Portola's Factor Xa Inhibitor Betrixaban Successfully Passes Futility Analysis in Phase 3 APEX Study; Trial Continues as Planned and Remains on Track for Enrollment Completion by Year-End

Betrixaban Has the Potential to be the First Approved Therapy for Hospital-to-Home Prevention of Fatal Blood Clots for the Over 20 Million High-Risk Acute Medically Ill Patients

SOUTH SAN FRANCISCO, Calif., Feb. 5, 2015  -- Portola Pharmaceuticals (PTLA) today announced that the Independent Data Monitoring Committee (IDMC) recommended that the Phase 3 APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) Study of betrixaban continue as planned without modification based on the successful completion of a pre-specified futility analysis. In making this recommendation, the IDMC evaluated preliminary efficacy trends and safety reports from the first half of the study. The APEX Study is assessing betrixaban, an oral, once-daily, investigational Factor Xa inhibitor, for both hospital and post-discharge prevention of venous thromboembolism (VTE), or blood clots, in acute medically ill patients. Acute medically ill patients are those who are hospitalized for serious medical conditions, such as heart failure, stroke, infection and pulmonary disease.

The APEX Study is over 65 percent enrolled at over 450 sites worldwide. The Company expects to complete enrollment by the end of this year and report top-line results in early 2016.

"Given the positive outcome of the APEX futility analysis and the observation that the blinded aggregate VTE event rates in the study to date are on track, we are confident that we are enrolling patients who are at high risk of blood clots and who are most likely to benefit from betrixaban," said John T. Curnutte, M.D., Ph.D., executive vice president, research and development for Portola. "Our goal is for betrixaban to be the first Factor Xa inhibitor approved for both in-hospital and post-discharge prevention of VTE in acute medically ill patients and to be the standard of care for this patient population."

Bill Lis, chief executive officer of Portola added, "This positive development with the APEX Study follows on the heels of recent positive Phase 3 data for our FDA breakthrough-designated Factor Xa inhibitor antidote, andexanet alfa, giving Portola a robust franchise in the growing multi-billion dollar global thrombosis market. Additionally, based on promising clinical data seen to date with our Syk-JAK inhibitor, cerdulatinib, we are making significant progress toward achieving our goal of becoming a fully commercialized biopharmaceutical company with potentially groundbreaking products in two of the largest fields of innovation -- thrombosis and hematologic cancers."

About the APEX Study

The global, pivotal Phase 3 APEX Study is evaluating the superiority of extended-duration anticoagulation with oral betrixaban (for at least 35 days) compared with standard of care anticoagulation with injectable enoxaparin (for up to 14 days) for prevention of VTE in acute medically ill patients. The study is using a biomarker-based trial design to identify and enroll patients who are at highest risk of VTE and most likely to benefit from betrixaban -- specifically those with an elevated level of D-dimer (a protein fragment present after a blood clot has developed) and those over age 75. The APEX Study is the only biomarker-based Phase 3 study for hospital-to-home prophylaxis of VTE in acute medically ill patients. It is also the only pivotal thrombosis trial evaluating a single anticoagulant for VTE prophylaxis in both the in-hospital and post-discharge settings. More than half of VTE events occur after hospital discharge in this patient population.ⁱ No anticoagulant is approved to treat these patients for this extended time period.

About Betrixaban

Betrixaban is an investigational small molecule anticoagulant that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent thrombosis. Betrixaban has distinct properties that may allow it to demonstrate clinical benefit without the significant imbalance in the risk of fatal bleeding seen with other agents in the class. These include a 19-25-hour half-life for true once-daily dosing; a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability; the lowest renal clearance in the class; and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions. Betrixaban has been studied in patients with all degrees of renal function, including those with severe renal impairment (excluding dialysis patients).

Portola Pharmaceuticals, Inc.

Portola Pharmaceuticals is a biopharmaceutical company developing product candidates that could significantly advance 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 potentially life-saving 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 20 million patients in the G7 countries alone.

Andexanet Alfa

Andexanet alfa, a recombinant modified human Factor Xa molecule, has the potential to be a first-in-class antidote to reverse the effects of Factor Xa inhibitors in patients who suffer a major bleeding episode or who require emergency surgery. Andexanet alfa has been designated as a breakthrough therapy by the U.S. Food and Drug Administration (FDA). Portola has entered into Phase 3 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^(R) [rivaroxaban]), and Daiichi Sankyo (edoxaban) -- while retaining all commercial rights to andexanet alfa. The Company is currently evaluating andexanet alfa in the Phase 3 ANNEXA(TM) (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies and in a Phase 4 study to support FDA approval under an Accelerated Approval pathway.

Cerdulatinib

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 1/2a proof-of-concept study in patients with B cell 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: enrollment of a patient population in APEX that is at a high risk of blood clots and most likely to benefit from betrixaban; timing of completion of APEX enrollment and Portola's report of trial results; potential of betrixaban to demonstrate efficacy without the significant increase in bleeding; potential indications and market acceptance of betrixaban; potential for betrixaban to become standard of care; and Portola's intention of becoming a commercialized biopharmaceutical company with potentially groundbreaking products for thrombosis and hematologic cancers. Risks that contribute to the uncertain nature of the forward-looking statements include: the accuracy of Portola's estimates regarding its ability to 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 most recent filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q for the third quarter of 2014, which was filed on November 4, 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.

ⁱ Source: Amin et al. (2012). Duration of Venous Thromboembolism Risk Across a Continuum in Medically Ill Hospitalized Patients. Journal of Hospital Medicine, 7(3), 231-238.

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