Threshold Pharmaceuticals Reports Updated Phase 2 Results

Threshold Pharmaceuticals Reports Updated Phase 2 Results Including
Analyses of Maintenance Therapy With TH-302 Following Induction
Therapy With TH-302 Plus Doxorubicin in Soft Tissue Sarcoma 
Data Presented at the 17th CTOS Annual Meeting 
PRAGUE, CZECH REPUBLIC -- (Marketwire) -- 11/15/12 --  Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD) today announced updated results
from a Phase 2 study of TH-302, the company's investigational
hypoxia-targeted drug, in patients with soft tissue sarcoma,
including additional results from patients who were administered
TH-302 as single agent maintenance therapy following induction with
TH-302 in combination with doxorubicin. The results were reported at
the 17th annual meeting of the Connective Tissue Oncology Society
(CTOS) taking place November 14-17, 2012, in Prague, Czech Republic. 
In the single-arm Phase 2 component of the study (403 trial),
previously untreated patients with metastatic or locally advanced
unresectable soft tissue sarcomas were treated with TH-302 (300 mg/m2
on days 1 and 8 of a 21-day cycle) and doxorubicin (75 mg/m2 on day
1) for a maximum of six cycles. After six cycles, patients with
stable disease, partial or complete responses, and with acceptable
toxicity, were eligible to receive TH-302 maintenance therapy (300
mg/m2 on days 1 and 8 of a 21-day cycle). Response was assessed using
RECIST criteria. 
Results for Overall Study Population (N=91)
 Updated results for the
91 patients in the Phase 2 component of the study include: 


 
--  Median progression free survival (PFS) of 6.7 months (95% CI: 6.2 to
    8.1 months).
--  Median overall survival of 21.5 months (95% CI 16.0 to 27.6 months).
--  One-year survival of 73% (95% CI: 63% to 82%), and two-year survival
    of 44% (95% CI: 32% to 55%).
--  Overall best response (partial and complete responses, unconfirmed) of
    36%.

  
Results for TH-302 Single Agent Maintenance Therapy Population (N=48) 
Of 91 patients enrolled in the study, 48 (53%) continued on TH-302
maintenance therapy. Available data indicate the following results
during maintenance (starting at treatment cycle seven, day 1): 


 
--  The median number of treatment cycles with TH-302 was 4.0 (range: 1-30
    cycles).
--  Median PFS was 3.7 months (95% CI: 2.5 to 5.5 mo
nths).
--  Median overall survival was 18.0 months (95% CI: 16.2 to 23.4 months).
--  Overall best response (partial and complete responses, unconfirmed) of
    54%; five patients who previously had stable disease prior to
    maintenance achieved a partial response, and one patient who
    previously had a partial response achieved a complete response.

  
The most common adverse events initiating in maintenance were skin rash
(21%), diarrhea, (21%), fatigue (17%), constipation (17%), pain in
extremities (17%), and stomatitis (15%). All of these were Grade 1 or
Grade 2. A total of five patients had a Grade 3 adverse event
assessed by the clinical investigator as at least possibly related to
TH-302: two patients each had pruritus and urticaria; one patient had
anemia; one patient had hypoalbuminemia; and one patient had
hypokalemia. There were no reports of Grade 3-4 thrombocytopenia,
neutropenia, or leukopenia. There was no evidence of renal or hepatic
toxicity. 
"We are pleased with these results suggesting that TH-302 can be
combined with doxorubicin and continued as single agent maintenance
treatment for patients with soft tissue sarcoma," said Tillman
Pearce, M.D., Chief Medical Officer of Threshold. "These results
support our ongoing Phase 3 clinical trial evaluating the potential
efficacy and safety of TH-302 plus doxorubicin in extending the lives
of patients with soft tissue sarcoma." 
TH-302 has been granted Orphan Drug Designation in the U.S. and
Europe for the treatment of soft tissue sarcoma.  
About the 403 Trial 
The 403 trial was a Phase 1/2, multi-center, dose-escalation study to
determine the safety, efficacy and pharmacokinetics of TH-302 in
combination with full-dose doxorubicin in patients with soft tissue
sarcomas followed by TH-302 maintenance monotherapy for patients who
had not progressed after six cycles. In this study, the maximum
tolerated dose (MTD) of 300 mg/m2 was established for the combination
of TH-302 and 75 mg/m2 doxorubicin with prophylactic growth factor
support. Dose-limiting toxicities at a TH-302 dose of 340 mg/m2 were
Grade 4 thrombocytopenia and Grade 3 infection with Grade 4
neutropenia. Enrollment was expanded at the MTD, and a total of 91
patients with advanced soft tissue sarcomas previously untreated with
systemic chemotherapy were enrolled and treated at the MTD. 
About the Ongoing Phase 3 Study (406 Trial) 
The 403 trial provided the basis for the ongoing pivotal Phase 3
study (406 trial), which will compare the same TH-302 plus
doxorubicin regimen investigated in the Phase 2 portion of the 403
trial against single agent doxorubicin. In February 2011, Threshold
announced that it had reached agreement with the U.S. Food and Drug
Administration on a Special Protocol Assessment of the Phase 3 study,
which includes a primary efficacy endpoint of overall survival. The
international, randomized, controlled clinical trial, being conducted
in partnership with the Sarcoma Alliance for Research through
Collaboration (SARC), was initiated in September 2011 and will enroll
450 patients with metastatic or locally advanced unresectable soft
tissue sarcoma. 
About Soft Tissue Sarcoma 
Sarcomas are a group of aggressive cancers of connective tissues of
the body for which there are currently limited treatment options.
Soft tissue sarcomas are treated with surgery, chemotherapy and
radiation. Usually a combination of these modalities offers the best
chance to treat the disease successfully. Doxorubicin and ifosfamide
are the most commonly used chemotherapeutic agents in patients with
advanced soft tissue sarcoma, but response rates are generally low
and toxicity can be significant. The American Cancer Society
estimates about 11,280 new soft tissue sarcomas will be diagnosed in
2012 and 3,900 Americans are expected to die from these cancers. 
About TH-302 
TH-302 is a hypoxia-targeted drug designed to be activated under
tumor hypoxic conditions, a hallmark of many cancers. Areas of low
oxygen levels (hypoxia) are common in many solid tumors due to
insufficient blood vessel growth. Similarly, the bone marrow of
patients with hematological malignancies has also been shown, in some
cases, to be extremely hypoxic. 
TH-302 has been investigated in over 700 patients in Phase 1/2
clinical trials to date in a broad spectrum of tumor types, both as a
monotherapy and in combination with chemotherapy treatments and other
targeted cancer drugs. Threshold has several additional ongoing
clinical trials, the most advanced of which is a Phase 3 pivotal
study evaluating TH-302 in combination with doxorubicin versus
doxorubicin alone in patients with soft tissue sarcoma. Results of
the Phase 2 study of TH-302 in patients with pancreatic cancer were
reported at the American Association for Cancer Research (AACR)
Annual Meeting 2012 and the European Society for Medical Oncology
(ESMO) 2012 Congress. In February 2012, Threshold signed a global
license and co-development agreement for TH-302 with Merck KGaA,
Darmstadt, Germany. 
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 soft tissue sarcoma 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, Threshold's ability to enroll or complete its anticipated
clinical trials, the time and expense required to conduct such
clinical trials and analyze data, whether later trials confirm the
results of earlier trials, 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 2, 2012 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. 
Contact:
Laura Hansen, Ph.D.
Senior Director, Corporate Communications
Phone: 650-474-8206
E-mail: lhansen@thresholdpharm.com