Portola Pharmaceuticals Announces Two Presentations of Data

--Initial Phase 1 Doses Associated with High Levels of Syk and JAK Inhibition–  

-- Activity in Cell Lines with CARD11 Mutation May Further Differentiate Cerdulatinib --

SOUTH SAN FRANCISCO, Calif., May 14, 2014 (GLOBE NEWSWIRE) -- 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) 50 ^th 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.

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).

Investor Contact: Alexandra Santos Portola Pharmaceuticals 650.246.7239 Media Contact: Joey Fleury BrewLife 415.946.1090