Pharmacyclics Initiates Phase 1 Clinical Trial of Novel Oral Btk Inhibitor for Refractory B-cell
`Non-Hodgkin's Lymphoma
`
`--Multiple Pharmacyclics Presentations to be made at the American Association of Cancer Research
`(AACR) 100th Annual Meeting 2009 in Denver, CO
`
`SUNNYVALE, Calif., April 13, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Pharmacyclics, Inc. (Nasdaq: PCYC)
`today announced that it has begun treating patients in a Phase 1 dose-escalation study to evaluate the safety and tolerability
`of PCI-32765, an orally available, selective inhibitor of Bruton's tyrosine kinase, or Btk, as a potential treatment for patients with
`relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). This is the first Btk selective inhibitor to be tested in humans, and
`is Pharmacyclics' fourth product in clinical development.
`
`Bruton's tyrosine kinase is the gene that is disrupted in the human disease X-linked agammaglobulenemia (XLA). Patients with
`XLA are devoid of mature B-lymphocytes and immunoglobulins in the bloodstream, but are otherwise healthy. XLA thus
`provides strong clinical rationale for development of a novel therapeutic drug targeting Btk for safe inhibition of B-cell mediated
`diseases. In preclinical studies, PCI-32765 has the remarkable ability to selectively inhibit human B-cell activation without
`effecting T cells. Strong preclinical validation of Btk as a target in lymphoma was generated using PCI-32765 in a mouse model
`of B-cell receptor-driven lymphoma and in spontaneous B-cell lymphoma in companion canines. These studies will be reported
`in presentations at the 2009 AACR annual meeting in Denver, Colorado (see below). Unlike anti-CD20 protein therapies,
`treatment with PCI-32765 in animal models is not myeloablative, which could result in prolonged and dangerous
`immunosuppression for the patient.
`
`"This is a very selective compound for B-cells, and it could represent an important alternative to rituximab therapy for the
`treatment of B-cell NHL. Other obvious applications include autoimmune disorders such as rheumatoid arthritis and lupus, and
`Pharmacyclics also has strong preclinical efficacy with PCI-32765 in these disease models," said Dr. Mark Genovese, Professor
`of Medicine and Co-Chief of the Division of Immunology and Rheumatology at Stanford University Medical Center and member
`of Pharmacyclics' Scientific Advisory Board.
`
`"Despite recent success with biologics in the treatment of B-cell NHL, there is still a large group of patients that do not respond
`to therapy or who experience recurrence," said Ranjana Advani, MD, Associate Professor, Stanford University Medical Center
`and principle investigator of the Phase 1 clinical trial. "A drug that could not only have an impact on this patient group, but also
`be delivered orally would represent a significant step forward in the treatment of this disease."
`
`This Phase 1 study is evaluating the safety and pharmacokinetics of PCI-32765 in patients with refractory B-cell non-Hodgkin's
`lymphoma at Stanford University, MD Anderson Cancer Center and the University of Chicago using a 28-day dose-escalation
`design. The study is also utilizing a proprietary pharmacodynamic assay developed by Pharmacyclics to directly assess Btk
`drug occupancy. Preliminary results from the Phase I trial shows good patient tolerability under conditions of Btk-drug
`occupancy with potent bioactivity in targeted cell populations derived from the B-cell lymphoma patients.
`
`Pharmacyclics Btk Presentations at AACR
`
`Monday April 20, 2009
`
`9:30 am - 1:00 pm; Minisymposium Novel Molecular Targets / Targeting Cell Death Pathways; Experimental and Molecular
`Therapeutics 12 Room 405-407, Colorado Convention Center 9:40am-9:55am
`
`#1984 Btk is a Novel Therapeutic Target to Treat Large B-cell Lymphomas Ryan M. Young, Ashley Smith, Lee Honigberg,
`Yosef Refaeli. National Jewish Health, Denver, CO, Pharmacyclics, Inc., Sunnyvale, CA
`
`Tuesday April 21, 2009
`
`8:00 am - 12:00 pm Poster Session Kinase Inhibitors 3 Experimental and Molecular Therapeutics 24 Hall B-F, Poster Section
`36
`
`8:00 am - 12:00 pm Poster Board Number 24
`
`#3740 A Clinical Trial of the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Naturally Occurring Canine Lymphoma. Lee
`Coalition for Affordable Drugs IV LLC - Exhibit 1047
`
`

`

`A. Honigberg, Ashley M. Smith, David J. Loury, Joseph J. Buggy, Douglas H. Thamm. Pharmacyclics, Sunnyvale, CA, Colorado
`State University Animal Cancer Center, Fort Collins, CO
`
`About Pharmacyclics' Btk Inhibitor Program
`
`PCI-32765 is currently targeted for oncology while other Pharmacyclics Btk inhibitors are being developed for application to
`autoimmune and inflammatory diseases. Bruton's tyrosine kinase is a critical enzyme involved in B-cell activation and function,
`and inhibition may be useful in the treatment of a number of immune mediated diseases. B-cells are a type of white blood cell
`that normally play an important role in the body's immune response. However, when B-cells are overactive, the immune system
`produces inflammatory cells and antibodies that begin to attack the body's own tissue, leading to autoimmune disorders. Also
`many lymphomas are caused by uncontrolled growth of B-cells where activation of the B-cell receptor and Btk signaling are
`thought to play important roles.
`
`In addition to being studied in a Phase 1 trial for refractory B-cell non- Hodgkin lymphoma, PCI-32765 has been evaluated in
`preclinical studies in collagen-induced arthritis, an established animal model for RA. In these studies, PCI-32765 dramatically
`reduced inflammation and induced regression of established disease as reported at the Federation of Clinical Immunology
`Societies (FOCIS) 2008 annual meeting .
`
`About B-cell Non-Hodgkin's Lymphoma
`
`Lymphoma is cancer of the lymphatic system, an integral part of the immune system, and is typically classified as either
`Hodgkin's or non-Hodgkin's lymphoma (NHL). NHL is the most prevalent type of lymphoma: the National Cancer Institute
`estimates there will be more than 66,000 new cases and over 19,000 deaths from NHL in the United States in 2008. There are
`many different types of NHL, which are generally divided as either B-cell, the most common, or T-cell NHL. Though treatment of
`NHL has improved significantly, nearly 25% of patients with B-cell lymphomas do not respond to standard therapy, which
`generally consists of high-dose radiotherapy, chemotherapy or a combination of both.
`
`About Pharmacyclics
`
`Pharmacyclics(R) is committed to creating and developing novel pharmaceutical products that treat serious unmet medical
`needs in oncology and autoimmune diseases. Its deep and broad pipeline includes four first in class/best in class drug
`candidates that are currently under clinical development. The Company 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 http://www.pharmacyclics.com.
`
`NOTE:
`
`This announcement may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A
`of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including
`statements regarding our expectations and beliefs regarding our future results or performance. Because these statements
`apply to future events, they are subject to risks and uncertainties. When used in this announcement, the words "anticipate",
`"believe", "estimate", "expect", "expectation", "should", "would", "project", "plan", "predict", "intend" and similar expressions are
`intended to identify such forward-looking statements. Our actual results could differ materially from those projected in the
`forward-looking statements. Additionally, you should not consider past results to be an indication of our future performance.
`For a discussion of the risk factors and other factors that may affect our results, please see the Risk Factors section of our
`filings with the Securities and Exchange Commission, including our annual report on Form 10-K and quarterly reports on Form
`10-Q. We do not intend to update any of the forward-looking statements after the date of this announcement to conform these
`statements to actual results, to changes in management's expectations or otherwise, except as may be required by law.
`
`SOURCE Pharmacyclics
`
`http://www.pharmacyclics.com
`
`Copyright (C) 2009 PR Newswire. All rights reserved
`
`Coalition for Affordable Drugs IV LLC - Exhibit 1047
`
`