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8-K - Molecular Templates, Inc. | v206391_8k.htm |
Exhibit
99.1
PRESS
RELEASE
|
Contact:
Denise T.
Powell
Sr.
Director, Corporate Communications
Threshold
Pharmaceuticals, Inc.
650-474-8206
dpowell@thresholdpharm.com
THRESHOLD
PHARMACEUTICALS ANNOUNCES PROMISING EARLY PHASE 1 CLINICAL TRIAL RESULTS IN
PATIENTS WITH ADVANCED LEUKEMIAS
Company
Also Starts Preclinical Leukemia Collaboration with MD Anderson Cancer
Center
REDWOOD
CITY, CA – December 22, 2010 — Threshold Pharmaceuticals, Inc. (Nasdaq: THLD),
today announced a preclinical collaboration with the MD Anderson Cancer Center
and early Phase 1 clinical trial results of TH-302 in patients with advanced
leukemias, which is also taking place at MD Anderson. TH-302 is a proprietary
Hypoxia-Activated Prodrug (HAP) that specifically targets tumor
hypoxia.
The
objectives of the Phase 1 trial are to determine the maximum tolerated dose
(MTD), dose limiting toxicity (DLT), safety, tolerability, clinical activity and
pharmacokinetics of TH-302 in patients with advanced leukemia. Eleven patients
with either acute myelogenous leukemia (AML) or acute lymphoblastic leukemia
(ALL) have been enrolled in the trial to date. The starting dose in the trial
was 120mg/m2 daily
for 5 days of a 21-day cycle. The second dose cohort was treated with TH-302 at
a dose of 170mg/m2 and the
third dose cohort has completed enrollment at 240mg/m2. The
dose of TH-302 will continue to be escalated until the MTD is established. To
date no DLTs have been reported in any of the dose cohorts. Preliminary efficacy
assessments have demonstrated activity in multiple subjects with
relapsed/refractory AML and ALL as evidenced by stabilization or reduction of
bone marrow blast counts.
"In the
initial three dosing cohorts, TH-302 has been well tolerated with no significant
drug related toxicities," said Dr. Deborah Thomas, M.D., Associate Professor in
the Department of Leukemia at MD Anderson Cancer Center. "We look forward to
further assessing the safety and efficacy of TH-302.”
The
preclinical collaboration is being conducted with Dr. Marina Konopleva,
M.D., Ph.D, Associate Professor in the Department of Leukemia at MD Anderson
Cancer Center. The research collaboration will focus on characterizing the
therapeutic efficacy of TH-302 as monotherapy and in combination with
conventional chemotherapeutics in both in vitro and in vivo models of
leukemia.
"There is
already a strong preclinical rationale to evaluate TH-302 in leukemia patients,"
said Dr. Charles Hart, Ph.D., Threshold’s Vice President of Biology. "While we
continue to explore the proof of concept in the ongoing human clinical trial, we
also want to fortify the preclinical basis for selectively targeting the hypoxic
niches in leukemic bone marrow as a therapeutic strategy. Greater understanding
may lead to the identification of specific patient subgroups most likely to
benefit and the identification of biomarkers for patient
selection.”
Clinical
Trial Design
Approximately
40 patients with advanced leukemias or other severe hematologic disorders
affecting the marrow are planned to enroll in the clinical trial at the MD
Anderson Cancer Center. Patients with relapsed/refractory chronic lymphocytic
leukemia (CLL), ALL, AML, advanced phase chronic myelogenous leukemia (CML),
high risk myelodysplastic syndrome (MDS) or advanced myelofibrosis (MF) will be
eligible for the trial.
1300
Seaport Boulevard, Suite 500, Redwood City, CA 94063 tel: 650.474.8200 fax:
650.474.2529 www.thresholdpharm.com
The
initial dose escalation phase of the trial will enroll cohorts of up to 6
patients per dose. All doses of TH-302 are being administered as a 30-60 minute
intravenous infusion daily for 5 days every 21 days. The primary objective of
the dose escalation component of the study is to establish the MTD and dose
limiting toxicities of TH-302 when administered daily for 5 days. The dose
escalation phase of the trial will enroll up to 30 patients. Once the MTD has
been established, up to 10 additional patients will be enrolled at the MTD in
the dose expansion component of the trial. The objective of the dose expansion
is to further assess the clinical activity of TH-302 in this population.
Patients for whom no curative therapy exists are eligible for this
trial.
Clinical
Rationale
TH-302 is
selectively activated in the hypoxic microenvironment of tumors. Preclinical
data support the hypothesis that TH-302 targets hypoxic regions of solid tumors.
Preclinical data from the Vrije Universiteit in Brussels and Threshold
Pharmaceuticals has shown diseased marrow to be significantly more hypoxic than
non-diseased marrow and that TH-302 has activity in multiple myeloma cells in vivo and in vitro. Additionally, data
from MD Anderson demonstrated the marked expansion of the hypoxic bone marrow
areas in diseased mice with ALL. These preclinical results suggest that an agent
that selectively targets the hypoxic regions of tumors may be useful in treating
advanced leukemias.
About
Advanced Leukemia
Advanced
leukemia is an acute or chronic cancer involving the blood-forming tissues in
the bone marrow. It may be classified as myeloid or lymphoid. According to the
American Cancer Society, leukemia accounts for 3% of all cancers diagnosed in
the United States in 2009, and about 22,000 people die annually of some form of
leukemia. Chronic lymphocytic leukemia is the most common leukemia in the United
States, accounting for a third of cases diagnosed each year. Acute myelogenous
leukemia accounts for approximately 30% of diagnosed adult
leukemias.
About
TH-302
Threshold
has evaluated TH-302 in over 400 patients with various solid tumors. In addition
to the advanced leukemia trial, the Company has several ongoing clinical trials
including, but not limited to, a controlled Phase 2 trial of TH-302 in
combination with gemcitabine in patients with advanced pancreatic cancer and a
Phase 1/2 study evaluating TH-302 in combination with doxorubicin in soft tissue
sarcoma.
About
Threshold Pharmaceuticals
Threshold
is a biotechnology company focused on the discovery and development of drugs
targeting Tumor Hypoxia, the low oxygen condition found in microenvironments of
most solid tumors. This approach offers broad potential to treat most solid
tumors. By selectively targeting tumor cells, we are building a pipeline of
drugs that hold promise to be more effective and less toxic to healthy tissues
than conventional anticancer drugs. For additional information, please visit our
website (www.thresholdpharm.com).
Forward-Looking
Statements
Except
for statements of historical fact, the statements in this press release are
forward-looking statements, including statements regarding TH-302 and its
potential therapeutic uses and benefits. These statements involve risks and
uncertainties that can cause actual results to differ materially from those in
such forward-looking statements. Potential risks and uncertainties include, but
are not limited to, Threshold's ability to continue to successfully enroll
patients in clinical trials, whether the Company’s clinical trials will show
results predicted by the Company’s pre-clinical trials or confirm the results of
earlier trials, the time and expense required to conduct such clinical trials
and analyze data, issues arising in the regulatory or manufacturing process and
any unanticipated or increased side-effects observed in patients receiving
TH-302. Further information regarding these and other risks is included under
the heading "Risk Factors" in Threshold's Quarterly Report on Form 10-Q, which
was filed with the Securities Exchange Commission on November 4, 2010 and is
available from the SEC's website (www.sec.gov) and on our website
(www.thresholdpharm.com) under the heading "Investors." We do not intend to
update any forward-looking statement made in this news release.
###
1300
Seaport Boulevard, Suite 500, Redwood City, CA 94063 tel: 650.474.8200 fax:
650.474.2529 www.thresholdpharm.com