Portola Pharmaceuticals Initiates Phase 3 Study of Andexanet Alfa, Potential First-in-Class Factor Xa Inhibitor Reversal Agent,

Portola Pharmaceuticals Initiates Phase 3 Study of Andexanet Alfa, Potential
First-in-Class Factor Xa Inhibitor Reversal Agent, Under Accelerated Approval

FDA-Designated Breakthrough Therapy is Portola's Second Drug to Enter Phase 3

SOUTH SAN FRANCISCO, Calif., March 19, 2014 (GLOBE NEWSWIRE) -- Portola
Pharmaceuticals (Nasdaq:PTLA) today announced that it has initiated a Phase 3
study of andexanet alfa, the company's investigational Factor Xa inhibitor
reversal agent. The study will evaluate the safety and efficacy of andexanet
alfa with Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc.'s (NYSE:
PFE) Factor Xa inhibitor Eliquis^® (apixaban). Portola is developing andexanet
alfa, an FDA-designated breakthrough therapy, as a potential first-in-class
antidote to reverse the anticoagulation activity of Factor Xa
inhibitor-treated patients who are suffering a major bleeding episode or who
require emergency surgery. The Company is pursuing an Accelerated Approval
pathway for andexanet alfa, which is the only agent that has demonstrated
reversal of the anticoagulation activity of Factor Xa inhibitors as measured
by biomarkers, including anti-Factor Xa activity, in human studies.

"The initiation of our first Phase 3 study for andexanet alfa represents a
significant milestone in the clinical development of this innovative drug to
address the important unmet medical need for a Factor Xa inhibitor antidote,"
said John C. Curnutte, M.D., Ph.D., executive vice president, research and
development at Portola. "We are strategically focused on using biomarker and
genetic approaches in our clinical development programs to identify the
patients who will most likely benefit from our products and potentially
accelerate their approval. For this Phase 3 study, we are using biomarker
endpoints that have been agreed to with the FDA to support potential
Accelerated Approval for the reversal of Factor Xa inhibitor anticoagulation.
We expect to report initial data from the first part of the study, in which
andexanet alfa is administered as a bolus infusion, in the fourth quarter of
this year, followed by bolus-plus-continuous infusion data from the second
part of the study in early 2015."

Phase 3 Study Design

The randomized, double-blind, placebo-controlled Phase 3 study is designed to
evaluate the efficacy of andexanet alfa in reversing Eliquis-induced
anticoagulation rapidly after an IV bolus and sustaining that effect through a
continuous infusion. The study will evaluate the efficacy of andexanet alfa in
older healthy volunteers (ages 50-75 years) as demonstrated by biomarker
endpoints, including anti-Factor Xa levels, plasma free fraction of the
anticoagulant and thrombin generation. In the first part of the study,
approximately 32 healthy volunteers will be given Eliquis 5 mg twice daily and
then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg IV
bolus or to placebo. In the second part of the study, approximately 32 healthy
volunteers will be randomized in a 3:1 ratio to andexanet alfa administered as
a 400 mg IV bolus followed by a continuous infusion of 480 mg at 4 mg/min for
120 minutes or to placebo. Study participants will be followed for up to 43
days to assess safety.

About the Need for a Factor Xa Inhibitor Reversal Agent

Currently, millions of patients are treated with Factor Xa inhibitors for
short-term use or chronic conditions, and the anticoagulant market is expected
to continue to grow. Clinical trial results suggest that, annually, between
1-4 percent of patients treated with Factor Xa inhibitors may experience major
bleeding, and an additional 1 percent may require emergency surgery, depending
on the patient's underlying medical condition. Development of an agent
specifically designed to reverse the activity of Factor Xa inhibitors may
provide an important treatment option for patients who experience a major
bleeding event or require emergency surgery.

About Andexanet Alfa

Andexanet alfa is a first-in-class recombinant, modified Factor Xa molecule
being developed as a direct reversal agent for patients receiving a Factor Xa
inhibitor who suffer a major bleeding episode or who may require emergency
surgery. Andexanet alfa acts as a Factor Xa decoy that targets and sequesters
with high specificity both direct and indirect Factor Xa inhibitors in the
blood. Once bound, the Factor Xa inhibitors are unable to bind to and inhibit
native Factor Xa, thus allowing for the restoration of normal hemostatic

Results from two Phase 2 proof-of concept studies demonstrated that andexanet
alfa immediately reversed the anti-Factor Xa activity of Eliquis and XARELTO^®
(rivaroxaban) in healthy volunteers. Andexanet alfa provided temporary
reversal through the administration of an IV bolus infusion or sustained
reversal with the addition of an extended infusion. In clinical practice,
patients with bleeding due to a traumatic injury may require short-acting
reversal of their anticoagulant, while those who need emergency surgery may
require long-acting reversal. Andexanet alfa has the potential to address
numerous clinical scenarios by allowing for flexible and controlled reversal.
Andexanet alfa has been shown to be well tolerated in clinical studies, which
have included more than 90 volunteers, with no thrombotic events, serious
adverse events or antibodies to Factor Xa or Factor X observed.

Additional Phase 2 proof-of-concept studies with the direct Factor Xa
inhibitors betrixaban and Savaysa^™ (edoxaban) and the indirect Factor Xa
inhibitor enoxaparin are either planned or ongoing.

Earlier this year, Portola and BMS/Pfizer entered into a Phase 3 collaboration
that included an upfront payment and provides additional milestone payments
that cover the clinical costs of the Phase 3 study. Portola retains 100
percent worldwide decision-making and commercialization rights to andexanet
alfa. Portola and Bayer HealthCare and Janssen Pharmaceuticals Inc. have a
similar Phase 3 collaboration and expect to begin a Phase 3 study of andexanet
alfa with XARELTO in the first half of 2014.

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 hematology. 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 lead compound, betrixaban, is an oral, once-daily Factor Xa
inhibitor 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 properties may be particularly suited to
potentially demonstrate efficacy without significantly increasing bleeding in
this patient population. Currently, there is no anticoagulant approved for
extended-duration VTE prophylaxis in acute medically ill patients.

Andexanet Alfa

Portola's second lead development candidate, 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, including
Bristol-Myers Squibb and Pfizer (Eliquis^®[apixaban]), Bayer HealthCare and
Janssen Pharmaceuticals (XARELTO^® [rivaroxaban]), and Daiichi Sankyo
(Savaysa^TM [edoxaban]), while retaining all decision-making and commercial
rights to andexanet alfa. Andexanet alfa has been designated as a Breakthrough
Therapy by the U.S. Food and Drug Administration.

Cerdulatinib* (PRT2070) and PRT2607

Portola's third wholly-owned product candidate, cerdulatinib (PRT2070), 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 studied 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. Portola's fourth program is
partnered with Biogen Idec and is focused on the development of PRT2607, a
selective Syk inhibitor.

For more information, visit www.portola.com and follow the Company on Twitter

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: Portola's plans for
future clinical studies and pursuit of an Accelerated Approval process for
andexanet alfa, anticipated growth in the market for anticoagulants, clinical
trial cost, design and timing, and the potential efficacy, safety and activity
of andexanet alfa, betrixaban and 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 Portola's 2013
Annual Report on Form 10-K filed with the Securities and Exchange Commission
on March 3, 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
         Media Contact:
         Joey Fleury

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