Portola Presents New Interim Data on its Oral SYK/JAK Inhibitor Cerdulatinib in Heavily Pre-Treated Patients with Relapsed/Refractory Follicular Lymphoma

SOUTH SAN FRANCISCO, Calif., June 19, 2019 /PRNewswire/ -- Portola Pharmaceuticals, Inc.^® (Nasdaq: PTLA) today announced new interim results from the Company's ongoing Phase 2a study of cerdulatinib, an investigational, oral SYK/JAK inhibitor, in patients with relapsed/refractory follicular lymphoma (FL) receiving cerdulatinib alone or in combination with rituximab. Data were presented this month in a poster session at the 24^th Congress of the European Hematology Association (EHA) in Amsterdam (June 13-16) and during an oral session today at the 15^th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (June 18-22).

Data included safety and efficacy findings for 40 patients who received single agent cerdulatinib at 30 mg twice daily (with the exception of two patients who initiated treatment at 35 mg) and 17 patients who received cerdulatinib at 30 mg twice daily in combination with a standard dosing regimen of rituximab. The number of prior treatment regimens including anti-CD20 antibody, bendamustine and anthracyclines ranged from one to nine, with a median of three.

Among the 40 patients in the cerdulatinib-only cohort, the objective response rate (ORR) was 45%; five patients (13%) achieved a complete response (CR), 13 patients (33%) achieved a partial response (PR) and 10 patients (25%) achieved stable disease (SD). Of the 27 patients with a PR or SD at first evaluation in the single agent cerdulatinib cohort, 17 (63%) had a further reduction in tumor volume at a subsequent efficacy evaluation. To date, 15 of the 40 patients (38%) in the cerdulatinib-only cohort have been on study drug for at least 10 months.

Among the 13 patients evaluated for efficacy in the cerdulatinib and rituximab combination cohort, the ORR was 62%; one patient (8%) achieved a CR, seven patients (54%) achieved a PR and five patients (39%) achieved SD. To date, 10 of the 13 patients have been on study drug from three to 10 months.

Cerdulatinib was generally well-tolerated and the safety profile appeared similar in both cohorts. The most common adverse events (AEs) occurring in ≥10% of patients were lipase increase (25%), neutropenia (15%), amylase increase (13%) and diarrhea (10%). The most common AEs in the combination cohort included lipase increase (35%), neutropenia (23%) and diarrhea (12%). The lipase and amylase increases were generally asymptomatic and not associated with pancreatitis. Additionally, there was no emergence of late-stage colitis, cardiac or liver abnormalities, or other evidence of cumulative toxicity among patients in the single-agent cerdulatinib arm.

"Despite recent advances, relapsed or refractory follicular lymphoma remains a challenging and heterogeneous disease. Oral therapies that can address multiple signaling pathways and overcome chemoresistance without cumulative side effects are urgently needed," said Paul Hamlin, M.D., medical director for the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center. "Cerdulatinib continues to show promise across a range of B- and T-cell malignancies, and I am encouraged by these interim results, indicating sustained clinical activity and good tolerability of cerdulatinib in these follicular lymphoma patients."

"We are very encouraged by these early findings and look forward to continuing to gather additional data that will further characterize the safety and efficacy profile of cerdulatinib in patients with relapsed/refractory follicular lymphoma," said Jeff Myers, Portola's interim chief medical officer. "Simultaneously, we are continuing to move forward with the development of cerdulatinib in relapsed/refractory peripheral T-cell lymphoma and plans to initiate a registrational trial by the end of the year."

ICML Oral Presentation Details
Wednesday, June 19, 2019 from 17:15 p.m. CEST/ 8:15 a.m. PDT

• Rapid and Durable Responses with the SYK/JAK Inhibitor Cerdulatinib in a Phase 2 Study in Relapsed/Refractory Follicular Lymphoma—Alone or in Combination With Rituximab (Abstract #30)
   
  Presenter: Stephen Smith, M.D., of the University of Washington/Fred Hutchinson Cancer Research Center.

Cerdulatinib has demonstrated broad clinical activity in both B- and T-cell malignancies. At the American Society of Hematology meeting in December 2018, the Company presented an update on cerdulatinib's activity in relapsed/refractory peripheral T-cell lymphoma (PTCL); angioimmunoblastic T-cell lymphoma (AITL), a subset of PTCL; and cutaneous T-cell lymphoma (CTCL). As of the November 1, 2018 cut-off date, the ORR in the PTCL cohort was 34% with 27% achieving a CR. Among the subset of patients in the PTCL cohort with AITL, the ORR was 57% with a CR of 50%. The ORR in the CTCL cohort was 26% with 7% of patients achieving a CR. Importantly, rapid improvements in pruritus, or severe itching – a common and often serious condition associated with CTCL – were observed. Follow-up analysis of these cohorts is ongoing with plans to start a registrational study in PTCL by the end of the year.

About the Phase 2a Study
The Phase 2a, open-label study was designed to assess the safety and efficacy of cerdulatinib in patients with relapsed/refractory FL (alone or in combination with rituximab), small lymphocytic lymphoma (SLL) and specific subtypes of T-cell Non-Hodgkin Lymphoma, including PTCL, AITL and CTCL.

Tumor response in the two cohorts evaluating patients with relapsed/refractory FL was assessed by Lugano classification, with treatment continued until disease progression or unacceptable toxicity. Tumor response assessments were performed at the end of cycle two and every three cycles thereafter.

About Cerdulatinib
Cerdulatinib is an investigational oral, dual spleen tyrosine kinase (SYK) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways implicated in certain hematologic malignancies and autoimmune diseases. There is a strong rationale for inhibiting both SYK (B-cell receptor pathway) and JAK (cytokine receptors) in B-cell malignancies where both targets have been shown to promote cancer cell growth and survival.

The U.S. Food and Drug Administration granted cerdulatinib Orphan Drug Designation for the treatment of PTCL in September 2018.

About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a global, commercial-stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics that could significantly advance the fields of thrombosis and other hematologic conditions. The Company's first two commercialized products are Andexxa^® [coagulation factor Xa (recombinant), inactivated-zhzo], marketed in Europe as Ondexxya^® (andexanet alfa), and Bevyxxa^® (betrixaban). The company also is advancing cerdulatinib, a SYK/JAK inhibitor being developed for the treatment of hematologic cancers. Founded in 2003 in South San Francisco, California, Portola has operations in the United States and Europe.

Forward-Looking Statements
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 anticipated development plan for cerdulatinib. Risks that contribute to the uncertain nature of the forward-looking statements include: the risk of unfavorable results from additional clinical trials involving cerdulatinib; our ability to successfully execute on our development strategy; the risk of unfavorable regulatory developments; our expectation that we will incur losses for the foreseeable future and will need additional funds to finance our operations; the effects of competition; the accuracy of our estimates regarding expenses and capital requirements; our ability to successfully build a hospital-based sales force and commercial infrastructure; our ability to obtain and maintain intellectual property protection for our product candidates; and our ability to retain 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 most recent annual report on Form 10-K and quarterly report on Form 10-Q. All forward-looking statements contained in this press release speak only as of the date on which they were made. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

SOURCE Portola Pharmaceuticals, Inc.®

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