Strong interim survival trend (15.2 vs
8.5 months) emerging in IL4R positive patients
TORONTO and
HOUSTON, TX, Feb. 7, 2019 /PRNewswire/ - Medicenna
Therapeutics Corp. ("Medicenna" or "the Company") (TSX: MDNA,
OTCQB: MDNAF), a clinical stage immunotherapy company developing
first-in-class Superkines and Empowered Cytokines, reported interim
data from its on-going Phase 2b trial
of MDNA55 for the treatment of recurrent glioblastoma ("rGBM").
MDNA55 is a fusion protein designed to target the Type II
interleukin-4 receptor (consisting of the IL4Rα and IL13Rα
1), a biomarker that is over-expressed in a majority of GBM
patients but not in healthy brain. GBM patients with a positive
Type 2 IL4R profile typically have a worse prognosis than the
overall glioblastoma population, including poor long term survival.
Results being presented today demonstrate promising signs of
clinical benefit, particularly in recurrent patients with an
aggressive form of GBM.
New clinical study results will be delivered today in a
podium presentation titled, "The IL4 Receptor as a Biomarker and
Immunotherapeutic Target for Glioblastoma: Preliminary Evidence
with MDNA55, a Locally Administered IL-4 Guided Toxin" by
John H. Sampson, MD,
PhD, Robert H. and Gloria Wilkins Distinguished Professor and Chair
of Neurosurgery at Duke University in
Durham, NC, during the
5th Annual Immuno-Oncology 360 Conference being
held in New York, NY.
"MDNA55 provides impressive prolonged survival, especially
in IL4R positive tumors, a marker highly expressed on brain cancers
and the tumor microenvironment and known to be associated with
aggressive disease," states Dr. Sampson. "Seeing evidence of
clinical benefit in trial participants treated thus far with low
doses of MDNA55 offers promise for patients with rGBM given the
overall bleak prognosis and response to current therapy for this
population."
A summary of the main results from the study so far are as
follows:
- Following treatment with MDNA55 at the low dose, the IL4R
positive group showed a remarkable increase in median overall
survival ("mOS") of 15.2 months when compared to 8.5 months in the
IL4R negative group. Survival rates at 6, 9, and 12 months were
100%, 67% and 55% versus 73%, 40%, and 30%, in the IL4R positive
and negative groups, respectively.
- Irrespective of IL4R expression, mOS was11.8 months in
all patients following a single treatment with MDNA55 at the low
dose with an overall survival rate of 89% at 6 months, 59% at 9
months and 46% at 12 months, substantially exceeding landmark mOS
and survival rates reported for approved drugs for rGBM (mOS is 8
months for Avastin and Lomustine and survival rates at 6, 9 and 12
months are 62%, 38%, 26% and 65%, 43%, 30%,
respectively).1
- In the above participants, patients with IL4R positive
tumors showed a faster time to relapse (10.3 months) following
initial diagnosis of GBM when compared to patients with low to no
expression of IL4R (16.7 months) supporting published research
showing that the Type 2 IL4R is a key biomarker for more aggressive
forms of GBM.2,3
"These preliminary data showing longer median survival in
MDNA55-treated subjects with positive IL4R expression are highly
encouraging and could help determine which
subjects will receive optimal therapeutic benefit from MDNA55
treatment," states Dr. Martin Bexon, Head of Clinical
Development at Medicenna. "As the second half of our trial
continues to enroll at higher doses of MDNA55, we expect to see
more data supporting IL4R as an important biomarker and
immunotherapeutic target for rGBM and to improve the benefit-risk
profile for subjects treated with MDNA55." The safety and
tolerability of MDNA55 has generally remained within the profile
established in previous studies.
"The interim data presented today are extremely
encouraging and continue to add to an impressive and consistent
data set for MDNA55 across multiple studies," said Fahar Merchant, Ph.D, President and CEO of
Medicenna. "We believe these interim data are clinically important
to patients with rGBM and, if the final data remain consistent, it
would be practice-changing for neurosurgeons treating glioblastoma
and offer new hope to patients and their families."
Enrolment in the second half of the study incorporating a
higher dose of MDNA55 is expected to be completed in the next
couple of months with top-line results expected in
mid-2019.
About the Interleukin-4 receptor
(IL4R)
The IL4R target for MDNA55 is an ideal but under-exploited
drug target for central nervous system ("CNS") tumors, including
glioblastoma ("GBM"). The majority of cancer biopsy samples from
adult and pediatric CNS tumors, including recurrent GBM,
over-express the IL4R while there is little or no IL4R expression
in normal adult and pediatric brain
tissue.4 Expression of IL4R correlates with
increased tumorigenicity in mouse models and poor long term
survival in clinical studies of patients with GBM2,3. In
addition, the IL4R is known to be expressed by Myeloid Derived
Suppressor Cells and Tumor Associated Macrophages, which are known
to be key components of the immunosuppressive tumor
micro-environment (TME), which hides the tumor from cancer killing
immune cells5,6.
About the MDNA55-05 Clinical Trial
MDNA55-05 is a 52 subject open-label study of MDNA55, an
IL4R directed toxin, in patients with GBM at first or second
relapse. In the study, investigators administer MDNA55 only once
directly into the brain tumor using a technique known as Convection
Enhanced Delivery (CED). CED allows precision delivery of MDNA55
directly into the tumor tissue and the surrounding healthy brain
containing infiltrative tumor cells, while avoiding exposure to the
rest of the body. Retrospective analysis of GBM tissue obtained at
first diagnosis is performed by immunohistochemistry for
IL-4Rα expression. Biopsy samples
are categorized based on IL4Rα expression levels and compared
against survival outcomes.
About Medicenna Therapeutics Corp.
Medicenna is a clinical stage immunotherapy company
focused on oncology and the development and commercialization of
novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines
and first in class Empowered Cytokines™ (ECs) for the treatment of
a broad range of cancers. Supported by a significant non-dilutive
grant from CPRIT (Cancer Prevention and Research Institute
of Texas), Medicenna's lead IL4-EC, MDNA55, is enrolling
patients in a Phase 2b clinical trial for rGBM, the most
common and uniformly fatal form of brain cancer, at top-ranked
brain cancer centres in the US. MDNA55 has completed three clinical
trials in 72 patients, including 66 adults with rGBM, demonstrated
compelling efficacy and obtained Fast-Track and Orphan Drug status
from the FDA and FDA/EMA respectively. For more information, please
visit www.medicenna.com.
References
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1.
|
Taal et al,
Single-agent bevacizumab or lomustine versus a combination of
bevacizumab plus lomustine in patients with recurrent glioblastoma
(BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol
2014 Aug;15(9):943-53.
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2.
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Kohanbash G,
McKaveney K, Sakaki M, Ueda R, Mintz AH, Amankulor N, Fujita M,
Ohlfest JR, Okada H. GM-CSF promotes the immunosuppressive activity
of glioma-infiltrating myeloid cells through interleukin-4
receptor-α. Cancer Res. 2013 Nov 1;73(21):6413-23.
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3.
|
Han J and Puri RK.
Analysis of the cancer genome atlas (TCGA) database identifies an
inverse relationship between interleukin-13 receptor α1 and α2 gene
expression and poor prognosis and drug resistance in subjects with
glioblastoma multiforme. J Neurooncol. 2018
Feb;136(3):463-474.
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4.
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Joshi BH, Leland P,
Asher A, Prayson RA, Varricchio F, Puri RK. In situ expression of
interleukin- 4 (IL-4) receptors in human brain tumors and
cytotoxicity of a recombinant IL-4 cytotoxin in primary
glioblastoma cell cultures. Cancer Res
2001;61:8058-8061.
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Roth F, De La Fuente
AC, Vella JL, et al. Aptamer-mediated blockade of IL4Rα
triggers apoptosis of MDSCs and limits tumor progression. Cancer
Res. 2012;72(6):1373-83.
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6.
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Bankaitis KV and
Fingleton B. Targeting IL4/IL4R for the treatment of epithelial
cancer metastasis. Clin Exp Metastasis. 2015
Dec;32(8):847-56.
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This news release contains forward-looking statements
relating to the future operations of the Company and other
statements that are not historical facts. Forward-looking
statements are often identified by terms such as "will", "may",
"should", "anticipate", "expects" and similar expressions. All
statements other than statements of historical fact, included in
this release, including, without limitation, statements
related to the ongoing Phase 2b clinical trial of MDNA55 for the treatment of
rGBM (including, without limitation, patient enrolment and top line
data reporting timelines, that MDNA55 could be practice changing
and offer new hope to patients) and the future
plans and objectives of the Company, are forward-looking statements
that involve risks and uncertainties. There can be no assurance
that such statements will prove to be accurate and actual results
and future events could differ materially from those anticipated in
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to differ materially from the Company's expectations include the
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June 26, 2018 and in other filings
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The reader is cautioned that assumptions used in the
preparation of any forward-looking information (including, without
limitation, the ability of the Company to fully replicate these
interim data results) may prove to be incorrect. Events or
circumstances may cause actual results to differ materially from
those predicted, as a result of numerous known and unknown risks,
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control of the Company. The reader is cautioned not to place undue
reliance on any forward-looking information. Such information,
although considered reasonable by management at the time of
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SOURCE Medicenna Therapeutics Corp.