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EISAI LAUNCHES IN-HOUSE DEVELOPED NOVEL ANTICANCER AGENT LENVIMA(R) (LENVATINIB MESYLATE) AS TREATMENT FOR UNRESECTABLE THYROID CANCER IN JAPAN

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]).

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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.

SignalRx Pharmaceuticals Inc. Awarded STTR Grant from the National Institutes of Health for Development of Dual PI3 Kinase/Bromodomain Inhibitors as Anticancer Agents

On May 19, 2015 SignalRx Pharmaceuticals Inc., focused on developing more effective oncology drugs though molecular design imparting selective multiple target inhibition, reported that it has received non-dilutive funding to advance the preclinical development of unique small molecule inhibitors designed to inhibit multiple critical cancer targets (Press release, SignalRx, MAY 19, 2015, http://www.ireachcontent.com/news-releases/signalrx-pharmaceuticals-inc-awarded-sttr-grant-from-the-national-institutes-of-health-for-development-of-dual-pi3-kinasebromodomain-inhibitors-as-anticancer-agents-504347611.html [SID1234527329]).

SignalRx was awarded a Phase 1 Small Business Technology Transfer Research (STTR) grant from the National Cancer Institute (NCI), a division of the National Institutes of Health (NIH), in support of the preclinical development of novel small molecules that simultaneously inhibit two key cancer targets: PI3kinase (PI3K) and the bromodomain protein BRD4. The principal investigator on the STTR grant is SignalRx’s scientific advisor Dr. Donald Durden, MD, PhD who also serves as the academic collaborator for the grant while in his capacity as the Associate Director for Pediatric Oncology at the Moores UCSD Cancer Center at the University of California, San Diego.

Inhibiting the key cancer promoting transcription factor MYC (both cMYC and MYCN) is vigorously pursued since this inactivates many genes that drive cancer cell growth and proliferation. To date, small molecule inhibitors of MYC have been elusive. SignalRx’s innovative approach is to indirectly orthogonally diminish the activity of MYC by enhancing its degradation using PI3K inhibition combined with simultaneous blocking the transcription of the gene producing MYC via inhibition of the bromodomain protein BRD4—all resulting from a single molecule. Combination treatments are necessary in cancer, and there is an ever increasing need for more complex combinations to inhibit multiple targets to maximize efficacy. However, combining single-action drugs becomes unfeasible due to prohibitive costs when combining expensive targeted therapies in addition to being a barrier to early clinical evaluation of such complex combinations of drugs. SignalRx provides proprietary single molecules designed to inhibit multiple specific key cancer targets and thus strive for more cost-effective efficacy-improved therapeutics.

SignalRx has discovered and patented a novel molecular scaffold whose members are potent PI3K inhibitors designed to simultaneously inhibit the bromodomain protein BRD4. These dual PI3K/BRD4 inhibitors are the subject of the awarded grant along with the development of molecular modeling tools to help facilitate the structure activity relationships now under study. Preliminary results of these dual PI3K/BRD4 inhibitors have demonstrated in vivo efficacy without toxicity in several mouse cancer models, confirming the advantage of circumventing potential safety concerns arising from the use of multiple drugs. Moreover, successful proof of concept by showing knockdown of both the PI3K pathway and MYC levels was confirmed from the examination of excised mouse tumors 4 hours after administration of a dual PI3K/BRD4 inhibitor.

"The STTR grant award by the NCI to develop a single molecule that inhibits both PI3K and BRD4 represents a major step forward in translating new findings in cancer biology to maximize the activity and durability of effect in new anticancer agents" said Donald L. Durden, MD, PhD. "This approach, in addition to challenging the current dogma of single-targeted oncology drugs, has promise to maximally block the tumor suppressor gene MYC which drives many cancers including CLL, medulloblastoma, multiple myeloma, and high-grade epithelial ovarian cancers exhibiting elevated MYCN expression."

Ipsen strengthens its presence in the oncology field with the acquisition of OctreoPharm Sciences, a company developing innovative radiopharmaceuticals for the diagnosis and treatment of neuroendocrine tumours

On May 19, 2015 Ipsen reported the signature of an agreement to acquire OctreoPharm Sciences (referred to as OctreoPharm), a private German life sciences company focusing on the development of innovative radioactive labeled compounds for molecular imaging diagnostics and therapeutic applications (Press release, Ipsen, MAY 19, 2015, View Source [SID:1234504593]). Ipsen plans to maintain the company location and staff to ensure successful transition of know-how and expertise. Ipsen expects to complete its acquisition once closing conditions have been cleared.

Under the terms of the agreement, which is subject to closing conditions, OctreoPharm’s shareholders are eligible to receive up to a total of approximately €50 million for the purchase of 100% of the company’s shares in the form of an upfront payment and downstream payments contingent upon clinical and regulatory milestones.

The transaction fits into Ipsen’s strategy to extend the scope of its portfolio and its leadership in neuroendocrine tumors (NET). OctreoPharm is developing an innovative theranostic approach for the management of NET based on a somatostatin receptor antagonist peptide. The therapeutic compound is a tumor cell-selective somatostatin antagonist peptide labeled with 177Lutetium ( 177Lu) for use as ‘peptide receptor radionuclide therapy’ (PRRT) for the treatment of neuroendocrine tumors, and is currently in preclinical development. The diagnostic compound is an NET imaging tool utilizing positron emission tomography (PET, PET/CT), and is currently in clinical development.

The acquisition includes an agreement with Eckert and Ziegler, one of OctreoPharm’s shareholders, to provide contract manufacturing services for the radio-labeling of the therapeutic compound.

Marc de Garidel, Chairman and CEO of Ipsen stated: "The acquisition of OctreoPharm will enlarge our footprint in the NET field, and gives Ipsen access to a new scientific field where OctreoPharm has a unique expertise in antagonist peptides for the diagnosis and treatment of neuroendocrine tumors. This is an important step in our ambition to become a global leader in the management of NET, and illustrates the pertinence of our business development strategy."

Advaxis and Sorrento Form Collaboration to Evaluate Combinations of Advaxis’s Lm-LLO Immunotherapy Technology and Sorrento’s Immunomodulatory Antibodies

On May 19, 2015 Advaxis reported it has entered into a non-exclusive research and clinical trial collaboration agreement with Sorrento Therapeutics to evaluate combinations of Advaxis’s Lm-LLO cancer immunotherapy technology platform, including ADXS-HPV, ADXS-PSA and ADXS-HER2, with Sorrento’s fully human antibodies targeting immune checkpoints, including GITR, OX40, LAG-3 and TIM-3 (Press release, Advaxis, MAY 19, 2015, View Source [SID:1234504592]). Sorrento has one of the largest and most diverse fully human antibody libraries in the industry designed to facilitate rapid identification and selection of highly specific therapeutic monoclonal antibody (mAb) product candidates.

Advaxis’s preclinical program for ADXS-HPV previously examined its therapeutic potential in combination with agonistic research antibodies, including anti-OX40 and anti-GITR. Preclinical data demonstrated that the combination of ADXS-HPV with agonistic research antibodies led to significant inhibition of tumor growth and prolonged survival in tumor-bearing mice. Complete regression of established tumors occurred in 40% and 60% of animals treated with ADXS-HPV in combination with anti-OX40 and anti-GITR antibodies, respectively (AACR Abstract #LB-229).

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"We welcome the collaboration with Sorrento to evaluate its immunomodulatory antibodies in combination with our Lm-LLO immunotherapy technology platform," said Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "Leveraging Sorrento’s fully human antibody library and Advaxis’s Lm-LLO immunotherapy technology offers a significant opportunity to target multiple cancer indications and extend the potential of our respective company’s technologies."

Under the terms of the agreement, Advaxis will conduct the studies and the companies will equally share the expenses. The companies hope to commence the first of the two planned combination studies in 2016. Results from the studies will be used to determine whether further clinical development of specific combinations is warranted.

"Clinical collaborations are an integral part of Sorrento’s strategy to accelerate the development of our diverse portfolio of immuno-oncology antibodies against a broad range of cancers," said Dr. Henry Ji, President and Chief Executive Officer at Sorrento. "We are encouraged by the data presented by Dr. Khleif at the AACR (Free AACR Whitepaper) Annual Meeting 2015, and believe there could be an important clinical benefit from the combination of our antibodies with Advaxis’s Lm-LLO immunotherapies."

Destum Partners acted as advisor to Advaxis for this collaboration agreement.

Genmab Enters Commercial DuoBody® Technology Agreement with BioNTech in Field of Immuno-oncology

On May 19, 2015 Genmab reported it has entered an agreement with BioNTech AG to jointly research, develop and commercialize bispecific antibody products using Genmab’s DuoBody technology platform (Press release, Genmab, MAY 19, 2015, View Source [SID:1234504586]).

Under the terms of the agreement, BioNTech will provide proprietary antibodies against key immunomodulatory targets that play an important role in activating the immune system against cancer, while Genmab provides access to its DuoBody technology platform. Genmab will pay an upfront fee of USD 10 million to BioNTech and additional potential near-term payments of up to USD 5 million if certain BioNTech assets are selected for further development. If the companies jointly select any product candidates for clinical development, development costs and product ownership will be shared equally going forward. If one of the companies does not wish to move a product candidate forward, the other company is entitled to continue developing the product on predetermined licensing terms. The agreement also includes provisions which will allow the parties to opt out of joint development at key points.

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"This collaboration with BioNTech focuses on two very interesting areas in the antibody therapeutic space — bispecific antibodies and immuno-oncology – and supports Genmab’s strategy of creating a broad pipeline of differentiated next-generation antibody therapeutics," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Today’s agreement does not impact Genmab’s 2015 financial guidance.