On November 1, 2016 Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, reported that it has received a milestone payment from Novartis in relation to the US FDA NDA filing by Novartis for LEE011 (ribociclib) plus letrozole as a first-line treatment for HR+/HER2- advanced breast cancer (Press release, Astex Pharmaceuticals, NOV 1, 2016, View Source [SID1234516166]).

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Novartis also announced that it had received FDA Priority Review for the NDA application of LEE011 as first-line treatment of postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in combination with letrozole.

LEE011 (ribociclib) was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex. Under the collaboration, which commenced in 2005, NIBR scientists worked with Astex on a programme of early drug discovery research resulting in the discovery of LEE011. Novartis then led LEE011 into preclinical and later clinical development. Under terms of the agreement, Astex is eligible to receive further milestone payments in respect of additional regulatory filing and approvals in Europe and Japan, as well as royalty payment on annual sales of ribociclib should the drug be approved.

Harren Jhoti, President and CEO of Astex, said, "We are absolutely delighted that Novartis has reached such a significant stage in the development of LEE011. If the product is approved, it will provide an important treatment option for many patients with advanced disease. We congratulate Novartis for an excellent job in developing LEE011 and on the achievement of US FDA Priority Review of the NDA filing."

About LEE011 (ribociclib)

LEE011 (ribociclib) is a selective cyclin dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated in a cell, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring cancer cells do not grow uncontrollably.

On November 1, 2016 TapImmune, Inc. (OTCMKTS: TPIV), a clinical-stage immuno-oncology company specializing in the development of innovative peptide and gene-based immunotherapeutics and vaccines for the treatment of cancer and metastatic disease, reported an update on the progression of a HER2neu vaccine into clinical trials (Press release, TapImmune, NOV 1, 2016, View Source [SID1234516164]). The vaccine (TPIV 110) consists of 4 proprietary Class II antigens and 1 proprietary Class I antigen. Both technologies were developed in the laboratory of Keith Knutson, Ph.D. and licensed from the Mayo Clinic.

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In a Phase I clinical trial on the 4 Class II antigens in HER2neu breast cancer patients performed at the Mayo Clinic, over 90 percent of patients developed a robust T-cell response against these antigens. Data on the novel Class I antigen, published in J. Immunol. (2013), 190, 479-488, showed that it was a naturally processed antigen which was at least four times more effective at killing human breast cancer cells than previously tested class 1 antigens. There is growing scientific evidence to suggest the mixture of Class 1 and Class 2 antigens is essential for obtaining a robust immune response with potential therapeutic effects.

As a result of this progress, and in accordance with the FDA, TapImmune plans to initiate clinical studies in 2017. The component peptides have been manufactured under GMP and a commercially viable formulation for the drug product has been developed. GMP manufacturing of the clinical supplies will begin toward the end of the year or early in Q1 2017. The Company expects to submit to the FDA an amended Investigational New Drug Application (IND) that includes the additional Type 1 antigen peptide at the end of 2016 or early in 2017. In addition to company-sponsored clinical trials, further studies on the treatment of ductal carcinoma in situ (DCIS) are being considered using non-dilutive capital.

"HER2neu is a well-known and important target in breast cancer treatments," said Dr. John Bonfiglio, President and CEO of TapImmune. "Our strategy is to highly leverage our HER2neu platform technology in treating this disease.".

On November 1, 2016 Propanc Health Group Corporation (OTCQB: PPCH) ("Propanc" or "the Company"), an emerging healthcare company focusing on development of new and proprietary treatments for cancer patients suffering from solid tumors such as pancreatic, ovarian and colorectal cancers, reported it has submitted an application for Orphan Medicinal Product Designation (OMPD) to the European Medicines Agency (EMA) for PRP, a solution for intravenous administration of pancreatic proenzymes trypsinogen and chymotrypsinogen (Press release, Propanc, NOV 1, 2016, View Source [SID1234516163]). The proposed orphan drug indication for PRP is for the treatment of ovarian cancer.

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"Obtaining orphan medicinal product designation from the EMA for our PRP therapy for ovarian cancer is a significant regulatory milestone that we are looking forward to, and will be a positive step forward in Propanc’s ongoing efforts to develop effective treatments for metastatic cancer," said James Nathanielsz, Propanc’s Chief Executive Officer. "This will reinforce our strategic investment in PRP, demonstrating progress in developing a potential best-in-class therapy that could transform treatment for patients with metastatic cancers, where there are limited treatment options. Once the OPMD is granted, we will work closely with the regulatory authorities and our clinical investigators to advance PRP promptly through the next stages of clinical research and development."

Ovarian cancer is a disease with the lowest survival rate of all gynecological cancers (Quaglia et al. 2009), making it the seventh most common cause of cancer death in women worldwide. More than 60% of women present with stage III or stage IV metastasized cancer at the time of first diagnosis and have a five-year survival of less than 20%. The therapy is very complex and presupposes expertise in both surgery and oncology (Roett and Evans, 2009). Thus, to date therapy of ovarian cancer is a challenge and prognosis is rather poor, creating a high unmet medical need for new efficacious and safe treatment options.

Orphan medicinal product designation is granted by the European Commission, following a positive opinion from the Committee for Orphan Medicinal Products (COMP), to a medicinal product that is intended for the diagnosis, prevention or treatment of a life-threatening or a chronically debilitating condition affecting not more than five in 10,000 persons in the European Community when the application for designation is submitted. An orphan designation allows a company to benefit from incentives from the European Union to develop a medicine for a rare disease, such as reduced fees and protection from competition once the medicine is placed on the market.

The rationale for developing PRP, a formulation of the pancreatic proenzymes trypsinogen and chymotrypsinogen for intravenous administration, in the proposed indication ovarian cancer is based on a set of in-vitro studies on cancer stem cells generated from ovarian cancer cell lines as well as xenograft and orthotopic mouse models of ovarian cancer. In summary, these data indicate that the dramatic reduction of cellular markers associated with the process of epithelial-mesenchymal transition (EMT) as a consequence of PRP treatment can not only reverse the EMT process with the implication to stop tumor progression and metastasis, but also seem to repress the development of cancer stem cells (CSCs). Consequently, these results are strong indicators of the therapeutic potential of PRP that could be categorized as an anti-CSC therapeutic drug.

Preliminary early clinical data on the treatment of six patients with ovarian cancer have been obtained with PRP in the context of a UK "Specials" License treatment. Together, these data support the medical plausibility of the proposed indication and a distinctive benefit-safety profile of PRP for the treatment of ovarian cancer.

On November 1, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM) and Ospedale Pediatrico Bambino Gesù (OPBG), a leading European pediatric research center and hospital, reported that they have entered into an expanded collaboration focused on preclinical and clinical development of CD19 and other CAR T and TCR therapeutics engineered with Bellicum’s CaspaCIDe molecular safety switch technology (Press release, Bellicum Pharmaceuticals, NOV 1, 2016, View Source [SID1234516154]).

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The two organizations agreed to jointly develop CARs and other cell therapies discovered by OPBG and engineered with Bellicum’s CaspaCIDe safety switch, which is designed to reduce or eliminate cells that become toxic or are no longer needed. Under terms of this agreement, Bellicum agreed to provide financial support to the research collaboration in exchange for exclusive worldwide rights to commercialize certain cell therapies that are developed, while OPBG maintains rights for research purposes. OPBG will conduct research and clinical studies of CAR T and TCR therapeutics in pediatric patients, with initial CD19 CAR T and GD2 CAR T clinical trials in pediatric acute lymphoblastic leukemia and neuroblastoma patients, respectively, expected to start in 2017. In addition, OPBG agreed to manufacture European clinical trial supplies for the investigational programs, as well as Bellicum’s PRAME-targeted TCR, BPX-701, in its GMP facility.

"The Ospedale Pediatrico Bambino Gesù is among the world’s leading cell and gene therapy research centers and hospitals, and we are enthusiastic about working with them to develop controllable engineered T-cell therapies," commented Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "This agreement builds on our highly successful clinical development collaboration with OPBG on BPX-501, our CaspaCIDe-enabled T-cell therapy in clinical development for patients undergoing haploidentical hematopoietic stem cell transplant. OPBG has developed several exciting and innovative new cell therapies, including a CD19 CAR T cell that we believe will be highly differentiated by virtue of our clinically validated CaspaCIDe safety switch."

"We have a highly productive and synergistic relationship with Bellicum, and look forward to building on our present research collaboration," commented Dr. Mariella Enoc, President of the Board of Directors of OPBG. "The combination of Bellicum’s innovative safety switch technology and our cell and gene therapy expertise, clinical study network and GMP vector and cell manufacturing capabilities, makes this an ideal partnership to rapidly advance controllable cell therapies that could benefit children and adults with life-threatening cancers throughout the world."

On November 1, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that it has completed the niraparib rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for the maintenance treatment of patients with platinum-sensitive, recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy (Press release, TESARO, NOV 1, 2016, View Source [SID1234516152]).

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The niraparib NDA is supported by data from the ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study that enrolled 553 patients with recurrent ovarian cancer who were in response to their most recent platinum-based chemotherapy. This trial was designed to assess progression free survival (PFS) in patients who were assigned to one of two cohorts based upon germline BRCA mutation status, as determined by the Myriad BRACAnalysis CDx test. Within the cohort of patients who were not germline BRCA mutation carriers (non-gBRCAmut), tumor samples were assessed for HRD status using the Myriad myChoice HRD test.

The ENGOT-OV16/NOVA trial successfully achieved its primary endpoint in both patient cohorts, demonstrating that niraparib treatment significantly prolonged PFS compared to control. The full results of the ENGOT-OV16/NOVA trial were presented in detail at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen on October 8, 2016 and were published simultaneously in The New England Journal of Medicine. Based upon the results of this trial, the indication proposed in the NDA provides for the use of niraparib regardless of tumor biomarker status, and it is anticipated that the BRACAnalysis CDx and myChoice HRD tests would be available to physicians as complementary diagnostics.

"TESARO is working daily to benefit the many women living with ovarian cancer," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Our niraparib NDA and MAA submissions represent a significant step in our efforts to bring meaningful therapies to these patients."

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in three pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial), a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial), and a Phase 3 trial for the treatment of patients with germline BRCA-mutated, metastatic breast cancer (the BRAVO trial). Several combination studies are also underway, including trials of niraparib plus pembrolizumab and niraparib plus bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

In September, the FDA granted Fast Track designation to niraparib. The FDA Fast Track designation is designed to facilitate the development and expedite the review of medicines that are intended to treat serious conditions and address unmet medical needs. As part of the Fast Track program, the FDA allows for the submission of completed portions of an NDA on an ongoing or rolling basis.

Niraparib is an investigational agent and, as such, has not been approved by the U.S. FDA, European Medicines Agency (EMA), or any other regulatory agencies.

The most common (≥10%) treatment-emergent grade 3/4 adverse events in the niraparib arm were thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%) with treatment discontinuation for these events of 3.3%, 1.4% and 1.9%, respectively. Thrombocytopenia was not associated with grade 3/4 bleeding events. The majority of these hematological laboratory abnormalities occurred within the first three cycles; following dose modifications the incidence of these lab abnormalities decreased and thrombocytopenia and neutropenia were infrequent beyond cycle 3. The rates of MDS/AML in the niraparib (1.4%) and control (1.1%) arms were similar. There were no deaths among patients during study treatment.

About Ovarian Cancer
Approximately 22,000 women are diagnosed each year with ovarian cancer in the United States, and more than 65,000 women are diagnosed annually in Europe. Ovarian cancer is the fifth most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85% of patients will experience recurrence within two years. If approved, niraparib may address the difficult "watchful waiting" periods experienced by patients with recurrent ovarian cancer in between cycles of platinum-based chemotherapy.