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Sep 30, 2019

TG Therapeutics Announces Publication of Clinical Data from the Phase I/Ib Combination Trial of Ublituximab and Umbralisib (“U2”) in Blood

U2 combination was generally well-tolerated with relatively low rates of immune-mediated toxicities

Combination treatment resulted in median progression free survival (PFS) of ~28 months in relapsed/refractory chronic lymphocytic leukemia (CLL)

NEW YORK, Sept. 30, 2019 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX) today announced the publication of results from the multicenter first-in-human Phase I/Ib combination trial of ublituximab, the Company’s anti-CD20 monoclonal antibody, and umbralisib, the Company’s oral once-daily PI3K delta inhibitor in Blood, the Journal of the American Society of Hematology.

Dr. Matthew Lunning, of the Fred and Pamela Buffett Cancer Center at the University of Nebraska Medical Center and lead enroller on this trial stated, “I have been involved in the development of umbralisib and ublituximab since 2014, and at our institution we have treated over 60 patients on clinical trials with umbralisib and ublituximab (U2) and/or in combination with other agents. In this dose-escalation study with U2, our goal was to identify the optimal dose for future studies. From a safety standpoint, the combination was generally well-tolerated. Some notable findings included that colitis and hepatic toxicity were nearly absent in this population and overall, we observed relatively low rates of immune-mediated toxicities and opportunistic infections, in contrast to the experience with other PI3K delta class members. We also saw activity across all B-cell lymphomas treated. Taken together, I believe the toxicity, tolerability and efficacy profile make this combination a promising treatment option across B-cell lymphomas and a potential backbone for future triple and quad combinations.”
 
 Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, “We are extremely pleased to see the U2 Phase I/Ib dose escalation study published in Blood. These data demonstrate the activity of the U2 combination across multiple B-cell cancers and we believe the efficacy demonstrated in our lead indications continue to support our on-going registration programs. Of note, the approximately 28 months of PFS for the CLL cohort at therapeutic doses of umbralisib in this Phase I/Ib study is consistent with our projections for the PFS of U2 in relapsed/refractory patients in our UNITY-CLL study.” Mr. Weiss continued, “We want to thank Dr. Matthew Lunning, the study’s lead enroller for the U2 cohort, as well as each of the participating trial sites and most importantly the patients who participated in this early study.”
 
The paper includes safety and efficacy information from patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin Lymphoma (NHL), including 22 patients with CLL or small lymphocytic lymphoma (SLL) and 53 patients with NHL treated with the combination of ublituximab and umbralisib, referred to as “U2”. Dose-escalation was performed with a 3+3 design evaluating fixed doses of ublituximab and escalating doses of umbralisib to establish the maximum tolerated dose (MTD). Safety data was available from all 75 patients and demonstrated that the U2 combination was well tolerated with the majority of adverse events (AEs) being grade 1 or 2 in severity and no maximum tolerated dose achieved in either CLL or NHL. Importantly, U2 exhibited low rates of immune-mediated toxicities typically associated with other PI3K-delta inhibitors including colitis, pneumonia/pneumonitis, or hepatic toxicity, and discontinuations due to AEs were limited (13%).

Efficacy data was available from 69 patients and showed the combination to be highly active with a 72.5% clinical benefit rate (defined as patients obtaining a Complete Response, Partial Response, or Stable Disease) across all subtypes of B-cell cancers enrolled in the study. Of note, a median PFS of 27.57 months was observed in patients with relapsed/refractory CLL (n=15) treated at therapeutic dose levels of umbralisib and a 65% overall response rate (ORR) was observed in patients relapsed/refractory indolent NHL (n=20), including a 100% ORR amongst MZL patients (n=5).

These data are described further in the manuscript entitled, “Ublituximab and Umbralisib in Relapsed/ Refractory B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia,” which was published online in the First Edition section of Blood, the Journal of the American Society of Hematology. The online version of the article can be accessed at www.bloodjournal.org.

ABOUT TG THERAPEUTICS, INC.

TG Therapeutics is a biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. Currently, the company is developing two therapies targeting hematological malignancies and autoimmune diseases. Ublituximab (TG-1101) 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 umbralisib (TGR-1202), an oral, once-daily inhibitor of PI3K-delta. Umbralisib uniquely inhibits CK1-epsilon, which may allow it to overcome certain tolerability issues associated with first generation PI3K-delta inhibitors. Both ublituximab and umbralisib, or the combination of which is referred to as "U2", are in Phase 3 clinical development for patients with hematologic malignancies, with ublituximab also in Phase 3 clinical development for Multiple Sclerosis. Additionally, the Company has recently brought its anti-PD-L1 monoclonal antibody, TG-1501, as well as its covalently-bound Bruton Tyrosine Kinase (BTK) inhibitor, TG-1701, into Phase 1 development and aims to bring additional pipeline assets into the clinic in the future. TG Therapeutics is headquartered in New York City.

Cautionary Statement

Some of the statements included in this press release may be 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.  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 are the following: our ability to successfully and cost effectively complete preclinical and clinical trials; the risk that early preclinical and clinical trial results, that may have supported the acceptance of our data for publication or influenced our decision to proceed with additional clinical trials, will not be reproduced in future studies or in future data presentations; the risk that umbralisib will not maintain its differentiated safety profile as patients continue to be treated on drug for longer durations and more patients are enrolled; the risk that the combination of ublituximab (TG-1101) and umbralisib (TGR-1202), referred to as U2 and being studied in the UNITY clinical trials, will not prove to be a safe and efficacious combination, or backbone for triple therapy combinations; the risk that the data from the UNITY clinical trials will not support any potential approvals. 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.

CONTACT:

Jenna Bosco
Senior Vice President,
Corporate Communications
TG Therapeutics, Inc.
Telephone: 212.554.4351
Email: ir@tgtxinc.com

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Source: TG Therapeutics, Inc.