On May 21, 2015 Celsion reported data from a preclinical study confirming that the Company’s TheraSilence technology platform can safely and effectively deliver RNA to the lungs in non-human primates (Press release, Celsion, MAY 21, 2015, View Source [SID:1234504615]). TheraSilence is designed to enable the delivery of synthetically-generated mRNA, inhibitory RNA (RNAi) such as small inhibitory RNAs (siRNAs), microRNAs, microRNA mimics, and related molecules that can regulate protein expression at the transcript level by exploiting endogenous cell mechanisms.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The findings from this study are consistent with the data observed in earlier preclinical studies and underscore the differentiating and widespread potential of our TheraSilence RNA delivery platform," stated Dr. Khursheed Anwer, Celsion’s Executive Vice President and Chief Scientific Officer. "Development for RNA therapeutics has been significantly limited due to the delivery challenges associated with nucleic acid-based therapies, with development efforts in the space focused primarily on diseases of the liver. Our chemically-flexible approach offers the opportunity to significantly expand the development of RNA therapies to include major unmet medical needs affecting the lung, such as lung cancer, asthma and pulmonary hypertension."

Know more, wherever you are:
Latest on Nucleic Acid Therapies in Oncology, book your free 1stOncology demo here.

The study was designed to evaluate the expression profile and safety of RNA formulated with Celsion’s TheraSilence delivery system in non-human primates. Three primates were dosed in the study, receiving either TheraSilence-formulated RNA intravenously at one of two doses, or intravenous RNA formulated with a liver-directed formulation used as a positive control. Following the treatment, an analysis for safety and RNA expression was performed.

In the study, TheraSilence-formulated signaling RNA resulted in preferential expression in the lungs, with expression in the liver at less than 15% of expression levels observed in the lungs. Expression levels in tissues other than the lung, spleen and liver were very low or at background levels. The TheraSilence-formulated RNA was well-tolerated at both dose levels as determined by safety analysis including complete blood cell count, blood chemistry, histopathology, interferon response and compliment activation. A liver-directed delivery system, used as a positive control for the study, yielded preferential expression in liver and spleen, with only background expression levels observed in the lung.

These data build on previous preclinical studies indicating the preferential delivery of RNA to the lung using the TheraSilence RNA delivery system. A murine study evidenced that the delivery of TheraSilence-formulated siRNA molecules targeting anti-vascular endothelial receptor 2 (VEGF2), a protein that is critical for the growth of new blood vessels in tumors, significantly inhibit lung tumor growth. Additionally, delivery of a TheraSilence-formulated anti-micro RNA molecule into rats with experimentally induced pulmonary arterial hypertension appeared to normalize vascular remodeling that occurs in the lung and help restore cardiac function that is compromised as a result of the disease.

"The data highlights the great potential of our TheraSilence technology platform to provide unique treatment options for lung diseases that are not addressable by conventional drugs," said Michael H. Tardugno, the Company’s Chairman, President and Chief Executive Officer. "TheraSilence has significant potential in a wide variety of indications, including those that fall outside our core focus of oncology. Our strategy is to seek to maximize the value of this platform in the near-term by pursuing collaborations and licensing agreements, while focusing internal development efforts on our two clinical stage candidates, ThermoDox and GEN-1, our DNA-based immunotherapy for the localized treatment of ovarian and brain cancers."

On May 21, 2015 Eureka Therapeutics and Boehringer Ingelheim reported that they have entered into a research agreement for the discovery of novel therapeutic antibodies in oncology (Press release, Boehringer Ingelheim, MAY 21, 2015, View Source [SID:1234504614]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Eureka Therapeutics will apply its proprietary human sequence antibody libraries and its unique technology platform to identify antibodies recognizing intracellular proteins, which represent approximately 90% of cancer-specific targets. Cancer-specific peptides that can be displayed via the MHC-complex (major histocompatibility complex) on the cell surface will be selected by Boehringer Ingelheim to develop better therapies for cancer patients, for whom treatment options are inadequate or non-existent. Boehringer Ingelheim will have the option to conduct further development and commercialization of the antibodies. Under the terms of the agreement, Eureka Therapeutics will receive an undisclosed upfront technology access fee and research funding for each program, and may receive technical success fees, option exercise fees, and other downstream payments.

Know more, wherever you are:
Latest on Antibodies in Oncology, book your free 1stOncology demo here.

"We are excited to partner with Boehringer Ingelheim, a leader in oncology research and development to develop next generation cancer immunotherapies targeting intracellular oncogenes", said Dr. Cheng Liu, President and Chief Executive Officer of Eureka Therapeutics. "Intracellular oncogenes represent 90% of cancer-specific antigens, many of which were considered "undruggable targets" until recently. This collaboration builds upon Eureka’s success in discovery and development of fully human antibodies against intracellular oncogenes. We look forward to working with Boehringer Ingelheim to advance the immuno-oncology frontier and address some of the most challenging unmet medical needs".

This collaboration underlines our long-term commitment to oncology and our interest in exploring new target spaces with antibodies that recognize intracellular proteins. It will open up entirely new opportunities for the development of tumor cell- as well as immune cell-targeted therapies. We are looking forward to working closely with Eureka´s scientists to develop novel, effective therapies targeting cancers that have proved particularly difficult to treat in the past", said Dr. Michel Pairet, Senior Corporate Vice President of Research and Non-clinical Development at Boehringer Ingelheim.

On May 21, 2015 Novartis reported that the Phase III study of Afinitor (everolimus) tablets plus best supportive care in patients with advanced nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin met its primary endpoint: significant extension of progression-free survival (PFS) compared to placebo plus best supportive care[1] (Press release, Novartis, MAY 21, 2015, View Source [SID:1234504609]). The RADIANT-4 study is part of one of the largest clinical trial programs in NET[1].

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

NET are a rare type of cancer that originate in neuroendocrine cells found throughout the body, and are most often found in the GI tract, lungs or pancreas[4]. NET can be functional or nonfunctional: functional NET produce symptoms caused by the secretion of hormones and other substances; nonfunctional NET do not secrete hormones, and may only produce symptoms caused by the tumor’s growth, such as intestinal blockage, pain and bleeding[5],[6],[7]. At time of diagnosis, up to 44% of patients with GI NET and 28% of patients with lung NET have advanced disease, meaning the cancer has spread to other parts of the body and is more difficult to treat[2],[3],[4]. There are limited treatment options for patients with advanced GI or lung NET[4].

"We look forward to presenting the findings from the RADIANT-4 trial of everolimus, which has the potential to become an important treatment option for patients with advanced nonfunctional GI or lung NET," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "The results will serve as the basis of planned worldwide regulatory filings for everolimus in these two types of NET, bringing us closer to our goal of offering Afinitor for these patients."

Full results from the RADIANT-4 study will be submitted to a major medical meeting. Worldwide regulatory filings are planned for 2015.

About RADIANT-4

RADIANT-4 is a Phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study. The trial examined the efficacy and safety of everolimus plus best supportive care versus placebo plus best supportive care in 302 patients with well differentiated advanced NET of GI or lung origin, and no history or active symptoms of carcinoid syndrome, who had documented disease progression within the previous 6 months. Patients were randomized 2:1 to receive either daily everolimus 10 mg or daily placebo orally.

The primary endpoint of RADIANT-4 was PFS. Secondary endpoints included safety, objective response rate and overall survival.

About Afinitor (everolimus) tablets

Afinitor (everolimus) is approved in more than 95 countries, including the United States and throughout the European Union, for locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin. It is also approved in 119 countries including the United States and European Union for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy.

Afinitor is approved in the European Union for the treatment of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor (NSAI). In the United States, Afinitor is approved for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2 negative (advanced HR+/HER2-) breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole.

Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names Afinitor or Votubia, Certican and Zortress and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.

Important Safety Information about Afinitor (everolimus) tablets

Afinitor/Votubia can cause serious side effects including lung or breathing problems, infections (including sepsis), and kidney failure, which can lead to death. Patients taking concomitant angiotensin-converting enzyme (ACE) inhibitors may be at an increased risk for angioedema. Mouth ulcers and mouth sores are common side effects. Afinitor/Votubia can affect blood cell counts, kidney and liver function, and blood sugar, cholesterol, and triglyceride levels. Afinitor/Votubia may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor/Votubia and for up to eight weeks after ending treatment. Women taking Afinitor/Votubia should not breast feed. Fertility in women and men may be affected by treatment with Afinitor/Votubia.

The most common adverse drug reactions (incidence >=10 percent) are mouth ulcers, skin rash, feeling tired or weak, diarrhea, absence of menstrual periods, infections (including upper respiratory tract infection, sore throat and runny nose, sinusitis, and pneumonia), nausea, decreased appetite, low level of red blood cells, high levels of cholesterol, abnormal taste, acne, irregular menstrual periods, inflammation of lung tissue, high level of blood sugar, weight loss, itching, swelling of extremities or other parts of the body, nose bleeds, and headache. The most common Grade 3-4 adverse drug reactions (incidence >=2 percent) are mouth ulcers, absence of menstrual periods, low level of red blood cells, infections (including pneumonia), high level of blood sugar, feeling tired or weak, low white blood cells, inflammation of lung tissue, diarrhea, and spontaneous bleeding or bruising. Cases of hepatitis B reactivation, blood clots in the lung or legs, and pneumocystis jirovecii pneumonia (PJP) have been reported. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

On May 20, 2015 Eisai reported that it has launched its in-house developed novel anticancer agent Lenvima Capsule 4 mg and 10 mg (lenvatinib mesylate, "Lenvima") as a treatment for unresectable thyroid cancer in Japan on May 20, 2015 (Press release, Eisai, MAY 20, 2015, View Source [SID:1234504597]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Lenvima is the first molecular targeted treatment in Japan approved with an indication for unresectable thyroid cancer which covers differentiated thyroid cancer as well as medullary thyroid carcinoma and anaplastic thyroid carcinoma. In a global Phase III study (the SELECT study) of Lenvima in differentiated thyroid cancer, Lenvima demonstrated a statistically significant extension in progression free survival and improved response rates compared to placebo(1). In the SELECT study, the five most common Lenvima treatment-related adverse events of any grade were hypertension, diarrhea, fatigue or asthenia, decreased appetite, and weight loss. Furthermore, a Phase II study (Study 208) conducted in Japan suggested tolerability and efficacy of Lenvima in medullary thyroid carcinoma and anaplastic thyroid carcinoma as well.

The number of patients with thyroid cancer in Japan is estimated to be between 13,000 and 29,000. Although treatment is possible for most types of thyroid cancer, there are few treatment options available for unresectable thyroid cancer and so there is a pressing need for the development of new treatment options. With a high degree of clinical malignancy and a prognosis among the worst of all types of cancer, anaplastic thyroid carcinoma in particular is a disease with significant unmet medical needs. Eisai hopes that Lenvima will make a contribution to patients as a new standard treatment for unresectable thyroid cancer, which has no established standard treatment in Japan at present.

Discovered at Eisai’s Tsukuba Research Laboratories and developed in-house, Lenvima is an orally administered molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR. In particular, the agent simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumor angiogenesis and proliferation of thyroid cancer. Furthermore, Lenvima has been confirmed through X-ray co-crystal structural analysis to demonstrate a new binding mode (Type V) to VEGFR2, and exhibits rapid binding to the target molecule and potent inhibition of kinase activity, according to kinetic analysis(2).

Lenvima was launched in the United States in February 2015, and received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use in March 2015. In addition, the agent is currently undergoing regulatory review in Switzerland, South Korea, Canada, Singapore, Russia, Australia and Brazil. Furthermore, Eisai is conducting a global Phase III study of Lenvima in hepatocellular carcinoma as well as Phase II studies of Lenvima in several other tumor types such as renal cell carcinoma and non-small cell lung cancer.

In addition to providing Lenvima as a new treatment option for thyroid cancer, in accordance with the conditions of approval, Eisai will work after launch to carry out a special use investigation (all-case study) and promote the appropriate use of Lenvima. Eisai is committed to exploring the potential clinical benefits of Lenvima in order to further contribute to, and address the diverse needs of, patients with cancer, and their families.