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EX-99.1 - EXHIBIT 99.1 - TG THERAPEUTICS, INC. | v061417_ex991.htm |
EX-99.2 - EXHIBIT 99.2 - TG THERAPEUTICS, INC. | v061517_ex992.htm |
8-K - 8-K - TG THERAPEUTICS, INC. | v061617_8k.htm |
TG Therapeutics, Inc. Recaps Positive
Data from the Phase 3 GENUINE Trial and Data from the Triple
Combination of TG-1101, TGR-1202, and Ibrutinib at the
14th
International Conference on Malignant
Lymphoma
GENUINE Phase 3 trial met its primary endpoint with TG-1101
(ublituximab) plus ibrutinib increasing Overall Response Rate (ORR)
by >70% over ibrutinib alone in patients with high-risk
CLL
Triple combination of TG-1101, TGR-1202 and ibrutinib produced 100%
ORR (19 of 19) in patients with CLL/SLL, including 32% CR rate,
with a favorable safety profile observed
NEW YORK, June 16, 2017-- TG Therapeutics, Inc. (NASDAQ: TGTX),
today recapped clinical data from its Phase 3 GENUINE trial of
TG-1101 (ublituximab), the Company’s novel glycoengineered
anti-CD20 monoclonal antibody in combination with Ibrutinib, the
BTK inhibitor, as well as data from the chemo-free triple
combination of TGR-1202 (umbralisib), the Company’s oral,
next generation PI3K delta inhibitor, TG-1101, and ibrutinib. Data
from these trials were presented today during oral sessions at the
14th
International Conference on Malignant
Lymphoma (ICML) in Lugano, Switzerland. These data sets were
presented previously at the American Society of Clinical Oncology
(ASCO) annual meeting earlier this month. Highlights from each of
these data sets are included below.
Michael S. Weiss, the Company’s Executive Chairman and Chief
Executive Officer stated, “CLL patients with high-risk
cytogenetics continue to represent a challenge and continue to
progress more rapidly on ibrutinib than other patients. Improving
ibrutinib therapy for these hard to treat patients still represents
an unmet medical need. We are pleased to be the first Company to
demonstrate in a randomized Phase 3 trial an approach to
potentially improve outcomes for those patients. As presented today
at ICML, and last week at ASCO, the GENUINE Phase 3 trial showed
that by adding TG-1101 to ibrutinib, we could improve overall
response rate, CR rate, and MRD negativity in high risk patients.
We believe the data provide a compelling case for accelerated
approval given the demonstrated clinical benefit with limited
additional safety risk, and we look forward to sharing these data
formally with the FDA later this year.” Mr. Weiss continued,
“Additionally, at ICML today, and last week at ASCO, we had
an opportunity to present data on a triple therapy where we layered
our proprietary PI3K-delta inhibitor, TGR-1202, to the TG-1101 plus
Ibrutinib combination, and demonstrated even further enhanced
activity, with 100% ORR by iwCLL criteria and a high level of
complete responses. These data further confirm our approach of
building toward multi-drug regimens to enhance the outcome for
patients, ideally achieving CRs and avoiding lifelong therapy. We
look forward to continuing to explore unique combinations, with
TG-1101 (ublituximab) plus TGR-1202 (umbralisib) or
‘U2’ as the backbone.”
Highlights from today’s presentations include the
following:
Oral Presentation:
Ublituximab and ibrutinib for previously treated genetically
high-risk chronic lymphocytic leukemia: Results of the GENUINE
Phase 3 study (Abstract #101)
This
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
approximately 20%.
The
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
One
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
arm was 3.
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
months.
Clinical Activity
Response Rates
|
TG-1101 plus
Ibrutinib
|
Ibrutinib
|
P-value
|
Treated Population
(n)
|
n=59
|
n=58
|
|
Overall Response
Rate (ORR)
|
78%
|
45%
|
P<0.001
|
Complete Response
(CR)
|
7%
|
0%
|
NS
|
MRD-Negative
|
19%
(n=53) *
|
2%
(n=53) *
|
P<0.01
|
*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
In
addition to the improvements in ORR, CR, and MRD-negativity, a
trend in improvement of Progression-Free Survival (PFS) in the
combination arm of TG-1101 plus ibrutinib as compared to ibrutinib
alone, however it was not statistically significant at the time of
the analysis.
ABOUT THE PHASE 3 GENUINE STUDY
The Phase 3 GENUINE study is a randomized, open label, multicenter
clinical trial to evaluate the safety and efficacy of TG-1101
(ublituximab) plus ibrutinib compared to ibrutinib alone in adult
patients with high risk Chronic Lymphocytic Leukemia (CLL) who
received at least one prior therapy for their disease.
The study was conducted at 160 clinical trial sites in the US and
Israel and randomized 126 patients. Patients received ibrutinib
orally at 420 mg once daily in both arms and in the treatment arm
those patients also received intravenous infusions of TG-1101 at
900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles
2-6. Patients in the treatment arm who had not progressed received
quarterly infusions of TG-1101 maintenance at 900 mg.
Oral Presentation:
Chemo-free triplet combination of TGR-1202, ublituximab, and
ibrutinib is well tolerated and highly active in patients with
advanced CLL and NHL (Abstract #102)
This oral presentation includes data from patients with Chronic
Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and
Non-Hodgkin’s Lymphoma (NHL) treated with the triple
combination of TGR-1202, TG-1101 and ibrutinib. All patients were
relapsed or refractory to prior therapy, except 3 CLL patients who
were treatment naïve. Three cohorts for each CLL/SLL
and NHL were evaluated with TGR-1202 dose escalation
starting with doses of 400 mg (cohort 1), followed by 600 mg
(cohort 2) and 800 mg (cohort 3), in combination with TG-1101 at
900 mg and ibrutinib daily at 420 mg (CLL) and 560 mg
(NHL).
Safety & Tolerability
Thirty-eight (38) patients were evaluable for safety (20 CLL/SLL
patients, and 18 NHL patients). The triple combination appeared to
be well tolerated in all patients, with neutropenia (32% all
grades, 18% Grade 3/4) and pneumonia (18% all grades, 11% Grade
3/4), being the only Grade 3/4 AEs in >10% of patients. Of the
38 patients treated to date, only two AEs (sepsis and pneumonia)
led to treatment discontinuation. Median time on study was 11.1
months (range 0.4 – 30+ months) with 81% of patients on study
>6 months.
Clinical Activity
Clinical activity was observed at all dose levels with 36 of 38
patients evaluable for efficacy (19 CLL/SLL patients, and 17 NHL
patients), with 2 patients having discontinued prior to first
efficacy assessment (1 pneumonia, and 1 investigator
discretion).
CLL/SLL Efficacy highlights include:
●
100%
(19 of 19) Overall Response Rate (ORR), including a 32% Complete
Response (CR) rate observed in patients with CLL/SLL (4 of 6
CR’s pending bone marrow confirmation)
●
50%
of the CLL patients had a 17p and/or 11q deletion
●
3
CLL patients had prior BTK and/or PI3Kd inhibitor therapy,
including one patient refractory to both idelalisib and ibrutinib
who attained a complete response (ongoing for 1.5+
years)
NHL Efficacy highlights include:
●
Response
Rates observed in patients with NHL:
o
100%
(2 of 2) ORR, including one CR in patients with Marginal Zone
Lymphoma (MZL)
o
100%
(4 of 4) ORR, including 50% CR rate in patients with Mantle Cell
Lymphoma (MCL)
o
80%
(4 of 5) ORR, including 20% CR rate in patients with Follicular
Lymphoma (FL)
o
17%
(1 of 6) ORR in patients with Diffuse Large B-cell Lymphoma
(DLBCL)
●
FL
patients were heavily pretreated including 2 with prior Autologous
Stem Cell Transplant (ASCT), 1 refractory to prior ibrutinib, and 1
with 5 prior lines of rituximab based therapy
●
DLBCL
patients had a median of 4 prior therapies, and 4 of 6 were of
non-GCB subtype
PRESENTATION DETAILS:
The
above referenced presentations are now available on the
Publications page, located within the Pipeline section, of the
Company’s website at
www.tgtherapeutics.com/publications.cfm.
ABOUT TG THERAPEUTICS, INC.
TG Therapeutics is a biopharmaceutical company focused on the
acquisition, development and commercialization of novel treatments
for B-cell malignancies and autoimmune diseases. Currently, the
company is developing two therapies targeting hematological
malignancies and autoimmune diseases. TG-1101 (ublituximab) is a
novel, glycoengineered monoclonal antibody that targets a specific
and unique epitope on the CD20 antigen found on mature
B-lymphocytes. TG Therapeutics is also developing
TGR-1202 (umbralisib), an orally available PI3K delta inhibitor.
The delta isoform of PI3K is strongly expressed in cells of
hematopoietic origin and is believed to be important in the
proliferation and survival of B‐lymphocytes. Both TG-1101 and
TGR-1202 are in clinical development for patients with hematologic
malignancies, with TG-1101 also in clinical development for
autoimmune disorders. The Company also has pre-clinical programs to
develop IRAK4 inhibitors, BET inhibitors, and anti-PD-L1
and anti-GITR antibodies. TG Therapeutics is
headquartered in New York City.
Cautionary Statement
Some of the statements included in this press release may be
forward-looking statements that involve a number of risks and
uncertainties. For those statements, we claim the protection
of the safe harbor for forward-looking statements contained in the
Private Securities Litigation Reform Act of 1995. In addition
to the risk factors identified from time to time in our reports
filed with the Securities and Exchange Commission, factors
that could cause our actual results to differ materially are the
following: the risk that early clinical trial results, that may
have supported the acceptance of our data for presentation or
influenced our decision to proceed with additional clinical trials,
will not be reproduced in future studies; the risk that the
combination of TG-1101 and TGR-1202, referred to as TG-1303 and
being studied in the chemo-free triple combination of TG-1101 plus
TGR-1202 plus ibrutinib and in the UNITY clinical trials and other
combination trials, will not prove to be safe and efficacious for
any indication or as a backbone for current or future triple and/or
quad therapies; the risk that even if the company is successful in
developing its drugs through FDA approval and on to the market,
that the cost efficiencies anticipated through proprietary
combinations may not be realized in the marketplace. Any
forward-looking statements set forth in this press release speak
only as of the date of this press release. We do not undertake to
update any of these forward-looking statements to reflect events or
circumstances that occur after the date hereof. This press release
and prior releases are available at www.tgtherapeutics.com.
The information found on our website is not incorporated by
reference into this press release and is included for reference
purposes only.
TGTX -
G
CONTACT:
Jenna
Bosco
Vice President,
Investor Relations
TG Therapeutics,
Inc.
Telephone:
212.554.4351
Email: ir@tgtxinc.com