Tg Therapeutics, Inc. · NASDAQ:TGTX
Tg Therapeutics — ASH 2019
18 slides from Tg Therapeutics's conference presentation, December 2019
Slide 1: Phase I/II Study of Umbralisib in Combination with Ublituximab and Venetoclax in R/R CLL
Phase I/II Study of Umbralisib in Combination with Ublituximab and Venetoclax (U2-Ven) in Patients with Relapsed/Refractory CLL Paul M. Barr, MD1, Brian T. Hill, MD, PhD2, Shuo Ma MD, PhD3, Andrea M. Baran, MS1, Andrew Bui, MS 1, Phil Meacham, MS1, Ashley Ochaba2, Jane L. Liesveld MD1, Deborah A. Mu
Slide 2: Background / Rationale: Venetoclax
Background / Rationale: Venetoclax ▪ Preclinical additive to synergistic cytotoxicity between inhibition of BCR signaling and BCL2 ▪ Targeting PI3K may prevent drug resistance to BCL2 inhibition ▪ Phase 1/2 study evaluating U2-Ven combination in a multicenter setting o PI3K + CD20 inhibition ideal t
Slide 3: Background / Rationale: Umbralisib + Ublituximab (U2)
Background / Rationale: Umbralisib + Ublituximab (U2) ▪ Umbralisib: novel PI3Kδ/CK1ε dual inhibitor, with a unique structure and improved tolerability1 o Preclinical: Greater retention of T-reg suppressive capacity compared to idelalisib & duvelisib2 o Clinical: Integrated analysis of long-term safe
Slide 4: Study Design and Objectives
Study Design and Objectives ▪ Study Design o Multi-center Phase I/II dose-escalation (3+3 design) study to assess the safety & efficacy of U2 + venetoclax in patients with R/R CLL • Fixed dose ublituximab (900 mg), escalating doses of umbralisib (600 mg and 800 mg) • Standard dosing of venetoclax (5
Slide 5: Study Design: Treatment Schedule
Study Design: Treatment Schedule Pre-Cycle 1 End of Cycle 3 End of Cycle 7 End of Cycle 12 TLS Staging Response Assessment Response Assessment Response Assessment TLS Restaging MRD (PB & BM) Induction/Debulking Consolidation Extended Cycle 1 Cycle 2 - 3 Cycle 4 - 12 Therapy (MRD+ Only) UBLITUXIMAB I
Slide 6: Key Eligibility Criteria
Key Eligibility Criteria ▪ CLL/SLL: progressed after at least one prior therapy and requiring treatment o Mid-study amendment required CLL pts to be BTKi intolerant or refractory (PD within 6 mos of prior BTK) ▪ 21 day washout from prior therapy except prior BTK inhibitor (longer of 3 days or 5 half
Slide 7: Baseline Characteristics
Baseline Characteristics Evaluable for Safety, n 27 Evaluable for Efficacy, n 23† Median Age, years (range) 63 (43 - 83) Molecular Aberrations Male/Female 18 / 9 At least 1 high risk feature (del17p, del11q, ECOG, 0/1/2 3 / 22 / 2 14 (52%) TP53mut, NOTCH1mut) Median Creatinine Clearance, mL/min (ran
Slide 8: Overall Disposition
Overall Disposition Enrolled (N=27) Phase I (N=9) / Phase II (N=18) Started Umbralisib + Ublituximab Induction (N=27) Induction Ongoing n=3 Off Study n=1 (Gr. 3 Rash) Started Umbralisib + Venetoclax Consolidation (n=23) Consolidation Ongoing n=13 Off Study n=1 (Gr. 3 Diarrhea) Completed 12 Cycles (n
Slide 9: Disposition
Disposition Enrollment by Cohort Dose Modifications Cohort Umbralisib Dose n Agent Reduction (n) Withdrawn (n) Dose level 1 600 mg 3 Ublituximab 0 2 Dose level 2 800 mg 6 Umbralisib 1 2 Phase II 800 mg 18 Venetoclax 1 1 ▪ DLT period: cycles 4 and 5 o 1 DLT at 800 mg • Lower GI bleed, Cycle 5 (not re
Slide 10: Adverse Events (All Causality) >15% (N=27)
Adverse Events (All Causality) >15% (N=27) All Grades Grade 3/4 N % N % ▪ Additional Grade 3/4 AEs: Infusion reaction 18 67% 2 7% o DVT (2) Neutropenia 15 56% 5 19% o Lower GI bleed (1) Leukopenia 13 48% 4 15% o Supraventricular tachycardia (1) Creatinine increase 13 48% - - Thrombocytopenia 13 48%
Slide 11: Cycles of U2 Induction Reduces Venetoclax TLS Risk
3 Cycles of U2 Induction Reduces Venetoclax TLS risk Shift in TLS Risk 100 3 3 90 TLS risk category, patients (%) 80 ▪ After 3 cycles of ublituximab 70 and umbralisib debulking: High 60 12 o No TLS High-Risk patients 50 Medium remaining 40 20 o No patients developed Low 30 clinical or laboratory TLS
Slide 12: Efficacy: ALC and Lymph Node Reduction
Efficacy ALC Reduction Through Cycle 6 Mean % Lymph Node Reduction from Baseline U2 Alone Umbra + Ven Cycle 3 Cycle 7 Cycle 12 60.0 0% n=23 n=13 n=9 Mean Absolute Lymphocyte Count 10% 50.0 48.0 20% 40.0 30% (1000/𝓊L) Venetoclax 40% 30.0 50% 20.0 61% 15.8 60% 14.1 10.0 9.3 70% 4.9 3.4 80% 84% 87%…
Slide 13: Efficacy: Response and MRD
Efficacy: Response and MRD Cycle 3 Cycle 7 Cycle 12 N=23 N=13 N=9 87% 100% 100% 100% 78% U2 Induction ORR ORR ORR PB MRD(-) BM MRD(-) Umbra + Ven 13% 22% SD 56% PR 100% 100% CR 87% 78% MRD Intermediate (0.01%-1.0%) 44% MRD Negative (<0.01%) Cycle 3 & 7 Assessments were by CT only without BM, therefo
Slide 14: Efficacy & Tolerability: Duration of Exposure
Efficacy & Tolerability: Duration of Exposure Prior Novel Agent BTKi Status Cycle 4 Cycle 12 - - Ibrutinib Intolerant INCB040093 - Ibrutinib Intolerant ibrutinib, idelalisib Refractory Ibrutinib Intolerant - - - - - - * Ibrutinib Intolerant Ibrutinib Refractory - - Ibrutinib Refractory Ibrutinib Ref
Slide 15: Efficacy: Progression-free survival (n=27)
Efficacy: Progression-free survival (n=27) Median follow up: 6.4 months (range 0.7 – 19.0+ months) 15
Slide 16: Conclusions
Conclusions ▪ Umbralisib, ublituximab and venetoclax is well tolerated at the Phase 2 doses o U2 induction mitigates TLS risk o Manageable myelosuppression and GI effects resulting in low rate (7%) of discontinuation due to AE ▪ Early evidence of MRD negativity with 12 cycles of therapy o 9/9 and 7/
Slide 17: Acknowledgments
Acknowledgments ▪ Thank you to the patients and their families for their participation. ▪ Participating Centers: 17
Slide 18: University of Rochester Medical Center
UNIVERSITY of OCHESTER MEDICAL CENTER So CY MEDICINE of THE HIGHEST ORDER