TetraLogic Pharmaceuticals Announces Selection of Phase 2 Dose for Randomized Clinical Study of Birinapant in Combination Wit...
May 27 2014 - 6:30AM
TetraLogic Pharmaceuticals Corporation (Nasdaq:TLOG) today
announced that, based upon data from its Phase 1b study of
birinapant in combination with azacitidine in patients with
relapsed/refractory or naïve higher risk MDS, it selected a dose of
13mg/m2 twice weekly for three weeks out of four to be used in its
Phase 2 clinical trial. The primary objective of the Phase 1b
clinical study is to characterize the safety and tolerability and
determine the recommended phase 2 dose of birinapant when
administered in combination with azacitidine. Additional
objectives of the study are to assess any preliminary indications
of efficacy and pharmacodynamics of the combination.
Based on the currently available data, no dose limiting
hematological toxicities of the combination have been
reported. A number of patients who received subcutaneous
azacitidine experienced local injection site skin
reactions/cellulitis. Although a known effect of azacitidine,
several of these were considered to be of increased severity with
the combination, possibly reflecting a localized synergistic
pharmacodynamic effect in the skin. This toxicity should be
mitigated by the use of IV azacitidine as no patient whose route of
administration has been changed to IV azacitidine experienced
further injection site cellulitis.
Birinapant, at the selected phase 2 dose, achieved inhibition of
NFkB in circulating blast cells. Although too early to detect
durable responses, preliminary data from the first nine evaluable
subjects enrolled into the Phase 1b study have shown the following:
one subject who received one prior cycle of azacitidine as a single
agent showed a bone marrow blast count reduction from 25% to 2% at
the end of cycle 1; one subject naïve to azacitidine showed a bone
marrow blast count reduction from 17% to 2% at the end of cycle 3
and is now scheduled to undergo a hematopoietic stem cell
transplant; and one subject refractory to single agent azacitidine
showed a bone marrow blast count reduction from 21% to 7% at the
end of cycle 2.
"Although this study is continuing to accrue patients, we are
proceeding with a randomized Phase 2 study to directly compare the
efficacy and safety of birinapant and azacitidine to azacitidine
alone in first line higher risk MDS patients," said Dr. Lesley
Russell, TetraLogic's Chief Operating Officer and Chief Medical
Officer. "We believe that the data showing inhibition of NFkB
in leukemic cells demonstrates that birinapant, at a dose of
13mg/m2 twice weekly for three weeks out of four, is
pharmacologically active and should have an acceptable tolerability
profile when administered with IV azacitidine. The fact that
we have also seen signs of early activity in terms of bone marrow
blast count reductions provides additional rationale to test this
combination in a randomized study."
About MDS
The myelodysplastic syndromes (MDS) are hematological conditions
with ineffective production (or dysplasia) of the myeloid class of
blood cells. The exact number of people with MDS is not known
because it can go undiagnosed and there is no mandated tracking of
the syndrome. Some estimates are on the order of 10,000 to 20,000
new cases each year in the United States alone. The outcome
is poor, and without treatment, most patients will progress within
a few months to refractory acute myeloid leukemia. The median
survival rate varies from years to months, depending on
type. Stem cell transplantation offers cure, with survival
rates of 50% at 3 years, although older patients do poorly.
Azacitidine (approved under the proprietary name Vidaza®) is
a hypomethylating agent (HMA) approved worldwide for the treatment
of patients with MDS, CMMoL and acute myelogenous leukemia (AML).
Even though this therapy has significantly improved outcomes
in patients with MDS, less than half achieve objective responses,
and most responders lose response within 1 to 2 years. As a
result there continues to be a great unmet need for effective
therapies specifically targeted to treat higher risk (i.e.,
intermediate-2 or high-risk disease as classified by the
International Prognostic Scoring System (IPSS)) MDS and CMMoL
patients. The improved understanding of the biologic
underpinnings of MDS has encouraged further development of
investigational agents that could target disrupted molecular
pathways critical to its pathogenesis. Combination treatment
strategies using an azacitidine backbone may demonstrate promising
response and survival outcomes.
About Birinapant
Birinapant (TL32711) is a potent, bivalent SMAC-mimetic that
binds with differential affinity to multiple members of the IAP
family including cIAP1, cIAP2, XIAP, and ML-IAP. Birinapant is
differentiated from other SMAC-mimetics in that it results in the
selective degradation of cIAP1 bound to TRAF-2 in the TNF receptor
complex, sparing non‑TRAF-2 bound cIAP1. This unique IAP antagonism
profile of birinapant may result in the improved tolerability and
therapeutic index observed with this agent.
About TetraLogic
TetraLogic is a clinical-stage biopharmaceutical company focused
on discovering and developing novel small molecule therapeutics in
oncology and infectious diseases. TetraLogic has two
clinical-stage product candidates in development: birinapant and
suberohydroxamic acid phenyl ester (SHAPE). Birinapant is
currently being tested in Phase 1 and Phase 2 clinical trials for
hematological malignancies and solid tumors. SHAPE is
entering Phase 2 trials for early-stage CTCL.
Forward Looking Statements
Some of the statements in this release are forward-looking
statements within the meaning of Section 27A of the Securities Act
of 1933, Section 21E of the Securities Exchange Act of 1934 and the
Private Securities Litigation Reform Act of 1995, which involve
risks and uncertainties. These statements relate to future
events or TetraLogic's pre-clinical and clinical development of
birinapant, SHAPE and other clinical programs, future expectations,
plans and prospects. Although TetraLogic believes that the
expectations reflected in such forward-looking statements are
reasonable as of the date made, expectations may prove to have been
materially different from the results expressed or implied by such
forward-looking statements. TetraLogic has attempted to
identify forward-looking statements by terminology including
''believes,'' ''estimates,'' ''anticipates,'' ''expects,''
''plans,'' ''projects,'' ''intends,'' ''potential,'' ''may,''
''could,'' ''might,'' ''will,'' ''should,'' ''approximately'' or
other words that convey uncertainty of future events or outcomes to
identify these forward-looking statements. These statements
are only predictions and involve known and unknown risks,
uncertainties, and other factors, including those discussed under
the heading "Risk Factors" in our Annual Report on Form 10-K filed
with the Securities and Exchange Commission on March 19,2014 and
our Quarterly Report of Form 10-Q filed with the Securities and
Exchange Commission on May 8,2014. Any forward-looking
statements contained in this release speak only as of its
date. We undertake no obligation to update any
forward-looking statements contained in this release to reflect
events or circumstances occurring after its date or to reflect the
occurrence of unanticipated events.
CONTACT: Company Contact:
Pete A. Meyers
Chief Financial Officer and Treasurer
TetraLogic Pharmaceuticals Corporation
(610) 889-9900, x103
pete.meyers@tlog.com
Investor Relations Contact:
Ami Bavishi
Burns McClellan, Inc.
(212) 213-0006
abavishi@burnsmc.com
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