On January 7, 2015 Medivation, Inc. (NASDAQ: MDVN) and NanoString Technologies, Inc., (NASDAQ: NSTG) reported they have entered into a collaboration, together with Astellas Pharma Inc., to pursue the translation of a novel gene expression signature algorithm from Medivation into a companion diagnostic assay using NanoString’s nCounter Dx Analysis System (Press release, Medivation, JAN 7, 2016, View Source [SID:1234508684]). Under the terms of the collaboration agreement, NanoString will be responsible for developing and validating the diagnostic test and, if the parties thereafter determine to proceed, NanoString would also be responsible for seeking regulatory approval for and commercializing the diagnostic test. NanoString is eligible to receive up to $22 million for technology access, near-term milestones and development funding, in addition to other potential undisclosed downstream payments.

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Under the Collaboration Agreement, NanoString will modify its PAM50-based Prosigna Breast Cancer Assay for potential use as a companion diagnostic test for enzalutamide for triple negative breast cancer. The modified test will be based upon data from a Phase 2 trial conducted by Medivation and Astellas that evaluated enzalutamide in patients with triple negative breast cancer.

"We are excited about the partnership with NanoString given their expertise in diagnostic development and that the Prosigna assay has regulatory clearance in the U.S. and European Union," said Amy Peterson, M.D., vice president, clinical development at Medivation. "Triple negative breast cancer has no recognized target and standard therapy is therefore cytotoxic chemotherapy. This diagnostic has the potential to identify patients with triple negative breast cancer appropriate for treatment with enzalutamide. We look forward to generating additional clinical data that validates this potential in a severely underserved patient population."

"We’re excited to work with Medivation and Astellas to translate their discoveries and Phase 2 findings into a potential label expansion for enzalutamide with a companion diagnostic," said Brad Gray, president and chief executive officer of NanoString Technologies. "We’re also pleased to have the opportunity to leverage our PAM50-based Prosigna breast cancer franchise, potentially expanding its role in informing breast cancer treatment decisions and enhancing the description of the intrinsic biology of breast cancer to aid in therapeutic treatment decisions. Furthermore, we believe this collaboration will provide additional validation of our nCounter Dx Analysis System as the platform-of-choice for development of multiplexed companion diagnostic assays."

XTANDI (enzalutamide) capsules is currently approved for the treatment of metastatic castration-resistant prostate cancer; it is not approved for use in women and is contraindicated in women who may become pregnant. Enzalutamide is not approved for women with advanced triple negative breast cancer. See Important Safety Information below.

About the Prosigna Breast Cancer Prognostic Gene Signature Assay
The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma. The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

In the United States, the Prosigna Assay has 510K clearance and is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand and Hong Kong.

In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as: (1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes. For more information, please visit www.prosigna.com.

On January 07, 2016 Kite Pharma, Inc. (NASDAQ:KITE) reported that it has entered into a Cooperative Research and Development Agreement (CRADA) with the NCI for the research and clinical development of a fully human anti-CD19 chimeric antigen receptor (CAR) product candidate for the treatment of B-cell lymphomas and leukemias (Press release, Kite Pharma, JAN 7, 2016, View Source [SID:1234508683]). Under the CRADA, Kite will collaborate with James (Jim) N. Kochenderfer, M.D., an investigator in the Experimental Transplantation and Immunology Branch of the NCI, to evaluate this product candidate in a Phase 1 clinical study this year.

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In addition, the newly established CRADA will focus on the development of next-generation CAR programs directed against other novel antigens for the treatment of B-cell lymphomas and leukemias. Kite will also continue to advance multiple CAR and T cell receptor (TCR) programs under its existing CRADA with the Surgery Branch of the NCI, led by Dr. Rosenberg, a recognized pioneer in immuno-oncology and special advisor to Kite.

"We are delighted to expand our partnership with the NCI by working with the Experimental Transplantation and Immunology Branch. Our close collaboration with the Surgery Branch over the past three years has enabled us to advance the science behind T cell therapy and to expand our clinical product candidate portfolio at Kite. The new CRADA is a natural step in our life cycle management strategy to further improve the success of CAR therapy for patients with advanced B-cell malignancies," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer.

"Dr. Kochenderfer is a world renowned expert in T cell therapy who pioneered innovative CAR T therapies for patients with aggressive non-Hodgkin lymphoma," added David Chang, M.D., Ph.D., Chief Medical Officer and Executive Vice President of Research and Development. "His seminal research in anti-CD19 CAR T cell therapy has been instrumental for our lead product candidate, KTE-C19, which is currently in four Kite-sponsored clinical trials in B-cell malignancies. We look forward to expanding our successful collaboration on next generation technologies with Jim."

On January 7, 2016 Celsion Corporation (NASDAQ: CLSN), reported new translational data from its Phase 1b study of GEN-1 in patients with platinum-resistant ovarian cancer (Press release, Celsion, JAN 7, 2016, View Source [SID:1234508682]). GEN-1 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. The new data demonstrate that intraperitoneally-administered GEN-1 produces an immunologically distinct IL-12 protein that is localized at the tumor site and lasts for up to one week after a single treatment. Furthermore, concomitant increases in IFN-γ and TNF- α indicate that the IL-12 produced following treatment with GEN-1 treatment is immunologically active. Celsion Corporation is a fully integrated oncology company focused on the development of a portfolio of innovative cancer treatments, including directed chemotherapies, immunotherapies and RNA- or DNA-based therapies for the treatment of cancer and other difficult-to-treat diseases.

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"We now have clear clinical evidence that treatment of platinum-resistant ovarian cancer with GEN-1 produces a sustained, localized immune response, which then translates to the compelling activity and tolerability profile we have seen in early clinical studies," said Khursheed Anwer, Ph.D., executive vice president and chief scientific officer of Celsion. "These data also provide additional evidence of GEN-1’s ability to overcome the limitations associated with recombinant IL-12, which has a very short half-life and results in high systemic levels of IL-12, leading to potentially severe toxicities. We plan to build on these data and advance our understanding of GEN-1’s mechanism of action further with additional translational research as part of our ongoing OVATION Study."

The Phase 1B dose escalating study enrolled 16 patients with platinum-resistant ovarian cancer and evaluated the safety, tolerability and efficacy of GEN-1 in combination with pegylated doxorubicin as well as the effect of intraperitoneal injection of GEN-1 on IL-12 and tumor cytokine levels. Patients received pegylated liposomal doxorubicin on day 1 and GEN-1 on days 1, 8, 15 and 22. This treatment regimen was repeated every 28 days in the absence of disease progression or toxicity.

Celsion reported clinical findings from the Phase 1b study at the 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Meeting in June 2015 demonstrating an overall clinical benefit of 57% for all treatment arms. The overall clinical benefit observed at the highest dose cohort in this difficult-to-treat patient population was 100% (PR=33% and SD=67%) in all six evaluable patients. A maximum tolerated dose was not reached and studies evaluating higher doses of GEN-1 are currently underway.

The new translational data reported today is highlighted below:

Intraperitoneal administration of GEN-1 in platinum-resistant ovarian cancer patients resulted in a significant increase in IL-12 levels in peritoneal fluid samples. IL-12 levels were quantifiable in 91% of evaluable fluid samples collected post GEN-1 treatment. None of the evaluable pre-treatment peritoneal fluid samples had any detectable IL-12 levels.

The IL-12 levels were detectable for at least seven days after GEN-1 treatment.

In comparison to peritoneal fluid, the IL-12 levels in plasma samples (systemic exposure) following GEN-1 treatment were not detectable or were very low in quantity.

Significant increases in levels of IFN-γ, a key downstream mediator of IL-12 action, were observed in peritoneal fluid but not in plasma samples. At least a 5-fold increase above pre-treatment level in IFN- γ was observed in most samples, with the highest increase observed at 120-fold. Similar results were observed with TNF-α levels, with the highest increase observed at 77-fold over pre-treatment control.

A publication of this data is being prepared for submission for major scientific review which will detail all cytokine levels observed in this study.

Celsion intends to collect additional translational data, including cellular responses in primary tumor tissue and peritoneal ascites, in its ongoing OVATION Study, a Phase I dose escalation study in newly diagnosed ovarian cancer patients in the neoadjuvant setting.

"With these remarkable findings we feel confident that the data we expect to collect from the OVATION Study will provide further evidence that GEN-1, our gene-mediated immunotherapy, has significant potential in oncology generally and in ovarian cancer specifically," noted Michael H. Tardugno, Celsion’s chairman, CEO and president. "Our clinical development program for ovarian cancer is now well positioned with compelling clinical and biological data, fully supporting our thesis for combining GEN-1 with Doxil and Avastin to treat platinum-resistant ovarian cancer patients in a study we expect to launch later this year."

On January 7, 2016 BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called ACCURINS, reported the presentation of complete data from its phase 2 clinical trial of BIND-014, a PSMA-targeted ACCURIN containing docetaxel, in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) who either were or were not exposed to anti-androgens (abiraterone acetate and/or enzalutamide) (Press release, BIND Therapeutics, JAN 7, 2016, View Source [SID:1234508681]). BIND-014 was clinically active and well-tolerated and the study met its primary endpoint with 71 percent of patients achieving rPFS of at least 6 months. The complete data are being presented on January 7, 2016 during a poster session at the 2016 Genitourinary Cancers Symposium held in San Francisco.

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"We are encouraged by the safety and activity profile of BIND-014 in this phase 2 trial, which support its potential to be a nanomedicine alternative superior to conventional docetaxel," said Hagop Youssoufian, M.D., M.Sc., chief medical officer, BIND Therapeutics. "Although these data are encouraging, recent advances with anti-androgen therapy limit our ability to compare BIND-014 data to historical benchmarks. At this time, we are not planning further development of BIND-014 in mCRPC given the evolving treatment landscape. We anticipate additional BIND-014 data from both the iNSITE 1 trial in squamous histology non-small cell lung cancer and the iNSITE 2 trial in multiple tumor types during the first quarter of 2016, which we expect to determine our next steps in the clinical development of BIND-014."

In addition to the primary endpoint, data presented from the trial included measurements of safety and tolerability, objective response rates (ORR), prostate-specific antigen (PSA) response, changes in circulating tumor cells (CTC) and overall survival (OS). Key results include:

BIND-014 administered at 60 mg/m² on day 1 of a 21-day cycle was clinically active and well-tolerated when administered to patients (n=42) with chemotherapy-naive mCRPC, including the 74% of patients with prior exposure to abiraterone acetate and/or enzalutamide.

Median rPFS of 9.9 months (95% CI, 7.1 – 12.6) was achieved (n=42 with 8 censored).
A confirmed ORR of 21% was observed in patients with measurable disease (n=19).
A 50% reduction in PSA was observed in 30% of PSA evaluable patients (n=40).
CTC conversion from ≥ 5 cells/7.5 mL blood at baseline to < 5 cells/7.5 mL blood was observed in 50% of patients.
Median OS was 13.4 months (95% CI, 9.9 – 18.6 months [n=42 with 10 censored]).