Threshold Pharmaceuticals Announces New Clinical Data on TH-302 and Avastin(R) (Bevacizumab) in Recurrent Glioblastoma

Threshold Pharmaceuticals Announces New Clinical Data on TH-302 and Avastin(R) 
(Bevacizumab) in Recurrent Glioblastoma Following
Bevacizumab Failure 
Data to Be Presented at the 2013 WFNO/SNO Meeting 
SOUTH SAN FRANCISCO, CA -- (Marketwired) -- 11/22/13 --  Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD), today announced early data from
the Phase 1 portion of an investigator-sponsored Phase 1/2 trial of
its investigational hypoxia-targeted drug TH-302 in combination with
Avastin(R) (bevacizumab) in patients with recurrent glioblastoma
following bevacizumab failure (Study 4003). No dose-limiting toxicity
has been reported to date at doses of TH-302 up to 670 mg/m2 plus
bevacizumab at 10 mg/m2 every two weeks. Preliminary data in 14
patients showed TH-302 in combination with bevacizumab was associated
with a median time to progression of 2.8 months. One patient achieved
a complete response and two patients achieved partial responses. The
data will be presented this evening from 7 p.m. to 9 p.m. at the 4th
Quadrennial World Federation of Neuro-Oncology (WFNO) meeting held in
conjunction with the 18th annual 2013 Scientific Meeting and
Education Day of the Society for Neuro-Oncology (SNO), San Francisco,
CA.  
Chemotherapy with radiotherapy is standard care for newly diagnosed
glioblastoma. Bevacizumab is approved in the U.S. for progressive
disease following prior therapy. After disease progression on
bevacizumab, patients may start a subsequent bevacizumab-containing
regimen. These patients typically progress in 5 to 8 weeks.(1,2)
Three-month progression-free survival is approximately 15%.(1)  
"There is a critical unmet need for new medicines to treat patients
with glioblastoma who experience recurrence of their disease," said
Andrew J. Brenner, M.D., Ph.D., Principal Investigator of the study
and Clinical Investigator with the Institute for Drug Development at
the Cancer Therapy & Research Center at The University of Texas
Health Science Center at San Antonio, Texas. "These preliminary data
signal that TH-302 in combination with bevacizumab may have activity
in patients with glioblastoma following single-agent bevacizumab
failure. We are looking forward to further evaluation of TH-302 as
this study continues to enroll patients."  
A total of 19 patients have been enrolled in the ongoing trial. Of 14
patients evaluable for tumor response, the median time to progression
was 86 days. Forty-six percent (95% CI: 18% - 74%) of patients were
alive without disease progression after three months of treatment.
Best tumor responses were one patient achieving a complete response,
two patients achieving a partial response, and seven patients
demonstrating stable disease; four patients experienced progressive
disease. The longest disease stabilization is currently ongoing in
one patient who achieved a partial response and is currently
receiving cycle 26 at 22 months. 
No grade 4 adverse events were observed at any dose. Two grade 3
adverse events were observed at 340 mg/m2 and 670 mg/m2 of skin
ulceration and thrombocytopenia, respectively. The primary TH-302
related toxicities were mucosal, with rectal mucositis in two of four
patients at 480 mg/m2 and four of four patients at 670 mg/m2. Limited
oral mucositis was observed. Mucositis was treated conservatively and
was not dose limiting.  
About the Phase 1/2 Trial (Study 4003)  
The ongoing phase 1/2 trial is a single-center, dose-escalation trial
in patients with recurrent glioblastoma whose disease has progressed
following initial combined modality treatment with radiotherapy and
temozolomide and subsequent treatment with bevacizumab. The
presentation at WFNO/SNO will include data from a total of 14
evaluable patients who received combination therapy of bevacizumab
(10 mg/m2) and TH-302 (240 to 670 mg/m2) every two weeks. Best
response was assessed by Response Assessment in Neuro-Oncology (RANO)
criteria. Enrollment continues at 670 mg/m2 TH-302.  
About Glioblastoma and Hypoxia 
Glioblastoma is the most common and most aggressive of the primary
malignant brain tumors in adults (also known as Grade IV
astrocytoma). Median survival is approximately 15 months; the
five-year survival rate is approximately three percent. There are an
estimated 30,000 new cases of glioblastoma per annum in the U.S. and
Europe. 
Hypoxia, a predominant characteristic of glioblastoma and most solid
tumors, is associated with tumor growth, progression and resistance
to conventional radiation and chemotherapies, as well as poor patient
survival. Bevacizumab is a biologic antibody designed to interfere
with the tumor blood supply by directly binding to a protein called
VEGF. Preclinical data suggest that antiangiogenic agents, such as
bevacizumab, may increase tumor hypoxia, which supports the rationale
for combination therapy with a hypoxia-targeted agent in
glioblastoma.  
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, 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 soft
tissue sarcoma and pancreatic cancer. 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. 
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 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 (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 the potential therapeutic uses and benefits of TH-302 to
treat patients with glioblastoma or other cancers. 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 additional trials are conducted to evaluate TH-302 in
combination with bevacizumab or other chemotherapy agents to treat
glioblastoma and whether such trials confirm the results of the
initial trial reported here, and 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
November 4, 2013 and is available from the SEC's website
(www.sec.gov) and on our website (www.thresholdpharm.com) under the
heading "Investors". We undertake no duty to update any
forward-looking statement made in this news release. 
References 
1. Quant EC, et al. Neuro-Oncology 11, 550-555, 2009 
 2. Iwamoto FM,
et al. Neurology 73, 1200-1206, 2009  
Contact
Laura Hansen, Ph.D.
Senior Director, Corporate Communications 
Phone: 650-474-8206
E-mail: lhansen@thresholdpharm.com 
 
 
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