Study of Mechanism of Action of Ibrutinib in Mantle Cell Lymphoma Published in Blood - Journal of the American Society of

Study of Mechanism of Action of Ibrutinib in Mantle Cell Lymphoma Published in
            Blood - Journal of the American Society of Hematology

PR Newswire

SUNNYVALE, Calif., Aug. 22, 2013

SUNNYVALE, Calif., Aug. 22, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq:
PCYC) announced today the publication of a study that investigated the
mechanism of ibrutinib's anti-tumor effect in patients with mantle cell
lymphoma (MCL) in Blood, the most cited peer-reviewed journal in the field of
hematology. The article was pre-published online shortly after acceptance in
manuscript format as a First Edition Paper.

Response of MCL patients to ibrutinib was noted during early clinical trials
to be accompanied by increases in absolute lymphocyte count (ALC) in the
peripheral blood. MCL cells typically grow in the lymph nodes and tissues
where they receive signals and support that are essential for their survival
and growth. In the current paper, Pharmacyclics Vice President of Research,
Betty Chang, along with colleagues and collaborators, showed that the
lymphocytes, which increase in the peripheral blood during ibrutinib
treatment, are MCL cells rather than normal cells. Moreover, the data
indicate ibrutinib may directly and potently inhibit MCL cell adhesion and
migration in the residing lymph nodes or tissues. This publication illustrates
these cells show decreases of markers of activation and growth as treatment
continued and nodal responses were observed.

"For the first time, we demonstrate that the increase in lymphocytes in the
peripheral blood is due to an egress of MCL cells from tissues, such as the
lymph nodes. Following ibrutinib treatment these cells are released in a
matter of days into the peripheral blood where they are then quickly cleared
systemically. This general mechanism was previously postulated for BCR
antagonists in CLL but it is now characterized in detail in MCL showing how
ibrutinib can lead to the observed responses," said Betty Chang, Vice
President of Research Biology at Pharmacyclics.

About Mantle Cell Lymphoma
MCL is a B-cell malignancy, an aggressive type of B-cell non-Hodgkin lymphoma
(NHL) that usually occurs in older adults.^i The disease typically begins in
the lymph nodes, but can spread to other tissues, such as bone marrow, liver,
and spleen.^ii Patients typically survive an average of five years.^iii There
are approximately 5,600 new cases of MCL each year in the G7 (U.S., France,
Germany, Italy, Spain, U.K., and Japan) and a prevalence of about 23,000
patients (Decision Resources 2012).

About Ibrutinib
Ibrutinib is an investigational agent designed to provide potent and sustained
inhibition of an enzyme called Bruton's tyrosine kinase (BTK). BTK is a key
mediator of at least three critical B-cell pro-survival mechanisms occurring
in parallel – regulation of apoptosis, adhesion, and cell migration and
homing. Through these multiple signals, BTK regulation helps to direct
malignant B-cells to lymphoid tissues, thus allowing access to a
micro-environment necessary for survival.

The effectiveness of ibrutinib alone or in combination with other treatments
is being studied in several B-cell malignancies, including chronic lymphocytic
leukemia/small lymphocytic lymphoma, mantle cell lymphoma, diffuse large
B-cell lymphoma, follicular lymphoma, Waldenstrom's macroglobulinemia and
multiple myeloma. To date, 7 Phase III trials have been initiated with
ibrutinib and a total of 31 trials are currently registered on Janssen and Pharmacyclics entered a collaboration and
license agreement in December 2011 to co-develop and co-commercialize

About Pharmacyclics
Pharmacyclics^® is a clinical-stage biopharmaceutical company focused on
developing and commercializing innovative small-molecule drugs for the
treatment of cancer and immune mediated diseases. Our mission and goal is to
build a viable biopharmaceutical company that designs, develops and
commercializes novel therapies intended to improve quality of life, increase
duration of life and resolve serious unmet medical healthcare needs; and to
identify promising product candidates based on scientific development and
administrational expertise, develop our products in a rapid, cost-efficient
manner and pursue commercialization and/or development partners when and where

Presently, Pharmacyclics has three product candidates in clinical development
and several preclinical molecules in lead optimization. The company is
committed to high standards of ethics, scientific rigor, and operational
efficiency as it moves each of these programs to viable commercialization.

Pharmacyclics is headquartered in Sunnyvale, California and is listed on
NASDAQ under the symbol PCYC. To learn more about how Pharmacyclics advances
science to improve human healthcare visit us at

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i "Lymphoma – Non-Hodgkin". Accessed
April 2013.

^ii Know Cancer. "Mantle Cell Lymphoma". Available at: Accessed April 2013.

^iii Geisler, C. (2010) "Front-line treatment of mantle cell lymphoma."
Haematologica, 95:8:1241-1243. Available at:

SOURCE Pharmacyclics, Inc.

Contact: Ramses Erdtmann, SVP of Investor Relations and Administration,
+1-408-215-3325, or Manisha Pai, Sr. Director Public Relations & Corporate
Communications, +1-408-215-3720, or U.S. Medical Information, Pharmacyclics,
+1-855-ibrutinib [(855)-427-8846],
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