NASDAQ: TGTX Jefferies Healthcare Conference June 2015

Transcription

1 NASDAQ: TGTX Jefferies Healthcare Conference June 2015

2 Forward Looking Safe Harbor Statement This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 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 or phrases. Such statements involve risks and uncertainties that could cause TG Therapeutics actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in clinical trials, drug development, and commercialization. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and TG Therapeutics undertakes no obligation to update these statements, except as required by law. 2

3 TG Therapeutics, Inc. Leaders in developing drugs for B-cell cancers CLL and NHL as well as B-cell disorders (e.g. RA, MS, Lupus) Pipeline designed for multiple combinations for best outcomes: TG-1101 Novel glycoengineered, anti-cd20 monoclonal antibody Phase 3 in combination with ibrutinib pursuant to SPA TGR-1202 Once-daily PI3Kδ inhibitor The once-daily PI3Kδ inhibitor; with potential best in class safety and tolerability profile IRAK4 Key signaling pathway independent of B-cell receptor Potential for synergistic combinations with other pipeline products Anti-PDL1 and Anti-GITR Antibody Research Programs Potential to engage T-cells to kill malignant B-cells 3

4 The Malignant B-cell is the Enemy Attacking multiple targets for better outcomes 4

5 Initial Phase 3 Development Plan Overview TG-1101 ibrutinib TG ibrutinib Phase 3: Rel/Ref CLL TG-1101 TGR-1202 TG-1303 Phase 3: CLL DLBCL inhl 5

6 Phase II: TG ibrutinib Safety All Causality AE s in > 5% of Patients (n=54) Adverse Event All Grades Grade 3/4 n (%) n (%) Infusion reaction 18 (33%) 3 (6%) Diarrhea 15 (28%) 2 (4%) Fatigue 14 (26%) 1 (2%) Rash 11 (20%) 2 (4%) Bruising 8 (15%) - Nausea 8 (15%) - Mucositis 8 (15%) - Cough 7 (13%) - Edema 7 (13%) - Fever 6 (11%) - Thrombocytopenia 6 (11%) 2 (4%) Neutropenia 3 (6%) 3 (6%) All rash and Grade 3/4 diarrhea events deemed related to ibrutinib per investigator assessment Dose Reductions & Treatment Discontinuations Ibrutinib dose reduced in 4 patients (diarrhea, rash, cough, fatigue) No patients had their ublituximab dose reduced 2 patients discontinued due to ibrutinib related AEs (rash, diarrhea) 2 patients discontinued due to non-related AEs (pre-existing AE s) Sharman et al, ASH

7 Phase II: TG ibrutinib Efficacy From ibrutinib label: The ORR was 58.3% (95% CI: 43.2%, 72.4%), all partial responses. None of the patients achieved a complete response * CR pending BM confirmation 30% of patients were considered anti-cd20-refractory, progressing on or within 6 months of an anti-cd20 based regimen, including: Rituximab Ofatumumab Obinutuzumab 7

8 Phase III Clinical Trial TG ibrutinib Phase 3 Clinical Trial Design, Endpoints, and Statistics agreed to via Special Protocol Assessment (SPA) Enrolling ~330 patients with high-risk CLL, anticipated months to complete ORR amongst first 200 patients for accelerated approval PFS amongst all enrolled patients for full approval Study Chair: Dr. Jeff Sharman Currently 90 sites open, over 100 sites expected 8

9 TGR-1202: Novel PI3Kδ (delta) Inhibitor TGR-1202 Idelalisib (GS-1101) Duvelisib (IPI-145) F F O F O Cl O O O N N H 2 N F N N N N N NH N N HN N N NH N N HN QD BID BID Highly selective to PI3K delta isoform PK profile that allows once-daily oral dosing Best-in-class safety profile 9 1 Burris et al, ASCO 2015

10 Phase I Single Agent TGR-1202 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 14% 1 2% Hypokalemia 9 14% 3 5% Anemia 8 12% 5 8% Dizziness 8 12% 0 0% Dyspnea 8 12% 3 5% Neutropenia 8 12% 7 11% Pyrexia 8 12% 0 0% Abdominal Pain 7 11% 0 0% Limited Gr. 3/4 events and no significant dose or time dependent trends in AEs observed with 31 patients on study 6+ months 3 patients (< 5%) have discontinued due to an adverse event, none of which for hepatic toxicity, colitis, or pneumonitis 10 Burris et al, ASCO 2015

11 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 15) 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%) 36% (10%) 26% (1%)** Pneumonia 17% (13%) N/A 24% (16%) 7% (4%) ALT Elevations N/A N/A 43% (11%) 2% (2%) AST Elevations N/A N/A 34% (7%) 4% (2%) ALT/AST Elevations 35% (13%) 28% (17%) N/A 3% (2%) Discontinuations due to AE ** No observed instances of colitis 31% 33% 12% 4% 11 1 Aggregated from Idelalisib Prescribing Information 2 Jones et al, ASCO Patel et al, ASCO Aggregated from Burris et al, Lunning et al, Fowler et al, ASCO 2015

12 Room for Improvement Idelalisib Prescribing Information July 2014 Avoid concurrent use of Zydelig with other drugs that may cause liver toxicity. Monitor ALT and AST in all patients every 2 weeks for the first 3 months of treatment, every 4 weeks for the next 3 months, then every 1 to 3 months thereafter. Monitor weekly for liver toxicity if the ALT or AST rises above 3 times the upper limit of normal until resolved 12

13 Single Agent TGR-1202 Efficacy in All Patients Best Percent Change from Baseline in Nodal Size All Patients Evaluable for Efficacy (N=51) High level of activity demonstrated across a wide variety of hematologic malignancies 13 Burris et al, ASCO 2015

14 Single Agent TGR-1202 Efficacy in CLL & FL Best Percent Change from Baseline in Nodal Size Evaluable CLL & FL Patients Treated at Higher Doses FL CLL Higher Doses of TGR-1202 (1200 mg initial formulation, or 600 mg micronized) demonstrated rapid and profound responses 14 Burris et al, ASCO 2015

15 TG TGR-1202 (aka TG-1303): Trial Design/Demographics TG-1101 TGR-1202 CLL: 600mg NHL: 900mg 800mg Completed CLL: 600mg NHL: 900mg 900mg 900mg 900mg 900mg 1200mg 400mg micronized 600 mg micronized 800 mg micronized 1200 mg micronized Completed Completed Completed Completed Completed Currently Enrolling Expansion Cohorts CLL: 800 mg micronized NHL: 1200 mg micronized 15

16 TG TGR-1202 (aka TG-1303): Safety Related AE s Occurring in 5% of Patients (n = 55) Adverse Event All Grades Grade 3/4 N % N % Infusion Related Reaction 16 29% 1 2% Neutropenia 15 27% 13 24% Nausea 15 27% - - Diarrhea 11 20% 1 2% Fatigue 10 18% - - Vomiting 6 11% - - Abd. Pain/Discomfort 4 7% - - Muscle Cramping 4 7% - - Anemia 3 5% - - Bruising 3 5% - - Hoarseness 3 5% - - Thrombocytopenia 3 5% patients (~5%) have come off study due to an adverse event, none related to hepatic toxicity or colitis Safety Profile supports additional combination regimens 16 Lunning et al, ASCO 2015

17 TG TGR-1202 (aka TG-1303) Efficacy CLL/SLL Patients Treated at the Higher Doses of TGR-1202 Type Best Percent Change from Baseline in Nodal Size Pts 25% 0% -25% -50% -75% -100% On Study CLL/SLL TGR-1202 Higher* Doses CR PR ORR n (%) SD PD Type Pts 70% of CLL patients had high-risk cytogenetics (17p del and/or 11q del) TGR-1202 Lower** Doses CR PR ORR n (%) CLL/SLL (83%) 1 - CLL/SLL (57%) 3 - DLBCL (43%) 3 1 DLBCL FL/MZL (64%) 4 - FL/MZL (25%) 3 - Richter s (100%) - - Richter s Overall (64%) 8 1 Overall (36%) 7 2 *Higher Dose = 1200 original formulation and 600 or > micronized SD **Lower Dose = 800 original formulation and 400 micronized 17 PD Lunning et al, ASCO 2015

18 TG TGR-1202 (aka TG-1303) Higher Doses NHL 25% 0% Patients Treated at the Higher Doses of TGR-1202 Best Percent Change from Baseline in Nodal Size Indolent NHL DLBCL RT G -25% -50% G G -75% -100% On Study G = GCB G G TGR-1202 Higher* Doses Type Pts CR PR ORR n (%) SD PD CLL/SLL (83%) 1 - DLBCL (43%) 3 1 FL/MZL (64%) 4 - Richter s (100%) - - Overall (64%) *Higher Dose = 1200 original formulation and 600 or > micronized Lunning et al, ASCO 2015

19 Triplet : TG TGR ibrutinib Ibrutinib TG-1101 TGR-1202 CLL 420mg + 900mg mg micro Enrolled mg micro Pending mg micro Pending NHL 560mg + 900mg mg micro Completed mg micro Completed mg micro Completed 19 Fowler et al, ASCO 2015

20 TG TGR Ibrutinib Demographics Evaluable for Safety 16 Evaluable for Efficacy 13 Median Age, years (range) 63 (51 85) Male/Female 12/4 ECOG, 0/1/2 5/8/3 Prior Treatment Regimens, median (range) 4 (1 5) Histologies 4 CLL 1 SLL 4 Follicular 1 MZL 3 DLBCL 2 MCL 1 Richter s Transformation 100% of CLL had 17p and/or 11q del 4/5 FL/MZL pts had > 4 prior lines of treatment 1 ibrutinib refractory 1 duvelisib refractory 2/3 DLBCL were ABC subtype and had > 4 prior lines of treatment 2 Prior R Chemo Regimens, n 13 (81%) Refractory to Prior Therapy, n 8 (50%) 1 removed per investigator discretion and 2 too early to evaluate 20 Fowler et al, ASCO 2015

21 TG TGR Ibrutinib Safety AE s (at least possibly related) in > 1 Patient N=16 All Grades Grade 3/4 Adverse Event n (%) n (%) Infusion reaction 4 (25%) - Diarrhea 3 (19%) - Nausea 3 (19%) - Fatigue 3 (19%) - Rash 3 (19%) - Anemia 2 (13%) - Neutropenia 2 (13%) 1 (6%) Leukopenia 2 (13%) 1 (6%) Insomnia 2 (13%) - Minimal adverse events with Grade 3 or 4 events seen in 6% of patients No patients discontinuing treatment due to an adverse event up through 800 mg micronized TGR-1202 Patients remaining on treatment now up to 9.5+ months 21 Fowler et al, ASCO 2015

22 TG TGR Ibrutinib Efficacy 25% BEST PERCENT CHANGE FROM BASELINE IN DISEASE BURDEN 0% -25% ABC ABC * * * * * * * * * * (4.5) (2.5) (3.5) (7) (9.5) (4.5) (7) (8) (7) (9.5) -50% -75% -100% * On Study (X) Months On Study PR PR PR PR PR PR PR PR CR Richter's DLBCL DLBCL FL CLL MCL FL FL CLL MZL CLL SLL MCL 100% (4/4) ORR in CLL/SLL patients at first efficacy assessment, all with 17p deletion 75% (3/4) ORR in heavily pre-treated ( 4 prior lines of therapy) Follicular or Marginal Zone lymphoma patients 22 Fowler et al, ASCO 2015

23 2015 Milestones Q H H H H H H 2015 Q Commence Phase 3 trial of TG-1101 plus Ibrutinib in High-Risk CLL Present updated clinical data at ASCO, EHA & Lugano Initiate 2 nd Phase 3 clinical trial Initiate at least one additional triple therapy clinical trial Initiate first clinical trial in Autoimmune Diseases Advance IRAK-4 inhibitor program into the clinic Initiate a 3 rd Phase 3 clinical trial Present updated clinical data at ASH

24 Corporate & Financial Key Financial Statistics Ticker: TGTX (NasdaqCM) Price: $16.38 (close as of June 1, 2015) Shares: ~48M (Primary); ~52M (fully-diluted) Cash: ~$113M (pro forma as of March 31, 2015) Burn: $6-$8M per quarter Time: 2+ years of cash 24

25 Key Takeaways TG-1101 Phase 3 in Combination with ibrutinib High probability of success, supported by strong Phase 2 data Conducted pursuant to SPA Very attractive regimen: tolerability and efficacy Proprietary combination entering Phase 3 in 2015 Safety and efficacy profile at higher doses could be best-in-class combination across CLL and NHL Pricing leverage Additional upside in autoimmune diseases and leadership in next generation triple therapy BTK underway, IRAK4 before YE, others? 25

26 NASDAQ: TGTX