Benzinga | Jun 18, 2021 07:36AM EDT

TG Therapeutics Highlights Presentation Of TG-1701 Data At International Congress On Malignant Lymphoma

TG Therapeutics, Inc. (NASDAQ:TGTX), today announced data from two presentations evaluating TG-1701, the Company's investigational once-daily, oral BTK inhibitor, presented today during the 16th International Congress on Malignant Lymphoma (ICML). One presentation evaluated TG-1701 preclinically and the other included Phase 1 data evaluating TG-1701 as a monotherapy and as a triple therapy in combination with ublituximab, the Company's novel glycoengineered anti-CD20 monoclonal antibody, and UKONIQ(r) (umbralisib), the Company's once-daily, inhibitor of PI3K-delta and CK1-epsilon in patients with front line or relapsed/refractory non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). The Phase 1 data presented today were previously presented at the 2021 American Society of Clinical Oncology (ASCO) annual meeting and the 2021 European Hematology Association annual meeting.



PRESENTATION HIGHLIGHTS:

Poster Presentation Title Antitumoral activity of the novel BTK inhibitor TG-1701 is associated with disruption of Ikaros signaling and improvement of anti-CD20 therapy in B-cell non-Hodgkin lymphoma

* TG-1701 is a novel irreversible BTK inhibitor currently in Phase 1 clinical development, as monotherapy or in combination with ublituximab and UKONIQ (umbralisib).

* In patient samples from a Phase 1 clinical trial of TG-1701, phosphoproteomic analysis differentiated early and late CLL responders to TG-1701 therapy.

* Disruption of an active Ikaros pathway is a signature of early responders, while absence of Ikaros modulation upon TG-1701 therapy is a signature of non-/late responders.

* TG-1701 did not impair Fc?R-driven ADCC and ADCP and cooperated with U2 in in vitro and in vivo models of BTKi-sensitive and BTKi-resistant B-NHL.

Poster Presentation Title TG-1701, A Selective Bruton Tyrosine Kinase (BTK) Inhibitor, as Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Patients with B-cell Malignancies

* A total of 125 patients with R/R CLL or B-cell lymphoma have been treated with TG-1701, with patients receiving monotherapy in the dose-escalation cohort (n=25), 200 mg in a dose-expansion cohort (n=61), 300 mg in a CLL dose-expansion cohort (n=20), or TG-1701 in combination with U2 in the dose escalation cohort (n=19).

* TG-1701 monotherapy was well tolerated and the maximum tolerated dose was not reached up to 400 mg QD.

* Adverse Events (AEs) of special interest in patients treated with 200 mg and 300 mg QD of TG-1701 (n=81), included Grade 3 hypertension (4.9%), atrial fibrillation (1.2%), and no instances of major bleeding observed. Grade 3 AEs occurring in ?10% of patients treated with U2+1701 included diarrhea (11%), neutropenia (11%), ALT increase (16%), and AST increase (16%), and Grade 4 AEs occurring in ?10% of patients treated with U2+1701 included neutropenia (11%).

* At a median follow up of 12.2 months in the 200 mg QD monotherapy expansion cohorts, overall response rates (ORR) were: 95% (19/20) in CLL, 65% (13/20) in mantle cell lymphoma (MCL), and 95% (19/20) in Waldenstrom macroglobulinemia (WM).

* 100% ORR observed at a median follow up of 8.6 months in the 300 mg CLL monotherapy cohort (n=19).

* At a median follow up of 15.6 months, the 1701+U2 dose escalation (using doses of 100mg to 300 mg QD of TG-1701) resulted in 79% ORR, with 21% CR rate across patients with WM, CLL, marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (n=19).

Data presented at ICML 2021 is available on the Publications page of the Company's website at https://www.tgtherapeutics.com/publications/.