TG Therapeutics, Inc. · NASDAQ:TGTX
TG Therapeutics — Technical Presentation (March 2019)
14 slides from TG Therapeutics's technical presentation, March 2019
Slide 1: Ublituximab in Combination with Ibrutinib Achieves 95% ORR in High-Risk R/R CLL
UBLITUXIMAB (TG-1101), A NOVEL GLYCOENGINEERED ANTI-CD20 MAB, IN COMBINATION WITH IBRUTINIB ACHIEVES 95% ORR IN PATIENTS WITH HIGH-RISK RELAPSED/REFRACTORY CLL Jeff Sharman1,2, Charles M. Farber3, Daruka Mahadevan4, Marshall T. Schreeder5, Heather D. Brooks6,2, Kathryn S. Kolibaba7,2, Suzanne Fannin
Slide 2: Ublituximab: Glycoengineered Anti-CD20 mAb
Ublituximab: Glycoengineered Anti- CD20 mAb • Type 1 chimeric IgG1 mAb • Unique binding sequence on CD20 (Green arrows in figure) • Glycoengineered to contain low fucose content • Activity in “low” CD20 expressing cell lines O’Connor et al, ASCO 2014 Figure Adapted from Ruuls et al 2008
Slide 3: Properties of ublituximab in preclinical and phase I studies
ior Rituximab * * 25 (71) 15 (75) 5 (63) 5 (71) mens: n (%) 0% * * * ctory to Prior * * Properties of ublituximab in preclinical 15 (43) 11 (55) 2 (25) 2 (29) * ment: n (%) -25% ctory to Prior 15 (43) 12 (60) 1 (13) 2 (29) mab: n (%) -50% and phase I studies ot evaluable: 4 patients off study prior
Slide 4: Study Design: Ublituximab + Ibrutinib
Study Design: Ublituximab + Ibrutinib Ibrutinib Once Daily Continuously Days 1, 8, 15 Day 1 Day 1 Day 1 Day 1 Day 1 Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Ublituximab Infusions Cohort Ublituximab Ibrutinib Dose Escalation 1 600 mg 420 mg Schema: 2 900 mg 420 mg • Two part study to determine
Slide 5: Endpoints
Endpoints • Part 1 (safety run-in) – Primary: safety • Part 2 (expansion) – Primary: ORR – Secondary: safety, CR rate, MRD negativity in CLL • Responses in CLL determined by IWCLL 2008
Slide 6: Eligibility Criteria
Eligibility Criteria • Relapsed CLL, small lymphocytic lymphoma, mantle cell lymphoma • Preliminary overall results presented as poster at ASH 20141 • CLL eligibility criteria – Age at least 18 years – At least 1 prior regimen – Indication for therapy – Cytogenetic and/or FISH available (determined
Slide 7: Patient Characteristics
Patient Characteristics Evaluable for Safety, (n) 44 Evaluable for Efficacy, † (n) 40 Median Age, years (range) 71 (39 – 86) Male/Female 22/22 ECOG, median 1 Prior Regimens, 2 (1 – 7) median (range) ≥ 3 Prior Regimens 16 (36%) Prior Anti-CD20 (rituximab, ofatumumab, 41 (93%) obintuzumab) Refractory
Slide 8: Safety
Safety All Causality AE’s in > 10% of Patients (n=44) All Grades Grade 3/4 Adverse Event n (%) n (%) Infusion reaction 20 (45%) 3 (7%) Diarrhea 16 (36%) 2 (5%) Fatigue 13 (30%) 1 (2%) Nausea 11 (25%) - Rash 10 (23%) - Pyrexia 8 (18%) - Arthralgia 7 (16%) 1 (2%) Constipation 7 (16%) - Cough 7 (16%) -
Slide 9: Efficacy: Nodal Reductions
Efficacy: Nodal Reductions 25% Best Percent Change from Baseline in Nodal Size Efficacy Assessed at Week 8 and Week 20 Only 0% -25% -50% -75% * High-Risk MRD(-) -100% *Detection of new lesion met iwCLL critieria for PD • 37/40 (93%) achieved > 50% reduction in nodal size
Slide 10: Efficacy: First vs. Second Scan
Efficacy: First vs. Second Scan Week 8 Week 20 0% -10% -20% -30% -40% -50% -60% -62% -64% -70% -76% -80% -85% -90% -100% All CLL High-Risk CLL • “High-Risk” = 17p del, 11q del, or p53 mutation
Slide 11: Efficacy: Best Overall Response Rate
Efficacy: Best Overall Response Rate 100% 95% ORR 90% 88% ORR 15% CR/PR* 80% 10% CR/PR* 70% Per study design, all 15% of High Risk patients were 60% patients were evaluated for MRD negative efficacy at Month 2 50% within 6 months and 5 only of therapy 40% 78% PR 80% PR 30% 20% 10% N=40 N=20 0% CLL H
Slide 12: Efficacy: Lymphocytosis
Efficacy: Lymphocytosis Absolute Lymphocytes in CLL Patients by Month on Treatment Median, Interquartile Range (25% - 75%) 80 70 Median Absolute Lymphocyte Count (K/uL) 60 50 40 30 20 10 0 Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 = Ublituximab Infusion • Median 75% decrease in ALC from baseline by th
Slide 13: Conclusions
Conclusions • Addition of ublituximab to ibrutinib in relapsed CLL is safe and effective. – Adverse events were as expected and not usually serious – Overall response rate 88%, 95% in high-risk – Complete response rate 10%, and 3 patients achieved MRD- negative status – Mitigates the transient lymph
Slide 14: The GENUINE Phase 3 Trial: High-Risk CLL
The “GENUINE” Phase 3 Trial: High-Risk CLL • Design, Endpoints, and Statistics agreed to via Special Protocol Assessment (SPA) with U.S. FDA • Enrolling 330 patients with High-Risk CLL – Presence of 17p del, 11q del, and/or p53 mutation • Study Chair: Jeff Sharman, MD
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