Pipeline-AMG 820

AMG 820 is a human monoclonal antibody that inhibits c-fms and decreases tumor-associated macrophage (TAM) function. It is being investigated as a treatment for various cancer types (Company Pipeline, Amgen, APR 21, 2016, View Source [SID:1234511229]).

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A somatic reference standard for cancer genome sequencing.

Large-scale multiplexed identification of somatic alterations in cancer has become feasible with next generation sequencing (NGS). However, calibration of NGS somatic analysis tools has been hampered by a lack of tumor/normal reference standards. We thus performed paired PCR-free whole genome sequencing of a matched metastatic melanoma cell line (COLO829) and normal across three lineages and across separate institutions, with independent library preparations, sequencing, and analysis. We generated mean mapped coverages of 99X for COLO829 and 103X for the paired normal across three institutions. Results were combined with previously generated data allowing for comparison to a fourth lineage on earlier NGS technology. Aggregate variant detection led to the identification of consensus variants, including key events that represent hallmark mutation types including amplified BRAF V600E, a CDK2NA small deletion, a 12 kb PTEN deletion, and a dinucleotide TERT promoter substitution. Overall, common events include >35,000 point mutations, 446 small insertion/deletions, and >6,000 genes affected by copy number changes. We present this reference to the community as an initial standard for enabling quantitative evaluation of somatic mutation pipelines across institutions.

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Selective sorting and destruction of mitochondrial membrane proteins in aged yeast.

Mitochondrial dysfunction is a hallmark of aging, and underlies the development of many diseases. Cells maintain mitochondrial homeostasis through a number of pathways that remodel the mitochondrial proteome or alter mitochondrial content during times of stress or metabolic adaptation. Here, using yeast as a model system, we identify a new mitochondrial degradation system that remodels the mitochondrial proteome of aged cells. Unlike many common mitochondrial degradation pathways, this system selectively removes a subset of membrane proteins from the mitochondrial inner and outer membranes, while leaving the remainder of the organelle intact. Selective removal of preexisting proteins is achieved by sorting into a mitochondrial-derived compartment, or MDC, followed by release through mitochondrial fission and elimination by autophagy. Formation of MDCs requires the import receptors Tom70/71, and failure to form these structures exacerbates preexisting mitochondrial dysfunction, suggesting that the MDC pathway provides protection to mitochondria in times of stress.

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Biogen Reports First Quarter 2016 Revenues of $2.7 Billion

On April 21, 2016 Biogen Inc. (NASDAQ: BIIB reported first quarter 2016 financial results, including:

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Total revenues of $2.7 billion, a 7% increase versus the same period in the prior year (Press release, Biogen, APR 21, 2016, View Source [SID:1234511220]). Growth was driven by a 15% increase in worldwide TECFIDERA revenues as well as increased revenues from ELOCTATE and ALPROLIX. Revenues were partially offset by a decrease in worldwide interferon sales.

Foreign exchange, including a $26 million reduction in hedging gains, negatively impacted total revenues by approximately $50 million compared to the first quarter of 2015.

Non-GAAP diluted earnings per share (EPS) of $4.79, a 25% increase versus the same period in the prior year. Growth was driven by a combination of increased revenues, lower SG&A and R&D expense, and a lower share count.
Non-GAAP net income attributable to Biogen Inc. increased 17% to $1.0 billion.
GAAP diluted EPS of $4.43, a 27% increase versus the same period in the prior year.
GAAP net income attributable to Biogen Inc. increased 18% to $971 million.
(In millions, except per share amounts) Q1 ‘16 Q4 ‘15 Q1 ‘15 Q1 ‘16 v. Q4 ‘15 Q1 ‘16 v. Q1 ‘15
Total revenues $ 2,727 $ 2,839 $ 2,555 (4%) 7%
Non-GAAP net income* $ 1,049 $ 995 $ 900 5% 17%
Non-GAAP EPS $ 4.79 $ 4.50 $ 3.82 6% 25%

GAAP net income* $ 971 $ 832 $ 823 17% 18%
GAAP EPS $ 4.43 $ 3.77 $ 3.49 18% 27%
*Net income attributable to Biogen Inc.
A reconciliation of GAAP to Non-GAAP quarterly financial results can be found in Table 3 at the end of this release.

"Our leading multiple sclerosis portfolio, a growing hemophilia business, and our ongoing focus on managing expenses led to robust earnings growth in the first quarter," said Chief Executive Officer George A. Scangos, Ph.D. "We are pleased with the recent European approval of BENEPALI and positive CHMP opinion for FLIXABI, both anti-TNF biosimilars. We are also encouraged by the recent positive CHMP opinion of ALPROLIX for hemophilia B in Europe."

"The remainder of 2016 will be an exciting period as we look to advance a number of potential breakthrough therapies in the clinic," Dr. Scangos continued. "We are executing Phase 3 clinical trials for aducanumab in early Alzheimer’s disease and, along with our collaboration partner Ionis, we are progressing nusinersen in spinal muscular atrophy. In the coming months, we expect opicinumab (anti-LINGO) Phase 2 data to provide us with a better understanding of its potential as a reparative therapy for multiple sclerosis."

Revenue Highlights

(In millions) Q1 ‘16 Q4 ‘15 Q1 ‘15 Q1 ‘16 v. Q4 ‘15 Q1 ‘16 v. Q1 ‘15
Multiple Sclerosis (MS):
TECFIDERA $ 946 $ 993 $ 825 (5%) 15%
Total Interferon $ 670 $ 740 $ 755 (9%) (11%)
AVONEX $ 564 $ 637 $ 693 (11%) (19%)
PLEGRIDY $ 106 $ 103 $ 62 4% 72%
TYSABRI $ 477 $ 481 $ 463 (1%) 3%
FAMPYRA $ 20 $ 28 $ 20 (27%) 1%

Hemophilia:
ALPROLIX $ 75 $ 71 $ 43 5% 74%
ELOCTATE $ 108 $ 101 $ 54 6% 101%

Other Product Revenues:
FUMADERM $ 11 $ 13 $ 14 (10%) (16%)
BENEPALI $ 2 $ - $ - N/A N/A

Total Product Revenues: $ 2,309 $ 2,426 $ 2,172 (5%) 6%

Anti-CD20 Revenues $329 $334 $331 (1%) (0%)
Other Revenues $88 $80 $52 11% 69%

Total Revenues $2,727 $2,839 $2,555 (4%) 7%
Note: Numbers may not foot due to rounding
Expense Highlights

R&D expense was $437 million compared to $542 million in the fourth quarter of 2015 and $461 million in the first quarter of 2015.
R&D expense decreased 19% versus the fourth quarter of 2015, reflecting a $60 million payment made to Mitsubishi Tanabe Pharma Corporation in the fourth quarter of 2015 along with the timing of clinical manufacturing runs and other R&D activities.
SG&A expense was $497 million compared to $583 million in the fourth quarter of 2015 and $560 million in the first quarter of 2015. The company remains focused on achieving additional savings in non-labor expenses, with the objective of reducing lower priority fees and services expenses.
Other Financial Highlights

For the first quarter of 2016, the Company’s weighted average diluted shares were 219 million.
At the end of the first quarter of 2016, Biogen had cash, cash equivalents and marketable securities totaling approximately $6.8 billion, and $6.5 billion in notes payable and other financing arrangements.
Recent Events

This week, Biogen is presenting new data supporting the Company’s marketed and pipeline MS therapies at the 68th American Academy of Neurology (AAN) Annual Meeting. Presentations include efficacy data for TECFIDERA in newly diagnosed patients; data highlighting efficacy on key cognitive outcomes and the reversibility of the targeted mechanism of action of ZINBRYTATM; 10 year real-world evidence of the proven long-term efficacy of TYSABRI in patients with high disease activity; and analyses showing that PLEGRIDY reduces conversion of MRI lesions to T1 black holes.

At this week’s AAN Meeting, Biogen’s collaboration partner Ionis Pharmaceuticals also presented an update from its ongoing open-label Phase 2 study of nusinersen in infants with spinal muscular atrophy.

In April 2016, Samsung Bioepis, the joint venture between Biogen and Samsung BioLogics, received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommending that marketing authorisation be granted for FLIXABI, an infliximab biosimilar candidate referencing Remicade. If approved, FLIXABI will be the second anti-TNF biosimilar manufactured and commercialized by Biogen in the European Union (EU).

In March 2016, Biogen announced the appointment of Michel Vounatsos as Executive Vice President and Chief Commercial Officer effective April 18, 2016. Mr. Vounatsos joins Biogen following a distinguished 20 year career at Merck.

In February 2016, Swedish Orphan Biovitrum AB (publ) (Sobi) and Biogen received a positive opinion from the CHMP recommending that marketing authorisation be granted for ALPROLIX, a recombinant factor IX Fc fusion protein therapy for the treatment of hemophilia B.

In February 2016, the Roche Group announced that the US Food and Drug Administration approved Gazyva plus bendamustine chemotherapy followed by Gazyva alone as a new treatment for people with follicular lymphoma who did not respond to a Rituxan-containing regimen, or had their follicular lymphoma return after such treatment. Follicular lymphoma is the most common type of indolent (slow-growing) non-Hodgkin lymphoma (NHL) and accounts for approximately one in five cases of NHL. In the U.S., Biogen shares operating profits and losses relating to GAZYVA with Genentech, a Roche Group company.

In February 2016, Biogen announced that it joined the Centre for Therapeutic Target Validation (CTTV), the pioneering public-private collaboration to improve the success rate for discovering new medicines. The CTTV fosters deep, ongoing interactions between academic and industry members for the purpose of developing open, transformative approaches to selecting and validating novel targets in drug development.

In January 2016, following approval from the European Commission, Biogen launched BENEPALI, the first etanercept biosimilar referencing Enbrel to be approved in the EU. BENEPALI is now available in the UK, Germany, Denmark, Norway, Sweden, and the Netherlands.

A Query Tool for Investigator Access to the Data and Images of the National Lung Screening Trial.

The National Cancer Institute (NCI), in conjunction with blinded university, provides a mechanism to enable public access to the study data, CT radiology images, and pathology images from the National Lung Screening Trial (NLST). Access to the data and images is through the NCI-sponsored, blinded university-hosted The Cancer Imaging Archive (TCIA), a repository of more than 40 study collections of cancer images. Once access to the NLST data has been granted by NCI, a Query Tool within TCIA is used to access the NLST data and images. The Query Tool is a simple-to-use menu-driven database application designed to quickly pose queries and retrieve/save results (from 53,452 NLST participants), download CT images (~20 million available), and view pathology images (~1200 available). NLST study data are contained in 17 Query Tool tables with ~370 variables to query. This paper describes Query Tool design, functionality, and usefulness for researchers, clinicians, and software developers to query data, save query results, and download/view images.

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