(PTLA) Publication of Phase 3 APEX Study Design and Rationale in AHJ

Global, Pivotal Phase 3 APEX Study of Betrixaban Enrolling Acute Medically Ill Patients Using Biomarker-Based Strategy to Identify Those Most Likely to Benefit From Therapy

SOUTH SAN FRANCISCO, Calif., April 14, 2014  — Portola Pharmaceuticals (Nasdaq:PTLA) today announced publication of the design and rationale of the Phase 3 APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) Study in the March 2014 issue of the American Heart Journal.ⁱ Betrixaban, the Company’s wholly-owned, oral, once-daily Factor Xa anticoagulant, is being evaluated in the only ongoing global, pivotal study of in-hospital and post-discharge prevention of venous thromboembolism (VTE), or blood clots, in patients who have been hospitalized for medical conditions, such as heart failure, stroke, infection and pulmonary disease.

“Extended VTE prevention in acute medically ill patients is an important unmet medical need because studies have shown that well-identified patients are at high risk for life-threatening blood clots beginning at hospital admission and for several weeks after discharge. However, no anticoagulant therapy has been approved to protect patients during this period of risk. APEX is the only ongoing pivotal study evaluating one continuous therapy for hospital-to-home VTE prevention for these patients,” said Alexander T. Cohen, M.D., co-chairman of the APEX Executive Committee and honorary consultant vascular physician, Department of Haemostasis and Thrombosis, Guy’s and St Thomas’ Hospitals at King’s College London, UK. “Additionally, these patients are often renally compromised, and because betrixaban has a lower level of renal clearance compared with other drugs in its class, APEX is the first pivotal study to allow inclusion of patients with severe renal impairment.”

The prospective, randomized, double-blind, multicenter, multinational APEX Study is evaluating the superiority of extended-duration anticoagulation with oral betrixaban (for up to 35 days in hospital and post-discharge) compared with standard of care anticoagulation with injectable enoxaparin (for 10 days) for VTE prevention in acute medically ill patients. The study will enroll close to 7,000 patients at more than 425 study sites worldwide. The primary efficacy endpoint is the composite of asymptomatic proximal deep venous thrombosis, symptomatic deep venous thrombosis, non-fatal pulmonary embolism or VTE-related death through day 35. The primary safety outcome is the occurrence of major bleeding.

“The APEX study is using biomarkers to identify and enroll patients at highest risk of blood clots who will most likely benefit from treatment with betrixaban, including those with elevated blood levels of D-dimer (a protein fragment present after a blood clot has developed) and those over age 75,” said John T. Curnutte, M.D., Ph.D., executive vice president, research and development at Portola. “We believe that betrixaban, because of its unique pharmacokinetic properties, has the potential to be the first novel oral anticoagulant to prevent VTE in this patient population without the significant increase in the rate of major bleeding seen with other Factor Xa inhibitors. Betrixaban could be the first anticoagulant approved for ‘hospital to home’ use and the standard of care in this large market of more than 30 million patients worldwide.”

About VTE Prevention in Acute Medically Ill Patients

Acute medically ill patients, who are at high risk for developing blood clots, are hospitalized due to a serious medical condition such as heart failure, stroke, infection, pulmonary disease or rheumatic disease. They are often elderly, frail, renally compromised and taking multiple concomitant medications. Acute medically ill patients represent the single largest category of patients at risk for thrombosis, with an estimated 30 million patients worldwide. Enoxaparin, the current standard of care, is limited to hospital use because it is administered by injection and is associated with an increase in major bleeding when administered in this population for extended use. The other novel oral Factor Xa inhibitors that have been studied in this population have also been associated with an increased rate of major bleeding. A well-identified population of medical patients is at risk for life-threatening blood clots during hospitalization and for several weeks after discharge, but currently no anticoagulant is approved to treat these patients for this extended time period.

About Betrixaban

Betrixaban is a small molecule anticoagulant that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent thrombosis. The compound has three properties that differentiate it from other oral anticoagulants: it has the longest half-life of all of the Factor Xa inhibitors for true once-daily dosing; it has a low level of clearance through the kidneys and has been studied in patients with severe renal impairment (excluding dialysis patients); and it is not metabolized by CYP3A4, a liver enzyme that metabolizes many drugs and can lead to drug-drug interactions. These properties are important for acute medically ill patients and may allow betrixaban to demonstrate efficacy in this population without the increase in major bleeding seen with other Factor Xa inhibitors.

Portola has full worldwide development and commercial rights to betrixaban.

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 hematology and inflammation. The Company is advancing its three wholly-owned hematology 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 a 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 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, including 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 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.

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: anticipated growth in the market for anticoagulants, clinical trial enrollment, cost, design and timing, and the potential efficacy, safety and activity of betrixaban, andexanet alfa 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).

ⁱCohen AT, Harrington R, Goldhaber SZ, Hull R, Gibson CM, et al. The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study. Am Heart J. 2014;167:335-41.

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