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Moxetumomab Pasudotox Pivotal Data in Patients with Previously-Treated Hairy Cell Leukemia Presented at the 2018 ASCO Meeting

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Study meets the primary endpoint of durable complete response

Majority of patients who had a complete response had no evidence of
any remaining detectable cancer cells

Phase III clinical trial results served as basis for recent US FDA
regulatory submission

AstraZeneca and MedImmune, its global biologics research and development
arm, today presented results from the Phase III (‘1053') clinical trial
(Abstract #7004) that evaluated moxetumomab pasudotox in 80 patients
with relapsed or refractory hairy cell leukemia (HCL) who had received
at least two prior lines of therapy.1

Moxetumomab pasudotox, an investigational anti-CD22 recombinant
immunotoxin, showed a 75% objective response (OR) rate, a 41% complete
response (CR) rate, and a 30% durable CR rate (primary endpoint). The
majority of patients with a complete response had a durable response
(73%; 24/33) and achieved a negative minimal residual disease (MRD)
status (82%; 27/33). Findings from this pivotal trial were presented for
the first time during an oral session at the 2018 American Society of
Clinical Oncology (ASCO) Annual Meeting in Chicago.

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer at AstraZeneca, said: "Moxetumomab pasudotox is an
investigational, first-in-class immunotoxin which we believe has the
potential to advance outcomes for patients with relapsed or refractory
hairy cell leukemia, a condition with a high unmet need. It is also the
first agent to be submitted for regulatory review from our Antibody Drug
Conjugates platform, and as such demonstrates our commitment to
developing novel treatments for blood cancer."

Robert J. Kreitman, MD, Senior Investigator, Head of Clinical
Immunotherapy Section, Laboratory of Molecular Biology, Center for
Cancer Research, National Cancer Institute, said: "Hairy cell leukemia
is a rare, chronic blood cancer with no established standard of care for
patients with relapsed or refractory disease following purine nucleoside
analog therapy. With very few treatments available, there remains
significant unmet medical need for people with relapsed or refractory
disease. The response rates observed in this trial, and elimination of
the residual leukemia cells that cause relapse in some patients,
highlight the potential impact this potential new medicine could have on
patients and the management of this disease."

Summary of key results from the Phase III ‘1053' single arm, multicenter
clinical trial in 80 patients with relapsed or refractory HCL (16.7
months median follow-up), as determined by a blinded independent central
review:

         
Endpoint       Moxetumomab pasudotox
OR rate       75% (60/80)
CR rate       41% (33/80)
Durable CR rate       30% (24/80)

Hematologic remission* (blood count
normalization, HR) rate

      80% (64/80)

MRD negative status (CR rate with
immunohistochemistry MRD
negativity)

      82% (27/33)

*Hematologic remission (HR) is defined by: neutrophils ≥ 1.5 x 109
/L, platelets ≥ 100 x 109 /L, hemoglobin ≥ 11 g/dL, no transfusions /
growth factors ≥ 4 weeks

The primary endpoint of the trial was durable CR, which is defined as CR
with HR for >180 days. The median time to HR was 1 month. MRD refers to
the small amounts of cancer cells that may remain after treatment.2
A high rate of negative MRD after therapy may further improve outcomes.3
The median duration of OR and median progression-free survival
were not reached.

The most frequent treatment-related adverse events (AEs) were nausea
(28%), peripheral edema (26%), headache (21%), and pyrexia (20%); 8% had
infections and 3% had neutropenia deemed treatment-related. Three
patient deaths occurred, none of which were determined to be
treatment-related. Treatment-related AEs leading to discontinuation were
hemolytic uremic syndrome (HUS; 4 [5%]), capillary leak syndrome (CLS; 2
[3%]), and increased blood creatinine (2 [3%]). Seven patients (9%) had
CLS and seven (9%) had HUS; this includes four (5%) patients who had
both CLS and HUS. CLS and HUS were manageable and reversible.

In April 2018, AstraZeneca announced that the US Food and Drug
Administration (FDA) accepted the Biologics License Application (BLA)
for moxetumomab pasudotox for the treatment of adult patients with HCL
who have received at least two prior lines of therapy. The BLA is based
on results from the Phase III ‘1053' clinical trial. The FDA has granted
Priority Review status with a Prescription Drug User Fee Act action date
set for the third quarter of 2018.

NOTES TO EDITORS

About Moxetumomab Pasudotox

Moxetumomab pasudotox (formerly CAT-8015 or HA22) is an investigational
anti-CD22 recombinant immunotoxin and a potential new medicine with the
opportunity to be a first-in-class treatment in the US for patients with
relapsed or refractory hairy cell leukemia (HCL) who have received at
least two prior lines of therapy. Immunotoxins are a class of anticancer
agents that combine the selectivity of antibodies to target drug
delivery and the potency of toxins to kill target cancer cells.4
Moxetumomab pasudotox is composed of a binding portion of an anti-CD22
antibody fused to a toxin. CD22 is a B-lymphocyte restricted
transmembrane protein with a higher receptor density in HCL cells
relative to normal B cells, making it an attractive therapeutic target
for the treatment of this cancer.5 After binding to CD22, the
molecule is internalized, processed and releases its modified protein
toxin that inhibits protein synthesis, leading to apoptotic cell death.
Moxetumomab pasudotox has been granted Orphan Drug Designation by the
FDA for the treatment of HCL.

About Hairy Cell Leukemia

HCL is a rare, incurable slow-growing leukemia in which the bone marrow
overproduces abnormal B cells or lymphocytes.6 HCL can result
in serious and life-threatening conditions, including infections,
bleeding and anemia.7 Approximately 1,000 people are
diagnosed with HCL in the US each year.8,9,10 While many
patients initially respond to treatment, up to 40% will relapse.11
With no established standard of care and very few treatments available,
there remains significant unmet medical need for people with relapsed or
refractory HCL.12,13

About the ‘1053' Phase III Trial

The ‘1053' trial is a single-arm, multicenter Phase III clinical trial
assessing the efficacy, safety, immunogenicity and pharmacokinetics of
moxetumomab pasudotox monotherapy in patients with relapsed or
refractory HCL who have received at least two prior therapies. The trial
is being conducted in 80 patients across 34 sites in 14 countries.14
The primary endpoint was durable complete response (CR), defined as CR
with hematologic remission (blood count normalization) for >180 days.
Secondary outcome measures included overall response rate, relapse free
survival, progression-free survival, time to response, safety,
pharmacokinetic and immunogenic potential.14

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly-growing portfolio of new medicines that has the potential to
transform patients' lives and the Company's future. With at least six
new medicines to be launched between 2014 and 2020, and a broad pipeline
of small molecules and biologics in development, we are committed to
advance Oncology as a growth driver for AstraZeneca focused on lung,
ovarian, breast and blood cancers. In addition to our core capabilities,
we actively pursue innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by our
investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – Immuno-Oncology,
Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug
Conjugates – and by championing the development of personalized
combinations, AstraZeneca has the vision to redefine cancer treatment
and one day eliminate cancer as a cause of death.

About AstraZeneca in Hematology

Leveraging its collective heritage in oncology, AstraZeneca has
established hematology as one of four key oncology disease areas of
focus, and is accelerating development of a broad portfolio of potential
blood cancer treatments. AstraZeneca and Acerta Pharma, its hematology
research and development center of excellence, received US FDA approval
for the first medicine in this franchise, CALQUENCE®
(acalabrutinib), in 2017.

About MedImmune

MedImmune is the global biologics research and development arm of
AstraZeneca, a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialization of small
molecule and biologic prescription medicines. MedImmune is pioneering
innovative research and exploring novel pathways across Oncology,
Respiratory, Cardiovascular, Renal & Metabolic Diseases, and Infection
and Vaccines. The MedImmune headquarters is located in Gaithersburg, MD,
one of AstraZeneca's three global R&D centers, with additional sites in
Cambridge, UK and South San Francisco, CA. For more information, please
visit www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in three
therapy areas - Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. The Company also is selectively active in the areas of
autoimmunity, neuroscience and infection. AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. For more information, please visit www.astrazeneca-us.com
and follow us on Twitter @AstraZenecaUS.

 

References

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Kreitman, R, Dearden C, Zinzani P, Delgado J et al. Moxetumomab
Pasudotox in Heavily Pretreated Patients with Relapsed/Refractory
Hairy Cell Leukemia: Results of a Pivotal International Study.
American Society of Clinical Oncology 2018; June 2018; Chicago,
IL. Abstract
#7004
.

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Leukemia & Lymphoma Society. Glossary Results – Minimal Residual
Disease. Available
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Thomas, Deborah A., Ravandi, F. et al. Importance of minimal
residual disease in hairy cell leukemia: monoclonal antibodies as
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G Aruna. Immunotoxins: A review of their use in cancer treatment.
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Hairy Cell Leukemia Foundation. Treatment. Available
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López-Rubio, M., Garcia-Marco, J. A. Current and emerging
treatment options for hairy cell leukemia. OncoTargets and
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National Institutes of Health. Hairy Cell Leukemia. Available
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ClinicalTrials.gov. Moxetumomab pasudotox for Advanced Hairy Cell
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