Initiates Phase II Clinical Trial of M200 (Volociximab) in Renal Cell Cancer;
Updates 2004 Financial Guidance; Sees Potential Acquisition Or In-License of
Marketed Drug in 2005 to Accelerate Path to Positive Cash Flow
FREMONT, Calif., Jan. 12 /PRNewswire-FirstCall/ -- Protein Design Labs,
Inc. (PDL) (Nasdaq: PDLI) today provided an update on the status of its
principal drug development programs, as well as an overview of its 2005
corporate partnering objectives.
"We are pleased to report that we have begun a Phase II study of M200, our
novel anti-angiogenesis agent, in patients with renal cell carcinoma," said
Steven Benner, M.D., Senior Vice President and Chief Medical Officer, PDL.
"Our highest development priority remains Nuvion for intravenous
steroid-refractory ulcerative colitis. We currently expect to conduct an
end-of-Phase I meeting with the FDA regarding Nuvion at the end of the current
quarter or early in the second quarter, at which time we expect to discuss
with the agency the future development pathway for this promising antibody.
Having received Fast Track status in September 2004, we continue to believe
that visilizumab represents a major potential advance in the treatment of I.V.
steroid-refractory ulcerative colitis.
"We also continue to be excited by the promise of daclizumab in asthma and
certain other diseases," Dr. Benner added. "Following our discussions with
the FDA, we altered our development plan to include both a Phase I single-dose
healthy volunteer study, followed by a Phase I multiple-dose, healthy
volunteer study. We expect to initiate the Phase I single-dose study in the
current quarter and the Phase I multiple-dose study in the second half of this
year. These studies are intended to gain additional experience with the
PDL-manufactured, subcutaneous formulation of daclizumab, as distinct from the
current intravenous formulation of marketed daclizumab which is manufactured
by our partner, Roche."
Nuvion Antibody Product (visilizumab, humanized anti-CD3).
PDL is currently conducting a Phase I/II dose-ranging clinical trial in
patients with ulcerative colitis who have not responded to treatment with
intravenous (I.V.) steroids. The trial is designed to evaluate four dose
levels escalating from 5 micrograms/kg to 12.5 micrograms/kg given I.V. on
days 1 and 2 as a bolus injection. PDL expects to enroll up to 20 patients
per dose cohort, or a total of approximately 80 patients in the Phase I
portion of the study. A total of 84 patients have been enrolled to date.
Following the Phase I portion, PDL will select the optimal clinical dose,
and will subsequently treat up to an additional 40 visilizumab-naive patients
at the optimal clinical dose in the Phase II portion of the study. The Phase
II portion is expected to begin in the first quarter of 2005. PDL has
submitted an abstract of results from this ongoing clinical trial for possible
presentation at the Digestive Disease Week meeting, to be held in Chicago in
early May 2005.
In a completed, 32-patient Phase I study of two dose cohorts that was
reported in May 2004, a strong signal of activity was observed in the first
dose cohort given at 15 micrograms/kg on days 1 and 2, in which all eight
patients achieved remission. A continued strong signal of activity
subsequently was observed in the second dose cohort given at 10 micrograms/kg
administered I.V. on days 1 and 2. At the 10 micrograms/kg dose level, 19 of
24 patients responded to treatment and of these, 13 achieved remission.
Specific milestones for Nuvion in 2005 include preparation for and meeting
with the FDA in an end-of-Phase I meeting targeted for the end of the first
quarter, or early in the second quarter. If the FDA agrees with PDL's plan to
move to pivotal trials as the appropriate next step, this meeting would be
followed by efforts to procure a Special Protocol Assessment for the two Phase
III trials, which trials PDL anticipates could be initiated by year end. In
addition, PDL plans to begin, in the first quarter, at least one of two small
studies in severe Crohn's disease with Nuvion and to begin a pediatric
ulcerative colitis study in the second half of 2005. However, the company
continues to focus on the induction regimen studies in steroid-refractory
ulcerative colitis as the basis for PDL's initial registration approach.
Daclizumab (humanized anti-CD25).
In September 2004, PDL and Roche announced a worldwide agreement to co-
develop and commercialize daclizumab for asthma and related respiratory
diseases. PDL now expects that the next trial of daclizumab in asthma will be
a single-dose, Phase I clinical trial intended to gather additional experience
with the PDL-manufactured subcutaneous formulation of daclizumab in healthy
volunteers. This single-dose subcutaneous study should begin in the first
quarter of this year.
"Because we now plan to conduct a single-dose trial followed by a
multiple-dose Phase I study, we anticipate that the subsequent Phase IIb
clinical trial in moderate-to-severe persistent asthma should begin in the
first quarter of 2006," Dr. Benner said.
In March 2004, PDL reported positive results from the initial clinical
study of intravenous daclizumab in patients with chronic, persistent asthma
whose disease is not well controlled with high doses of inhaled
corticosteroids. There were statistically significant treatment differences
(p=0.05) observed for the primary endpoint, percent change in FEV1 from
baseline to 12 weeks (day 84). Secondary clinical endpoints also supported
these findings. Treatment with daclizumab was generally well tolerated.
Preparatory work for a PDL study of daclizumab in multiple sclerosis (MS)
remains on track, and the company currently plans to initiate a Phase II study
in MS at the end of the current quarter.
"ZENAPAX(R) (daclizumab) is marketed by Roche for the prophylaxis of acute
organ rejection in patients receiving renal transplants," Dr. Benner
commented. "We see additional potential for daclizumab in solid organ
transplantation, and are looking at various options for that indication."
M200 (volociximab, anti-alpha5beta1 integrin).
M200 is a novel anti-angiogenic antibody that targets the endothelium of
tumor neovasculature. Earlier this month, PDL began a Phase II clinical trial
in patients with renal cell carcinoma using M200 as a single agent, the first
in a series of up to five open-label, Phase II trials of M200 in selected
solid tumors. The trials currently contemplated include three combination
studies with chemotherapy, as well as single-agent use. The planned
combination studies would include M200 plus standard of care treatment in each
of melanoma, pancreatic cancer and non-small cell lung cancer (NSCLC). The
single- agent studies include M200 in renal cell cancer, now underway, while a
planned study in melanoma could be initiated later in 2005.
In September 2004, PDL presented interim clinical data from a Phase I
dose-escalation study of M200 for the treatment of refractory solid tumors.
Tumor types included colorectal, melanoma, hepatic, pancreatic and non-small
cell lung cancers. Patients were enrolled as follows: one patient at 0.5
mg/kg, 2 patients at 1 mg/kg, 3 patients at 2.5 mg/kg, 3 patients at 5.0 mg/kg
and 6 patients at 10 mg/kg. Each patient received 5 doses of M200 on study
days 1, 15, 22, 29 and 36. The study data showed that adverse events were
generally mild to moderate in intensity and included fatigue, nausea,
constipation, headache and anorexia. There were no severe or serious adverse
events that were dose limiting or considered by investigators to be related to
M200.
In addition, as part of the September 2004 interim analysis, 10 of 15
evaluable patients had stable disease as their best response, and five of six
patients treated at the 10 mg/kg dose level, achieved stable disease. Four
patients with stable disease after 5 doses of M200 in the Phase I study
continued treatment with M200 in a Phase I extension study.
Since September, PDL has completed enrollment into the Phase I portion of
the trial with a total of 21 patients treated. Of interest, a partial
response has been observed in one patient with renal cell cancer during
treatment in the extension study.
PDL does not currently anticipate major conference or scientific
presentations related to M200 in 2005, given the fact that the new Phase II
studies are being initiated, but are not expected to be completed, in calendar
2005. PDL anticipates that abstracts for some of these studies should be
available for submission prior to the 2006 ASCO meeting.
Financial and Business Update.
PDL updated its financial guidance for the full year 2004, from that
provided on November 1, 2004. The company now anticipates that its non-GAAP
net loss for 2004 will be approximately $0.01 to $0.03 per basic and diluted
share less than its previously estimated net loss, and therefore is now
expected to be in the range of $0.50 to $0.55 per basic and diluted share.
The GAAP net loss for the full year 2004 is now expected to be in the range of
$0.55 to $0.60 per basic and diluted share. Non-GAAP results do not include
expenses resulting from amortization of intangible assets, restructuring
charges and stock-based compensation. The company expects to provide a review
of 2004 as part of its year-end conference call to be scheduled in the second
half of February 2005, and will also provide 2005 financial guidance on that
call.
In advance of the call, however, the company has provided a brief outline
of partnering objectives and business goals for 2005. These include (i)
entering into a daclizumab global alliance, for development and
commercialization in multiple sclerosis; (ii) establishing a corporate
partnership around further development and commercialization of HuZAF, PDL's
anti-gamma interferon antibody for potential use in Crohn's disease; (iii)
completing 1 to 2 patent license or humanization agreements; (iv) meeting
commissioning and validation steps necessary for 2006 clinical supply
production at its Brooklyn Park, Minn. manufacturing plant; and (v)
potentially in-licensing or acquiring a hospital-marketed novel therapeutic
agent.
PDL's Chief Executive Officer, Mark McDade, commented, "We believe that
these aggressive aims for 2005 clearly demonstrate the PDL team's commitment
to accelerate our path to a positive cash flow. Forging product partnerships
can enable additional resources for optimized product development while
potentially reducing PDL's overall burn. And the acquisition or in-license of
a currently marketed drug, synergistic with our therapeutic areas or our
hospital-focused future plans for Nuvion and ZENAPAX, could also accelerate
our timeline to get to cash flow breakeven and beyond. If we accomplish these
partnering-related aims, 2005 should be an exciting and truly transforming
year for PDL."
The foregoing contains forward-looking statements involving risks and
uncertainties and PDL's actual results may differ materially from those,
express or implied, in the forward-looking statements. In particular, there
can be no assurance that results from completed and ongoing clinical studies,
described above, will be successful or completed or initiated on the
anticipated schedules or that partnering objectives will be achieved during
the year, or at all. Financial results for 2004 are unpredictable and may
fluctuate from quarter to quarter. PDL expenses, in principal part, depend on
the total headcount of the organization and the timing of expenses. PDL
revenues depend on the success and timing of sales of our licensees and
partners, including in particular the continued successful launch of Avastin
antibody product by Genentech, as well as the seasonality of sales of Synagis
from MedImmune, Inc. In addition, quarterly revenues may be impacted by our
ability to maintain and increase our revenues from licensing, which revenues
depend on third parties entering into new patent licensing arrangements,
exercising rights under existing patent rights agreements, paying royalties
under existing patent licenses and the timing of the recognition of revenues
under any new and existing agreements. Our revenues and expenses would also
be affected by the continuation of our asthma collaboration with Roche, new
collaborations, material patent licensing arrangements or other strategic
transactions. Partnering may be impacted by competitive forces, or the lack
of PDL's existing commercial infrastructure, so there can be no assurance that
the out-licensing, in-licensing or potential product acquisitions will occur
during 2005, or at all, which could impact our timeline to positive cash flow.
Other factors that may cause our actual results to differ materially from
those, express or implied, in the forward-looking statements in this press
release are discussed in our Annual Report on Form 10-K for the year ended
December 31, 2003, in our quarterly report on Form 10-Q for the period ended
September 30, 2004, and in other filings with the Securities and Exchange
Commission.
Protein Design Labs is a leader in the development of humanized antibodies
to prevent or treat various disease conditions. PDL currently has antibodies
under development for autoimmune and inflammatory conditions, asthma and
cancer. PDL holds fundamental patents for its antibody humanization
technology. Further information on PDL is available at http://www.pdl.com.
NOTE: Protein Design Labs, the PDL logo and Nuvion are registered U.S.
trademarks and HuZAF is a trademark of Protein Design Labs, Inc. Zenapax is a
registered trademark of Roche.
SOURCE Protein Design Labs, Inc.
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Related links:
http://www.pdl.com
CONTACT:
James R. Goff, Senior Director, Corporate
Communications of PDL, +1-510-574-1421, or jgoff@pdl.com
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