Tg Therapeutics, Inc. · NASDAQ:TGTX
Tg Therapeutics — Technical Presentation (October 2021)
22 slides from Tg Therapeutics's technical presentation, October 2021
Slide 1: Phase 3 Results of the ULTIMATE I & II Global Studies: Ublituximab Versus Teriflunomide
Phase 3 Results of the ULTIMATE I & II Global Studies: Ublituximab Versus Teriflunomide in Relapsing Multiple Sclerosis Lawrence Steinman, MD1; Edward Fox, MD, PhD2; Hans-Peter Hartung, MD3,4,5,6; Enrique Alvarez, MD, PhD7; Peiqing Qian, MD8; Sibyl Wray, MD9; Derrick Robertson, MD10; DeRen Huang, MD
Slide 2: Disclosures
Disclosures ▪ Lawrence Steinman has received compensation from TG Therapeutics, Inc. 2
Slide 3: Ublituximab Is a Novel Glycoengineered Anti-CD20 mAb
Ublituximab Is a Novel Glycoengineered Anti-CD20 mAb Ublituximab Rituximab Ocrelizumab Ofatumumab mouse human glycoengineered Glycoengineered Chimeric IgG1 Humanized IgG1 Recombinant Structure chimeric IgG1 fully human IgG1 150mg D1, 450mg D15, 1g D1 & D15, then 300mg D1 & D15, then Regimen 20mg eve
Slide 4: ULTIMATE I & II: Study Design
ULTIMATE I & II: Study Design Identical phase 3, randomized, multi-center, double-blinded, active-controlled studies that were conducted in parallel Screening Treatment Period Follow-up Population Teriflunomide ▪ Age 18-55 14 mg PO QD until last day of W95 ▪ Diagnosis of MS per 2010 Infusion placebo
Slide 5: ULTIMATE I & II: Study Objective and Key Endpoints
ULTIMATE I & II: Study Objective and Key Endpoints Objective: To evaluate the efficacy and safety of ublituximab compared with teriflunomide teriflunomideininpatients patientswith withrelapsing relapsingmultiple multiplesclerosis sclerosis By individual study Primary endpoint Annualized relapse rate
Slide 6: ULTIMATE I & II: Independent Global Studies
ULTIMATE I & II: Independent Global Studies ▪ First patient first infusion: 22 September 2017 ▪ Last patient first infusion: 04 October 2018 ▪ 1094 patients were randomized across 106 sites in 10 countries Country, n (%) ULTIMATE I ULTIMATE II Belarus 64 (11.7) 64 (11.7) Croatia - 49 (9.0) Georgia 8
Slide 7: Patient Disposition & Analysis Population
Patient Disposition & Analysis Population Patients ULTIMATE I ULTIMATE II screened N = 673 N = 660 Patients Teriflunomide Ublituximab Teriflunomide Ublituximab randomized N = 275 N = 274 N = 273 N = 272 Discontinued Treatment 23 (8.4) 34 (12.4) 34 (12.5) 18 (6.6) ▪ Adverse event ▪ 1 (0.4) ▪ 17 (6.2)
Slide 8: Patient Demographics & Baseline Characteristics
Patient Demographics & Baseline Characteristics ULTIMATE I & II populations are consistent and poolable Characteristic ULTIMATE I (N = 545) ULTIMATE II (N = 544) Teriflunomide Ublituximab Teriflunomide Ublituximab Mean ± standard deviation or n (%) N = 274 N = 271 N = 272 N = 272 Age, years 37.0 ± 9
Slide 9: Primary Endpoint: Annualized Relapse Rate (ARR)
Primary Endpoint: Annualized Relapse Rate (ARR) ULTIMATE I ULTIMATE II 0.2 0.188 0.178 59.4% 49.1% 0.15 Relative reduction Relative reduction p < 0.0001 p = 0.0022 Adjusted ARRa 0.1 0.091 0.076 0.05 0 Teriflunomide Ublituximab Teriflunomide Ublituximab N = 274 N = 271 N = 272 N = 272 ARR ratio (95%
Slide 10: MRI: Total Number of Gd+ T1 Lesions
MRI: Total Number of Gd+ T1 Lesions ULTIMATE I ULTIMATE II 0.6 0.3 0.491 0.250 Number of Gd+ T1 lesionsa Number of Gd+ T1 lesionsa 0.5 0.25 0.4 0.2 0.3 96.7% 0.15 96.5% Relative reduction Relative reduction 0.2 p < 0.0001 0.1 p < 0.0001 0.1 0.05 0.016 0.009 0 0 Teriflunomide Ublituximab Teriflunomid
Slide 11: MRI: Number of New or Enlarging T2 Lesions
MRI: Number of New or Enlarging T2 Lesions ULTIMATE I ULTIMATE II 3 2.789 2.831 Number of new or enlarging 2.5 2 T2 lesionsa 92.4% 90.0% 1.5 Relative reduction Relative reduction p < 0.0001 p < 0.0001 1 0.5 0.282 0.213 0 Teriflunomide Ublituximab Teriflunomide Ublituximab N = 270 N = 265 N = 267 N =
Slide 12: Confirmed Disability Progression (CDP)
Confirmed Disability Progression (CDP) Pre-specified pooled analysis Ublituximab Teriflunomide 12-week CDP 24-week CDP Proportion of Patients having CDP (%) Proportion of Patients having CDP (%) 10 10 Censored Censored 9 9 8 8 7 5.9% 7 6 6 4.8% 5 5 5.2% 4 4 3 3 3.3% 2 2 1 Hazard ratio (95% CI): 1 Ha
Slide 13: Confirmed Disability Improvement (CDI)
Confirmed Disability Improvement (CDI) Pre-specified pooled tertiary analysis Ublituximab Teriflunomide 12-week CDI 24-week CDI Proportion of Patients Achieving CDI (%) Proportion of Patients Achieving CDI (%) 20 20 Censored Censored 18 116% 18 103% 16 increase vs 16 increase vs 14 teriflunomide 12.
Slide 14: No Evidence of Disease Activity (NEDA)
No Evidence of Disease Activity (NEDA) ULTIMATE I ULTIMATE II 50 44.6% 45 43.0% Proportion of patients with 40 197% 277% 35 Improvement vs Improvement vs NEDA (%) 30 teriflunomide teriflunomide p < 0.0001 p < 0.0001 25 20 15.0% 15 11.4% 10 5 0 Teriflunomide Ublituximab Teriflunomide Ublituximab N =
Slide 15: MRI: Brain Volume Change
MRI: Brain Volume Change Baseline to Week 96 0.4 ULTIMATE I 0.4 ULTIMATE II Adjusted mean difference in slope Teriflunomide between W24 and W96 (95% CI): Teriflunomide Adjusted mean difference in slope Ublituximab 0.0001 (-0.0012, 0.0014) Ublituximab between W24 and W96 (95% CI): 0.2 0.2 0.0017 (0.0
Slide 16: MRI: Brain Volume Change (post-hoc analysis)
MRI: Brain Volume Change Week 24 to Week 96 (post-hoc analysis) 0 ULTIMATE I 0 ULTIMATE II Teriflunomide -0.2 Ublituximab -0.2 Mean PBVC -0.4 -0.4 -0.6 -0.6 -0.8 -0.8 24 48 72 96 24 48 72 96 Week Week 16 MRI modified Intent-to-Treat population (mITT-MRI) . PBVC: percent brain volume change from W24
Slide 17: Change from Baseline in Multiple Sclerosis Functional Composite (MSFC)
Multiple Sclerosis Functional Composite (MSFC) ULTIMATE I ULTIMATE II 0.6 76.4% 89.6% 0.521 0.5 Improvement vs 0.469 Improvement vs Change from Baseline in teriflunomide teriflunomide 0.4 p = 0.0484 p = 0.0171 MSFC Score 0.3 0.266 0.275 0.2 0.1 0 Teriflunomide Ublituximab Teriflunomide Ublituximab N
Slide 18: Adverse Events
Adverse Events Most common AEs, n (%) Teriflunomide Ublituximab ≥5% in any treatment group N=548 N=545 Any AE 486 (88.7) 483 (88.6) IRR 67 (12.2) 260 (47.7) Headache 138 (25.2) 165 (30.3) Nasopharyngitis 96 (17.5) 97 (17.8) Lymphopenia 5 (0.9) 51 (9.4) Back pain 53 (9.7) 48 (8.8) Respiratory tract i
Slide 19: Serious Adverse Events
Serious Adverse Events Teriflunomide Ublituximab SAEs, n (%) N = 548 N = 545 Any serious AEs 34 (6.2) 52 (9.5) Most common SAEs by SOC ≥1% in any treatment group Infections and infestations 14 (2.6) 22 (4.0) Nervous system disorders 7 (1.3) 5 (0.9) ▪ Three total malignancies were reported ▪ 2 ublitu
Slide 20: Infusion Related Reactions by Dose & Severity
Infusion Related Reactions by Dose & Severity 50 50 Teriflunomide Grade 4 Ublituximab Grade 3 0.2 2.2 40 Grade 2 40 Patients with IRR (%) Grade 1 16 30 30 20 20 25 10 0.2 10 0.2 3.1 3.9 0.2 3.0 3.3 1.4 6.4 0.2 0.2 2.9 0.8 0.6 0.6 5.4 5.1 3.5 3.7 0 0 1 3 24 48 72 1 3 24 48 72 N at risk Week N at risk
Slide 21: Proportion of Patients With Ig Levels <LLN
Proportion of Patients With Ig Levels <LLN 25 IgM IgG IgA Proportion of patients (%) 20.9 20 Teriflunomide Ublituximab 15 12.8 10 5.9 6.3 6.4 6.5 4.6 4.9 5.3 4.9 5 2.4 2.7 2.0 2.4 1.9 1.1 1.1 0.6 0 Baseline Week 48 Week 96 Baseline Week 48 Week 96 Baseline Week 48 Week 96 LLN Threshold LLN Threshold
Slide 22: Conclusions
Conclusions ▪ In the Phase III ULTIMATE I & II studies ublituximab met its primary endpoint of ARR and reduced MRI parameters compared with teriflunomide ▪ A very low rate of disability progression was observed with ublituximab, with >94% of patients showing no 12-week CDP, and >96% of patients show
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