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Clinical research protocol of gene therapy targeting B cell non-Hodgkin Lymphoma was approved by Japanese Ministry

On March 13, 2014 Takara Bio reported that its application to conduct clinical research in Japan using CD19 antigen specific CAR (Chimeric Antigen Recepter) gene therapy to target B cell non-Hodgkin Lymphoma, which Takara Bio has been preparing in collaboration with Jichi Medical University, Utsunomiya/Tochigi, Japan, was approved as of March 4th, 2014, by Health Science Council of Japanese Ministry of Health, Labour and Welfare (MHLW).

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CAR gene therapy is one method for ex-vivo gene therapy. In the United States and Europe, many CAR clinical trials targeting Malignant Lymphoma (ML), Acute Lymphocytic Leukemia (ALL), and Chronic Lymphocytic Leukemia (CLL) have been conducted. Since a research team at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, US) reported remarkable efficacies of CD19-CAR gene therapy, it has been actively developed as a promising new cancer therapy. In 2011 Takara Bio and MSKCC executed an agreement, whereby MSKCC would provide its clinical data and materials relevant to the clinical trials of the CD19-CAR gene therapy that MSKCC has been conducting in the United States since 2007, so that Takara Bio and Jichi Medical University could start their planned clinical research in Japan. In this clinical research, Takara Bio will manufacture a GMP-grade CD19-CAR retrovirus vector itself utilizing virus producer cells provided by MSKCC, which will be used for the gene transduction in combination with the RetroNectin reagent, Takara Bio’s efficient gene transduction reagent.

Takara Bio positions the CD19-CAR gene therapy as one of the most important pipelines in its gene therapy portfolio and will accelerate clinical development for it, evaluating its safety and efficacy in this clinical research.

[ Outline of planned clinical research ]
Title Clinical Research of gene therapy for refractory B-cell non-Hodgkin Lymphoma using autologous T cells expressing a chimeric antigen receptor specific to the CD19 antigen
Subjects CD19 antigen positive patients with refractory B cell non-Hodgkin Lymphoma
Location of clinical research Jichi Medical University, Utsunomiya/Tochigi, Japan
Method CAR genes that are capable of specifically recognizing CD19 antigens of cancer cells are transduced into the patient’s own lymphocytes obtained from peripheral blood, which are expanded and then re-infused into the patient.
Primary outcomes To evaluate the safety of the CD19-CAR gene therapy
Secondary outcomes To evaluate clinical effect (Anti-tumor effect)
Number of subjects 6 subjects (max. 18)
Trial period To evaluate clinical effect (Anti-tumor effect)

Progenics Pharmaceuticals Announces Fourth Quarter and Year-End 2013 Financial Results and Initiates Clinical Development of Small Molecule Targeted Therapeutic

MIP-1095 is a PSMA-targeted small molecule radiopharmaceutical which is under development by Progenics for the treatment of prostate cancer (Press release Progenics Pharmaceuticals, MAR 13, 2014, View Source [SID:1234500273]).

TESARO and AnaptysBio Announce Collaboration and Exclusive Worldwide License Agreement for Multiple Immuno-Oncology Programs

On March 13, 2014 TESARO and AnaptysBio announced an exclusive, worldwide license agreement and immuno-oncology antibody collaboration (Press release TESARO, MAR 13, 2014, View Source [SID:1234500270]). Under the terms of the agreement, TESARO receives rights to monospecific antibody drug candidates targeting TIM-3, LAG-3 and PD-1 and dual reactive antibody drug candidates targeting PD-1/TIM-3 and PD-1/LAG-3. Therapeutic antibodies selected from these programs will form the basis of a strategic platform that will enable TESARO to develop novel monotherapy and combination-based approaches with immuno-oncology and other anti-cancer agents in a variety of indications. Antibody candidates from these programs are expected to enter clinical trials over the next 18 to 24 months.
Tesaro is also interested in evaluating combinations of these antibodies with TSR-011, ALK/TRK inhibitor, and niraparib, PARP inhibitor, in addition to other anti-tumor agents with complementary mechanisms, such as immune modulating agents. The first clinical trial from this collaboration is projected to begin in mid-2015, and Tesaro expects to advance an additional candidate into clinical trials every one to two quarters thereafter.

Agreement Terms

Under the terms of this agreement with AnaptysBio, TESARO will pay an upfront license fee of $17 million, as well as provide funding of costs incurred by AnaptysBio related to the development programs. For each development program, AnaptysBio is eligible to receive milestone payments of $18 million if certain research and development events are achieved and an additional $90 million associated with certain U.S. and ex-U.S. regulatory submissions and approvals in multiple indications. AnaptysBio will also be eligible to receive tiered single-digit royalties related to worldwide net sales of products developed under the collaboration and certain commercial milestone payments if specified levels of annual worldwide net sales are attained. AnaptysBio and TESARO will together complete preclinical development of the antibody candidates, with TESARO being solely responsible for all clinical development, manufacturing, regulatory and commercial activities.

Immuno-Oncology Platform

Antibodies to immune checkpoint receptors have recently demonstrated promise in the treatment of certain solid tumors, including metastatic melanoma, renal cell carcinoma and non-small cell lung cancer. Although the normal function of immune checkpoint receptors is to maintain immune homeostasis, they are co-opted by certain tumors to evade immune surveillance. PD-1, TIM-3 and LAG-3 are each checkpoint regulators that modulate the function of the immune system via different mechanisms, and may limit the ability of the immune system to respond effectively to tumors. By blocking the interaction of PD-1, TIM-3 and LAG-3 with their respective ligands, the antibodies exclusively licensed under this collaboration aim to restore immune anti-cancer function in patients across a variety of tumor types.

PD-1, or programmed death-1, is a key immune checkpoint molecule that can limit T-cell-mediated immune responses. The presence of the PD-1 ligand, PD-L1 has been identified on many tumor types, and expression of PD-L1 has been linked to poor clinical outcomes in a variety of cancers. Anti-PD-1 antibodies have demonstrated in vivo efficacy in tumor models and have shown promising results in several clinical studies. TSR-042 is anticipated to begin clinical trials in mid-2015, and combination preclinical pharmacology studies with TSR-011, niraparib and other anti-tumor agents are planned to initiate during 2014.

TIM-3, or T-cell immunoglobulin and mucin domain-3, functions as a pattern recognition receptor that dampens the anti-tumor immune response. Anti-TIM-3 antibodies have shown preclinical anti-tumor activity and may enhance anti-tumor immunity in combination with an anti-PD-1 agent or other immune modulating molecules. In collaboration with AnaptysBio, TESARO expects to select a TIM-3 antibody for clinical development during the second quarter of 2014.

LAG-3, or lymphocyte activation gene-3, is a negative regulator of T-cell activity. Preclinical studies have demonstrated anti-tumor activity by blocking LAG-3 and PD-1 in tumor models, and LAG-3 IgG fusion protein has demonstrated promising results in clinical trials for various solid tumors. In collaboration with AnaptysBio, TESARO expects to select a LAG-3 antibody for clinical development in the third quarter of 2014.

TNI BioTech, Inc. Granted Additional Patent for Methods for Inducing Sustained Immune Response of T-Cells

On March 12, 2014 TNI BioTech reported the U.S. Patent and Trademark Office (USPTO) has granted a key patent for IRT-101 (MENK) for inducing sustained immune response of T-Cells (Press release, TNI BioTech, MAR 12, 2014, View Source [SID:1234501364]).

The present invention relates to methods of stimulating and promoting a sustained natural immune system response, resulting in increased resistance and inhibition of infectious agents, including viruses, bacteria, fungi and parasites, and other immunodeficiency-related ailments. More specifically, the invention relates to an intermittent dose schedule for promoting a sustained increased level of T-cell production (cytotoxic T-cells) including CD3, CD4, CD8, natural killer (NK) cells, CD38 cells, and interleukin II receptor. Pursuant to the patent, these therapies can be used on immunocompromised individuals including patients with cancer, or undergoing x-ray, surgery, or chemotherapy treatments.

The patent assigned to TNI BioTech from Nicholas Plotnikoff, which is already the subject of a previously granted U.S. patent, protects the activated NK cells. Similar patent protection has been obtained in India, Russia and the United Kingdom.

IRT-101 (MENK) is an active immunotherapy with MENK for patients with deficient functioning of the immune system. It works by restoring the patient’s immune functions and by activating the lymphocytes to attack cancer cells and infectious diseases, such as HIV/AIDS. This is accomplished because MENK binds to opioid receptors on both immune cells and on cancer cells, which directly inhibits the growth of cancer cells and increases the number and functions of T-cells, NK cells, NK-T cells, and gamma/delta T-cells. These cells then destroy infective organisms and tumor cells while simultaneously inhibiting the ability of T regulatory (Treg) cells to block the functions of anti-cancer or anti-infectious disease lymphocytes.

Noreen Griffin, CEO of TNI BioTech said, "We are pleased to be able to expand our patent portfolio and believe this patent plus the many other patents surrounding MENK provide us with broad composition-of-matter protection for our suite of immunotherapy treatments."

AMHR2 and 3C23K

The anti-AMHR2 product (3C23K) which is under development by GamaMabs is an Emabling engineered humanized mAb directed against the receptor of the anti-Müllerian hormone (AMHR2), alternatively known as Müllerian Inhibiting Substance Receptor II (MISRII) (Company Pipeline GamaMabs Pharma, MAR 12, 2014, View Source [SID:1234500268]).