Threshold Announces Acquisition of Investigational Hypoxia PET Imaging Agent [18F]HX4 From Siemens

Threshold to Develop PET Tracer [18F]HX4 as a Potential Companion Diagnostic for Its Hypoxia-Targeted Therapeutics


SOUTH SAN FRANCISCO, CA -- (Marketwire) -- 03/21/13 -- Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced a global agreement with Siemens Healthcare to acquire its investigational agent [18F]HX4 [flortanidazole (18F)], a radiolabeled hypoxia Positron Emission Tomography (PET) tracer. [18F]HX4 could potentially be used as a companion diagnostic to hypoxia-targeted therapeutics based on Threshold's drug discovery platform. Threshold initially intends to develop [18F]HX4 to determine a patient's tumor hypoxia profile, which may identify patients who will best respond to Threshold's hypoxia-targeted therapeutics.

Under the terms of the agreement, Siemens will transfer ownership and existing preclinical, clinical and manufacturing data related to [18F]HX4 to Threshold. Threshold will be responsible for the development and commercialization of [18F]HX4. Siemens' PET radiopharmaceutical manufacturer, PETNET Solutions, a wholly-owned subsidiary of Siemens Medical Solutions, will provide technical expertise and manufacturing capability to support clinical and commercial supply of the tracer [18F]HX4 through its extensive global network of integrated PET radiopharmaceutical drug manufacturing facilities and dispensing nuclear pharmacies. Financial terms of the agreement were not disclosed. Threshold does not expect the acquisition of, or development activities related to, [18F]HX4 to have a material impact on its operating expenses in 2013.

"We believe this acquisition of [18F]HX4 strengthens Threshold's position as a leader in the field of hypoxia-targeted therapies for cancer," said Barry Selick, Ph.D., Chief Executive Officer of Threshold. "Siemens is a leader in PET imaging hardware and software technology as well as PET radiopharmaceutical manufacturing and supply reach, and we look forward to collaborating with them on developing this promising new tool with the goal of identifying patients who may be most likely to benefit from hypoxia-targeted therapeutics."

"The further development of our hypoxia-targeted PET tracer with Threshold's hypoxia-targeted therapeutics carries potential to improve patient care," said Britta Fuenfstueck, Chief Executive Officer, Siemens Healthcare Molecular Imaging. "Siemens' PETNET Solutions will continue to provide technical expertise and resources to support Threshold development and potentially commercialize this tracer through its worldwide network of best-in-class radiopharmaceutical manufacturing and distribution facilities."

About [18F]HX4
[18F]HX4 [flortanidazole (18F)] is a novel investigational tumor hypoxia tracer developed by Siemens Healthcare Molecular Imaging to potentially identify and quantify the degree of hypoxia in tumors in vivo. Positron emission tomography (PET) is a nuclear medical imaging technique that non-invasively produces a three-dimensional image of functional processes in the entire body. PET is routinely used to inform physicians on diagnosis and treatment of cancer and is used in cancer treatment centers globally. [18F]HX4 has a 2-nitroimidazole "trigger" that is designed to be activated under the extreme hypoxic conditions generally found in tumors but not typically in normal healthy tissue.(1) Clinical data has demonstrated the potential of [18F]HX4 to quantify the degree of hypoxia within different tumors.(2-4)

Hypoxia-Targeted Therapeutics for the Treatment of Cancer
Hypoxia, or abnormally low oxygen concentration, is a common feature of the tumor microenvironment in most solid tumors and in the bone marrow of patients with some hematological malignancies (for example, leukemia and multiple myeloma). Tumor hypoxia is associated with the development of resistance to traditional anticancer treatments, including chemotherapy and radiotherapy, enhanced metastatic potential, and ultimately treatment failure. Normal healthy tissues, in contrast, are well oxygenated and typically are not hypoxic. Threshold seeks to design prodrugs of known chemotherapeutic agents or related analogs that remain essentially inactive in normal tissues but are activated under conditions of extreme hypoxia found within tumors. With such relatively selective activation, Threshold's hypoxia-targeted therapeutics are designed to target tumor hypoxia while minimally impacting healthy cells and tissues.

AboutThreshold Pharmaceuticals, Inc.
Threshold Pharmaceuticals, Inc., is a biotechnology company focused on the discovery and development of drugs targeting tumor hypoxia, the low oxygen condition found in the microenvironments of most solid tumors as well as the bone marrows of some patients with 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 uses and benefits of [18F]HX4 to identify patients with tumor hypoxia and contribute to therapy for such patients, and development plans for [18F]HX4 as a companion diagnostic. 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 conduct or manage clinical trials of [18F]HX4, Threshold's ability to obtain regulatory approval for [18F]HX4 as a diagnostic, and Threshold's ability to continue development of [18F]HX4. Further information regarding risks faced by Threshold is included under the heading "Risk Factors" in Threshold's Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission on March 7, 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. Dubois, L.J. et al. Preclinical evaluation and validation of [18F]HX4, a promising hypoxia marker for PET imaging. Proc Natl Acad Sci USA 108: 14620-14625, 2011.
2. van Loon, J. et al. PET imaging of hypoxia using [18F]HX4: a phase I trial. Eur J Nucl Med Mol Imaging 37: 1663-1668, 2010.
3. Doss, M. et al. Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT. Nucl Med Commun 31: 1016-1024, 2010.
4. Chen, L. et al. [18F]-HX4 hypoxia imaging with PET/CT in head and neck cancer: a comparison with [18F]-FMISO. Nucl Med Commun 33: 1096-1102, 2012.

Contact
Laura Hansen, Ph.D.
Senior Director, Corporate Communications
Phone: 650-474-8206
E-mail: lhansen@thresholdpharm.com