TG Therapeutics, Inc. · NASDAQ:TGTX
TG Therapeutics — ECTRIMS 2018 Annual Congress
20 slides from TG Therapeutics's conference presentation, Oct 11, 2018
Slide 1: Final Results of a Placebo Controlled, Phase 2 Study of Ublituximab in RMS
Final Results of a Placebo Controlled, Phase 2 Multicenter Study of Ublituximab (UTX), a Novel Glycoengineered Anti-CD20 Monoclonal Antibody (mAb), in Patients with Relapsing Forms of Multiple Sclerosis (RMS) Edward Fox, MD, PhD Director, MS Clinic of Central Texas Central Texas Neurology Consultant
Slide 2: Disclosures
Disclosures Research Support: Consultancy/Advisory/Speaker: • TG Therapeutics • TG Therapeutics • Acorda • Acorda • Biogen • Bayer • Celgene • Biogen • Chugai • EMD Serono • EMD Serono • Genentech • MedDay • Novartis • Novartis • Roche-Genentech • Roche-Genentech • Sanofi Genzyme • Sanofi Genzyme •
Slide 3: Ublituximab (TG-1101)
Ublituximab (TG-1101) ▪ Novel Glycoengineered Anti-CD20 mAb ▪ 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 resis
Slide 4: Ublituximab Phase 2 RMS: Design
Ublituximab Phase 2 RMS: Design Primary Efficacy Endpoint: Responders Rate Responders Rate = Subjects who have ≥95% B-cell depletion at Week 4 4
Slide 5: Key Inclusion and Exclusion Criteria
Ublituximab Phase 2 RMS: Key Inclusion and Exclusion Criteria Key Inclusion Criteria: ▪ 18-55 age ▪ Diagnosis of RMS (McDonald criteria 2010) ▪ ≥ 2 relapses in prior 2 years or 1 relapse in the year prior to screening and/or ≥1 Gd enhancing lesion ▪ Active disease ▪ EDSS 0-5.5 (inclusive) Key Exclus
Slide 6: Treatment Regimen
Ublituximab Phase 2 RMS: Treatment Regimen Randomization Treatment Period Cohort Treatment Day 1/ Infusion Time Day 15/ Infusion Time Week 24/ Infusion Time Placebo (n=2) Placebo / 4h Placebo / 3h - 1 UTX (n=6) 150 mg / 4h 450 mg / 3h 450 mg / 1.5h Placebo (n=2) Placebo / 4h Placebo / 1.5h - 2 UTX (
Slide 7: Baseline Characteristics
Ublituximab Phase 2 RMS: Baseline Characteristics Baseline Demographics Subjects and Age (Years)1 Gender (% Female) Disease Duration Cohort treatment (Years)1,2 1 Placebo (n=2) 39±14 50% 15.5±20.4 UTX (n=6) 43±12 67% 7.1±7.3 Placebo (n=2) 44±1 0% 0.9±1.2 2 UTX (n=6) 33±10 100% 5.3±7.0 Placebo (n=2)
Slide 8: Primary Endpoint – B cell Depletion
Ublituximab Phase 2 Results: Primary Endpoint – B cell Depletion 30 Arrow represents treatment timepoint 25 %CD19+ B Cells 20 15 10 5 0 12 16 20 25 28 36 40 44 48 en 0 2 1 2 2 3 4 8 ay ay ay ay k k k k re k k k k k k k k k ee ee ee ee D D D D ee ee ee ee ee ee ee ee ee Sc W W W W 4 4 k1 k1 W W W W W
Slide 9: Safety & Tolerability
Ublituximab Phase 2 RMS: Safety & Tolerability Adverse Event Summary* Regardless of Related to Causality Ublituximab n (%) n (%) Patients with an 48 (100%) 12 (25%) Adverse Event (AE) Patients with a Serious 8 (17%) 1 (2%) Adverse Event (SAE) AEs leading to 1 (2%) 0 (0%) Withdrawal *Excludes Infusio
Slide 10: Safety & Tolerability: Adverse Events Related to Ublituximab
Ublituximab Phase 2 RMS: Safety & Tolerability Adverse Events (AEs) Related to Ublituximab Event, n (%) (N=48) Most frequently reported ▪ Most common Adverse adverse events All Grades Grade 3/4 Event (AE) was infusion- Infusion Related Reaction 23 (48%) - (-) related reactions Headache 4 (8%) - (-)
Slide 11: Infusion Related Reaction (IRR)
Ublituximab Phase 2 RMS: Infusion Related Reaction (IRR) All IRRs Related to Ublituximab Ublituximab Infusions Total ▪ IRRs were most frequent with Patients Day 1 Day 15 Week 24 with ≥1 the first infusion (Day1) (n=48) (n=48) (n=46) IRRs Total ▪ Day 1 dose infused in ≤3 hours IRRs by 21 (44%) 5 (10%
Slide 12: MRI T1 Gd Enhancing Lesions
Ublituximab Phase 2 RMS: MRI T1 Gd Enhancing Lesions T1 Gd Enhancing Lesions Baseline vs. Week 24 & Week 48 Baseline (n=46): 4.00 3.63 ▪ Mean Number of Gd Enhancing Lesions Mean = 3.63 ± 7.80 T1 Gd lesions 100% Reduction ▪ 39% had ≥ 1 T1 Gd lesions 3.00 ▪ 26% had ≥ 4 T1 Gd lesions Week 24 & Week 48
Slide 13: MRI T2 Lesion Volume
Ublituximab Phase 2 RMS Results: MRI T2 Lesion Volume 16,500 T2 Lesion Volume from Baseline to Week 24 & Week 48 Mean T2 Lesion Volume (mm 3) 16,000 15,500 -10.6% (p=0.002) 15,000 -7.3% 14,500 (p=0.006) -3.6% 14,000 (p=0.019) 13,500 13,000 Baseline Week 24 Week 48 (n=46) (n=46) (n=46) ▪ Decrease of
Slide 14: Annualized Relapse Rate (ARR)
Ublituximab Phase 2 RMS Results: Annualized Relapse Rate (ARR) Relapse History at Study Entry 30 25 ▪ 86% of subjects experienced ≥1 Number of Subjects relapse in the year prior to 20 screening 15 10 ▪ Mean number of relapses = 1.45 Median = 2 5 0 0 1 2 3 4 5 Relapses in Year Prior to Screening At W
Slide 15: RMS Results: Disability
Ublituximab Phase 2 RMS Results: Disability ▪ Mean EDSS at baseline was 2.44 ± 1.36; Median=2.5 (n=48) ▪ Disability at Week 48: ▪ 7% of subjects met criteria for 24 Week Confirmed Disability Progression (CDP) ▪ 17% of subjects met criteria for 24 Week Confirmed Disability Improvement (CDI) 15
Slide 16: RMS Results: NEDA at Week 48
Ublituximab Phase 2 RMS Results: NEDA at Week 48 ▪ At Week 48, 46* subjects received all assessments to be evaluated for NEDA: No Relapses No Evidence of No 24 Week CDP 93% Clinical Disease 93% ▪ 93% of subjects were relapse free 87% NEDA ▪ 93% of subjects did not experience 74% 24 week confirmed di
Slide 17: Conclusions
Ublituximab Phase 2 RMS: Conclusions ▪ B cells are efficiently depleted in most patients within 24 hours of receiving the first dose of ublituximab ▪ Median 99% B cell depletion was observed at Week 4, and maintained at Week 24 and Week 48 ▪ Ublituximab was well tolerated and the most frequent AEs (
Slide 18: Efficacy Conclusions
Ublituximab Phase 2 RMS: Efficacy Conclusions At Study Conclusion (Week 48 of Ublituximab Treatment): ▪ Annualized Relapse Rate (ARR) of 0.07 ▪ 93% of subjects were relapse free ▪ No T1 Gd enhancing lesions were detected in any subjects at Week 24 or at Week 48 ▪ 74% of subjects fulfilled the criter
Slide 19: ULTIMATE I and II Study Design
ULTIMATE I and II Study Design ▪ Primary Endpoint: Annualized Relapse Rate (ARR) at 96 weeks in RMS subjects treated with ublituximab ▪ Enrollment complete in the ULTIMATE Phase 3 Program 19
Slide 20: Thank You to Our Study Sites and Their Patients
Thank You to Our Study Sites and Their Patients ▪ Hope Neurology, Knoxville, TN: Sibyl Wray, MD ▪ Coordinator: Brenda Whitehead, CCRP ▪ SC3 Research Group, Arcadia, CA: Richard Shubin, MD ▪ Coordinator: Ngoc Nguyen ▪ Ohio State University, Columbus, OH: Richard Kissel, MD ▪ Coordinator: Misty Green