TG Therapeutics, Inc. · NASDAQ:TGTX
TG Therapeutics — Technical Presentation (2019)
16 slides from TG Therapeutics's technical presentation, 2019
Slide 1: Umbralisib monotherapy in relapsed/refractory marginal zone lymphoma: phase 2 study
Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/ refractory marginal zone lymphoma: a multicenter, open- label, registration directed phase 2 study Pier Luigi Zinzani1, Felipe Samaniego2, Wojciech Jurczak3, Ewa Lech-Maranda4, Nilanjan Ghosh5, Bertrand Anz6, Piers Pa
Slide 2: Conflict of Interest Disclosure – Pier Luigi Zinzani
Conflict of Interest Disclosure – Pier Luigi Zinzani, MD, PhD (Presentation 133) - Employment or leadership position: N/A - Consultant or advisory role: Verastem, MSD, Eusapharma, Sanofi - Stock ownership: N/A - Honoraria: Verastem, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, MSD, Immune
Slide 3: Background / Rationale
Background / Rationale • Marginal Zone Lymphoma (MZL) is an indolent B-cell lymphoma accounting for ~10% of NHL • Although responses are high to frontline therapy, most patients still relapse following induction • Therapeutic options are limited for MZL pts who have progressed following anti-CD20-ba
Slide 4: PI3K Signaling in Marginal Zone Lymphoma
PI3K Signaling in Marginal Zone Lymphoma • B cell receptor (BCR) signaling is The B cell Receptor (BCR) and its Downstream Pathways1 critical to the development of normal B cells and has been implicated in lymphomagenesis • PI3K is a downstream intermediary in the BCR pathway essential for BCR-depen
Slide 5: Umbralisib (TGR-1202)
Umbralisib (TGR-1202) • Next generation PI3Kδ inhibitor, with a unique structure and improved tolerability1 • Improved selectivity to PI3Kδ isoform • Inhibition of CK1ε • Potential regulator of Treg count and function • Ongoing long-term safety analyses demonstrate low rates of immune- mediated toxi
Slide 6: UNITY-NHL Study Design
UNITY-NHL Study Design • UNITY-NHL is an ongoing Phase 2b, multicenter, multi-cohort trial evaluating umbralisib as monotherapy and in multiple combinations in previously treated NHL patients • The MZL cohort receives single agent umbralisib 800 mg oral QD until disease progression or unacceptable t
Slide 7: Demographics
Demographics All Treated Patients Interim Efficacy (Safety Population) Population* N 69 42 • Enrollment is complete MZL Subtype, n (%) Extranodal 38 (55%) 23 (55%) • 72 patients enrolled Nodal 20 (29%) 12 (29%) Splenic 11 (16%) 7 (17%) between July 2017 and Median Age, median (range) 67 (34 – 81) 67
Slide 8: Adverse Events Regardless of Causality, All Treated Patients (N=69)
Adverse Events Regardless of Causality, All Treated Patients (N=69) • Umbralisib was well tolerated Grade 1 Grade 2 Grade 3 Grade 4 Diarrhea 33% 19% 10% - • No events of colitis reported Nausea 17% 14% - - • AE’s leading to dose reduction occurred in Fatigue 19% 9% 3% - 6 subjects (9%) AST increased
Slide 9: Adverse Events of Interest & Long Term Tolerability
Adverse Events of Interest & Long Term Tolerability Demographics Adverse Events of Interest Patients on Study >6 Cycles Occurring After 6 Cycles on Umbralisib All Grades Grade 3/4 N % N % Evaluable for Safety, n 41 Diarrhea 10 24% 2 5% Age, median (range) 66 (34 - 80) ALT increased 1 2% - - Prior Th
Slide 10: Disposition of Interim Efficacy Population (N=42)
Disposition of Interim Efficacy Population (N=42) • Median duration of umbralisib exposure was 10.1 months (range, 0.7 – 15.7) • At a median follow-up of 12.5 months (range 8.3 – 18.5), 55% of patients continue on study treatment • Primary reasons for discontinuing umbralisib during study were • Dis
Slide 11: Best Overall Response of Interim Efficacy Population (N=42)
Best Overall Response of Interim Efficacy Population (N=42) 100 90 IRC Assessment Investigator Assessment 80 (Primary Endpoint) 70 60 ORR 52% ORR 52% 50 CR 12% CR 19% 40 30 20 PR 33% SD 36% PR 40% SD 31% 10 PD 7% PD 10% - • Clinical benefit rate (PR+CR+SD) was 88% by IRC assessment • All patients in
Slide 12: Best Percent Change in Target Lesions from Baseline
Best Percent Change in Target Lesions from Baseline for Interim Efficacy Population 25% Extranodal Splenic Nodal Maximum Percent Change 0% From Baseline SPD (%) -25% -50% -75% ▪ 86% of patients (36/42) had a reduction in tumor burden ▪ Median time to initial response: 2.7 months -100% Data based on
Slide 13: Best ORR For Patients with ≥2 Prior Lines (N=23)
Best ORR For Patients with ≥2 Prior Lines in Efficacy Population (N=23) 25% IRC Assessment for ≥2 Prior Line Population 0% Maximum Percent Change From Baseline SPD (%) -25% ORR 52% CR 17% -50% -75% PR 35% SD 35% 1 Prior Line PD 9% 2+ Prior Lines -100% • ORR by IRC assessment was internally consisten
Slide 14: DOR & PFS by Investigator Assessment
DOR & PFS by Investigator Assessment for Interim Efficacy Population Duration of Response (N=22) Progression-Free Survival (N=42) Proportion Progression-Free Proportion in Response • Median DOR not reached • Median PFS not reached (95% CI: 8.4 mos – NE) • Estimated PFS at 12 months was 66% Months Mo
Slide 15: Conclusions
Conclusions • The oral inhibitor of PI3Kδ, umbralisib, is highly active as a single agent with tolerable side effects in relapsed or refractory marginal zone lymphoma. • Single agent dosing was active across subtypes, as well as in patients with extensive prior therapy. • Durable responses were obse
Slide 16: Acknowledgements
Acknowledgements • Thank you to the patients and their families for their participation • Thank you to the investigators, nurses, and study coordinators • This study was sponsored by TG Therapeutics, Inc. 16