`
`Pharmacyclics, Inc. Announces Presentation of Interim Results From Phase I Trial of Its
`First-In-Human Btk Inhibitor PCI-32765
`
`NEW ORLEANS and SUNNYVALE, Calif., Dec 07, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Pharmacyclics,
`Inc. (Nasdaq: PCYC) today announced interim data from a Phase I study of their novel orally administered Bruton's tyrosine
`kinase (Btk) inhibitor PCI-32765 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) or chronic
`lymphocytic leukemia (CLL). These data are being presented at the American Society of Hematology (ASH) 51st Annual
`Meeting taking place this week in New Orleans, LA.
`
`The multi-center dose escalation Phase I study is being conducted in collaboration with investigators at leading lymphoma
`centers including Stanford University, MD Anderson Cancer Center, the University of Chicago, the University of Vermont, and
`US Oncology group. The trial was designed to explore up to 6 dose levels with a minimum of 4 evaluable patients per cohort.
`Each cycle of treatment consists of 28 consecutive days of dosing followed by 7 days of rest. Safety is evaluated at the end of
`the first cycle and efficacy at the end of the second. At least one full cycle of treatment has been completed for each patient in
`the first 3 cohorts. Data from the second cohort demonstrated that PCI-32765 fully occupied the active site of the target
`enzyme Btk in peripheral blood cells with minimal variability, fully inhibited surrogate biomarkers for up to 24 hours, and was
`well tolerated by patients.
`
`In the first 2 dose cohorts, 16 heavily pretreated and progressing lymphoma patients with a variety of B-cell malignancies were
`evaluated. In the first dose cohort, 7 patients were treated with PCI-32765 resulting in 2 partial responses (e.g. a 50%
`decrease in sum of the product of the diameters of up to 6 largest dominant masses; no increase in size of other nodes per the
`Revised Response Criteria for Malignant Lymphoma Bruce D. Cheson J Clin Oncol 25:579-586,) one in mantle cell lymphoma,
`one in follicular lymphoma and one patient with stable disease for approximately 5 cycles. In the second dose cohort, 9 patients
`were treated resulting in 3 partial responses (one patient with mantle cell lymphoma and two patients with chronic lymphocytic
`leukemia (CLL/SLL)) and 2 patients with stable disease for approximately 2 cycles. The overall response rate (ORR),
`considering only partial and complete responses, was 31% for the first two dose cohorts.
`
`Additionally, as of December 5, 2009, an interim evaluation has been made on 3 of the 6 patients in the third dose cohort.
`Each of these 3 patients suffered from CLL/SLL. All three have been evaluated as partial responders. At this point the Partial
`Response Rate in CLL/SLL patients is 5 out of 6.
`
`The trial is currently enrolling at a rapid rate. We anticipate the fourth dose cohort to commence in December 2009. At this time
`the company anticipates dosing only the first 5 dose cohorts to complete this Phase I study, as per the protocol dosing will
`continue to three levels above full kinase occupancy.
`
`As of December 5, 2009, all stable and responding patients remain on study with 2 patients from cohort 1 dosed for more than
`6 months. Only 3 of 16 patients experienced adverse events greater than Grade 2: one patient had a dose limiting toxicity with
`the onset of neutropenia, an abnormal reduction of white blood cells; one patient had hypokalemia, a lower than normal
`amount of potassium in the blood, the same patient also had hypophosphatemia, a low level of phosphorus in the blood; and
`one patient had viral adenitis a viral infection of the lymph nodes, which is a common occurrence in this type of patient. The
`drug was well tolerated in the remaining 13 patients.
`
`"PCI-32765 appears to be well tolerated by patients at oral doses that are able to fully inhibit the enzyme Btk," said Dr. Ranjana
`Advani, Associate Professor, Stanford University Medical Center and principal investigator of the trial. "In addition, we now have
`evidence of drug activity."
`
`A conference call to discuss these trial results has been set up for Tuesday December 8, 2009 at 8:00 a.m. PDT (11:00 a.m.
`EDT). To participate in the conference call, please dial 877-700-2945 for domestic callers and 706-643-1591 for international
`callers. The conference ID is 45071660. To access the audio broadcast or the subsequent archived recording, log on to
`http://ir.pharmacyclics.com/events.cfm. The archived version of the webcast will be available on the company's website for one
`month.
`
`Bruton's Tyrosine Kinase and Immune Diseases
`
`B-cells are immune cells, which are activated by antigens, pathogens or, in the case of autoimmunity, by host tissues. B-cells
`produce antibodies, which when self-reactive can trigger autoimmune disease. Activation of B-cells is also thought to play a
`major role in lymphomas where continuous, or tonic, stimulation results in uncontrolled B-cell proliferation. Btk is a type of
`enzyme known as a tyrosine kinase inside B-cells that plays an early key role in B-cell activation. Drugs that can inhibit Btk may
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`Coalition for Affordable Drugs IV LLC – Exhibit 1004
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`prevent B-cell activation and therefore may play a role in the treatment of lymphomas or autoimmune disease. Other tyrosine
`kinases are important in cell signaling and have been targets for other drugs such as Gleevec(R) (imatanib mesylate), which is
`approved for treatment of certain leukemias. New drug or biological candidates targeting B-cells, including Rituxan for
`lymphomas and rheumatoid arthritis, are aimed at eliminating abnormally functioning B-cells.
`
`About Non-Hodgkin's Lymphoma
`
`Non-Hodgkin's lymphoma (NHL) is a type of malignant disease that occurs within the lymphatic system and the fifth most
`common form of cancer. It is caused by the abnormal proliferation of white blood cells, which spreads through the lymphatic
`system. NHL can occur at any age and are often marked by lymph nodes that are larger than normal, fever, and weight loss.
`NHL can be broadly classified into two main clinical categories: indolent lymphomas, mainly characterized as follicular
`lymphomas, which tend to grow relatively slowly; and aggressive lymphomas, mainly typified as diffuse large B-cell lymphomas
`(DLBCL), which grow much more rapidly.
`
`According to the National Cancer Institute's SEER database the incidence of NHL (all types including Follicular and Aggressive)
`is projected at nearly 66,000 in 2009 and that 19,500 patients are expected to die from this disease in the United States in
`2009. According to the Leukemia & Lymphoma Society (LLS), there are approximately 452,723 people in the U.S. living with
`NHL (with active disease or in remission).
`
`About Pharmacyclics
`
`Pharmacyclics(R) is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative small-
`molecule drugs for the treatment of immune mediated disease and cancer. The purpose of the company is to create a
`profitable business by generating income from products it develops, licenses and commercializes, either with one or several
`potential partners or alone as may best forward the economic interest of its stakeholders. The Company endeavors to create
`novel, patentable, differentiated products that have the potential to significantly improve the standard of care in the markets it
`serves. Presently, Pharmacyclics has four product candidates in clinical development and two product candidates in pre-clinical
`development. It is Pharmacyclics' business strategy to establish collaborations with large pharmaceutical and biotechnology
`companies for the purpose of generating present and future income in exchange for adding to their product pipelines.
`Pharmacyclics strives to generate collaborations that allow it to retain valuable territorial rights and simultaneously fast forward
`the clinical development and commercialization of its products. 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, Inc.
`
`http://pharmacyclics.com
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`Copyright (C) 2009 PR Newswire. All rights reserved
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