
compared to non-responders, with a mean improvement of 4.4 in those
showing a >0% biomarker decrease and 6.1 in those with >5%
biomarker decrease (P=0.05 and p=0.02 respectively), compared to
those on alvelestat without biomarker decrease. This association
was not observed in the patients who received placebo. These data
support a potential association between the effect of alvelestat on
the NE pathway and improvement in how a patient feels and functions
based on SGRQ score. Data from ASTRAEUS and other research support
the hypothesis that longer term treatment is expected to lead to a
deepening of the biomarker and associated clinical response.
Alvelestat has been generally safe, with no
safety signals of concern observed to date. Adverse events leading
to study drug discontinuation (one liver function and one prolonged
QTc) resolved on study drug cessation. Three treatment-related SAEs
of headache were reported in the alvelestat arms. Headache is a
known adverse event associated with alvelestat and is being
addressed through dose-escalation during initiation of alvelestat
treatment.
“We are very pleased to have these data
presented to the scientific community for the first time at
ATS2023. These findings have informed our recent and ongoing
discussions with both the FDA and EMA, and validate the proposed
design for our planned Phase 3 trial, which we believe will be the
first registrational study in AATD-LD to use both a PRO approach
and an objective clinical outcome measure as independent primary
endpoints,” said Dr. Denise Scots-Knight, CEO of Mereo BioPharma.
"We are excited by the potential of alvelestat to become the
first-in-class oral neutrophil elastase inhibitor for the treatment
of AATD-LD and look forward to continued collaboration with the
regulatory authorities, scientific and patient communities as we
further refine our development plans ahead of the pivotal study. We
look forward to sharing further updates on the progress of the
alvelestat program, including the results of the investigator-led
Phase 2 ATALANTA study evaluating alvelestat in combination with
augmentation therapy, which is expected to read out in Q3
2023.”
Details of the ATS data presentations
are as follows:Abstract Title:
Alvelestat, an Oral Neutrophil Elastase Inhibitor in Alpha-1
Antitrypsin Deficiency (AATD): Results of a Phase II
TrialSession Date & Time: Tuesday, May 23 at
9AM ETPresenter: Prof. Robert
StockleySession Title: Emerging COPD Diagnostics
and TreatmentsAbstract ID: 10172
Abstract Title: Analysis From
Phase II Clinical Trial, Alvelestat, NE (Neutrophil Elastase)
Inhibitor in AATD-LD: Correlation Between Biomarker Response
(Desmosine and Aa-val360) and Clinical Outcome
(SGRQ)Session Date & Time: Monday, May 22 at
9AM ETPresenter: Jackie ParkinSession
Title: New Treatments and Novel Targets for COPD and
ALPHA-1 Abstract ID: 10358
“We are grateful that the alvelestat data presented this week
has been received with such interest and enthusiasm by the
respiratory community,” added Dr. Jackie Parkin, SVP and
Therapeutic Head, Mereo BioPharma. “The attendance at our poster
session yesterday and active engagement with thought leaders during
and outside of Professor Stockley’s oral presentation earlier today
are a clear reflection of the excitement toward alvelestat and its
potential to improve the lives of patients with AATD-LD. I would
like to thank Professor Stockley and the other ASTRAEUS
investigators and their staff for their ongoing commitment to
advancing alvelestat, as well as the patients, their caregivers and
families who participated in the study, and to The Alpha-1 Project
for their contribution to funding this work. We look forward to
further collaboration as we advance toward the planned Phase 3
study and remain firmly committed to our mission.”
ASTRAEUS Study Design
Overview
ASTRAEUS (ClinicalTrials.gov Identifier:
NCT03636347) was a randomized double-blind placebo-controlled study
in patients naïve to augmentation or following a 6-month wash-out
period. The study enrolled 99 adults with severe AATD-related Lung
Disease across 26 sites in North America, EU and U.K. of which 98
were dosed. To support the use of a biomarker development strategy
interrogating the pathogenic pathway, an amendment elevated two
secondary biomarkers (NE activity and Aα-val360) to primary
endpoints in addition to desmosine, resulting in three biomarker
primary endpoints. Patients were randomized to one of three
different arms, high dose, low dose or placebo, following
Independent Safety Data Monitoring Committee (IDMC) review of the
safety from the initial cohorts. As previously announced, the
protocol allowed prioritization of enrollment to the high dose arm
in the case of recruitment challenges and this change was
implemented during the COVID-19 pandemic.
Patients underwent a twelve-week dosing period
followed by a four-week follow-up. The primary endpoints included
within-patient individual % change from baseline up to
end-of-treatment, within the treatment arms and in comparison to
placebo, at weeks four, eight and 12 in blood neutrophil elastase
activity, Aα-Val360 levels and desmosine levels. The secondary
endpoints were the proportion of patients with NE below the limit
of quantitation and PK, safety and tolerability. Exploratory
endpoints included rate of acute exacerbations of COPD, pulmonary
function tests, St George’s Respiratory Questionnaire, inflammatory
and lung damage biomarkers.
The study was originally designed to enroll 165
patients, however, the Company took the decision to close the study
when it was determined an adequate number of subjects were
recruited to the high dose arm to assess the primary endpoints,
with a total of 99 patients enrolled, 98 of whom were dosed.
About Mereo BioPharmaMereo BioPharma is a
biopharmaceutical company focused on the development of innovative
therapeutics for rare diseases. The Company has two rare disease
product candidates, setrusumab for the treatment of Osteogenesis
Imperfecta (OI) and alvelestat for the treatment of severe
alpha-1-antitrypsin deficiency-associated lung disease (AATD-LD)
and Bronchiolitis Obliterans Syndrome (BOS). The Company’s partner,
Ultragenyx Pharmaceutical, Inc., has initiated a pivotal Phase 2/3
pediatric study in young adults (5-25 years old) for setrusumab in
OI and expects to initiate a study in pediatric patients (<5
years old) in the first half of 2023. The partnership with
Ultragenyx includes potential milestone payments of up to $254
million and royalties to Mereo on commercial sales in Ultragenyx
territories. Mereo has retained EU and UK commercial rights and
will pay Ultragenyx royalties on commercial sales in those
territories. Alvelestat has received U.S. Orphan Drug Designation
for the treatment of AATD, Fast Track designation from the FDA, and
positive data were reported from a Phase 2 proof-of-concept study
in North America, Europe and the UK. In addition to the rare
disease programs, Mereo has two oncology product candidates in
clinical development. Etigilimab (anti-TIGIT) has completed
enrollment in a Phase 1b/2 basket study evaluating its safety and
efficacy in combination with an anti-PD-1 in a range of tumor types
including three rare tumors and three gynecological carcinomas -
cervical, ovarian, and endometrial; navicixizumab, for the
treatment of late line ovarian cancer, has completed a Phase 1
study and has been partnered with OncXerna Therapeutics, Inc. in a
global licensing agreement that includes payments of up to $300
million in milestones and royalties.
Forward-Looking StatementsThis press release
contains “forward-looking statements.” All statements other than
statements of historical fact contained in this press release are
forward-looking statements within the meaning of Section 27A of the
United States Securities Act of 1933, as amended (the “Securities
Act”), and Section 21E of the United States Securities Exchange Act
of 1934, as amended (the “Exchange Act”). Forward-looking
statements usually relate to future events and anticipated
revenues, earnings, cash flows or other aspects of our operations
or operating results. Forward-looking statements are often
identified by the words “believe,” “expect,” “anticipate,” “plan,”
“intend,” “foresee,” “should,” “would,” “could,” “may,” “estimate,”
“outlook” and similar expressions, including the negative thereof.
The absence of these words, however, does not mean that the
statements are not forward-looking. These forward-looking
statements are based on the Company’s current expectations, beliefs
and assumptions concerning future developments and business
conditions and their potential effect on the Company. While
management believes that these forward-looking statements are
reasonable as and when made, there can be no assurance that future
developments affecting the Company will be those that it
anticipates. All of the Company’s forward-looking statements
involve known and unknown risks and uncertainties some of which are
significant or beyond its control and assumptions that could cause
actual results to differ materially from the Company’s historical
experience and its present expectations or projections. Such risks
and uncertainties include, among others, the uncertainties inherent
in the clinical development process; the Company’s reliance on
third parties to conduct and provide funding for its clinical
trials; the Company’s dependence on enrollment of patients in its
clinical trials; and the Company’s dependence on its key
executives. You should carefully consider the foregoing factors and
the other risks and uncertainties that affect the Company’s
business, including those described in the “Risk Factors” section
of its latest Annual Report on Form 20-F, reports on Form 6-K and
other documents furnished or filed from time to time by the Company
with the Securities and Exchange Commission. The Company wishes to
caution you not to place undue reliance on any forward-looking
statements, which speak only as of the date hereof. The Company
undertakes no obligation to publicly update or revise any of our
forward-looking statements after the date they are made, whether as
a result of new information, future events or otherwise, except to
the extent required by law.
Mereo BioPharma
Contacts: |
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|
Mereo |
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+44 (0)333 023
7300 |
Denise Scots-Knight, Chief
Executive Officer |
|
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Christine Fox, Chief Financial
Officer |
|
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Burns McClellan
(Investor Relations Adviser to Mereo) |
|
+01 646 930
4406 |
Lee Roth |
|
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Investors/
media |
|
investors@mereobiopharma.com |
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