Tg Therapeutics, Inc. · NASDAQ:TGTX
Tg Therapeutics — Technical Presentation (September 2021)
15 slides from Tg Therapeutics's technical presentation, September 2021
Slide 1: A Phase 1/2 Study of Umbralisib, Ublituximab, and Venetoclax in Relapsed/Refractory CLL
A Phase 1/2 Study of Umbralisib, Ublituximab, and Venetoclax in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) Paul M. Barr, MD}, Brian T. Hill, MD, PhD2, Clive S. Zent, MD, Andrea M. Baran, MS!, Mijamin Friend?, Diksha Biswat, Anjali Advani, MD?, Allison Winter, MD2, Kelsey
Slide 2: Disclosures
Disclosures = Consulting and research support from TG Therapeutics
Slide 3: Background / Rationale
Background / Rationale = Inhibition of BCR signaling and BCL2 is synergistic in vitro = Targeting PI3K may prevent drug resistance to BCL2 inhibition = Phase 1/2 study evaluating U2-Ven combination in a multicenter setting o Umbralisib and ublituximab (U2) combination ideal to minimize TLS risk © Go
Slide 4: Background / Rationale: Umbralisib + Ublituximab (U2)
Background / Rationale: Umbralisib + Ublituximab (U2) = Umbralisib is an oral, once-daily, novel, teil teihl teil inhibitor of PI3K5 and CK1e Umbralisib Idelalisib Duvelisib Oo Preclinical: Greater retention of T-reg suppressive capacity compared to idelalisib & duvelisib? Oo Clinical: Integrated an
Slide 5: Study Design and Objectives
Study Design and Objectives = Study Design o Multi-center Phase 1/2 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-we
Slide 6: 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 [ \ \{ 3 } (Detectabl
Slide 7: 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 8: Baseline Characteristics
Baseline Characteristics Evaluable for Safety, n Molecular Aberrations High Risk Features: n/N (%) 11q deletion 10/46 (22%) 17p deletion 10/46 (22%) TP53 mutation 10/33 (30%) NOTCH1 mutation 8/27 (30%) SF3B1 mutation 5/27 (19%) IGHV unmutated 29/39 (74%) At least 1 high risk feature 34/47 (72%) Eval
Slide 9: Adverse Events (All Causality) >20% (N=47)
Adverse Events (All Causality) >20% (N=47) All Grades Grade 3/4 = G3/4 AEs of Special Interest: N % N % / P oO Pneumonia: 3 (6%) ji js 9 9 Infusion reaction 80 84% 4 9% oO Colitis: 2 (4%) — 1 of whom had c-diff Neutropenia 25 53% 13 28% oO TLS: 1 (2%) - ublituximab related, prior to Leukopenia 25 53
Slide 10: Cycles of U2 Induction Reduces Venetoclax TLS risk
3 Cycles of U2 Induction Reduces Venetoclax TLS risk TLS risk category, patients (%) Shift in TLS Risk 100 5 90 + 80 | = After 3 cycles of ublituximab 70 | High and umbralisib debulking: 60 4 : o 79% relative reduction in TLS 50 = Medium risk after 3 cycles of U2 20 | © Low o No patients developed c
Slide 11: Efficacy: Response and MRD
Efficacy: Response and MRD Best Post Cycle 12 Follow Up Response Cycle 12 Cycle 18 Cycle 24 100% ORR m PR m CR Detectable MRD (21.0% ) MRD Intermediate (0.01%-1.0%) Undetectable MRD (<0.01%) At Cycle 12 90% (9/10*) uMRD in PB 78% (7/9) uMRD in BM in BTK-refractory pts BM: bone marrow; ORR: Overall r
Slide 12: Efficacy: Progression-free survival (n=46)
Efficacy: Progression-free survival (n=46) 100 Tt Censored g 90 4 = «804 > S 704 2 A 604 ov B80 prance nnn nnn g 40 4 BS 304 Median Follow up: 24.5 months ov m 204 (range 9.3 — 40.4 months) 2 a 10 4 0 T T T T T T T T 0 5 10 15 20 25 30 35 40 Time (months) AtRisk 46 46 45 34 29 20 9 6 0 1 death due t
Slide 13: Conclusions
Conclusions = Combination of umbralisib, ublituximab and venetoclax is well tolerated o U2 induction mitigates TLS risk = Encouraging efficacy in relapsed/refractory CLL patients including those refractory to prior BTKi o 100% ORR, 37% CR rate o Undetectable MRD of 91% and 72% in peripheral blood an
Slide 14: Acknowledgments
Acknowledgments = Thank you to the patients and their families for their participation. = Participating Centers: GL WILMOT CANCER INSTITUTE ») Northwestern £3 Cleveland Clinic University Taussig Cancer Institute Hicnest Orver Se ROCHESTER
Slide 15: University of Rochester Medical Center
eyo) UNIVERSITY of 188 ROCHESTER MEDICAL CENTER MEDICINE of THE HIGHEST ORDER
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