TG Therapeutics Announces Publication of Final Results from the Phase 3 GENUINE Trial Evaluating Ublituximab Plus Ibrutinib in Patients with Relapsed/Refractory High-Risk Chronic Lymphocytic Leukemia in The Lancet Haematology

NEW YORK, Feb. 23, 2021 (GLOBE NEWSWIRE) — TG Therapeutics, Inc. (NASDAQ: TGTX) today announced the publication of final results from the Phase 3 GENUINE trial evaluating ublituximab, the Company’s investigational glycoengineered anti-CD20 monoclonal antibody, in combination with ibrutinib, in patients with relapsed or refractory high-risk chronic lymphocytic leukemia (CLL), in The Lancet Haematology.

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, “The Phase 3 data published yesterday, and previously presented, demonstrated that the addition of ublituximab to ibrutinib significantly improved overall response rate, complete response rate as well as prolonged progression-free survival. Significant unmet need still exists within the CLL landscape, and patients with high-risk relapsed or refractory CLL progress more rapidly than those without high-risk cytogenetics. The outcome of the GENUINE study is therefore very encouraging, and we believe these data are supportive of pursuing combination strategies with ublituximab for high-risk CLL patients.” Mr. Weiss continued, “We look forward to bringing ublituximab to market as soon as possible as we pursue completion of a BLA submission with the FDA in the first half of 2021 for the combination of ublituximab plus umbralisib for patients with CLL.”

Jeff P. Sharman, MD, Director of Research at Willamette Valley Cancer Institute and Medical Director of Hematology Research for The US Oncology Network and Study Chair for the GENUINE trial stated, “The utility of adding anti-CD20 therapy in combination with BTK inhibitors, such as ibrutinib, has long been unclear with prior studies using rituximab having failed to demonstrate an improvement in long-term outcomes. These results published from the GENUINE study are encouraging and may suggest that next generation anti-CD20 antibodies could have value in combination approaches to treating CLL.”

The manuscript includes data from 126 patients with relapsed or refractory high-risk CLL who were randomized on study, of which 117 received at least one dose of treatment and were included in safety analyses, with 59 receiving ublituximab plus ibrutinib and 58 receiving ibrutinib monotherapy. Ibrutinib was given orally daily at 420 mg for all cycles. Ublituximab was given intravenously in 28-day cycles with up to 150 mg on day 1, 750 mg on day 2, and 900 mg on days 8 and 15 of cycle 1, and continuing at 900 mg on day 1 of cycles 2 through 6. Beyond cycle 6, ublituximab was given at 900 mg every 3 months. Ublituximab and ibrutinib were continued until unacceptable toxicity, disease progression, or withdrawn consent. The primary endpoint was independent review committee (IRC) assessed overall response rate (ORR) per iwCLL 2008 criteria. Key highlights from this manuscript include:

• The IRC-assessed ORR among treated patients was 90% (53 of 59) in the ublituximab-ibrutinib arm and 69% (40 of 58) in the ibrutinib arm (p=0.0060), with a CR/CRi rate of 20% (12 of 59) and 5% (3 of 58), respectively (p=0.024).
• After a median follow-up of 41.6 months, median IRC-assessed progression-free survival (PFS) in all treated patients was not reached in the ublituximab-ibrutinib group (95% CI, not estimable [NE]) after 15 PFS events and 35.9 months (95% CI, 17·0-NE) in the ibrutinib group after 25 PFS events (hazard ratio [HR], 0.46; 95% CI, 0.24-0.87).
• The most common grade 3/4 adverse events in the ublituximab-ibrutinib group and the ibrutinib group were neutropenia (19%; 12%), anaemia (8%; 9%), and diarrhea (10%; 5%).

These data are described further in the manuscript entitled, “A Phase 3, Randomized Trial of Ublituximab Plus Ibrutinib for Patients With Relapsed/Refractory High-Risk Chronic Lymphocytic Leukaemia,” which was published [online yesterday] in The Lancet Haematology. The online version of the article can be accessed at https://www.thelancet.com/journals/lanhae/home.

ABOUT TG THERAPEUTICS, INC. 
TG Therapeutics is a fully-integrated, commercial stage biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. In addition to an active research pipeline including five investigational medicines across these therapeutic areas, TG has received accelerated approval from the U.S. FDA for UKONIQ™ (umbralisib), for the treatment of adult patients with relapsed/refractory marginal zone lymphoma who have received at least one prior anti-CD20-based regimen and relapsed/refractory follicular lymphoma who have received at least three prior lines of systemic therapies. Currently, the Company has two programs in Phase 3 development for the treatment of patients with relapsing forms of multiple sclerosis (RMS) and patients with chronic lymphocytic leukemia (CLL) and several investigational medicines in Phase 1 clinical development. For more information, visit www.tgtherapeutics.com, and follow us on Twitter @TGTherapeutics and Linkedin.
UKONIQ™ is a registered trademark of TG Therapeutics, Inc.

Cautionary Statement
This press release contains forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

Such forward looking statements include but are not limited to statements regarding expectations for the timing of the Company’s BLA submission for ublituximab in combination with umbralisib for the treatment of CLL and our research and development program evaluating ublituximab in different combinations in CLL. In addition to the risk factors identified from time to time in our reports filed with the Securities and Exchange Commission, factors that could cause our actual results to differ materially include the following: the Company’s ability to complete the BLA submission for ublituximab in combination with umbralisib for the treatment of CLL within the projected timeframe or at all; regulatory challenges that prevent the FDA from accepting the ublituximab BLA submission or, if the submission is accepted, prevent the FDA from approving the BLA; the risk that clinical trial results (both safety and efficacy), that may have supported the acceptance of our data for presentation or publication or influenced our decision to proceed with additional clinical trials, will not be reproduced in ongoing and future clinical studies, including in the ongoing and planned studies evaluating ublituximab in different combination regimens in CLL; the risk that the GENUINE study will not be utilized for any regulatory submission, or support any regulatory approvals for ublituximab; the uncertainties inherent in research and development; and the risk that the ongoing COVID-19 pandemic and associated government control measures have an adverse impact on our research and development plans or commercialization efforts. Further discussion about these and other risks and uncertainties can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2019 and in our other filings with the U.S. Securities and Exchange Commission.

Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at www.tgtherapeutics.com. The information found on our website is not incorporated by reference into this press release and is included for reference purposes only.