Endocyte's Investigational Diagnostic Imaging Agent Etarfolatide Identifies Ovarian Cancer and Non-Small Cell Lung Cancer Patients Most Likely to Benefit From Folate Receptor-Targeted Treatment, New Analysis Shows

Patients With 100 Percent Folate Receptor-Positive Tumor Lesions Experienced Substantial Progression-Free Survival When Treated With Vintafolide

New Data Presented at AACR-SNMMI Joint Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy

SAN DIEGO, March 1, 2013 (GLOBE NEWSWIRE) -- Endocyte, Inc. (Nasdaq:ECYT), a biopharmaceutical company developing targeted small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized therapy in cancer and other serious diseases, today announced a new analysis demonstrating that the investigational diagnostic imaging agent etarfolatide (EC20) can identify ovarian cancer and non-small cell lung cancer (NSCLC) patients who could benefit from folate receptor-targeted therapeutics, such as the novel investigational cancer candidate vintafolide (MK-8109/EC145). Patients with all target tumor lesions positive as assessed by etarfolatide imaging, FR(100%) experienced substantial progression-free survival (PFS) compared to patients with 10 to 90 percent of target lesions positive for folate receptor, FR(10-90%), when treated with single-agent vintafolide. Additional data demonstrate etarfolatide's potential to predict in which tissues or lesions folate receptor-targeting drugs will accumulate and therefore potentially respond to folate receptor-targeted therapy. These results were presented at the first AACR-SNMMI Joint Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy in San Diego, Calif.

"Etarfolatide allows for a non-invasive, full-body assessment of target lesions that over-express the folate receptor in real time, providing physicians with deeper information that guides patient selection for the investigational folate receptor-targeted therapy, vintafolide," said Phillip Kuo, M.D., Ph.D., associate professor, radiology, medicine and biomedical engineering, University of Arizona Cancer Center. "These studies, conducted in heavily pre-treated patients, provide additional support that this personalized therapy approach enables the identification of patients who will most likely benefit from folate receptor-targeted therapy."

Vintafolide and etarfolatide are currently being evaluated in a Phase 3 randomized, double-blind clinical trial for platinum-resistant ovarian cancer (PROCEED trial; ClinicalTrials.gov Identifier NCT01170650) and a Phase 2b trial in patients with NSCLC (TARGET trial; ClinicalTrials.gov Identifier NCT01577654). Endocyte recently announced that the European Medicines Agency (EMA) has accepted for review the marketing authorization application (MAA) filings for vintafolide and etarfolatide for the targeted treatment of patients with folate receptor-positive ovarian cancer in combination with pegylated liposomal doxorubicin (PLD). Both vintafolide and etarfolatide have been granted orphan drug status by the European Commission.

In abstract number 41, "99mTc-etarfolatide (EC20) SPECT imaging for the identification of ovarian and non-small cell lung cancer patients who are most likely to benefit from folate receptor-targeted agent vintafolide (EC145)," heavily pre-treated ovarian cancer and non-small cell lung cancer patients in two single-arm Phase 2 trials were imaged with etarfolatide single-photon emission computed tomography (SPECT) scans to assess etarfolatide uptake in target lesions and then treated with single-agent vintafolide. Vintafolide was administered in an induction phase (1.0 mg intravenous [IV] bolus daily x 5 days for 3 weeks of a 4-week cycle x 2 cycles) followed by a maintenance phase (2.5 mg IV bolus daily x 3 days, weeks 1 and 3 of a 4-week cycle). Patients received therapy until disease progression or unacceptable toxicity.

Among both NSCLC and ovarian cancer patients with at least one target tumor lesions positive as assessed by etarfolatide imaging, the greatest efficacy was observed in FR(100%) patients compared to the FR(10 to 90%) patients: (15.2 versus 7.4 weeks in ovarian cancer patients and 31.1 versus 7.3 weeks in NSCLC patients). The PFS hazard ratios with 95 percent confidence interval between the two folate receptor subgroups were 0.797 (0.362, 1.756) and 0.326 (0.115, 0.919) for the ovarian cancer and NSCLC studies, respectively. The FR(100%) subgroup also had greater than 50 percent improvement in disease control rate (ovarian cancer, 57.1 percent versus 36.4 percent; NSCLC, 57.1 percent versus 14.3 percent) and overall survival (ovarian cancer, 63.6 versus 41.7 weeks; NSCLC, 47.2 versus 14.9 weeks) compared with FR(10-90%) patients. The overall survival hazard ratios (95 percent confidence interval) between the two folate receptor subgroups were 0.574 (0.213, 1.542) and 0.539 (0.209, 1.395) for the ovarian cancer and NSCLC studies, respectively. Furthermore, analyses of tumor lesions showed that the percentage of lesions that were decreased (at least 20 percent decrease in size from baseline) or stable (less than 20 percent increase in size from baseline) was greater in folate receptor-positive lesions than in folate receptor-negative lesions, supporting the target-specific mechanism of action of vintafolide. There were no drug-related grade 4 toxicities reported. The most common drug-related adverse events (all grades) were constipation (47 percent and 33 percent in ovarian cancer and NSCLC studies, respectively) and fatigue (37 percent for both ovarian cancer and NSCLC).

In vitro and in vivo data presented showed that etarfolatide binds with high affinity (Kd around 3 nM) to the folate receptor, independent of cell type. Furthermore, the binding specificity of etarfolatide to cells or its accumulation within tumors depends on folate receptor expression. The pharmacologic properties of both etarfolatide and vintafolide were investigated in human and murine cell lines as well as in xenograft (transplants into other species) models.

"These data indicate that we can predict with our companion diagnostic etarfolatide which tissues will accumulate, and potentially respond to, folate-containing therapeutics like the SMDC vintafolide, which is a much needed personalized approach," said Christopher Leamon, Ph.D., vice president of research and development for Endocyte and presenter of the study.

Endocyte has a pipeline of folate receptor-targeted SMDCs in various stages of clinical and preclinical development for the treatment of folate receptor-positive cancers and inflammatory diseases.

About Ovarian Cancer

It was estimated that in 2012, there were 22,280 new cases of ovarian cancer in the United States and over 40,000 new cases in the European Union. Ovarian cancer causes more deaths than any other cancer of the female reproductive system. Overall, approximately 80 percent of patients relapse after first-line platinum-based chemotherapy. Ovarian cancer is a challenging disease with a high unmet need: it typically recurs within six months of completion with a platinum-containing regimen, the standard of care for ovarian cancer. An estimated 80 percent of ovarian cancer patients have been found to have folate receptor-positive disease, and 40 percent express the receptor in all of their target tumor lesions. Compared to patients who do not express folate receptors on their tumors, folate receptor-positive patients have been shown to have a poorer overall prognosis.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths in the industrialized world. More than 200,000 new cases of lung cancer are diagnosed each year in the United States, and more than 160,000 deaths occur annually from the disease, according to the American Cancer Society. The disease is frequently undiagnosed until it has already developed to advanced stages, resulting in a five-year survival rate of only approximately 15 percent. Approximately 85 percent of patients diagnosed with lung cancer are identified with non-small cell lung cancer, and of these patients 40 to 50 percent have adenocarcinoma and 30 to 35 percent have squamous cell carcinoma.

About Etarfolatide (EC20)

Etarfolatide is a folate receptor-targeted companion diagnostic imaging agent that is being developed as a non-invasive method to identify tumors that over-express folate receptors. These tumors are the molecular target of Endocyte's folate receptor-targeted therapeutic compounds such as vintafolide. Folic acid is used with etarfolatide for the enhancement of image quality. To date, etarfolatide and folic acid have been administered to over 590 patients.

About Vintafolide (MK-8109/EC145)

Vintafolide is a proprietary, injectable, conjugate consisting of folate (vitamin B9) linked to a potent vinca alkaloid anti-cancer agent, desacetylvinblastine hydrazide (DAVLBH). Folate is essential for cell division, and cancer cells generally consume higher levels of folate than normal cells to fuel their rapid rate of growth and division. In order to satisfy the demand for folate, some cancer cell types – including ovarian – express high concentrations of folate receptors on their surface. Vintafolide, a novel small molecule drug conjugate (SMDC), is designed to exploit this characteristic by selectively targeting the folate receptor to deliver the anti-cancer agent DAVLBH intracellular to the tumor.

Endocyte is developing and commercializing vintafolide with Merck, known as MSD outside the United States and Canada; both studies are also using Endocyte's investigational companion diagnostic imaging agent, etarfolatide.

About Endocyte

Endocyte is a biopharmaceutical company developing targeted therapies for the treatment of cancer and inflammatory diseases. Endocyte uses its proprietary technology to create novel SMDCs and companion imaging diagnostics for personalized targeted therapies. The company's SMDCs actively target receptors that are over-expressed on diseased cells, relative to healthy cells. This targeted approach is designed to enable the treatment of patients with highly active drugs at greater doses, delivered more frequently, and over longer periods of time than would be possible with the untargeted drug alone. The companion imaging diagnostics are designed to identify patients whose disease over-expresses the target of the therapy and who are therefore more likely to benefit from treatment.

For additional information, please visit Endocyte's website at www.endocyte.com.

Forward-Looking Statement

Certain of the statements in this press release are forward looking, such as those, among others, relating to the potential effectiveness of folate receptor-targeted therapies and the ability to determine the folate receptor expression status of patients. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. More information about the risks and uncertainties faced by Endocyte, Inc. is contained in the company's periodic reports filed with the Securities and Exchange Commission. Endocyte, Inc. disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

CONTACT: Stephanie Ascher Stern Investor Relations, Inc. (212) 362-1200 stephanie@sternir.com Martina Schwarzkopf, Ph.D. Russo Partners (212) 845-4292 martina.schwarzkopf@russopartnersllc.com Tony Russo, Ph.D. Russo Partners (212) 845-4251 tony.russo@russopartnersllc.comSource:Endocyte, Inc.