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10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

(Filing, 10-K, Array BioPharma, AUG 21, 2015, View Source [SID:1234507318])

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Takeda Announces European Medicines Agency Acceptance of Ixazomib’s Marketing Authorization Application for Patients with Relapsed/Refractory Multiple Myeloma

On August 21, 2015 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for ixazomib, an investigational oral proteasome inhibitor for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Takeda, AUG 21, 2015, View Source [SID:1234507307]). On July 23, ixazomib was granted accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the EMA, a designation reserved for those medicines deemed to be of major public health interest and, in particular, therapeutic innovation.

"The ixazomib applications in Europe and the United States are the first of several that we anticipate submitting by the end of this fiscal year," said Melody Brown, Vice President of Regulatory Affairs, Takeda. "By filing in many regions in rapid succession, we hope to bring ixazomib to as many people living with relapsed/refractory multiple myeloma as soon as possible. We express our thanks to the patients and physicians participating in the TOURMALINE clinical trial program globally as their support has been critical in making these filings possible."

The MAA submission was primarily based on the results of the first pre-specified interim analysis of the pivotal Phase 3 trial TOURMALINE-MM1, an international, randomized, double-blind, placebo controlled clinical trial of 722 patients designed to evaluate the superiority of ixazomib plus lenalidomide and dexamethasone over placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Patients continue to be treated to progression in this trial and will be evaluated for long-term outcomes.

In addition to the ixazomib MAA submission with the EMA, a New Drug Application for ixazomib was filed with the U.S. Food and Drug Administration (FDA). Additional filings in other countries are planned to begin later this fiscal year.

About Multiple Myeloma
Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of plasma cells, or myeloma cells, becomes cancerous and multiplies, increasing the number of plasma cells to a higher than normal level. Because plasma cells circulate widely in the body, they have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anemia. Multiple myeloma is a rare form of cancer with approximately 39,000 new cases in the EU and 114,000 new cases globally per year.

About Ixazomib
Ixazomib is an investigational oral proteasome inhibitor which is being studied in multiple myeloma, systemic light-chain (AL) amyloidosis, and other malignancies. Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials.

Ixazomib’s clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. Five global Phase 3 trials are ongoing:

TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT
TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis
For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.

Interim Report for Kancera AB (publ) Q2 2015, January 1 – June 30, 2015

On August 21, 2015 Interim Reported for Kancera AB (publ) Q2 2015, January 1 – June 30, 2015 (Press release, Kancera, AUG 21, 2015, View Source [SID:1234507306]).

The period January to June 2014 and the second quarter 2015 in brief

R&D expenses for the period amounted to SEK 8.8m (SEK 6.9m) of which the second quarter constituted SEK 4.6m (SEK 3.4m).

Operating income for the period amounted to SEK -10.3m (SEK -8.0m) of which the second quarter constituted SEK -5.5m (SEK -3.9m).

Income after financial items for the period amounted to SEK -10.3m (SEK -7.9m) of which the second quarter constituted SEK -5.4m (SEK -3.8m).

Earnings per share for the period were SEK -0.10 (SEK -0.10) of which the second quarter constituted SEK -0.05 (SEK -0.05).

Cash flow from operating activities for the period amounted to SEK -10.9m (SEK -7.2m) of which the second quarter constituted SEK -5.8m (SEK -4.0m).

Equity as of June 30, 2015 amounted to SEK 31.2m (SEK 33.8m) or SEK 0.30 (SEK 0.44) per share. The equity/assets ratio as of June 30, 2015 was 76 percent (77 percent).

Cash and cash equivalents as of June 30, 2015 amounted to SEK 25.4m (SEK 31.1m).
Significant events during the period

Kancera reported that a second efficacy study of the drug candidate KAN0439834 has been completed in an animal model of an advanced stage of chronic lymphocytic leukemia characterized by a genetic change which makes the disease more difficult to treat. The results show that KAN0439834 reduces the number of ROR expressing leukemia cells in the lymphatic system (spleen) after 14 days of treatment. Further, Kancera reported that a second patent application EP15153394.0 has been filed covering small-molecule ROR inhibitors, including the drug candidate KAN0439834.

Kancera reports that the patent WO 2011/079902 concerning monoclonal antibodies against ROR1 has been approved in China. Kancera has acquired partial rights to this patent from Bioinvent under an agreement that does not involve any financial burden for Kancera (except patent expenses) before revenues are generated. Kancera through the company’s co-founder Professor Håkan Mellstedt has been involved in the development of these antibodies. These antibodies have mainly been used to identify and validate new indications for a future ROR-inhibiting drug. Any further development of the ROR-targeted monoclonal antibodies for therapeutic purposes will only be done in a partnership that provides funding and access to expertise in development of antibody-based drugs.

Kancera reported an operational update of the cancer projects ROR, PFKFB3, and HDAC6.

The ROR project reported that that Kancera’s candidate drug KAN0439834 is effective against both leukemic cells circulating in the blood and leukemic cells that have invaded the lymph nodes in humans.

Recent studies of clinical samples from leukemia patients underscore that ROR inhibitors mainly target the white blood cells causing cancer while the healthy white blood cells, including T cells, are spared. These results are of significance for the possibility to combine ROR inhibitors with the new generation of immuno-stimulating cancer drugs that have been developed since the effect of those requires functional T-cells.

A new generation of ROR inhibitors is being developed against solid tumors.

The PFKFB3 project reported a new discovery showing that Kancera’s PFKFB3 inhibitor KAN0438757 kills cancer cells by preventing them to repair their DNA. The discovery indicates that KAN0438757 could be an efficient complement to radiation for the treatment of advanced cancer.

The HDAC6 project reported that Kancera’s HDAC6 inhibitors counteract the migration of cancer-associated fibroblast cells and that an international patent application has been filed in May.

Kancera’s Annual General Meeting on May 28, 2015 decided to re-elect the current Board of Directors and auditor (Ernst & Young). The General Meeting also decided to authorize the Board, on one or more occasions until the next Annual General Meeting, to issue new shares. A new share issue may be made with or without preferential rights and against cash payment and / or in kind or set-off. The purpose of the authorization and the reason for the deviation from shareholders’ preferential rights is to enable the acquisition of capital for corporate acquisitions and the company’s operation. If the share issue is made against cash payment and without preferential rights for the shareholders, the number of shares issued may not exceed ten percent of the total number of shares outstanding at the time the authorization is exercised.

Kancera announced that a new share issue, with the authorization of the Annual General Meeting in 2014, was closed on May 27, 2015. The issue comprised a maximum of 4,927,386 shares. In total 25,926,793 shares were signed, of which 4,644,304 with preferential rights (with the support of subscription rights) and 21,282,489 without preferential rights. The share issue was thus oversubscribed to about 500 percent. This issue raised Kancera AB approximately SEK 12.3m before issue costs.

Kancera announced that the first subscription period for the exercise of the employee warrants was closed in June 2015. In total 450,246 new shares were signed giving Kancera SEK 1.7m before issue costs. There remain 2,349,754 warrants, of which 560,000 are held by Kancera to cover social security costs that are part of the employee warrants program.

Kancera announced that the company’s HDAC6 project has been awarded a grant totaling SEK 2m from the Swedish innovation agency VINNOVA. The grant is directed to projects that can develop into new strong innovations in a range of common diseases, including cancer. The grant is paid on four occasions during the two-year project. The project will be implemented in collaboration with the Cancer Center Karolinska (CCK), and is also planned to involve Swedish companies such as SARomics Biostructures, MetaSafe and Adlego Biomedical.

Significant events after the end of the reporting period

No significant news have been reported after the end of the period.

Statement from the CEO

In May, Kancera reported progress in the ROR, HDAC6 and PFKFB3 projects in an operational update showing that we have taken significant steps toward our main objectives during the period. The objectives include to demonstrate efficacy of ROR inhibitors against solid cancers, improve the pharmaceutical properties of the HDAC6 inhibitors and to investigate how PFKFB3 inhibitors are best combined with existing cancer therapies. However, several steps remain before we reach our objectives. Kancera’s projects were presented at two international scientific conferences in June yielding a good scientific response. Kancera’s unique small-molecule ROR project was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the exciting discovery that Kancera’s PFKFB3 inhibitors prevent DNA repair in irradiated cancer cells was presented at the Tomas Lindahl Conference on DNA repair in Oslo.

American research groups have progressed the development of biological drugs directed against ROR during the last 12 months such as the MD Anderson Cancer Center in Texas (genetically modified T cells that express ROR receptors on the cell surface) and the University of Southern California in San Diego (monoclonal antibodies) while Kancera remains in the forefront when it comes to development of small-molecule drugs against ROR. The development of biological drugs against ROR we consider as positive since these can contribute to the understanding of how a ROR-targeted drug works in different patient groups and provide information on what is required of a small molecule drug against ROR to be competitive.

During May and June, Kancera’s working capital was strengthened through a fully subscribed share issue and also through the exercise of employee warrants which together brought in SEK 14m before issue costs. In addition, Vinnova announced that its strategic innovation program for common diseases (SWElife) allocates SEK 2m to Kancera’s HDAC6 project over a two year period. The interest in HDAC6 as a drug target remains strong, which e.g. is reflected in the "Discovery on Target" conference in Boston in September where attention is paid to the contribution of HDAC6 to control the immune system’s ability to attack cancer. In July, Kancera conducted a screening campaign as part of the EU-funded anti-parasite project which means that the company has delivered according to plan up to the midterm report. This report constitutes the basis for a possible approval of an additional payment of about € 285,000 from the European Union in the fourth quarter.

The focus of the autumn’s product development is the continued development of ROR inhibitors for the treatment of solid tumors, and enhancement of the pharmaceutical properties of the already highly potent HDAC6 inhibitors.

Axelar and Cadila Pharmaceuticals Announce Co-Development Agreement for Non-Small Cell Lung Cancer Treatment

On August 20, 2015 Axelar AB (‘Axelar’) and Cadila Pharmaceuticals Sweden AB (‘Cadila Pharma’) reported that they have entered into a co-development agreement for further formulation development and clinical development of AXL1717 in patients with non-small cell lung cancer (NSCLC) (Press release, Axelar, AUG 20, 2015, View Source [SID1234571469]).

AXL1717 is a first-in-class, orally available compound with potential in multiple cancers. Under the terms of the agreement, Cadila Pharmaceuticals will perform formulation development on AXL1717, as well conduct a multicentre randomized Phase II study in patients with non-small cell lung cancer in India. Cadila Pharma will co-invest a proportion of the projected costs for the formulation development and clinical trials and will in return, receive defined geographic market rights for AXL1717 and revenue sharing in future licence deals for AXL1717.

As part of our quest to develop and commercialize AXL1717, this is the most exciting, and perhaps the most important transition in the history of the company," said Jonas Ekblom, Chairman of Axelar. "With a new ownership configuration, a new leadership team, and with Cadila Pharmaceuticals as a powerful strategic ally, I strongly feel that we have optimized our chances for success."

Commenting on the development, Dr. Rajiv I Modi, Chairman and Managing Director, Cadila Pharmaceuticals Ltd.,said: "We are very excited to take forward the AXL1717 project for non-small cell lung cancer, which is one of our focus areas of research. This is also in line with our vision to make available effective therapeutic options for patients who have failed prior treatments of the disease. This partnership reaffirms Cadila Pharmaceuticals’ commitment to developing novel cutting edge medical products through innovative, co-development model which we believe, has the potential to generate significant value for all partners."

Non Small Cell Lung Cancer is a key focus area for Cadila Pharmaceuticals. In 2013, the company had launched a first-in-the-world, active immunotherapy treatment in the management of squamous cell NSCLC.

Navidea Reports Publication of Lymphoseek® Comparative Results in Injection Site Pain Study in Breast Cancer

On August 20, 2015 Navidea Biopharmaceuticals (NYSE MKT: NAVB), reported publication of the results from an investigator-initiated, comparative study of Lymphoseek (technetium Tc 99m tilmanocept) injection versus filtered Tc-99m Sulfur Colloid (fTcSC) measuring injection site pain in patients with breast cancer undergoing lymphoscintigraphy (Press release, Navidea Biopharmaceuticals, AUG 20, 2015, View Source;p=RssLanding&cat=news&id=2080893 [SID:1234507304]). The paper titled, "Comparison of Post-injection Site Pain Between Technetium Sulfur Colloid and Technetium Tilmanocept in Breast Cancer Patients Undergoing Sentinel Lymph Node Biopsy," was published online in the Annals of Surgical Oncology [DOI – 10.1245/s10434-015-4802-y] and indicated, with patient-reported data, a statistically significant reduction in the level of post-injection associated pain using Lymphoseek compared with use of an fTcSC tracer.

"The publication of these investigator-initiated study findings affirms the value that surgeons place on minimizing pain and discomfort for their patients and continues to reinforce the clinical importance of Lymphoseek," said Michael Tomblyn, M.D., Navidea’s Chief Medical Officer. "We believe that these results will enhance the visibility and awareness of Lymphoseek with surgical oncologists and illustrate both the clinical utility and clear benefits for patients."

"As surgeons who perform sentinel lymph node (SLN) biopsy procedures in breast cancer patients, one of our key focuses is optimizing a patient’s overall experience," said Dr. Anne Wallace, M.D., professor of surgery, UC San Diego School of Medicine, director of the Comprehensive Breast Health Center at UC San Diego Moores Cancer Center and the study’s lead investigator. "We designed this study to understand if Lymphoseek injection is less painful and could improve the patient experience. The results demonstrated that Lymphoseek, in fact, minimizes patient discomfort while allowing for effective SLN mapping."

The publication included results of the randomized, double-blind clinical trial comparing post-injection site pain using fTcSC versus Lymphoseek in 52 [(27) fTcSC and (25) Lymphoseek] breast cancer patients undergoing lymphoscintigraphy. Pain was evaluated with a visual analogue scale and short form McGill Pain Questionnaire at 1, 2, 3, 4, 5, 15 and 30 minutes post-injection. Analysis of the data indicated baseline pain scores were similar between groups. At one minute post-injection, patients receiving fTcSC experienced a mean change in pain of 16.8mm (standard deviation (SD) 19.5) compared to 0.2mm (SD 7.3) in the Lymphoseek group (p =0.0002). Overall, patients receiving Lymphoseek experienced statistically significant less change in pain scores compared to patients receiving fTcSC at 1-3 minutes post-injection.

About Lymphoseek
Lymphoseek (technetium Tc 99m tilmanocept) injection is the first and only FDA-approved receptor-targeted lymphatic mapping agent. It is a novel, receptor-targeted, small-molecule radiopharmaceutical used in the evaluation of lymphatic basins that may have cancer involvement in patients. Lymphoseek is designed for the precise identification of lymph nodes that drain from a primary tumor, which have the highest probability of harboring cancer. Lymphoseek is approved by the U.S. Food and Drug Administration (FDA) for use in solid tumor cancers where lymphatic mapping is a component of surgical management and for guiding sentinel lymph node biopsy in patients with clinically node negative breast cancer, melanoma or squamous cell carcinoma of the oral cavity. Lymphoseek has also received European approval in imaging and intraoperative detection of sentinel lymph nodes in patients with melanoma, breast cancer or localized squamous cell carcinoma of the oral cavity.

Accurate diagnostic evaluation of cancer is critical, as it guides therapy decisions and determines patient prognosis and risk of recurrence. Overall in the U.S., solid tumor cancers may represent up to 1.2 million cases per year. The sentinel node label in the U.S. and Europe may address approximately 235,000 new cases of breast cancer, 76,000 new cases of melanoma and 45,000 new cases of head and neck/oral cancer in the U.S., and approximately 367,000 new cases of breast cancer, 83,000 new cases of melanoma and 55,000 new cases of head and neck/oral cancer diagnosed in Europe annually.

Lymphoseek Indication and Important Safety Information
Lymphoseek is a radioactive diagnostic agent indicated with or without scintigraphic imaging for:

Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management.
Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma.
Important Safety Information
In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs).

Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection.

Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers.

In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1%).

FULL LYMPHOSEEK PRESCRIBING INFORMATION CAN BE FOUND AT: WWW.LYMPHOSEEK.COM.