Combo therapy demonstrates compelling clinical activity in chronic lymphocytic leukemia and mantle cell lymphoma

TG Therapeutics, Inc., a clinical-stage biopharmaceutical company, has announced preliminary clinical results from its ongoing Phase 2 study of TG-1101 (ublituximab), the company's novel glycoengineered anti-CD20 monoclonal antibody, in combination with ibrutinib (IMBRUVICA™), the oral BTK inhibitor from Pharmacyclics/Janssen

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NEW YORK—TG Therapeutics, Inc., a  clinical-stage biopharmaceutical company, has announced preliminary clinical results from its ongoing Phase 2 study of TG-1101 (ublituximab), the company's novel glycoengineered anti-CD20 monoclonal antibody, in combination with ibrutinib (IMBRUVICA™), the oral BTK inhibitor from Pharmacyclics/Janssen. Data from the Phase 2 study is being presented during the 19th Annual European Hematology Association (EHA) meeting being held in Milan, Italy.

The poster presentation includes data from 28 patients with relapsed and/or refractory CLL or MCL treated with TG-1101 at doses of 600 mg or 900 mg, in combination with ibrutinib at an oral daily dose of 420 mg for patients with CLL and 560 mg for patients with MCL.

The overall response rate (ORR) at the first planned efficacy assessment for the 10 evaluable patients was 90 percent. Among the CLL patients (including 4 with high risk cytogenetics) 86 percent (6/7) achieved a partial response (PR) at the first assessment, with the remaining patient achieving a 40 percent nodal reduction pending next response assessment and, among  MCL patients,  100 percent (3/3) achieved a response (1 CR and 2 PRs).
Of the 28 patients enrolled on study to date, including patients with high risk CLL, no patients have progressed while on the combination, with patients on study now for upwards of 5 months.

Dr. Jeff Sharman, medical director of hematology research for the US Oncology Network, and study chair for the Phase 2 trial stated: "We are impressed with the clinical activity and safety profile seen with ublituximab in combination with ibrutinib to date. We believe there is an important role for combination therapy with the newer agents in CLL. Ublituximab is specifically designed to overcome specific weaknesses of traditional anti-CD20 therapy. This data shows ublituximab can safely be combined with ibrutinib and may both accelerate and deepen the response compared to prior trials of ibrutinib alone."

Michael S. Weiss, the company's executive hacirman and interim CEO commented on the data, "From the inception of TG Therapeutics, we have been focused on developing novel combination therapies with the goal of driving very high response rates without the toxicity associated with chemotherapy. We believe that today's data represent early evidence that we can achieve that goal. The rapid and deep responses seen in 9 out of 10 patients evaluable for response at the first assessment compares quite favorably to published data on ibrutinib monotherapy at early efficacy assessments. While still early, we are very encouraged by the results seen thus far and look forward to presenting data on additional patients with longer-term follow-up at ASH at year's end."

TG-1101 in combination with ibrutinib was well tolerated in the 28 patients evaluable for safety, with Day 1 infusion related reactions IRR) being the most frequently reported adverse event for TG-1101. All but one IRR were Grade 1 or 2 in severity and were manageable without use reductions. Ibrutinib related adverse events included diarrhea and rash with one patient discontinuing treatment due to ibrutinib related diarrhea. This was the only patient to discontinue from the study to date.

The addition of TG-1101 appears to abrogate ibrutinib-related lymphocytosis in patients with CLL, with patients experiencing a median ~80 percent reduction in their absolute lymphocyte count (ALC) by month 4 following initiation of combination therapy.

In addition to the data from the ongoing TG-1101 plus ibrutinib combination study, the company is also presenting data from ongoing single agent studies of TG-1101 and TGR- 1202, the company's novel, oral PI3K delta inhibitor, both of which, as previously reported at ASCO, were well tolerated and demonstrated significant single agent response rates in patients with relapsed and/or refractory B-cell malignancies. The company's presentation for TGR-1202 includes updates from the ASCO data cutoff, where it was previously reported that 78 percent (7/9) CLL patients treated at 800 mg QD or higher had achieved a nodal partial response or a partial response. Updated data presented at the EHA meeting demonstrates an 89 percent nodal response rate with 8/9 CLL patients now achieving a nodal or partial response on TGR-1202 monotherapy at doses greater than or equal to 800 mg.

Mr. Weiss added "We are also excited to note the evolving responses seen in our Phase 1 single-agent study of TGR-1202, with an additional CLL patient achieving a nodal PR, bringing our nodal response rate in CLL patients treated at 800mg or higher to nearly 90 percent. These encouraging results, coupled with the ibrutinib combination data, drive our confidence in our proprietary combination of TG-1101 and TGR-1202, which we will report data for at the Pan Pacific Lymphoma Conference in July 2014."

TG Therapeutics is a clinical-stage biopharmaceutical company focused on the acquisition, development and commercialization of medically important pharmaceutical products for the treatment of cancer and other underserved therapeutic needs. Currently, the company is developing two therapies targeting hematological malignancies. TG-1101 (ublituximab) is a novel, glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. TG Therapeutics is also developing TGR-1202, an orally available PI3K delta inhibitor. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-lymphocytes. Both TG-1101 and TGR-1202 are in clinical development for patients with hematologic malignancies. TG Therapeutics is headquartered in New York City.

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