6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]

On March 29, 2016 AstraZeneca reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Tagrisso (osimertinib, AZD9291) 80mg once-daily tablets for the treatment of patients with epidermal growth factor receptor (EGFR) T790M mutation-positive inoperable or recurrent non-small cell lung cancer (NSCLC) that is resistant to EGFR tyrosine kinase inhibitor (TKI) therapy (Filing, 6-K, AstraZeneca, MAR 29, 2016, View Source [SID:1234510105]).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "We continue to move at an unprecedented pace with osimertinib, with the full approval in Japan following closely the recent US and EU approvals. As first-in-class lung cancer treatment directed at the T790M mutation, we are delighted that this targeted medicine is now available to patients in Japan to address the existing unmet medical need."

Dr. Tetsuya Mitsudomi, Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine said: "A significant proportion of Japanese patients with lung cancer have the EGFR mutation and about 60% of them are likely to develop the T790M resistance mutation following initial TKI treatment. Osimertinib enables us to respond to this disease progression in a precise and logical way as clearly demonstrated in clinical trials, with potential to make a meaningful difference to the lives of Japanese patients."

Approximately 30-40% of Asian patients with NSCLC have the EGFR mutation at diagnosis. Nearly two out of three patients with NSCLC whose disease progresses after treatment with an EGFR-TKI develop the T790M mutation, for which treatment options are currently limited. Osimertinib targets both the EGFR mutation involved in cancer development and T790M, a mutation that makes tumours resistant to existing treatment with EGFR-TKIs. Patients with EGFRm NSCLC, who experience disease progression, should be tested for their mutation status through a validated diagnostic test. AstraZeneca has collaborated with Roche to develop the cobas EGFR Mutation Test v2 as the companion diagnostic for osimertinib.

The Japanese approval is based on data from the two multinational AURA Phase II trials (AURA extension and AURA2), with 22% of patients enrolled from Japan. The studies demonstrated efficacy in patients who had progressed on or after treatment with an EGFR-TKI and whose tumours tested positive for the EGFR T790M mutation. The overall objective response rate (ORR, a measurement of tumour shrinkage) was 61.3% (95% CI: 54.2% to 68.1%) in AURA extension (n=199), and 70.9% (95% CI: 64.0% to 77.1%) in AURA2 (n=199) (1 May 2015 cut-off).

In the two AURA Phase II studies (n=411), the most commonly reported adverse events assessed by the investigator were rash/acne (37.7%), diarrhoea (36.5%), dry skin/eczema, etc. (28.5%), nail disorder including paronychia, etc (23.4%). In Japanese patients (n=80), the incidence of interstitial lung disease (ILD; including pneumonitis etc.), as assessed by the investigator, for all grades was 6.3% (1 May 2015 cut-off). Warnings and precautions include ILD, QT interval prolongation, hepatic impairment and haematological changes.

AstraZeneca has agreed a Risk Management Plan with the Japanese Health Authority.

The full Japanese approval was granted seven months after the New Drug Application submission in August 2015. The Japanese approval for osimertinib was granted under the Priority Review mechanism of the MHLW, in recognition of the submitted data and the life-threatening nature of the disease. The Japanese approval follows US FDA Accelerated Approval in November 2015 and European Commission conditional marketing authorisation in February 2016. Interactions with regulatory authorities in the rest of the world are ongoing.

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Argos Therapeutics Reports Fourth Quarter and Full-Year 2015 Financial Results and Operational Highlights

On March 29, 2016 Argos Therapeutics, Inc. (Nasdaq:ARGS), an immuno-oncology company focused on the development and commercialization of truly individualized immunotherapies for the treatment of cancer based on the Arcelis technology platform, reported financial results for the fourth quarter and full-year ended December 31, 2015 and provided an update on the Company’s clinical programs (Press release, Argos Therapeutics, MAR 29, 2016, View Source [SID:1234510104]).

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"In the past year we have achieved a number of important milestones, both from a clinical and a corporate perspective," said Jeff Abbey, president and chief executive officer. "In July, we successfully completed enrollment of our Phase 3 ADAPT trial of AGS-003 in metastatic renal cell carcinoma. The ADAPT trial also successfully navigated two data analyses, in June and December, by the Independent Data Monitoring Committee (IDMC). The next review of data by the IDMC is scheduled to take place in June of 2016. We expect a subsequent IDMC meeting and review of data to occur in late 2016 and anticipate having a sufficient number of events from the ADAPT trial to permit the primary analysis and assessment of overall survival to occur in the first half of 2017."

"We also successfully formed our Scientific Advisory Board in 2015. These highly-regarded individuals are a significant resource as we continue to advance our clinical development programs," said Mr. Abbey. "Additionally, we also saw the initiation of an early stage investigator-sponsored RCC trial of AGS-003 at Roswell Park Cancer Institute in Buffalo, NY. With this study, for the first time we will assess the effects of AGS-003 in patients with kidney cancer that has not spread to nearby lymph nodes or other parts of the body. As we have emphasized, this is an important opportunity to manufacture AGS-003 using a needle biopsy procedure for tumor collection prior to surgery, while directly studying immune changes within the primary tumor before and after administration of AGS-003."

Mr. Abbey continued, "With the accomplishments of 2015 and those we have already announced in 2016, including the hiring of Dr. Lee Allen as our chief medical officer, the initiation of an investigator-sponsored trial of AGS-003 in non-small cell lung cancer, and our recently announced financing of up to $60 million, which, if it is funded in full, should fund our operations into the second quarter of 2017 when we anticipate final data of the ADAPT trial, we believe we have taken many of the necessary steps to be successful."

2015 Operational Highlights:

In June and December 2015, following data reviews, the IDMC recommended continuation of the pivotal Phase 3 ADAPT clinical trial of AGS-003 in combination with standard targeted therapy for the treatment of mRCC
In July 2015, the ADAPT clinical trial reached its enrollment goal of at least 450 randomized patients
462 patients enrolled
The breakdown of patients enrolled in the ADAPT study is approximately 73% intermediate risk patients, meaning they present with 1 or 2 risk factors at diagnosis, and approximately 27% poor risk patients, meaning they present with either 3 or 4 risk factors at diagnosis
In July 2015, the Company established a Scientific Advisory Board (SAB)
Inaugural members include distinguished oncologists and immunologists to provide perspectives in further research and development of AGS-003
In July 2015, an investigator-initiated early stage RCC trial of AGS-003 commenced at Roswell Park Cancer Institute in Buffalo, NY
Preliminary data expected in the fourth quarter of 2015

Selected Third Quarter 2015 Financial Results

Net loss attributable to common stockholders for the three months ended December 31, 2015 was $17.6 million, or $0.84 per share, compared to a net loss attributable to common stockholders of $16.2 million, or $0.83 per share, for the same period in 2014. Net loss attributable to common stockholders for the full-year ended December 31, 2015 was $74.8 million, or $3.66 per share, compared to a net loss attributable to common stockholders of $54.2 million, or $3.12 per share, for the same period in 2014.

Revenue for the three months ended December 31, 2015 totaled $0.1 million compared to $0.3 million for the same period in 2014. Revenue for the full-year ended December 31, 2015 totaled $0.5 million compared to $2.0 million for the same period in 2014.

Research and development expense for the three months ended December 31, 2015 totaled $14.0 million compared to $13.5 million for the same period in 2014. Research and development expense for the full-year ended December 31, 2015 totaled $62.1 million compared to $45.5 million for the same period in 2014.

General and administrative expense for the three months ended December 31, 2015 totaled $3.0 million compared to $2.5 million for the same period in 2014. General and administrative expense for the full-year ended December 31, 2015 totaled $11.0 million compared to $8.6 million for the same period in 2014.

As of December 31, 2015, Argos’ cash, cash equivalents and short-term investments totaled $7.2 million compared to $56.2 million as of December 31, 2014.

About the Arcelis Technology Platform
Arcelis is a truly personalized immunotherapy technology that captures mutated and variant antigens that are specific to each patient’s disease. It is designed to overcome immunosuppression by producing a durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to a wide range of different cancers, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized cancer immunotherapies. The Arcelis process uses only a small tumor or blood sample and the patient’s own dendritic cells, which are optimized from cells collected by a single leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease specific antigens. The activated, antigen-loaded dendritic cells are then formulated with the patient’s plasma and administered via intradermal injection.

6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]

On March 29, 2016 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported financial results for the three months and fiscal year ended December 31, 2015 and reported on corporate developments (Filing, Q4/Annual, Aptose Biosciences, 2015, MAR 29, 2016, View Source [SID:1234510103]). Unless specified otherwise, all amounts are in Canadian dollars.

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Effective July 17, 2014, the Company changed its fiscal year end from May 31 to December 31. As a result, the current period being reported is for the year ended December 31, 2015, while the prior year comparative period is for the seven months ended December 31, 2014.

The net loss for the year ended December 31, 2015 was $14.6 million ($1.23 per share) compared with $7.8 million ($0.67 per share) in the seven months ended December 31, 2014. Total cash and cash equivalents and investments as of December 31, 2015 were $19.7 million.

"From an operations, development and clinical perspectives, the first quarter of 2016 has been an extremely busy and dedicated time for our teams working on APTO-253," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We undertook a thorough and comprehensive approach to evaluating the manufacturing issue responsible for the previously announced clinical delay of APTO-253 and to optimizing a new methodology to formulate APTO-253 into a soluble and stable drug product. We continue to work diligently through this process and, ultimately, the FDA will need to review our analysis and approve our new formulation methodology for APTO-253 as a potential clinical drug product. In the meantime, we have made great progress towards bringing additional clinical sites on board, and expect to emerge from the clinical delay at an accelerated enrollment pace."

Corporate Highlights

During the fourth quarter, Aptose engaged an independent third party to review the manufacturing batch records and to search for issues that might be responsible for the filter clogging event that led to the delay in the APTO-253 clinical trial.

Aptose qualified a new contract manufacturing organization (CMO) that optimized the synthetic chemistry process to manufacture reliably the freebase and HCl salt forms of the API. The CMO now has manufactured new GMP batches of the API to provide material for formulation studies and to supply the clinical trials into the future.

Aptose also qualified a separate CMO with expertise in liquid formulations to perform formulation development studies and to manufacture the final form of the drug product for return to the clinic. The CMO has performed numerous formulation studies using a variety of methodologies and is now evaluating their solubility and stability over time to select the best methodology to manufacture the new batch of drug product to take to the FDA. Aptose will need to demonstrate to the FDA that the fresh batch of GMP clinical supply is unlikely to cause filter clogging in the future.

Aptose’s clinical team has identified additional clinical sites to enroll patients as soon as the company resumes dosing for APTO-253. The advance preparation of these sites is intended to ensure an accelerated pace of patient accrual into the future.

The Company has demonstrated that treatment of AML cells with APTO-253 can induce expression of KLF4 and p21 (as described in prior disclosures), but also inhibits expression of the c-Myc oncogene at the mRNA and protein level. APTO-253 can lead to the transcriptional regulation of these key genes and yet not cause myelosuppression of normal bone marrow.

In the fourth quarter of 2015, Aptose and its partners presented several abstracts at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting (ASH) (Free ASH Whitepaper).

Researchers from the Knight Cancer Institute at Oregon Health & Science University (OHSU) presented data demonstrating the ability of APTO-253 to kill acute myeloid leukemia (AML) cells in the majority of patient samples, with a trend toward correlation with baseline KLF4 expression level. Moreover, APTO-253 exhibited enhanced killing ability of AML cells in patient samples when combined with either the BET inhibitor JQ1 or with the FLT3 inhibitor quizartinib. These data also demonstrated APTO-253 activity against other hematologic malignancies, in particular CLL.

Researchers from Moffitt Cancer Center described the in vitro activity of dual-targeting bromodomain/kinase inhibitor, MA2-014, which is a representative candidate from a new family of small molecule, dual-targeting BRD/kinase inhibitors licensed to Aptose. The MA2-014 program was developed to inhibit both the bromodomain 4 (BRD4) protein and the Janus kinase 2 (JAK2) for the potential treatment of various hematologic and solid tumor cancers. MA2-014 demonstrated activity in myeloproliferative neoplasm, or MPN, cell lines, which include rare blood cancers such as polycythemia vera, essential thrombocythemia and myelofibrosis.

MA2-014 exhibits similar anti-JAK2 activity as TG101209, a known JAK2 inhibitor, with an approximate ten-fold improvement in anti-BRD activity. Data also demonstrated a ten-fold improvement in the ability of MA2-014 to inhibit JAK2-V617F signaling over TG101209 and comparable to ruxolitinib, the only FDA-approved JAK inhibitor for MPNs.

Financial Results
THREE MONTHS ENDED DECEMBER 31, 2015 AND 2014 (UNAUDITED)

(Amounts in 000’s except for
per common share data) Dec 31,
2015 Dec 31,
2014
Revenue $ ― $ ―
Research and development expense 2,340 1,093
General and administrative expense 2,364 2,554
Operating expenses 4,704 3,647
Finance expense − 55
Finance income (273 ) (118 )
Net financing income (273 ) (63 )
Net loss (4,431 ) (3,584 )
Basic and diluted net loss per share $ (0.38 ) $ (0.31 )

Our net loss and comprehensive loss for the three months ended December 31, 2015 increased to $4.4 million compared with $3.6 million in the three months ended December 31, 2014. The increase in net loss is primarily due to costs associated with increased research and development activities of $1.2 million offset by reduced general and administrative costs of $190 thousand in the three months ended December 31, 2015, compared with the three months ended December 31, 2014. There was also an increase in net financing income of $210 thousand in the three months ended December 31, 2015 which reduced the net loss in comparison to the prior year period.

The increased research and development expense in the three months ended December 31, 2015, compared with the three months ended December 31, 2014, results from the APTO-253 Phase Ib clinical trial for which the first patient was enrolled in January 2015 and related personnel and consulting costs.

General and administrative expenses decreased to $2.4 million in the three months ended December 31, 2015 compared with $2.6 million in the three months ended December 31, 2014. This decrease, despite the increased cost of our US dollar expenditures due to the devaluation of the Canadian dollar, is related to a reduction in bonus expense for executives. In addition, costs related to the termination of our Toronto lease were recognized in the final quarter of 2014, for which no comparable costs exist in the current year.

FULL YEAR RESULTS

Consolidated Statements of Loss and Comprehensive Loss

Year ended
December 31,

7 months ended
December 31,
(amounts in Canadian thousands except for per common share data) 2015 2014
REVENUE $ — $ —

EXPENSES
Research and development 6,254 2,404
General and administrative 9,845 5,542
Operating expenses 16,099 7,946
Finance expense 43 104
Finance income (1,516 ) (279 )
Net finance (income) (1,473 ) (175 )
Net loss and total comprehensive loss for the period 14,626 7,771
Basic and diluted loss per common share $ 1.23 $ 0.67
Weighted average number of common shares
outstanding used in the calculation of:
Basic and diluted loss per share 11,906 11,605

Research and Development

Research and development expenses totaled $6.3 million in the year ended December 31, 2015 compared with $2.4 million in the seven months ended December 31, 2014. Research and development expenses consist of the following:

Year ended 7 months ended
December 31, December 31,
(in thousands) 2015 2014

Research and development costs $ 6,015 $ 2,371
Stock-based compensation 210 29
Depreciation of equipment 29 4
$ 6,254 $ 2,404

Expenditures for the year ended December 31, 2015 increased significantly over the seven months ended December 31, 2014 (on an annualized basis) due to the following:

Costs associated with the Phase 1b clinical trial of APTO-253 in patients with relapsed or refractory hematologic malignancies including clinical site costs, patient costs, contract research organization and consulting charges. The first patient in the trial was enrolled in January 2015;
Development costs related to the Moffitt/LALS programs that were initiated in the fourth quarter of 2015;
Formulation, manufacturing and compliance costs related to the development of APTO-253 including costs related to the clinical hold described above;
Additional payroll related costs in the clinical department due to restructuring to support ongoing activities; and
The increased cost of US dollar denominated expenditures due to the devaluation of the Canadian dollar.

Stock-based compensation expense increased in the year ended December 31, 2015 compared with the seven months ended December 31, 2014 primarily due to option grants to new employees and advisors during the year.

General and Administrative

General and administrative expenses totaled $9.8 million for the year ended December 31, 2015 compared with $5.5 million in the seven months ended December 31, 2014. General and administrative expenses consisted of the following:

(in thousands) 12 months ended 7 months ended
December 31, December 31,
2015 2014

General and administrative excluding salaries $ 4,327 $ 2,421
Salaries 2,849 1,505
Stock-based compensation 2,602 1,598
Depreciation and amortisation 67 18
$ 9,845 $ 5,542

On an annualized basis, general and administrative costs excluding salaries have increased slightly in the year ended December 31, 2015 compared with the seven months ended December 31, 2014. The increase is attributable to increased costs associated with our NASDAQ listing (initiated late 2014) including listing fees and insurance charges, internal control documentation work completed during the year as well as the devaluation of the Canadian dollar which has increased the cost of our US dollar denominated expenditures including, board fees, legal and other corporate costs. These increases have been offset by the charges related to the termination of the Toronto lease in December 2014 as well as costs incurred in 2014 related to our rebranding for which no comparable costs were incurred in the current year.

Salary costs on an annualized basis, a majority of which are incurred in US dollars, increased slightly in the year ended December 31, 2015 compared with the seven months ended December 31, 2014. This increase, however, has been offset by a reduction in bonus payments made to executives in the year ended December 31, 2015.

Stock-based compensation on an annualized basis in the year ended December 31, 2015 is consistent compared with the seven months ended December 31, 2014.

Finance Income

Finance income totaled $1.5 million in the year ended December 31, 2015 compared with $279 thousand in the seven months ended December 31, 2014. The components of finance income are as follows:

Year ended 7 months ended
December 31, December 31,
2015 2014
Interest income $ 286 $ 279
Foreign exchange gain on cash and cash equivalents 1,230 −
$ 1,516 $ 279

Interest income represents interest earned on our cash and cash equivalent and investment balances.

The foreign exchange gain realized in the year ended December 31, 2015 is due to the depreciation of the Canadian dollar and the subsequent increase in value of our US dollar currency balances.

The reported financial results were prepared in accordance with the International Financial Reporting Standards (IFRS) as issued by the International Accounting Standards Board (IASB).

Targeting NEK2 as a promising therapeutic approach for cancer treatment.

Never in Mitosis (NIMA) Related Kinase 2 (NEK2) plays a key role in regulating mitotic processes, including centrosome duplication and separation, microtubule stabilization, kinetochore attachment and spindle assembly checkpoint. NEK2 is aberrantly overexpressed in a wide variety of human cancers and has been implicated in various aspects of malignant transformation, including tumorigenesis, drug resistance and tumor progression. The close relationship between NEK2 and cancer has made it an attractive target for anticancer therapeutic development; however, the mechanisms of how NEK2 coordinates altered signaling to malignant transformation remains unclear. In this paper, we discuss the functional roles of NEK2 in cancer development; highlight some of the significant NEK2 signaling in cancer, and summarize recent advances in the development of NEK2 inhibitors.

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Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs.

Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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