Pharmacyclics® Announces Updated Results for BTK Inhibitor Ibrutinib (PCI-32765) at American Society of Hematology (ASH) Annual

     Pharmacyclics® Announces Updated Results for BTK Inhibitor Ibrutinib
      (PCI-32765) at American Society of Hematology (ASH) Annual Meeting

Investigational agent ibrutinib (PCI-32765) demonstrates prolonged progression
free survival with a manageable and predictable safety profile in high unmet
need indications; relapsed and refractory, high risk, advanced CLL/SLL and MCL
patients and in addition in treatment naive elderly CLL patients

PR Newswire

ATLANTA, Dec. 11, 2012

ATLANTA, Dec. 11, 2012 /PRNewswire/ --Pharmacyclics, Inc (Nasdaq: PCYC) and
its collaborators providedclinical and pre-clinical presentations on
ibrutinib and ibrutinib combinations at the 2012 ASH Annual Meeting. Ibrutinib
inhibits Bruton's tyrosine kinase (BTK), which is known to be expressed in
chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle
cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular
lymphoma (FL) and multiple myeloma (MM). All ASH presentations can be found on
the corporate website in the investor relations section.

"This meeting at ASH has been filled with exciting validations of ibrutinib
and its potential in blood cancers. We are concluding ASH with 9 poster
presentations and 9 oral presentations, of which two were included in the 'ASH
Annual Press Program' and both were honored as a 'Best of ASH'," said Bob
Duggan, CEO and chairman of Pharmacyclics. "We are very proud of these
clinical and research accomplishments and I would like to thank all our
investigators and employees for their support and continued efforts in
developing this compound for patients in need. Together with our partner
Janssen we have now successfully entered several pivotal Phase III trial
programs and are broadly developing ibrutinib in a multitude of hematologic
cancer settings. The results we have shown over the past couple of days have
been very encouraging, demonstrate our commitment to a comprehensive program
and we are looking forward to further emerging data in the coming year."

Recent Developments & Highlights

Chronic Lymphocytic Leukemia

At the 2012 ASH Annual Meeting Pharmacyclics and its investigators presented
six oral presentations and three posters describing the recent clinical trials
and further insights into the mechanism of action of ibrutinib in CLL/SLL
patients. These presentations are available for investor review on the
company's website. The following summarizes two oral presentations showing
recent trial results.

ASH Annual Meeting 'Press Program' and 'Best of ASH' Oral Presentation
Abstract 189: The Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib Promotes
High Response Rate, Durable Remissions, and Is Tolerable in Treatment Naïve
(TN) and Relapsed or Refractory (RR) CLL or SLL Patients Including Patients
with High-Risk (HR) Disease: New and Updated Results of 116 Patients in a
Phase Ib/II Study
John C. Byrd, M.D., The Ohio State University, Columbus, OH
A multicenter, open-label, single agent Phase Ib/II study of ibrutinib in
subjects with CLL/SLL either relapsed/refractory or treatment-naive (65 years
of age or older). This study, which completed enrollment in July 2011 with 116
patients (31 patients treatment naive and 85 patients
relapsed-refractory/high-risk patients) treated with ibrutinib monotherapy,
was designed to assess safety, tolerability, and efficacy of ibrutinib at two
dose levels. With a maximum follow up of 26 months, it wasestimated that 96%
of the treatment-naive and 75% of the relapsed-refractory/high-risk patients
are without progression. Responses were independent of high risk clinical
genetic features. Continuous dosing was well tolerated with a reported lack of
detrimental impact on immunoglobulins or hematologic parameters. Most adverse
events were Grade 2 or less in severity, with the most common being diarrhea,
fatigue, upper respiratory tract infection, rash, nausea and arthralgias
(joint pain). The majority of events were managed with over the counter
medicines and outpatient care. Hematologic events potentially related to
ibrutinib were relatively infrequent.

ASH Annual Meeting 'Press Program' and 'Best of ASH' Oral Presentation
Abstract 187 The Btk inhibitor Ibrutinib in combination with rituximab is well
tolerated and displays profound activity in high-risk Chronic Lymphocytic
Leukemia (CLL) patients
Jan A Burger, M.D., Ph.D., MD Anderson Cancer Center, Houston, TX
This presentation was based on findings from a Phase 2, single-center trial
with 40 high risk CLL patients treated with 420 mg/day ibrutinib in
combination with rituximab, an anti-CD20 monoclonal antibody. The high risk
patients had one of the following characteristics, all predictive of poor
outcome to standard chemotherapy: deletion in chromosome 17p, mutation in the
tumor suppressor gene TP53, deletion in chromosome 11q or relapse less than 36
months after chemo-immunotherapy. The results after a median follow-up of 4.8
months were profound in these high-risk patients, with an overall response
rate of 83%. Treatment was well tolerated, with grade 3/4 adverse events
reported in 13 cases that were largely unrelated to ibrutinib or the
combination and transient, such as neutropenia (low white blood cell count),
fatigue, pneumonia, insomnia, and bone aches.

In addition to the updates presented at ASH, Pharmacyclics and its partner
Janssen Biotech recently announced the following clinical trials of ibrutinib:


In frontline newly diagnosed elderly CLL/SLL patients, Pharmacyclics most
recently initiated a Phase III trial RESONATE™ -2 (PCYC-1115/1116). This trial
is a randomized, multicenter, open-label study of ibrutinib (PCI-32765) as a
monotherapy versus chlorambucil in patients 65 years or older with treatment
naïve CLL/SLL. The study design is in accord with a Special Protocol
Assessment (SPA). The study is designed to demonstrate superiority of
ibrutinib with the primary endpoint of progression-free survival (PFS); the
comparator is single agent chlorambucil. This global study is planned to
enroll 272 patients worldwide.

In relapsed/refractory CLL/SLL patients Pharmacylics initiated RESONATE^TM
(PCYC-1112), ^ which is a randomized, open–label, pivotal Phase III trial. The
trial is designed to demonstrate superiority of ibrutinib versus ofatumumab.
The primary endpoint of the study is to demonstrate a clinically significant
improvement in progression-free survival in relapsed or refractory CLL/SLL
patients. This global study is open and Pharmacyclics plans to enroll 350
patients worldwide.

Pharmacylics has also initiated the RESONATE^TM-17p study (PCYC-1117), which
is a randomized, open–label Phase II trial using ibrutinib as a monotherapy in
patients who have deletion 17p and who did not respond to or relapsed after at
least one prior treatment with chemoimmunotherapy (a high unmet need
population). The primary outcome of the study will be overall response rate.
The key secondary endpoints will be duration of response and other measures of
clinical benefit. This study is planned to enroll 111 patients worldwide.

Pharmacyclics' worldwide partner Janssen most recently initiated a randomized,
multi-center, double blinded, placebo controlled, pivotal Phase III trial of
ibrutinib in combination with bendamustine and rituximab in
relapsed/refractory CLL/SLL patients who received at least one line of prior
systemic therapy. The primary endpoint of the study is to demonstrate a
clinically significant improvement in progression-free survival versus
bendamustine and rituximab therapy alone. The key secondary endpoints include
overall response rate, overall survival and other measures of clinical
benefit. This global study is open and Janssen plans to enroll 580 patients
worldwide.

Mantle Cell Lymphoma

At the 2012 ASH Annual Meeting Pharmacyclics and its investigators presented
one oral presentation describing the recent clinical trial of ibrutinib in MCL
patients. This presentation is available for review on the company's website.
The following summarizes the oral presentation showing the recent trial
result.

ASH Annual Meeting Oral Presentation
Interim Results of an International, Multicenter, Phase 2 Study of Bruton's
Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in Relapsed or
Refractory Mantle Cell Lymphoma (MCL): Durable Efficacy and Tolerability with
Longer Follow-up
Michael Wang, M.D., Associate Professor in the Department of Lymphoma and
Myeloma at The University of Texas MD Anderson Cancer Center
This presentation showed an overall response rate (ORR) in 110 evaluable MCL
patients of 68 %, including complete responses (CRs) of 22 % and partial
responses (PRs) of 46 % and with a median PFS estimated at 13.9 months. An
analysis of the initial 51 patients presented last year at ASH 2011
demonstrated an incremental improvement in the response rate over time. The
ORR increased in this subset from 69% as reported at ASH in 2011 to an ORR of
75% as reported at ASH in 2012, with the CR rate increasing from 16% to 39%
over the same period. The treatment emergent adverse events were consistent
with safety data previously reported for ibrutinib monotherapy.

In addition to this update presented at ASH, Pharmacyclics and its partner
Janssen Biotech recently announced the following clinical trials of ibrutinib
in relapsed/refractory MCL patients:

Our partner Janssen initiated a single-arm, multi-center Phase II study using
ibrutinib as monotherapy in relapsed/refractory MCL patients who received at
least one prior rituximab-containing chemotherapy regimen and who progressed
after bortezomib therapy. The primary endpoint of the study is overall
response rate. The key secondary endpoints include duration of response,
progression-free survival rate, and other measures of clinical benefit. This
global study is open and Janssen plans to enroll 110 patients worldwide.

A Phase III study comparing ibrutinib versus temsirolimus has been recently
initiated by Janssen. This is a randomized, multi-center Phase III trial of
ibrutinib as a monotherapy in relapsed/refractory MCL patients who received at
least one prior rituximab-containing chemotherapy regimen. The primary
endpoint of the study is progression-free survival when compared to
temsirolimus. This study is planned to enroll 280 patients outside the US.

Other Clinical Development Highlights

At the 2012 ASH Annual Meeting, Pharmacyclics and its investigators gave a
multitude of presentations showing research and clinical results of using
ibrutinib in a variety of diseases. The following summarizes two oral
presentations and one poster showing recent trial results in diffuse large
B-cell lymphoma (DLBCL), follicular lymphoma (FL) and multiple myeloma (MM).

ASH Annual Meeting Oral Presentation
The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, has Preferential
Activity in the ABC Subtype of Relapsed/Refractory de Novo Diffuse Large
B-cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-label, Phase 2
Study
Wyndham H. Wilson, M.D., Ph.D., National Cancer Institute
Preliminary results were reported from the multicenter, open-label, Phase II
study of ibrutinib in 70 subjects with relapsed or refractory DLBCL in two
genetically distinct subtypes of DLBCL, the activated B-cell (ABC) subtype and
the germinal center (GC) subtype. The ABC subtype appears to be more driven by
B cell receptor signaling. The ORR in the heavily pre-treated population was
23% (16 of 70 patients). Responses were primarily in the ABC subtype with 12
of 29 patients (41%) responding (5 complete responses and 7 partial
responses). In the 20 GC patients only 1 patient (5%) had a partial response.
This study supports the use of ABC DLBCL molecular subtype as a biomarker for
enrichment of patients for future ibrutinib studies. The safety profile is
favorable, with Grade 3 or higher Adverse Events, related and unrelated, in
typically 5% - 10% of the patients.

Pharmacyclics and its partner Janssen recently announced a Phase I dose
escalating study of ibrutinib in combination with R-CHOP in newly diagnosed
DLBCL patients. The primary objective is to define a safe and tolerable dose
for this combination. This area of ibrutinib development continues to evolve
and further updates are planned for the second half of 2013.

ASH Annual Meeting Oral Presentation
The Bruton's Tyrosine Inhibitor Ibrutinib (PCI-32765) is Active and Tolerated
in Relapsed Follicular Lymphoma
Nathan Fowler, M.D. Dept of Lymphoma, UT MD Anderson Cancer Center, Houston,
TX
Long term results on 16 relapsed / refractory evaluable follicular patients
dosed with ibrutinib as monotherapy from the Phase I dose escalation study
(PCYC-04573) were presented. Patients were heavily pretreated with a median of
3 prior therapies, and 44% had high risk Follicular Lymphoma International
Prognostic Index scores. The ORR in 16 subjects was 44% with 3 CRs and 4 PRs.
For those patients with at least 1 tumor response assessment, the media PFS in
dose cohorts greater or equal 2.5 mg/kg (n=11) was reported at 13.4 months
with an ORR=55%. With patients treated at greater or equal 5 mg/kg (n=9) the
median PFS was reported as 19.6 months with an ORR=56%. The drug was well
tolerated with no apparent cumulative toxicity upon extended dosing in this
study. 

ASH Annual Meeting Poster Presentation
Multiple Myeloma (MM) Early Changes in Cytokines, Chemokines and Indices of
Bone Metabolism in a Phase 2 Study of the Bruton Tyrosine Kinase (Btk)
Inhibitor, Ibrutinib (PCI-32765) in Patients with Relapsed or
Relapsed/Refractory MM
Ravi Vij, M.D., Washington University, School of Medicine, Saint Louis, MO
This poster presented clinical results and biomarker studies on 13 MM patients
accrued in the first cohort where ibrutinib monotherapy was dosed at 420mg.
Patients were heavily pretreated, with a median of 4 prior therapies (range 2
to 10). All patients previously had prior exposure to bortezomib,
lenalidomide, and dexamethasone or prednisone and 92% had progressed following
stem cell transplant. A total of 39% of the patients had del17p. Signals of
biologic and clinical activity were observed. Reductions in paraprotein of at
least 50% were observed in 3 patients onibrutinib monotherapy, and one
patient went on to have a confirmed PR following addition of dexamethasone.
As anticipated from pre-clinical studies, decreases of several biomarkers of
bone metabolism, angiogenesis and chemotaxis were observed following the start
of treatment. The most common treatment related adverse events were Grade 1/2
nausea and diarrhea. We have expanded the study to explore ibrutinib
administration at 840 mg and a 560 mg dose in combination
withdexamethasone.As we obtain further data from these cohorts over the next
12 months, we will assess the clinical outcome of ibrutinib in this patient
population.

Conference Call and Webcast Details
Pharmacyclics will be holding a conference call on Wednesday, December 12,
2012 at 8:30 AM ET. To participate in the conference call, please
dial1-877-407-0778 for domestic callers and 1-201-689-8565 for international
callers. To access the live 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 for 30 days on the Investor Relations
section of the company's website at www.pharmacyclics.com.

About Pharmacyclics and Janssen Collaboration
As previously announced on December 8, 2011, Pharmacyclics entered into a
worldwide collaboration with Janssen to develop and commercialize ibrutinib.
To date, $150 million in upfront and $150 million in milestones have been
earned. Pharmacyclics may receive up to an additional $675 million in
development and regulatory milestone payments; for total upfront and potential
milestone payments of $975 million. Following regulatory approval,
Pharmacyclics will book US sales and take the lead role in US commercial
strategy development. Both Pharmacyclics and Janssen will share in
commercialization activities. Outside the United States, Janssen will book
sales and lead and perform commercialization activities. Profits and losses
from the commercialization activities will be split 50/50 on a worldwide
basis. Development and commercialization activities under the collaboration
will be managed through a shared governance structure. Each company will lead
development for specific indications as stipulated in a global development
plan, with development costs shared on a 40/60 basis (Pharmacyclics 40% and
Janssen 60%).

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 medial 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
appropriate.

Presently, Pharmacyclics has three product candidates in clinical development
and several research molecules in lead optimization. We are committed to high
standards of ethics, scientific rigor, and operational efficiency as we move
each of these programs to viable commercialization.

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, among others, relating to our future capital
requirements and the sufficiency of our current assets to meet these
requirements, our future results of operations, our expectations for and
timing of ongoing or future clinical trials and regulatory approvals for any
of our product candidates, and our plans, objectives, expectations and
intentions. 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. These forward-looking
statements are based on information currently available to us and are subject
to a number of risks, uncertainties and other factors that could cause our
actual results, performance or achievements to differ materially from those
projected in, or implied by, these forward-looking statements. Factors that
may cause such a difference include, without limitation, our need for
substantial additional financing and the availability and terms of any such
financing, the safety and/or efficacy results of clinical trials of our
product candidates, our failure to obtain regulatory approvals or comply with
ongoing governmental regulation, our ability to commercialize, manufacture and
achieve market acceptance of any of our product candidates, for which we rely
heavily on collaboration with third parties, and our ability to protect and
enforce our intellectual property rights and to operate without infringing
upon the proprietary rights of third parties. Although we believe that the
expectations reflected in the forward-looking statements are reasonable, we
cannot guarantee future results, performance or achievements and no assurance
can be given that the actual results will be consistent with these
forward-looking statements. For more information about the risks and
uncertainties 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.

Website: http://www.pharmacyclics.com
Contact: Joshua T. Brumm, Executive Vice President, Finance, +1-408-215-3311,
or Ramses Erdtmann, Vice President of Investor Relations, +1-408-215-3325
 
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