ASCO15: Portola Pharmaceuticals, Inc. Presents Updated Data From Ongoing Phase I/IIa Study Of Dual Kinase Inhibitor Cerdulatinib

SOUTH SAN FRANCISCO, Calif., May 29, 2015 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced updated positive safety and efficacy data from the Phase 1 part of its ongoing Phase 1/2a proof-of-concept study of cerdulatinib in patients with hematologic cancers who have failed multiple therapies. Cerdulatinib is an oral, dual Syk-JAK kinase inhibitor that Portola is developing to treat patients with hematologic cancers, specifically those who have relapsed or who have not responded to prior therapies. The new data will be presented on Sunday, May 31, in a poster discussion session at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The Company previously presented interim data from the Phase 1 part of the study at the American Society of Hematology (ASH) 2014 Annual Meeting in December 2014.

The results to be presented at ASCO demonstrated evidence of clinical activity in this study of patients with relapsed/refractory B-cell malignancies. To date, partial responses have been observed, including in patients with chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and transformed FL. Tumor reductions were seen in multiple patients, including those whose disease progressed on (or who could not tolerate) other BCR pathway inhibitors. Results also showed that cerdulatinib was well tolerated in these heavily pre-treated patients, with no dose-limiting toxicities identified. Grade 3/4 adverse events included fatigue. Dose-escalation is ongoing in the Phase 1 part of the study as the maximum tolerated dose has not yet been achieved.

"The clinical activity that we have seen with cerdulatinib in this hematologic cancer study is particularly notable given that these patients have advanced disease and have failed previous therapies," said Manish Patel, M.D., an investigator in the Phase 1/2a study and associate director of drug development at Sarah Cannon Research Institute and associate director of research at Florida Cancer Specialists and Research Institute in Sarasota, Fla. "New treatment options are urgently needed for these patients, and we are looking forward to continuing to study cerdulatinib, a unique dual pathway anti-cancer agent."

"These preliminary results from the ongoing dose-escalation Phase 1 part of the study, including partial responses, provide additional evidence that cerdulatinib is active and well tolerated in patients with hematologic cancers who have failed multiple therapies," said John T. Curnutte, M.D., Ph.D., executive vice president, research and development for Portola. "We recently opened enrollment in larger expansion cohorts in the Phase 2a part of the study, which will include patients with CLL/small lymphocytic leukemia (SLL) or FL whose cancer has progressed or relapsed following treatment with multiple agents. We hope to identify a genetically-defined patient population for whom the inhibition of both Syk and JAK by cerdulatinib may provide clinical benefit beyond current treatment options. If we are successful, we plan to work closely with the FDA to seek an accelerated development path for this agent."

Additional findings from the Phase 1 part of the study to be presented at ASCO include the following:

• Cerdulatinib significantly reduced multiple serum proteins in blood that are markers of inflammation.
• Significant correlations were observed between tumor response and inhibition of serum markers of inflammation.
• Cerdulatinib selectively and dose-dependently inhibited SYK/JAK signaling, with maximal inhibition greater than 80 percent.
• Once-daily dosing of cerdulatinib was supported by pharmacokinetic data.

New Treatment Options Needed for CLL and FL Patients

Current treatment options for patients who fail standard therapies for CLL, SLL and FL are limited. A recent article in Bloodⁱ highlights the need for additional therapies for CLL in particular. An analysis of patients with relapsed/refractory CLL who were enrolled in clinical trials found that those whose disease progressed following treatment with the U.S. Food and Drug Administration-approved therapy ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, had an extremely poor prognosis, with a median overall survival rate of 3.1 months. Some of these patients progress due to a mutation at the BTK binding site, rendering ibrutinib ineffective. Primary patient leukemia cells that have lost sensitivity to ibrutinib due to this mutation have responded to cerdulatinib.

About the Phase 1/2a Study

The open-label, multicenter, Phase 1/2a proof-of-concept study is assessing the safety, pharmacokinetics, pharmacodynamics and clinical activity of oral cerdulatinib in patients with CLL, SLL, FL or B-cell non-Hodgkin lymphoma. 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. It has not yet been identified and the study is continuing.

The clinical expansion cohorts in the Phase 2a part of the study will evaluate the safety and efficacy of cerdulatinib in cancer types identified based on responses seen in the dose-escalation phase of the study. Two groups of up to 40 patients each will be enrolled in the clinical expansion cohorts. One group will include patients with CLL or SLL whose disease has progressed following prior therapies. The other group will include patients with FL who have progressed or relapsed on prior therapies (such as rituximab and bendamustine).

About Cerdulatinib

Cerdulatinib is an oral, dual Syk-JAK inhibitor with a unique mechanism of action. It uniquely inhibits two key signaling pathways that promote cancer cell growth in certain hematologic malignancies: the B-cell receptor pathway via Syk and key cytokine receptors via JAK. With its dual pathway mechanism, cerdulatinib may be more effective in specific patients than a single pathway agent, such as those resistant to current therapies or those with known heterogeneous cellular mutations. Preclinical data suggested that cerdulatinib has anti-tumor activity in patients who did not adequately respond to, or relapsed on, other treatments due to defined mutations.

About 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 programs are 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, an FDA-designated breakthrough therapy, is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable Factor Xa inhibitor. Andexanet alfa has the potential to be a first-in-class antidote for anticoagulated patients who suffer a major bleeding episode or require emergency surgery. Portola has entered into Phase 3 clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors while retaining all commercial rights to andexanet alfa. The Company is currently evaluating andexanet alfa in the Phase 3 and Phase 4 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors) registration studies.

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: Portola's plans for future clinical studies and pursuit of an Accelerated Approval process for andexanet alfa, anticipated growth in the market for anticoagulants, the potential indications, efficacy, safety and activity of andexanet alfa, and the potential market and indications for its other product candidates. 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; Portola's ability to manufacture andexanet alfa; 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-Q, which was filed on May 7, 2015. 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 Pinilla-Ibarz J, Chavez JC. Life after ibrutinib? A new unmet need in CLL. Blood. 2015;125;2013-2014.

CONTACT: Investor Contact: Michele Mantynen Portola Pharmaceuticals ir@portola.com Media Contact: Jani Bergan BrewLife jbergan@brewlife.com

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