Portola Pharmaceuticals Announces Two Presentations of Data on Cerdulatinib, an Oral Dual Syk/JAK Inhibitor, at 2014 ASCO Ann...
14 Mai 2014 - 11:00PM
--Initial Phase 1 Doses Associated
with High Levels of Syk and JAK Inhibition–
--Activity in Cell Lines with CARD11 Mutation May Further
Differentiate Cerdulatinib--
Portola Pharmaceuticals (Nasdaq:PTLA) today announced two upcoming
data presentations on cerdulatinib*, the Company's novel, oral,
dual Syk-JAK kinase inhibitor, at the upcoming American Society of
Clinical Oncology (ASCO) 50th Annual Meeting, which is taking place
in Chicago from May 30-June 3. Cerdulatinib is currently being
studied in an open-label, multicenter, Phase 1/2 study in patients
with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma
(NHL).
New pharmacokinetic and pharmacodynamic (PK/PD) data from the
first three patient dose cohorts (15 mg, 30 mg, and 45 mg given
orally once per day) in the dose-escalation Phase 1 part of the
Company's Phase 1/2 study of cerdulatinib will be presented in a
general poster session. Cerdulatinib has a favorable PK profile
with a half-life of 14-18 hours that supports once-daily dosing. In
whole blood assays, B cell antigen receptor-mediated Syk and
cytokine-mediated JAK/STAT signaling were both inhibited by up to
50 percent with the 15 mg dose of cerdulatinib and by up to 70
percent with the 30 mg dose, when compared with the pre-dose levels
of receptor signaling. Data from the third dosing cohort at 45 mg
will be available for presentation at the meeting. Collectively,
these data demonstrate that cerdulatinib has a favorable PK/PD
profile and is a potent inhibitor of the SYK- and JAK1/3-dependent
pro-survival signaling pathways in B cell malignancies. Additional
PK/PD results will be included in the poster presentation.
A second poster reviewing data from a preclinical study
investigating the effect of cerdulatinib on IL6 receptor signaling
in a CARD11 mutated B cell lymphoma cell line will also be
presented at the meeting. This CARD11 mutation activates an
NFκB-mediated IL6 autocrine survival pathway in this NHL cell line.
Cerdulatinib inhibits the IL6 signaling pathway in the OCI-Ly3 cell
line and results in potent anti-tumor activity in this pre-clinical
model. Currently approved targeted therapies are not active in cell
lines or in NHL patients with a CARD11 mutation, differentiating
cerdulatinib from other therapies in its class.
"Cerdulatinib is a potent dual kinase inhibitor that has the
potential for broad activity in cancers such as chronic lymphocytic
leukemia and non-Hodgkin lymphoma. We are particularly interested
in subtypes with genetic mutations that alter cytokine signaling or
that cause resistance to other targeted therapies," said John T.
Curnutte, M.D., Ph. D., executive vice president of research and
development for Portola. "Our long-term goal for this clinical
program is to reproduce the in vitro activity that was seen in
hematologic cancer cells, including cell lines with NFkB activating
mutations and tumor samples with an acquired mutation causing
resistance to ibrutinib."
The cerdulatinib abstracts are now publically available at
abstracts.asco.org Details of the poster presentations
follow.
Abstract title:
Pharmacokinetics and pharmacodynamics of the dual Syk/JAK inhibitor
PRT062070 (cerdulatinib) in patients with advanced B-cell
malignancies (Abstract #2619; Poster Board #82) |
Poster Presenter: Ian Flinn,
M.D., Ph.D., hematologist/oncologist at Tennessee Oncology,
Nashville |
Date/Time: Sunday, June 1,
8-11:45 a.m. CT |
Session: General Poster
Session |
Track: Developmental
Therapeutics |
Location: S Hall A2,
McCormick Place |
|
Abstract title: Reverse
phase protein microarray identifies IL6 receptor ligation induced
PI3K/AKT, insulin receptor, and JAK/STAT signaling pathways in the
CARD11 mutated lymphoma cell line OCI-Ly3 (Abstract #8574; Poster
Board #261) |
Poster Presenter: Greg
Coffey, Ph.D., Senior Scientist in Biology at Portola |
Date/Time: Monday, June 2,
1:15-5 p.m. CT |
Session: General Poster
Session |
Track: Lymphoma and Plasma
Cell Disorders |
Location: S Hall A2,
McCormick Place |
About Cerdulatinib
Cerdulatinib, Portola's wholly-owned product candidate in the
area of hematologic cancer, is a novel, oral, dual Syk-JAK
inhibitor that uniquely inhibits two validated tumor proliferation
pathways that contribute to tumor cell growth and survival in
certain hematologic malignancies. Cerdulatinib blocks the B-cell
receptor pathway via Syk and cytokine pathways via JAK 1, 3, and
Tyk 2.
Cerdulatinib is currently being evaluated in an open-label,
multicenter, Phase 1/2 proof-of-concept study in chronic
lymphocytic leukemia and non-Hodgkin lymphoma patients. The study
is assessing the safety, pharmacokinetics, pharmacodynamics and
clinical activity of oral cerdulatinib. In the multi-dose,
dose-escalation Phase 1 part of the study, cerdulatinib is being
administered orally once a day to sequential dose cohorts at
increasing dose levels until the maximum tolerated dose is
identified. The Phase 2 part of the study is a cohort expansion
that will evaluate measures of safety and efficacy in cancer types
identified based on the responses seen in the dose-escalation
phase.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company
developing product candidates that have the potential to represent
significant advances in the fields of thrombosis and other
hematologic diseases. The Company is advancing its three
wholly-owned programs using novel biomarker and genetic approaches
that may increase the likelihood of clinical, regulatory and
commercial success of its first-in-class therapies. Portola's
partnered program is focused on developing selective Syk inhibitors
for inflammatory conditions.
Betrixaban
Portola's wholly-owned, oral, once-daily Factor Xa inhibitor
betrixaban is being evaluated in the only biomarker-based Phase 3
study for hospital-to-home prophylaxis of venous thromboembolism
(VTE) in acute medically ill patients. Betrixaban's distinct
properties may have the potential to allow the agent to demonstrate
efficacy without the significant increase in the rate of major
bleeding that was seen in this patient population with other Factor
Xa inhibitors. If approved, betrixaban could be the first
anticoagulant for both hospital and post-discharge VTE prophylaxis
and the standard of care in this large market of more than 30
million patients worldwide.
Andexanet Alfa
Portola's second product candidate in the area of thrombosis,
andexanet alfa, has the potential to be a first-in-class reversal
agent to reverse the effects of Factor Xa inhibitors in patients
who suffer a major bleeding episode or who require emergency
surgery. Portola has entered into clinical collaboration agreements
with all of the manufacturers of direct Factor Xa inhibitors
– Bristol-Myers Squibb and Pfizer (Eliquis® [apixaban]),
Bayer HealthCare and Janssen Pharmaceuticals (XARELTO®
[rivaroxaban]), and Daiichi Sankyo (edoxaban) – while retaining all
commercial rights to andexanet alfa. Andexanet alfa has been
designated as a Breakthrough Therapy by the U.S. Food and Drug
Administration.
Cerdulatinib* (PRT2070)
Portola's product candidate in the area of hematologic cancer,
cerdulatinib, is an orally available molecule that uniquely
inhibits two validated tumor proliferation pathways -- spleen
tyrosine kinase (Syk) and janus kinase (JAK). It is currently being
evaluated in a Phase 1/2 proof-of-concept study in patients with
leukemias or lymphomas with a focus on genetically-defined
subtypes, as well as in patients who have failed therapy due to
relapse or acquired mutations.
For more information, visit www.portola.com and follow the
Company on Twitter @Portola_Pharma.
Forward-looking statement
Statements contained in this press release regarding matters
that are not historical facts are "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Such
statements include, but are not limited to, statements regarding:
the potential efficacy, safety and activity of cerdulatinib. Risks
that contribute to the uncertain nature of the forward-looking
statements include: the accuracy of Portola's estimates regarding
its ability to initiate and/or complete its clinical trials; the
success of Portola's clinical trials and the demonstrated efficacy
of Portola's product candidates thereunder; the accuracy of
Portola's estimates regarding its expenses and capital
requirements; regulatory developments in the United States and
foreign countries; Portola's ability to obtain and maintain
intellectual property protection for its product candidates; and
the loss of key scientific or management personnel. These and other
risks and uncertainties are described more fully in our most recent
filings with the Securities and Exchange Commission, including our
Annual Report on Form 10-K and our Quarterly Report on Form 10-Q
for the first quarter of 2014. All forward-looking statements
contained in this press release speak only as of the date on which
they were made. Portola undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
*Cerdulatinib is a proposed International Nonproprietary Name
(pINN).
CONTACT: Investor Contact:
Alexandra Santos
Portola Pharmaceuticals
ir@portola.com
650.246.7239
Media Contact:
Joey Fleury
BrewLife
jfleury@brewlife.com
415.946.1090
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