On July 10, 2017 Medigene AG (MDG1, Frankfurt, Prime Standard, TecDAX) reported it has filed a clinical trial authorization application (CTA) to begin the Company’s first clinical trial with its proprietary T-cell receptor- (TCR) modified T cells as an immunotherapy to treat a range of blood cancer indications (Press release, MediGene, JUL 10, 2017, View Source [SID1234519785]). The CTA was submitted to the German authority Paul-Ehrlich-Institute (PEI) today. As previously announced, Medigene expects to start this trial by year end 2017.

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Medigene intends to start a combined Phase I/II safety and feasibility clinical trial of its TCR therapy MDG1011, subject to regulatory approval. MDG1011 targets PRAME and will be evaluated in patients with advanced hematological diseases, namely acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM). The final study design will be made available after CTA approval by PEI. To date, no clinical trials utilizing TCR- modified T cells have been conducted in Germany.

The CTA submission triggers a final milestone payment of EUR 2.0 million from Medigene AG to the former contributing shareholders of Medigene Immunotherapies GmbH (formerly: Trianta Immunotherapies GmbH) within the next five months. Medigene intends to settle this payment through the issuance of new shares from authorized capital. The milestone payment was an agreed part of the purchase price for the acquisition of Trianta in January 2014. With this third and final milestone payment, the total purchase price of approximately EUR 10 million will have been entirely settled.

Dr. Kai Pinkernell, SVP and CMO of Medigene AG, noted: "Starting this TCR trial will be a major development for Medigene. We are excited to begin one of the first TCR trials in Germany so far, utilizing a cellular immunotherapy approach that could one day make a significant difference for cancer patients. In addition to our ongoing clinical trial with DC vaccines, this TCR study will move Medigene’s second immunotherapy technology into clinical stage."

Prof. Dolores J. Schendel, CEO/CSO of Medigene AG, said: "Through several decades of research, it has been my and my group’s driving focus to develop treatments for patients with advanced hematological diseases. I would like to thank our fine team of scientists for their dedication in helping to fulfill this vision. We are proud of reaching the final milestone in connection with the Trianta acquisition which marks the completion of a successful corporate repositioning, transforming Medigene into a T-cell immunology company with our ‘living immunotherapies’ in clinical development."

About Medigene’s TCR technology: Medigene’s TCR technology for adoptive T-cell therapy is one of the company’s three highly innovative and complementary immunotherapy platforms in immuno-oncology.

The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors (TCRs). The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex vivo).

TCR therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR T) therapy. Medigene is preparing the clinical development of its first TCR candidates and is establishing a pipeline of recombinant T-cell receptors, and has established Good Manufacturing Practice (GMP)-compliant processes for their combination with patient-derived T cells.

Medigene’s first TCR immunotherapy "MDG1011" will be tested in a clinical Phase I/II trial intended to be started by the end of 2017.

Besides the planned company-sponsored TCR trial, Medigene is involved in the preparation of an investigator-initiated trial (IIT) with TCRs in multiple myeloma (MM) to be conducted by the Charité – Universitätsmedizin Berlin in cooperation with the Max Delbrück Centre (MDC), Berlin.

On July 10, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima" the "Company") reported that its collaboration partner, the Institute of Clinical Cancer Research, Krankenhaus Nordwest GmbH in Frankfurt Germany ("IKF"), has received the regulatory and ethical approvals for the clinical trial investigating IMP321 in new settings, called "INSIGHT".

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Approval has been received from the Paul-Ehrlich-Institut ("PEI"), the Federal Institute for Vaccines and Biomedicines for the German Federal Ministry of Health, which is the competent regulatory authority in the field of medicinal products that assesses and monitors antibodies for the treatment of cancer and autoimmune diseases for human use. Approval has also been received from the Institute of Clinical Cancer Research ethics committee. The clinical trial will commence in due course.

The investigator sponsored INSIGHT clinical trial will explore different routes of administration of IMP321 in solid tumours.

The lead investigator of the study, Dr Salah-Eddin Al-Batran, commented, "We are thrilled by the prospect of injecting an active immunotherapy directly at the tumour site to see whether the locally induced antigen presenting cell activation leads to a regression of distant tumour masses, a characteristic of anti-tumour CD8 T cell responses. In addition, analysis of local tumour biopsies before and after IMP321 injection will inform us about the immune infiltrates induced by this APC activator."

Marc Voigt, Chief Executive of Prima, commented, "We are pleased to see the initiation of this new therapeutic application for IMP321. It is the first ever investigation of whether direct injection of IMP321 into a solid tumour can activate the antigen presenting cells located inside the tumour to boost the body’s immune response."

About INSIGHT
INSIGHT is an explorative, single centre, open-label, Phase I clinical trial to evaluate the feasibility and safety of intra-tumoural, intra-peritoneal, and subcutaneous injections with IMP321 (LAG-3Ig fusion protein) for advanced stage solid tumour entities. The Lead Investigator of this up to 40 patient clinical trial is Professor Doctor Salah-Eddin Al-Batran, the Medical Director of the IKF.

On July 10, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to entrectinib for "treatment of NTRK fusion-positive solid tumors (Press release, Ignyta, JUL 10, 2017, View Source [SID1234519777])." NTRK fusions are molecular alterations that occur in a broad variety of adult and pediatric solid tumor types. Entrectinib is the company’s investigational, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor NTRK1/2/3, ROS1, or ALK gene fusions.

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About Orphan Drug Designation

Under the FDA’s Orphan Drug Designation program, orphan drug designation is granted by the FDA to novel drugs or biologics that treat rare diseases or conditions affecting fewer than 200,000 patients in the U.S. The designation allows the drug developer to be eligible for a seven-year period of U.S. marketing exclusivity upon approval of the drug, as well as tax credits for clinical research costs, the ability to apply for annual grant funding, clinical trial design assistance, and the waiver of Prescription Drug User Fee Act (PDUFA) filing fees.

About Entrectinib

Entrectinib is a novel, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor activating alterations to NTRK1/2/3 (encoding TRKA/TRKB/TRKC), ROS1 or ALK. Entrectinib is the only TRK inhibitor with clinically demonstrated activity against primary and metastatic CNS disease, and has not shown undesirable off-target activity. This product candidate is in a Phase 2 clinical trial called STARTRK-2, which is the second of the "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases." The trial is a global, multicenter, open label, potentially registration-enabling Phase 2 clinical trial of entrectinib that utilizes a basket design with screening of patient tumor samples for the relevant targets. Such a basket design takes full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types and molecular targets.

On July 10, 2017 Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) has accepted and filed its New Drug Application (NDA) for abemaciclib, a cyclin-dependent kinase (CDK)4 & 6 inhibitor, and given the NDA a Priority Review designation (Press release, Eli Lilly, JUL 10, 2017, View Source [SID1234519775]). The NDA includes the company’s submission of abemaciclib for two indications: abemaciclib monotherapy for patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who had prior endocrine therapy and chemotherapy for metastatic disease; and for abemaciclib in combination with fulvestrant in women with HR+, HER2- advanced breast cancer who had disease progression following endocrine therapy. This submission is based on the MONARCH 1 and MONARCH 2 studies, respectively.

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"We are pleased that the FDA has granted abemaciclib Priority Review, both as a potential monotherapy and combination therapy [with fulvestrant] for patients with advanced breast cancer," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "Breast cancer is a complex disease, and the need still exists for new treatment options as patients face a significant disease burden. We look forward to working with the FDA and bringing this important potential treatment option to patients as soon as possible."

In 2015, the FDA granted abemaciclib Breakthrough Therapy Designation based on data from the breast cancer cohort expansion of the company’s Phase 1 trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. A drug that receives Breakthrough Therapy Designation may be eligible for Priority Review, which aims to expedite the review of applications for drugs that, if approved, would represent a significant advance in treatment. With Priority Review of a new drug, the FDA’s goal is to take action within eight months of receiving an application, compared with the standard review timeframe of 12 months.1 Lilly is working closely with the FDA and anticipates agency action on this application in the first quarter of 2018.

In addition, Lilly intends to submit abemaciclib to European regulators in the third quarter of 2017 and to Japanese regulators before the end of 2017.

Notes to Editor

About Advanced Breast Cancer
Breast cancer is the most common cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.2 Advanced breast cancer includes metastatic breast cancer, cancer that has spread from the breast tissue to other parts of the body, and locally or regionally advanced breast cancer, meaning the cancer has grown outside the organ where it started but has not yet spread to other parts of the body.3 Of all early stage breast cancer cases diagnosed in the U.S., approximately 30 percent will become metastatic and an estimated six to ten percent of all new breast cancer cases are initially diagnosed as being metastatic.4 Survival is lower among women with a more advanced stage at diagnosis: 5-year relative survival is 99 percent for localized disease, 85 percent for regional disease, and 26 percent for metastatic disease. Other factors, such as tumor size, also impacts 5-year survival estimates.5

About Abemaciclib
In many cancers, uncontrolled cell growth arises from a loss of cell cycle regulation due to increased signaling from CDK4 and CDK6. Abemaciclib (LY2835219) is an investigational, oral cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting cyclin-dependent kinases, CDK4 and CDK6, and was most active against Cyclin D1 and CDK4 in cell-free enzymatic assays. In breast cancer, Cyclin D1/CDK4 has been shown to promote phosphorylation of the retinoblastoma protein (Rb), cell proliferation and tumor growth. In hormone receptor-positive breast cancer cell lines, sustained target inhibition by abemaciclib reduced phosphorylation of Rb, inducing cell cycle arrest.

In addition to its current MONARCH clinical trials evaluating abemaciclib in breast cancer, a Phase 3 trial of abemaciclib in lung cancer is also underway.

For more information on additional abemaciclib trials, a complete listing can be found on ClinicalTrials.gov (in the search box on the home page, type in "abemaciclib").

About the MONARCH Clinical Trial Program
Lilly is evaluating abemaciclib in the comprehensive MONARCH clinical program, which includes the following studies:

MONARCH 1: a global Phase 2 study evaluating the efficacy and safety of abemaciclib monotherapy in patients with HR+, HER2- advanced breast cancer who had prior endocrine therapy and chemotherapy for metastatic disease.

MONARCH 2: a global Phase 3 study evaluating the efficacy and safety of abemaciclib, in combination with fulvestrant, in patients with HR+, HER2- advanced breast cancer who progressed on endocrine therapy.

MONARCH 3: a global Phase 3 study evaluating the efficacy and safety of abemaciclib, in combination with an aromatase inhibitor, as initial endocrine-based therapy for postmenopausal women with HR+, HER2- advanced breast cancer who have had no prior systemic treatment for advanced disease.

monarcHER: a global Phase 2 study evaluating abemaciclib plus trastuzumab (with or without fulvestrant) in women with HR+, HER2+ advanced breast cancer.

MONARCH plus: a Phase 3 study evaluating the efficacy and safety of abemaciclib, in combination with endocrine therapies, to support registration in China.

neoMONARCH: a Phase 2 study evaluating abemaciclib in the neoadjuvant setting, alone or in combination with the non-steroidal aromatase-inhibitor anastrozole, in postmenopausal women with previously untreated early stage HR+, HER2- breast cancer.

monarchE: a global Phase 3 study evaluating the efficacy and safety of abemaciclib in the adjuvant setting in patients with high-risk, early breast cancer.