Threshold Pharmaceuticals Announces Early Clinical Data for Combining TH-302 With Antiangiogenic Agents in Advanced Solid

Threshold Pharmaceuticals Announces Early Clinical Data for Combining TH-302 
With Antiangiogenic Agents in Advanced Solid Tumors 
Clinical Data on TH-302 Combinations With Votrient(R) (Pazopanib) and
Sutent(R) (Sunitinib) as Well as Preclinical Data on TH-302
Combination With Abraxane(R) (Nab-Paclitaxel) to Be Presented at the
AACR-NCI-EORTC International Conference on Molecular Targets and
Cancer Therapeutics 
SOUTH SAN FRANCISCO, CA -- (Marketwired) -- 10/21/13 --  Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD) today announced early clinical
data from two single-arm, open-label Phase 1 trials evaluating
TH-302, an investigational, hypoxia-targeted drug, in combination
with antiangiogenic agents for the treatment of advanced solid
tumors. New data from an investigator-sponsored trial (Study 4001) in
patients with advanced solid tumors showed that combination treatment
with TH-302 plus Votrient(R) (pazopanib) achieved a clinical benefit
rate of 76% (partial response rate of 12% plus stable disease rate of
64%). Updated data from a company-sponsored trial (Study 410) in
patients with renal cell carcinoma (RCC) and gastrointestinal stromal
tumors (GIST) showed partial responses to treatment with TH-302 plus
Sutent(R) (sunitinib). Detailed results for Studies 410 and 4001 will
be presented this Monday and Tuesday, respectively, at the 2013
AACR-NCI-EORTC International Conference on Molecular Targets and
Cancer Therapeutics in Boston, Massachusetts (Abstracts #B77 and
#C61, respectively).  
"While antiangiogenics have proven to be an important new class of
targeted cancer therapy, essentially all tumors eventually become
resistant to these treatments. Novel therapeutic approaches that
address treatment resistance are greatly needed," said Herbert I.
Hurwitz, MD, Professor of Medicine at Duke Cancer Institute and
principal investigator of Study 4001. "Co-targeting tumor
angiogenesis and tumor hypoxia, which is believed to be a key driver
of treatment resistance, is one approach to potentially prevent or
reverse this mechanism of resistance. These early clinical data
combining pazopanib and TH-302 in refractory cancers demonstrate
preliminary signals of activity that warrant further investigation." 
The combination study with TH-302 plus pazopanib was conducted in 30
patients with a variety of solid tumors for whom standard therapy or
palliative measures were nonexistent or no longer effective. The
clinical benefit rate was 76% (n=25 evaluable patients) with three
patients with partial responses (12%) and 16 patients with stable
disease (64%). The partial responses were observed in patients with
neuroendocrine cancer, ovarian cancer, and chondrosarcoma.  
Treatment-related grade 3 hematological adverse events were reported
for neutropenia (7%), thrombocytopenia (7%), and anemia (13%).
Treatment-related, grade ≥ 2 nonhematologic adverse events
included vomiting/nausea/diarrhea (7% grade 3), mucositis (7% grade
3), hand foot syndrome (all grade 2), and hypertension (all grade 2).
No grade 4 adverse events have been reported. The study has completed
enrollment and treatment is ongoing.  
In addition, updated preliminary results from the combination study
with TH-302 plus sunitinib (n=12) showed that partial responses were
achieved by one of four (25%) evaluable GIST patients (confirmed) and
three of six (50%) evaluable RCC patients (two confirmed). All four
patients with partial responses had received prior sunitinib. Grade 3
thrombocytopenia and neutropenia were reported in 3 (25%) and 4 (33%)
patients, respectively; grade 4 neutropenia was reported in one
patient (8%). Fatigue, nausea, and vomiting were the most common
nonhematologic adverse events occurring in 83%, 75%, and 67% of
patients, respectively. All cases were grade 1 or 2 except for one
report of grade 3 nausea.  
Preclinical Data on TH-302 in Pancreatic Cancer Also to be Presented
at Meeting
 Preclinical data on the combination of TH-302 with
Gemzar(R) (gemcitabine) and Abraxane(R) (nab-paclitaxel) in models of
pancreatic cancer will be presented at the meeting on Tuesday October
22 (Abstract #C287) showing in xenograft models greater anti-tumor
activity associated with the "triplet" (TH-302 plus gemcitabine plus
nab-paclitaxel) compared with that of the doublet (gemcitabine plus
nab-paclitaxel), and without additive hematological toxicity or
peripheral neuropathy.  
About TH-302
 TH-302 is an investigational hypoxia-targeted drug that
is designed to be activated under tumor hypoxic conditions, a
hallmark of many cancers. Areas of low oxygen levels (hypoxia) in
solid tumors are due to insufficient blood supply as a result of
aberrant vasculature. Similarly, the bone marrow of patients with
hematological malignancies has also been shown, in some cases, to be
severely hypoxic. 
TH-302 is currently under evaluation in two Phase 3 trials: one in
combination with doxorubicin versus doxorubicin alone in patients
with soft tissue sarcoma (STS), and the other in combination with
gemcitabine versus gemcitabine and placebo in patients with advanced
pancreatic cancer (MAESTRO). Both Phase 3 trials are being conducted
under Special Protocol Agreements with the U.S. Food and Drug
Administration (FDA). The FDA and the European Commission have
granted TH-302 Orphan Drug Designation for the treatment of STS.
TH-302 is also being investigated in hematological malignancies and
in combination with other therapies in a variety of solid tumors. 
Threshold has a global license and co-development agreement for
TH-302 with Merck KGaA, Darmstadt, Germany, which includes an option
for Threshold to co-commercialize in the U.S. 
Abstracts for the 2013 AACR-NCI-EORTC Meeting Available Online 
Abstracts are available on the 2013 AACR-NCI-EORTC International
Conference on Molecular Targets and Cancer Therapeutics Online
Proceedings and Itinerary Planner Web page, which can be accessed at
About Threshold Pharmaceuticals 
 Threshold Pharmaceuticals, Inc. 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 as well as the bone marrows of
some hematologic malignancies. This approach offers broad potential
to treat a variety of cancers. 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 ( 
Forward-Looking Statements
 Except for statements of historical fact,
the statements in this press release are forward-looking statements,
including statements regarding the potential therapeutic uses and
benefits of TH-302 in combination with antiangiogenic agents and
ongoing clinical trials of TH-302. 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, whether early trial
results will be confirmed in subsequent larger trials, Threshold's
ability to enroll or complete its anticipated clinical trials, the
time and expense required to conduct such clinical trials and analyze
data, issues arising in the regulatory or manufacturing process and
the results of such clinical trials (including product safety issues
and efficacy results). Further information regarding these and other
risks is included under the heading "Risk Factors" in Threshold's
Quarterly Report on Form 10-Q, which has been filed with the
Securities and Exchange Commission on August 1, 2013 and is available
from the SEC's website ( and on our website
( under the heading "Investors." We undertake
no duty to update any forward-looking statement made in this news
Laura Hansen, Ph.D.
Senior Director, Corporate Communications
Threshold Pharmaceuticals
Phone: 650-474-8206
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