Tg Therapeutics, Inc. · NASDAQ:TGTX
Tg Therapeutics — 2015 ASCO Analyst & Investor Event
42 slides from Tg Therapeutics's conference presentation, Jun 1, 2015
Slide 1: 2015 ASCO Analyst & Investor Event
2015 ASCO Analyst & Investor Event May 31, 2015
Slide 2: Forward Looking Safe Harbor Statement
This presentation contains forward - looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are often, but not always, made through the use of words or phrases such as “anticipates”, “expects”, “plans”, “believes”, “intends”, and similar words
Slide 3: Event Agenda & Speakers
Event Agenda & Speakers 3 AGENDA SPEAKER Overview & Introductions Michael S. Weiss, CEO of TGTX TG - 1101 & TGR - 1202 Overview Dr. Owen A. O’Connor TG - 1101 & TGR - 1202 in NHL Dr. Nathan Fowler TG - 1101 & TGR - 1202 in CLL Dr. Anthony Mato Q&A Session Dr.’s O’Connor, Fowler & Mato Closing Remark
Slide 4: Owen A. O'Connor, MD, PhD
Owen A. O'Connor, MD, PhD Professor of Medicine and Experimental Therapeutics Director of the Center for Lymphoid Malignancies Columbia University Medical Center TG - 1101 & TGR - 1202 Single Agent
Slide 5: TG-1101 (Ublituximab)
TG - 1101 ( UBLITUXIMAB )
Slide 6: Ublituximab: A Novel Glycoengineered Anti-CD20 mAb
Ublituximab : A Novel Glycoengineered Anti - CD20 mAb 6 • Unique protein sequence • Type 1 Chimeric IgG1 mAb • Potential advantages over current standard of care: • Glycoengineered for significantly enhanced ADCC • Activity in “low” CD20 expressing cell lines, a characteristic of rituximab resistanc
Slide 7: Safety of Ublituximab
7 Safety of Ublituximab At Least Possibly Related Lab Abnormalities At Least Possibly Related AE’s • Day 1 Infusion Related Reaction most common adverse event – manageable with infusion interruptions only and recovered without sequelae • Infusion times decreased to an average of 90 minutes for the 4
Slide 8: Demonstrated single agent activity: TG-1101 Phase 1 Efficacy Results
8 Demonstrated single agent activity: TG - 1101 Phase 1 Efficacy Results ASCO/EHA 2014 Overall Response by Lymphoma Sub - type 43 % ORR in rituximab relapsed and refractory patients N=6 N=18 N=6 N=30
Slide 9: Ublituximab – Take Home Messages
9 Ublituximab – Take Home Messages • Well tolerated with minimal IRR complications • Promising activity in both rituximab relapsed and rituximab refractory patients across all histologies – Interesting activity in iNHL — e.g. one rituximab refractory MZL patient transition from hospice to durable (2
Slide 10: TGR-1202 Single Agent
TGR - 1202 SINGLE AGENT
Slide 11: Clinical activity and safety profile of TGR-1202 in CLL and B-cell lymphoma
Clinical activity and safety profile of TGR - 1202, a novel once daily PI3Kδ inhibitor, in patients with CLL and B - cell lymphoma. Howard A. Burris III, MD 1,2 , Manish R. Patel, MD 1,3 , Timothy S. Fenske , MD 4 , Owen A. O'Connor, MD, PhD 5 , Changchun Deng, MD, PhD 5 , Danielle M. Brander, MD 6
Slide 12: TGR-1202: Novel PI3K delta Inhibitor
TGR - 1202: Novel PI3K delta Inhibitor ▪ PK profile that allows once - daily oral dosing ▪ 93% nodal PR rate in patients with rel /ref CLL 1 1 Burris et al, ASCO 2015, Abstract # 7069 12
Slide 13: Patient Demographics
† Patient’s evaluable for efficacy included only patients treated with 800 mg of initial formulation or higher, and any micronized dose level of which the following were excluded: 4 were Too Early To Evaluate, 2 Non - Compliant (both at 1800 mg Fasted), 1 removed per investigator discretion, and 1 F
Slide 14: Adverse Events in Treated Patients
Adverse Events in TGR - 1202 Treated Patients Safety All Events in >10% of Pts (N=66) AE All Grades Gr. 3/4 N % N % Nausea 27 41% 0 0% Diarrhea 21 32% 1 2% Fatigue 21 32% 2 3% Headache 15 23% 0 0% Vomiting 15 23% 0 0% Cough 14 21% 0 0% Decreased Appetite 11 17% 0 0% Rash 11 17% 3 5% Constipation 9 1
Slide 15: PI3K-Delta Class AE Profile
PI3K - Delta Class AE Profile Idela + Ofa (ASCO ’15) 2 (n=173) Duvelisib (ASCO ‘15) 3 (n=18) Idelalisib Label (CLL & NHL) 1 (n=256) TGR - 1202 All Studies (ASCO 2015) 4 (n=137) All Grades ( > Gr 3) All Grades ( > Gr 3) All Grades ( > Gr 3) All Grades ( > Gr 3) Diarrhea/ Colitis 49% (20%) 78% (22%) 3
Slide 16: Overall Efficacy
Overall Efficacy Best Percent Change from Baseline in Nodal Size Patients Evaluable for Efficacy (N=51) □ High level of activity demonstrated across a wide variety of hematologic malignancies 16
Slide 17: Efficacy in CLL & FL Patients at Higher Doses
Efficacy Best Percent Change from Baseline in Nodal Size Evaluable CLL & FL Patients Treated at “Higher Doses” □ “Higher Doses” of TGR - 1202 ( 1200 mg initial formulation, or ≥ 600 mg micronized) demonstrated rapid and profound responses 17 FL CLL
Slide 18: Take Home Messages
18 TGR - 1202 Take Home Messages • Once - daily PI3Kδ inhibitor with single agent activity across B - cell malignancies – 88 % nodal response rate in rel /ref CLL; – 42 % ORR in rel /ref FL – P atients remaining on therapy pending further efficacy assessments • Differentiated safety profile from oth
Slide 19: Nathan Fowler, MD: Combination of TG-1101 & TGR-1202
Nathan Fowler, MD Associate Professor Lead, New Drug Development MD Anderson Cancer Center Combination of TG - 1101 & TGR - 1202 “TG - 1303”
Slide 20: Ublituximab + TGR-1202 in Relapsed/Refractory B-Cell NHL and High-Risk CLL
Ublituximab + TGR - 1202 Demonstrates Activity and Favorable Safety Profile in Relapsed/Refractory B - Cell NHL and High - Risk CLL Matthew Lunning , DO 1 , Julie Vose , MD 1 , Nathan Fowler, MD 2 , Loretta Nastoupil , MD 2 , Jan A. Burger, MD 2 , William G. Wierda , MD 2 , Marshall T. Schreeder , M
Slide 21: Study Design
Study Design Cohort Ublituximab NHL Dose Ublituximab CLL Dose TGR Dose (QD) 1 900 mg 600 mg 800 mg 2 900 mg 600 mg 1200 mg 3 900 mg 900 mg 400 mg (micronized) 4 900 mg 900 mg 600 mg (micronized) 5 900 mg 900 mg 800 mg (micronized) 6 900 mg 900 mg 1200 mg (micronized) Expansion Currently Enrolling Ex
Slide 22: Demographics
Demographics Evaluable for Safety (n) 55 Evaluable for Efficacy † (n) 39 Median Age, years (range) 64 (29 – 86) Male/Female 36/19 Histology CLL/SLL 15 DLBCL 16 FL 16 MZL 5 MCL 2 Richter’s 1 ECOG , 0/1/2 17/37/1 Prior Therapies, median (range) 3 (1 – 9) Patients with ≥ 3 Prior Therapies (%) 60% Prior
Slide 23: Safety: Related AEs in ≥5% of Patients
Safety Related AE’s Occurring in ≥ 5% of Patients (n = 55) □ 3 patients (~ 5 % ) have come off study due to an adverse event, none related to hepatic toxicity or colitis Adverse Event All Grades Grade 3/4 N % N % Infusion Related Reaction 16 29% 1 2% Neutropenia 15 27% 13 24% Nausea 15 27% - - Diarr
Slide 24: TG-1101 + TGR-1202 – NHL Best Percent Change in Nodal Size
TG - 1101 + TGR - 1202 – NHL Best Percent Change from Baseline in Nodal Size Type TGR - 1202 Higher* Doses Type TGR - 1202 Lower** Doses Pts (n) CR (n) PR (n) ORR n (%) SD (n) PD (n) Pts (n) CR (n) PR (n) ORR n (%) SD (n) PD (n) CLL/SLL 6 - 5 5 (83%) 1 - CLL/SLL 7 1 3 4 (57%) 3 - DLBCL 7 2 1 3 (43%)
Slide 25: TG-1101 + TGR-1202 – Higher Doses NHL
TG - 1101 + TGR - 1202 – Higher Doses NHL Best Percent Change from Baseline in Nodal Size Patients Treated at the “Higher Doses” of TGR - 1202 Type TGR - 1202 Higher* Doses Pts (n) CR (n) PR (n) ORR n (%) SD (n) PD (n) CLL/SLL 6 - 5 5 (83%) 1 - DLBCL 7 2 1 3 (43%) 3 1 FL/MZL 11 2 5 7 (64%) 4 - Richt
Slide 26: TG-1101 + TGR-1202 Take Home Messages
26 TG - 1101 + TGR - 1202 Take Home Messages • Combination is well tolerated – Grade 3/4 AE’s and discontinuations due to AE’s have been limited (~5%) • Activity of the combination has been observed in indolent NHL, and GCB - DLBCL • Safety profile supports additional multi - drug combination regime
Slide 27: ASH 2014: TGR-1202 + Ublituximab + Ibrutinib
27 ASH 2014: TGR - 1202 + Ublituximab + Ibrutinib Clinical Response at First Assessment (8 Weeks) Histology Description Prior # Rx Prior Ibrutinib Rel /Ref Rituximab Refractory Response % ↓ Follicular Stage IV 4 Refractory Refractory Yes PR 74% MCL Advanced 2 No rAuto txp No CR PET - Richter’s 17p 3
Slide 28: Anthony R. Mato, MD: The GENUINE Phase 3 Study
Anthony R. Mato , MD Director, Center for CLL University of Pennsylvania The GENUINE Phase 3 Study & TGR - 1202 + TG - 1101 Combination
Slide 29: GENUINE Phase 3 Study
GENUINE PHASE 3 STUDY 29
Slide 30: Phase II: Ublituximab + Ibrutinib Overall Efficacy
Phase II: Ublituximab + Ibrutinib Overall Efficacy Sharman et al, ASH 2014 CLL assessed by iwCLL ( Hallek 2008) Criteria; MCL/SLL assessed by Cheson , 2007 Criteria PR* = Complete Response per iwCLL criteria, pending bone marrow confirmation 30
Slide 31: The GENUINE Phase 3 Trial
The GENUINE Phase 3 Trial STRATIFICATION By Prior Lines of Therapy Ibrutinib Ublituximab + Ibrutinib N=100 N=100 Part 1 ORR Subset Part 2 PFS on All Patients ▪ Design, Endpoints, and Statistics agreed to via Special Protocol Assessment (SPA) ▪ Enrolling ~330 patients with high - risk CLL ▪ Part 1 :
Slide 32: Single Agent TGR-1202 & TG-1101 + TGR-1202 in CLL
TGR - 1202 SINGLE AGENT & TG - 1101 + TGR - 1202 IN CLL 32
Slide 33: Single Agent – CLL Best Percent Change in Nodal Size
-100% -75% -50% -25% 0% 25% TGR - 1202 Single Agent – CLL Best Percent Change from Baseline in Nodal Size Patients Evaluable for Efficacy (N=16) • 88% of CLL patients (14/16) achieved a nodal PR, remaining 2 patients still on study pending further evaluation • 63% of CLL patients (10/16) achieved a
Slide 34: TG-1101 + TGR-1202 – CLL
TG - 1101 + TGR - 1202 – CLL On Study Best Percent Change from Baseline in Nodal Size Patients Treated at the “Higher Doses” of TGR - 1202 -100% -75% -50% -25% 0% 25% CLL/SLL 70% of CLL patients had high - risk cytogenetics (17p del and/or 11q del) Type TGR - 1202 Higher* Doses Type TGR - 1202 Lower
Slide 35: Safety Supports Further Combination Studies
TG - 1101 + TGR - 1202 S afety supports further combination studies Related AE’s Occurring in ≥ 5% of Patients (n = 55) □ ~ 5 % have come off study due to an adverse event □ No patients at ≥ 800 mg micronized TGR - 1202 have discontinued due to an AE Adverse Event All Grades Grade 3/4 N % N % Infusi
Slide 36: Phase I/II Study of Pembrolizumab with TG-1101 and TGR-1202 in CLL
Phase I/II study of pembrolizumab in combination with TG - 1101 (ublituximab) and TGR - 1202 in patients with relapsed - refractory CLL A unique opportunity to correct immunological defects which allow CLL to escape immune surveillance Newest Triple Combination Study 36 A research collaboration betw
Slide 37: Study Rationale: PD-Blockade and CLL
Study Rationale: PD - 1 Blockade and CLL • Malignant cells utilize PD - 1 receptor - ligand pathway to evade immune surveillance by inactivating cytotoxic T cells via PD - L1 expression. • CLL: Preclinical data demonstrates the importance PD - 1 / PD - L1 signaling • PD - 1 expression is significant
Slide 38: Response Rates
Lesokhin et al. ASH 2014, Abstract 291. Response Rates Objective Response Rate, n (%) Complete Responses, n (%) Partial Responses, n (%) Stable Disease n (%) B - Cell Lymphoma* (n=29) 8 (28) 2 (7) 6 (21) 14 (48) Follicular Lymphoma (n=10) 4 (40) 1 (10) 3 (30) 6 (60) Diffuse Large B - Cell Lymphoma (
Slide 39: Hypothesis
Hypothesis TG1101 + TG1202 doublet is an ideal platform for combination with anti - PD1 therapy based on clinical activity and non overlapping safety profile. Pembrolizumab will enhance the efficacy of host T cells to induce apoptosis in CLL patients following TG - 1101 and TGR - 1202 induction . 39
Slide 40: Objectives
Objectives Primary objective: Determine the safety of pembrolizumab + ublituximab + TGR - 1202 following ublituximab and TGR - 1202 in patients with relapsed - refractory CLL. Secondary objectives: • Describe the clinical efficacy of pembrolizumab triplet combination therapy in patients with relapse
Slide 41: Q&A Questions?
Q&A 41 Questions?
Slide 42: 2015 ASCO Analyst & Investor Event
2015 ASCO Analyst & Investor Event May 31, 2015