On January 3, 2017 Cellectis (Alternext: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), reported the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) requesting approval to initiate Phase 1 clinical trials of UCART123 the Company’s most advanced, wholly owned TALEN gene edited product candidate in patients with acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Cellectis, JAN 3, 2017, View Source [SID1234517253]).

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Pending regulatory clearance, Cellectis plans to initiate Phase 1 clinical trials in the first half of 2017. This is the first IND filing for human clinical applications of a gene edited allogeneic "off-the-shelf" product candidate in the U.S. UCART123 is a gene edited T-cell investigational drug that targets CD123, an antigen expressed at the surface of leukemic cells in AML, as well as on leukemic and other tumoral cells in BPDCN.

The UCART123 program was subject to a public hearing by the National Institutes of Health’s Recombinant DNA Advisory Committee (RAC) in December 2016, where it received the unanimous approval of the RAC committee members.

AML is a devastating clonal hematopoietic stem cell neoplasm that is characterized by uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues. These cells disrupt normal hematopoiesis and rapidly cause bone marrow failure and death. In the U.S. alone, there are an estimated 19,950 new AML cases per year, with 10,430 estimated deaths per year.

The clinical research at Weill Cornell will be led by principal investigator Dr. Gail J. Roboz, Director of the Clinical and Translational Leukemia Programs and Professor of Medicine. BPDCN is a very rare and aggressive hematological malignancy that is derived from plasmacytoid dendritic cell precursors. BPDCN is a disease of bone marrow and blood cells but also often affects skin and lymph nodes.

The UCART123 clinical program at MD Anderson will be led by Dr Naveen Pemmaraju, MD, Assistant Professor, and Professor Hagop Kantarjian, MD, Department Chair, Department of Leukemia, Division of Cancer Medicine.

The manufacturing process of Cellectis’ allogeneic CAR T-cell product line, Universal CARTs or UCARTs, yields frozen, off-the-shelf, engineered CAR T-cells. UCARTs are meant to be readily available CAR T-cells for a large patient population. Their production can be industrialized and standardized with defined pharmaceutical release criteria.

"Following a Pre-IND meeting with the FDA in August 2016 and a NIH-RAC public hearing in December 2016, filing this IND is an important regulatory milestone for the Company. It represents many years of research and development by a dedicated team focused on developing highly innovative UCART products for the benefit of patients", stated Stephan Reynier, Chief Regulatory and Compliance Officer, Cellectis.

Chief Medical Officer, Dr. Loan Hoang-Sayag, commented: "UCART123 represents a unique therapeutic approach for patients with unmet medical needs such as relapsed or refractory AML, high risk AML and BPDCN and we are excited to move this experimental product into clinical development. We have designed robust Phase 1 clinical trials to better understand the potential of UCART123 to address the needs of different patient populations."

Information about ongoing clinical trials are publically available on dedicated websites such as:

www.clinicaltrials.gov in the U.S.

www.clinicaltrialsregister.eu in Europe

On January 3, 2017 Inspyr Therapeutics (OTCQB:NSPXD), a clinical-stage biotechnology company developing a novel prodrug therapeutic for the treatment of cancer, reported the initiation of development programs focused on Mipsagargin combination therapies (Press release, Inspyr Therapeutics, JAN 3, 2017, View Source [SID1234517252]).

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To evaluate the potential of Mipsagargin in combination with Nexavar, Inspyr plans to conduct a preclinical study in liver PDX tumor models that express PSMA, the target of Mipsagargin. The tumor models selected express different levels of PSMA, including one that is resistant to Nexavar. The Company expects to share initial results of this study in the second quarter of 2017.

Concurrently, the Company is finalizing the design of a clinical study to examine the potential benefits of Mipsagargin in combination with Nexavar in patients with advanced hepatocellular carcinoma (HCC), or liver cancer.

"Combining Mipsagargin and Nexavar, each targeting the tumor vasculature through different mechanisms of action, may be synergistic and deliver enhanced anti-tumor activity, potentially resulting in an improved therapy option for patients with liver cancer," said Dr. Ron Shazer, Inspyr’s Senior Vice President and Chief Medical Officer. "We expect this non-clinical study to be the first of several planned studies examining the potential of Mipsagargin across different types of cancer as an effective combination agent addressing unmet needs for oncology patients."

About Mipsagargin
Mipsagargin is a novel clinical stage thapsigargin-based, PSMA-activated prodrug that consists of an analog of thapsigargin coupled to a masking peptide which inhibits its activity until proteolytic cleavage at the tumor site. Prostate-Specific Membrane Antigen (PSMA) is expressed on tumor vasculature endothelial cells in a wide variety of solid tumors. Thapsigargin inhibits the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump which is essential for cell viability. Mipsagargin is being developed for the treatment of multiple cancers.

On January 3, 2017 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration (AMD) and fibrotic diseases, reported that it has reached an agreement with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the protocol design, clinical endpoints and statistical analysis approach for the Company’s Phase 3 study evaluating TRC105 for the treatment of patients with advanced angiosarcoma (Press release, Tracon Pharmaceuticals, JAN 3, 2017, View Source [SID1234517251]).

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"The SPA agreement represents a significant milestone for TRACON, as it provides us with a clearly defined development and regulatory pathway for TRC105, our lead clinical program, for the treatment of angiosarcoma," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "We appreciate the FDA’s engagement and guidance during the SPA process and look forward to dosing the first patients in the trial during early 2017."

TRACON intends to conduct the Phase 3 TAPPAS trial (a randomized Phase 3 trial of TRC105 And Pazopanib versus Pazopanib alone in patients with advanced AngioSarcoma) at sites in both the United States and Europe. This one-to-one randomized trial of TRC105 in combination with Votrient (pazopanib) versus Votrient alone will initially enroll 124 patients. The trial features an adaptive design that, based on an interim analysis, can allow for sample size re-estimation up to a maximum of 200 patients, as well as possible enrichment of more responsive patients with cutaneous angiosarcoma. The primary endpoint of the trial is progression-free survival (PFS), with overall survival (OS) as a secondary endpoint.

Further details of the Phase 3 clinical trial are available on www.clinicaltrials.gov under NCT02979899.

About Special Protocol Assessment (SPA)

The SPA process is one in which a sponsor asks the FDA to evaluate the proposed design and size of Phase 3 clinical trials that are intended to form the primary basis for determining a drug product’s efficacy. An SPA agreement indicates concurrence with the adequacy and acceptability of specific critical elements of protocol design, endpoints and analysis. Additionally, it provides a binding agreement with FDA’s review division with respect to the elements agreed to in the SPA process that are considered critical to ensuring the trial has the potential to support a future marketing application. However, final marketing approval depends upon the results of efficacy, the safety profile, and an evaluation of the risk/benefit of treatment demonstrated in the Phase 3 clinical trial, among other requirements, and the FDA may revoke or alter its agreement under certain circumstances. For further information regarding the SPA process, please visit the FDA website at www.fda.gov.

About TRC105 (carotuximab)

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute (NCI) for the treatment of solid tumor types in combination with VEGF inhibitors. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. TRC205, a second generation antibody to endoglin, is undergoing preclinical testing in models of fibrosis.

About Angiosarcoma

Angiosarcoma is an aggressive form of soft tissue sarcoma (STS) of endothelial cell origin that is associated with poor prognosis. Angiosarcoma has a 5-year survival rate of less than 12%, which highlights the aggressive nature of this tumor when compared to a 5-year survival rate of approximately 56% for all STS. Angiosarcoma can arise in any soft tissue structure. About half of patients present with a primary cutaneous lesion. Risk factors include prior radiation exposure as well as inflammatory damage in chronically sun exposed skin. Angiosarcoma has also been associated with chronic lymphedema. Although resection with curative intent followed by adjuvant radiotherapy is the treatment of choice for localized disease amenable to surgery, approximately 50% of these patients will develop metastases and die from the disease. Furthermore, metastases are frequently present at diagnosis, and resection of metastases is rarely feasible.

Angiosarcoma is an extremely rare disease and meets the definition for an orphan disease in the US and European Union (EU), the two regions for which the Phase 3 TAPPAS study is planned. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the US and EU. The annual incidence of angiosarcoma in the US was reported by the NCI in 2015 to be 475 cases. In the EU the incidence of angiosarcoma is 0.01 per 10,000, accounting for an estimated 508 cases annually.

On January 3, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that it has submitted an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 trial of KITE-718, a T cell therapy engineered to express T cell receptors (TCRs) that target MAGE A3 and MAGE A6 (Press release, Kite Pharma, JAN 3, 2017, View Source [SID1234517250]). MAGE A3/A6 are frequently found in common tumors including bladder, esophageal, head and neck, lung and ovarian cancers. KITE-718 recognizes the MAGE A3 and MAGE A6 fragments bound to a Class II HLA (DPB1*04:01) and therefore has the potential to kill tumor cells both directly and indirectly through activation of the immune system given it incorporates a class II TCR. Class II HLA (DPB1*04:01) is found in 50 percent to 70 percent of Caucasians. The trial is designed to assess the safety and anti-tumor effect of KITE-718 on these solid tumors.

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"Submission of this IND is an important milestone for our solid tumor strategy utilizing engineered T cell therapy based on both TCR and CAR platform technology," said David Chang, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Kite. "TCRs have the potential to access a broad spectrum of tumor targets and we have incorporated our next generation cell manufacturing technologies into KITE-718 to exploit targets naturally expressed in common solid tumors for which there is a great unmet medical need."

KITE-718 is built on the proof of concept data established by the National Cancer Institute’s (NCI) MAGE A3/A6 TCR program (NCT02111850). No off-target toxicity was observed in the NCI study, and evidence of tumor regression was seen in patients with multiple types of solid tumors. KITE-718 has been optimized from the foundational work at the NCI by streamlining the manufacturing process through advanced technologies and next-generation cell manufacturing conditions.

On January 3, 2016 Eagle Pharmaceuticals, Inc. (Nasdaq:EGRX) ("Eagle" or "the Company") reported that the 505(b)(2) New Drug Application (NDA) for its novel pemetrexed drug product has been submitted to the U.S. Food and Drug Administration (FDA) (Press release, Eagle Pharmaceuticals, JAN 3, 2017, View Source [SID1234517249]).

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This 505(b)(2) NDA requests FDA approval of Eagle’s ready-to-dilute (RTD) Pemetrexed Injection product for the treatment of Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer, and Mesothelioma (in combination with cisplatin).

"We look forward to the FDA’s decision on this NDA this year, and to continuing to work closely with the FDA through the review process. We believe our RTD liquid formulation will be well received, adding to Eagle’s growing commercial portfolio of improved formulations, benefiting patients and shareholders alike," said Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

Eagle’s RTD Pemetrexed Injection product is administered as an IV infusion.