Blueprint TG Therapeutics Announces Positive Data from Phase 3 GENUINE Trial of TG-1101 in Combination with Ibrutinib in Patients with High Risk Chronic Lymphocytic Leukemia at the 53rd Annual Meeting of the American Soc

TG Therapeutics Announces Positive

Data from Phase 3 GENUINE Trial of TG-1101 in Combination with

Ibrutinib in Patients with High Risk Chronic Lymphocytic Leukemia

at the 53rd Annual Meeting of the American Society of

Study met its primary endpoint with TG-1101 (ublituximab) plus

ibrutinib increasing Overall Response Rate (ORR) by >70% over

TG-1101 plus ibrutinib achieved 78% ORR, with 7% Complete Responses

(CR), compared to 45% ORR with 0% CR's for Ibrutinib Alone,

p<0.001 (median follow-up 11.4 months), with all responses now

confirmed as per iwCLL 2008 criteria

Combination of TG-1101 and ibrutinib resulted in 19% Minimal

Residual Disease (MRD) negativity compared to 2% for Ibrutinib

A trend in improvement of PFS was observed with the combination of

TG-1101 plus ibrutinib compared to ibrutinib alone (Hazard

The combination was well tolerated and TG-1101 did not appear to

alter the safety profile of ibrutinib monotherapy, apart from

infusion related reactions associated with TG-1101 which were

New York, NY, June 3, 2017 TG Therapeutics

(NASDAQ: TGTX) today announced positive results from its Phase 3

GENUINE trial of TG-1101 (ublituximab) plus ibrutinib in patients

with previously treated high risk Chronic Lymphocytic Leukemia

(CLL). Data from this trial was presented today

Jeff Sharman, Medical Director, Hematology Research, US Oncology in

an oral session during the 53rd

American Society of Clinical Oncology

(ASCO) Annual Meeting in Chicago, IL.

Michael S. Weiss, Executive Chairman and Chief Executive Officer of

TG Therapeutics stated, Patients with high-risk CLL have the

poorest outcomes on ibrutinib and are in need of a more efficacious

treatment. We believe the data presented today demonstrate that the

addition of TG-1101 to ibrutinib improves patient outcomes across

multiple measures. Mr. Weiss continued, In addition

to increasing the overall number of patients that responded to

treatment with ibrutinib, adding TG-1101 to ibrutinib increased the

number of patients with bone marrow confirmed CR's, MRD

negativity in peripheral blood, deepened nodal responses, and

resulted in fewer patients progressing on therapy. Collectively, we

see the consistent pattern of enhanced benefit as providing a

compelling case for combining TG-1101 with ibrutinib in these hard

to treat patients with high-risk CLL. We look forward to sharing

these data with the FDA later this year to discuss filing for

accelerated approval. We would like to thank our investigators and

their patients for their participation in this important clinical

Highlight's from this presentation include the

Oral Presentation: Ublituximab and ibrutinib for previously treated

genetically high-risk chronic lymphocytic leukemia: Results of the

GENUINE Phase 3 study

presentation includes data from the GENUINE Phase 3 trial, a

multicenter, randomized trial (NCT02301156), which assessed the

efficacy and safety of TG-1101 plus ibrutinib versus ibrutinib

alone in patients with high risk CLL. For the trial, high-risk was defined as having any

one or more of the following centrally confirmed features: 17p

deletion, 11q deletion or p53 mutation. The GENUINE study

was designed to demonstrate the value of adding TG-1101, a potent

next generation glycoengineered anti-CD20 monoclonal antibody to

ibrutinib monotherapy in high-risk CLL, and was powered to show a

statistically significant improvement in ORR of 30%, with a minimal

absolute detectable difference between the two arms of

trial met its primary endpoint, demonstrating a statistically

significant improvement in Overall Response Rate (ORR), as assessed

by blinded independent central radiology and hematology review

by iwCLL (Hallek 2008) criteria, compared to ibrutinib alone in

both the Intent to Treat (ITT) population (p=0.001) and Treated

population (p<0.001). Per iwCLL guidelines, all responders

required confirmation of response for a minimum duration of 2

months. The ITT population includes all 126 randomized patients (64

in the TG-1101 plus ibrutinib arm and 62 in the ibrutinib alone

arm) while the Treated population includes all ITT patients that

received at least one dose of either study drug (59 in the TG-1101

plus ibrutinib arm and 58 in the ibrutinib alone arm).

Patient Demographics

hundred and twenty-six (126) patients were randomized on the

GENUINE Phase 3 trial. 100% of patients were high-risk and had

either 17p deletion, 11q deletion, or p53 mutation. Sixty-four

percent (64%) of patients in the TG-1101 plus ibrutinib arm and 66%

of patients in the Ibrutinib alone arm had 17p deletion and/or a

p53 mutation while 36% and 34% of patients in the TG-1101 plus

ibrutinib and ibrutinib alone arms, respectively, had an 11q

deletion only. The median age of patients on either arm was 67

years and the median number of prior lines of therapy for either

Safety & Tolerability

One hundred and seventeen (117) patients were evaluable for safety

(59 patients in the TG-1101 plus ibrutinib arm, and 58 patients in

the ibrutinib alone arm). The combination was well tolerated and,

apart from infusion related reactions, the addition of TG-1101 did

not appear to alter the safety profile of ibrutinib monotherapy.

Neutropenia, occurring in 9% of patients, was the most commonly

reported Grade 3/4 Adverse Event (AE) in the combination arm,

followed by infusion related reactions and anemia, each reported in

5% of patients. Notably, the majority of infusion related reactions

(IRR) were Grade 1 or 2 in severity, with only 5% Grade 3/4 IRR

observed. Median follow-up for this study was approximately 11.4

*Patients evaluable for MRD included those enrolled >4 months

prior to data cutoff date of February 15, 2017. MRD analyzed by

central lab, 7-color flow cytometry

addition to the improvements in ORR, CR and MRD-negativity, a trend

in improvement of Progression Free Survival (PFS) was observed in

the combination arm of TG-1101 plus ibrutinib as compared to

ibrutinib alone (Hazard Ratio = 0.559; p=NS).