UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
_______________
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
May 30, 2014
THRESHOLD PHARMACEUTICALS, INC.
(Exact name of registrant as specified
in its charter)
| Delaware |
001-32979 |
94-3409596 |
|
(State or other jurisdiction
of incorporation) |
(Commission File Number) |
(IRS Employer
Identification No.) |
170 Harbor Way, Suite 300
South San Francisco, California 94080
(Address of principal executive offices)(Zip
Code)
(650) 474-8200
(Registrant’s telephone number,
including area code)
Check the appropriate box below if the Form 8-K filing is intended
to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
o Written communications
pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material
pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement
communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement
communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
On May 30, 2014, Threshold Pharmaceuticals, Inc. (the “Company”)
issued a press release announcing new clinical data from an ongoing investigator-sponsored Phase 1/2 trial of the Company’s
investigational hypoxia-activated prodrug, TH-302, in combination with bevacizumab (Avastin®) in patients with recurrent
glioblastoma following progression on single-agent bevacizumab.
Also on May 30, 2014, the Company issued a press release announcing
new preliminary clinical data from an ongoing Company-sponsored Phase 1/2 trial of the Company’s investigational hypoxia-activated
prodrug, TH-302, in combination with low-dose dexamethasone in patients with relapsed/refractory multiple myeloma, a cancer of
the bone marrow.
The press releases are attached as Exhibit 99.1 and 99.2, respectively,
to this Form 8-K.
| Item 9.01 | Financial Statements and Exhibits. |
| Exhibit 99.1 | Press release dated May 30, 2014. |
| Exhibit 99.2 | Press release dated May 30, 2014. |
SIGNATURES
Pursuant to the requirements
of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned
thereunto duly authorized.
| |
THRESHOLD PHARMACEUTICALS, INC. |
|
| |
|
|
|
| |
By: |
/s/ Joel A. Fernandes |
|
| |
|
Joel A. Fernandes |
|
| |
|
Vice President, Finance and Controller |
|
Date: June 2, 2014
Exhibit Index
| | Exhibit No. | Description |
| | | |
| Exhibit 99.1 | Press release dated May 30, 2014. |
| | | |
| Exhibit 99.2 | Press release dated May 30, 2014. |
Exhibit 99.1
 |
PRESS RELEASE |
Threshold Announces Data from Ongoing
Phase 1/2 Trial of TH-302 Plus Bevacizumab (Avastin®) in Patients with Recurrent Glioblastoma
| · | Objective response rate of 24% (one complete response and three partial responses) in patients with recurrent glioblastoma
following progression on single-agent bevacizumab |
| · | Median progression-free survival of 3.1 months on combination therapy vs. 2.4 months on prior single-agent bevacizumab |
| · | Enrollment at 670 mg/m2 TH-302 in combination with bevacizumab is ongoing |
Chicago, Illinois – May 30, 2014
– Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced new clinical data from an ongoing investigator-sponsored
Phase 1/2 trial of its investigational hypoxia-activated prodrug, TH-302, in combination with bevacizumab (Avastin®)
in patients with recurrent glioblastoma following progression on single-agent bevacizumab. The results are being presented today
as part of the poster highlights session on Central Nervous System Tumors at the 50th Annual Meeting of the American
Society of Clinical Oncology (ASCO) in Chicago [Abstract #2029 (Poster #20)]. The data will also be discussed at Threshold’s
Analyst Event to be held Sunday, June 1, 2014, at 6:00 PM Central Time in Chicago and accompanied by a live webcast.
“Effective treatments for patients
with recurrent glioblastoma who become refractory to bevacizumab are clearly needed,” 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. “In the limited number of patients
treated, it is notable that some patients experienced objective tumor shrinkage with TH-302 plus bevacizumab, particularly given
that objective responses are rarely seen at this advanced stage of the disease. Moreover, median progression-free survival with
TH-302 plus bevacizumab was longer than with prior single-agent bevacizumab. Based on these early signals of clinical activity,
we are continuing evaluation of TH-302 in this extremely challenging-to-treat population of patients with glioblastoma. Our next
steps are to further investigate the 670 mg/m2 TH-302 dose given with bi-weekly bevacizumab in a multi-center study
in this bevacizumab-refractory patient population.”
The objectives of the ongoing Phase 1/2
investigator-sponsored trial include evaluating the safety and tolerability of TH-302, determining the dose-limiting toxicities
and the maximum-tolerated dose of TH-302, and assessing preliminary signals of clinical activity in patients with bevacizumab-refractory
recurrent glioblastoma. The ASCO poster reports on a total of 17 patients treated with bevacizumab 10 mg/kg every two weeks and
TH-302 dose escalated 240-670 mg/m2 every two weeks (four-week cycle) until disease progression. Patients had received
a median of three prior systemic anticancer regimens including both chemoradiation and bevacizumab.
Key findings to be reported at ASCO are
as follows:
Preliminary assessment of safety and tolerability
No Grade 4 adverse events were observed
at any dose. Three Grade 3 adverse events were observed: skin ulceration at 340 mg/m2, oral mucositis at 670 mg/m2,
and thrombocytopenia at 670 mg/m2. The primary TH-302 related toxicities were mucosal: rectal/anal mucositis in one
of four patients at 480 mg/m2 (Grade 2) and six of seven patients at 670 mg/m2 (all Grade 1or 2). Limited
oral mucositis was observed.
|
PRESS RELEASE |
Preliminary assessment of clinical activity
In 17 patients evaluable for response according
to Response Assessment in Neuro-Oncology (RANO) criteria, best responses included one complete response (1CR) and three partial
responses (3PR) for a response rate of 24%, and eight stable disease (8 SD) assessments for a clinical benefit rate of 65%; five
patients had progressive disease (5 PD). The longest disease stabilization is ongoing at 30 months.
The median progression-free survival (PFS)
for patients treated with TH-302 plus bevacizumab was 3.1 months, while these patients experienced PFS of 2.4 months on their first
bevacizumab regimen. The 4-month PFS rate was 26%. Median overall survival of patients treated with TH-302 plus bevacizumab was
4.9 months.
Poster Details
The poster titled, “Phase 1/2 study
of investigational hypoxia-targeted drug, TH-302, and bevacizumab in recurrent glioblastoma following bevacizumab failure”
[Abstract #2029 (Poster #20)] is being presented at the Poster Highlights Session on Central Nervous System Tumors
from 1:00 PM – 4:00 PM Central Time, Friday, May 30, 2014, in Room E354b, to be followed by a Discussion from 4:30 PM - 5:45
PM in Room E450.
Analyst Event with Clinical Experts
on Sunday, June 1, 2014
Threshold will host an evening event for
investors and analysts on Sunday, June 1, 2014, at 6:00 PM Central Time at the Four Seasons Hotel Chicago (120 East Delaware Place,
Walton Room). The event will include presentations highlighting TH-302 data presented at ASCO. Guest speakers scheduled to give
presentations include Dr. Paul G. Richardson, Clinical Program Leader, Director of Clinical Research, Jerome Lipper Multiple Myeloma
Center, Dana-Farber Cancer Institute, R.J. Corman Professor of Medicine, Harvard Medical School, Boston, Massachusetts, and Dr.
Andrew J. Brenner, 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. RSVP to lhansen@thresholdpharm.com.
The event is open to investors and analysts.
Threshold invites the public and the media to listen to the presentations via the live webcast, which will be available under Webcasts
in the Investors section of www.thresholdpharm.com or can be accessed using the following link: http://psav.adobeconnect.com/thresholdpharmaceuticals/.
The presentations are scheduled to begin at approximately 6:15 PM Central Time. A replay of the presentations will be archived
on the site for 30 days.
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 3%. 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-activated
prodrug 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.
|
PRESS RELEASE |
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 Designations for the treatment of soft tissue sarcoma and pancreatic
cancer. TH-302 is also being investigated in earlier-stage clinical trials of other solid tumors and hematological malignancies,
in combination with chemotherapy and antiangiogenic therapy, and for certain cancers, is being investigated as a monotherapy.
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 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 (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 and statements regarding the expected completion and enrollment of current and potential future 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: the ability of Threshold, Merck
KGaA, Darmstadt, Germany, and third-party investigators to enroll or complete TH-302 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); the risk that the final data from ongoing trials may
be materially different from the preliminary data that Threshold or third-party investigators have reported; the risk that later
trials may not confirm the results of earlier trials; Threshold's and Merck KGaA's (Darmstadt, Germany) dependence on single source
suppliers, including the risk that these single source suppliers may be unable to meet clinical supply demands for TH-302 which
could significantly delay the development of TH-302; risks related to Threshold's dependence on its collaborative relationship
with Merck KGaA, Darmstadt, Germany, including its dependence on decisions by Merck KGaA, Darmstadt, Germany regarding the amount
and timing of resource expenditures for the development of TH-302; and Threshold's need for and the availability of resources to
develop TH-302 and to support Threshold's operations. 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 May 1, 2014 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: 650-703-6523
E-mail: lhansen@thresholdpharm.com
Exhibit 99.2
|
PRESS RELEASE |
Threshold Announces Data from Ongoing
Phase 1/2 Trial of TH-302 Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
| · | Preliminary clinical benefit rate of 31% (three partial responses and two minimal responses) in patients treated at the
maximum-tolerated dose of TH-302 and low-dose dexamethasone |
| · | Objective responses observed in heavily pretreated patients including prior treatment with proteasome inhibitors [including
carfilzomib (Kyprolis®)] and IMiDs [including pomalidomide (Pomalyst®)] |
| · | Enrollment completed at the previously established TH-302 maximum-tolerated dose (340 mg/m2) |
| · | Combination regimen of TH-302 and proteasome inhibitor bortezomib (Velcade®) to be investigated in final
stage of ongoing trial |
Chicago, Illinois – May 30, 2014
– Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced new preliminary clinical data from an ongoing company-sponsored
Phase 1/2 trial of its investigational hypoxia-activated prodrug, TH-302, in combination with low-dose dexamethasone in patients
with relapsed/refractory multiple myeloma, a cancer of the bone marrow. The results are being presented today as part of the poster
highlights session on Lymphoma and Plasma Cell Disorders at the 50th Annual Meeting of the American Society of Clinical
Oncology (ASCO) in Chicago [Abstract #8534 (Poster #14)]. The data will also be discussed by clinical experts at Threshold’s
Analyst Event to be held Sunday, June 1, 2014, at 6:00 PM Central Time in Chicago and accompanied by a live webcast.
“Effective treatments for patients
with advanced multiple myeloma who become refractory to current standards of care with proteasome inhibitors or immunomodulatory
drugs (IMiDs) remains an area of exquisite unmet medical need,” said Paul Richardson, M.D., Clinical Program Leader, Director
of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, R.J. Corman Professor of Medicine, Harvard
Medical School, Boston, Massachusetts. “The presence of hypoxia in the diseased bone marrow may present a new therapeutic
target for treating multiple myeloma and underlies the rationale for evaluating hypoxia-targeted agents in this disease. In the
limited number of patients treated, it is noteworthy that objective responses were observed in this heavily pretreated patient
population, including patients who received prior therapy with a proteasome inhibitor (including carfilzomib) and an immunomodulatory
agent (including pomalidomide), which are typically used in advanced and later stage multiple myeloma patients. Based on these
early signals of clinical activity, we are looking forward to initiating the final stage of the ongoing trial in which patients
will receive TH-302 and bortezomib, a combination that demonstrated synergistic activity in preclinical models of multiple myeloma.”
The objectives of the ongoing Phase 1/2
trial include determining the safety and tolerability of TH-302 and dexamethasone, the dose-limiting toxicities and the maximum-tolerated
dose of TH-302, and assessing preliminary signals of clinical activity in patients with relapsed/refractory multiple myeloma. The
dose of TH-302 administered in the dose escalation portion of the study was 240, 340, or 480 mg/m2 (depending on the
dose cohort into which a patient enrolled) given on days 1, 4, 8, and 11 of a 21-day cycle, with 40 mg dexamethasone given on the
same days as TH-302. Previously, the maximum tolerated dose was reported to be 340 mg/m2 TH-302.1
Enrollment of patients with relapsed/refractory
multiple myeloma in the dose-escalation and dose-expansion portions of the study is now complete, including 24 patients enrolled
at the maximum tolerated dose of TH-302 (340 mg/m2). Patients had received a median of 6.5 systemic therapies prior
to enrollment. The ASCO presentation includes data from 24 patients in the dose-escalation and dose-expansion portions of the study
who initiated treatment prior to March 1, 2014; analyses reflect the clinical database as of May 19, 2014. Of these 24 patients,
17 were treated at the maximum tolerated dose of TH-302.
|
PRESS RELEASE |
Key findings to be reported at ASCO are
as follows:
Preliminary assessment of safety and tolerability
The most common adverse events related
to TH-302 occurring in at least 25% of patients were nausea and fatigue. The most common Grade 3/4 hematologic adverse events related
to TH-302 were thrombocytopenia (29%) and leukopenia (25%). Dose-limiting toxicities of Grade 3 stomatitis were reported during
the first treatment cycle for the first two patients treated at 480 mg/m2 TH-302; therefore, the maximum tolerated dose
of TH-302 was established at 340 mg/m2.
Preliminary assessment of clinical activity
Of the 24 patients included in the ASCO
presentation, 23 were evaluable for response. According to modified International Myeloma Working Group (IMWG) criteria, best responses
included four partial responses (4 PR), two minimal responses (2 MR), and 15 stable disease (15 SD) assessments; two patients had
progressive disease (2 PD). The clinical benefit rate for patients treated at the maximum tolerated dose of TH-302 (n=16 evaluable
patients) was 31% (comprised of 3 PR and 2 MR).
Poster Details
The poster titled, “Preliminary safety
and efficacy of TH-302, an investigational hypoxia-targeted drug, and dexamethasone in patients with relapsed/refractory multiple
myeloma” [Abstract #8534 (Poster #14)] is being presented at the Poster Highlights Session on Lymphoma and Plasma Cell Disorders,
1:00 PM - 4:00 PM Central Time, Friday, May 30, 2014, in Room S405; Discussion follows, 4:30 PM - 5:45 PM, Room S406.
Analyst Event with Clinical Experts
on Sunday, June 1, 2014
Threshold will host an evening event for
investors and analysts on Sunday, June 1, 2014, at 6:00 PM Central Time at the Four Seasons Hotel Chicago (120 East Delaware Place,
Walton Room). The event will include presentations highlighting TH-302 data presented at ASCO. Guest speakers scheduled to give
presentations include Dr. Paul G. Richardson, Clinical Program Leader, Director of Clinical Research, Jerome Lipper Multiple Myeloma
Center, Dana-Farber Cancer Institute, R.J. Corman Professor of Medicine, Harvard Medical School, Boston, Massachusetts, and Dr.
Andrew J. Brenner, 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. RSVP to lhansen@thresholdpharm.com.
The event is open to investors
and analysts. Threshold invites the public and the media to listen to the presentations via the live webcast, which will
be
available under Webcasts in the Investors section of www.thresholdpharm.com or can be accessed using the following link:
http://psav.adobeconnect.com/thresholdpharmaceuticals/. The presentations are scheduled to begin at approximately 6:15
PM Central Time. A replay of the presentations will be archived on the site for 30 days.
About TH-302
TH-302 is an investigational hypoxia-activated
prodrug 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.
|
PRESS RELEASE |
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 earlier-stage clinical trials of other solid tumors and hematological malignancies,
in combination with chemotherapy and antiangiogenic therapy, and for certain cancers, is being investigated as a monotherapy.
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 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 (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 and statements regarding the expected initiation of the final stage of the ongoing Phase 1/2 trial. 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: the ability of Threshold and Merck KGaA, Darmstadt,
Germany, to enroll or complete TH-302 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); the risk that preclinical studies in animal models of disease may not accurately predict the results
of human clinical trials of TH-302; the risk that the final data from ongoing trials may be materially different from the preliminary
data that Threshold has reported; Threshold's and Merck KGaA's (Darmstadt, Germany) dependence on single source suppliers, including
the risk that these single source suppliers may be unable to meet clinical supply demands for TH-302 which could significantly
delay the development of TH-302; risks related to Threshold's dependence on its collaborative relationship with Merck KGaA, Darmstadt,
Germany, including its dependence on decisions by Merck KGaA, Darmstadt, Germany regarding the amount and timing of resource expenditures
for the development of TH-302; and Threshold's need for and the availability of resources to develop TH-302 and to support Threshold's
operations. 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 May 1, 2014 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: 650-703-6523 E-mail:
lhansen@thresholdpharm.com
References
| 1. | Ghobrial IM, et al. Phase 1 study of TH-302, an investigational hypoxia-targeted drug, and dexamethasone in patients with relapsed/refractory
multiple myeloma Blood 122:1948, 2013. |
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