Safety Assessment

Shanghai, China

Safety Assessment

Shanghai, China

Time filter

Source Type

Waaler J.,University of Oslo | Boggs J.,Drug Metabolism and Pharmacokinetics | Blake R.A.,Biochemical and Cellular Pharmacology | Magnuson S.,Discovery Chemistry | And 10 more authors.
Cancer Research | Year: 2013

Most colorectal cancers (CRC) are initiated by mutations of APC, leading to increased β-catenin-mediated signaling. However, continued requirement of Wnt/β-catenin signaling for tumor progression in the context of acquired KRAS and other mutations is less well-established. To attenuate Wnt/β-catenin signaling in tumors, we have developed potent and specific small-molecule tankyrase inhibitors, G007-LK and G244-LM, that reduce Wnt/β-catenin signaling by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thereby promoting β-catenin destabilization. We show that novel tankyrase inhibitors completely block ligand-driven Wnt/β-catenin signaling in cell culture and display approximately 50% inhibition of APC mutation-driven signaling in most CRC cell lines. It was previously unknown whether the level of AXIN protein stabilization by tankyrase inhibition is sufficient to impact tumor growth in the absence of normal APC activity. Compound G007-LK displays favorable pharmacokinetic properties and inhibits in vivo tumor growth in a subset of APC-mutant CRC xenograft models. In the xenograftmodel most sensitive to tankyrase inhibitor, COLO-320DM, G007-LK inhibits cell-cycle progression, reduces colony formation, and induces differentiation, suggesting that β-catenin-dependent maintenance of an undifferentiated state may be blocked by tankyrase inhibition. The full potential of the antitumor activity of G007-LK may be limited by intestinal toxicity associated with inhibition of Wnt/β-catenin signaling and cell proliferation in intestinal crypts. These results establish proof-of-concept antitumor efficacy for tankyrase inhibitors in APC-mutant CRC models and uncover potential diagnostic and safety concerns to be overcome as tankyrase inhibitors are advanced into the clinic. Cancer Res; 73(10); 3132-44. © 2013 AACR.


PubMed | University of Wisconsin - Madison, Leiden University, Safety Assessment, Drug Metabolism & Pharmacokinetics and 6 more.
Type: Journal Article | Journal: Journal of controlled release : official journal of the Controlled Release Society | Year: 2016

A potent anti-vascular endothelial growth factor (VEGF) biologic and a compatible delivery system were co-evaluated for protection against wet age-related macular degeneration (AMD) over a 6month period following a single intravitreal (IVT) injection. The anti-VEGF molecule is dimeric, containing two different anti-VEGF domain antibodies (dAb) attached to a human IgG1 Fc region: a dual dAb. The delivery system is based on microparticles of PolyActive hydrogel co-polymer. The molecule was evaluated both in vitro for potency against VEGF and in ocular VEGF-driven efficacy models in vivo. The dual dAb is highly potent, showing a lower IC


The US Department of Transportation issued Federal policy for highly automated vehicles (HAVs)—i.e., SAE Levels 3-5 vehicles with automated systems that are responsible for monitoring the driving environment as defined by SAE J3016. Although the primary focus of the Federal Automated Vehicle Policy is on highly automated vehicles, or those in which the vehicle can take full control of the driving task in at least some circumstances, portions of the policy also apply to lower levels of automation, including some of the driver-assistance systems already being deployed by automakers today. The newly released policy embodies four key elements: 15 Point Safety Assessment. The Vehicle Performance Guidance for Automated Vehicles for manufacturers, developers and other organizations includes a 15 point “Safety Assessment” for the safe design, development, testing and deployment of automated vehicles. Model State Policy. This section presents a clear distinction between Federal and State responsibilities for regulation of highly automated vehicles, and suggests recommended policy areas for states to consider with a goal of generating a consistent national framework for the testing and deployment of highly automated vehicles. NHTSA’s Current Regulatory Tools. This discussion outlines NHTSA’s current regulatory tools that can be used to ensure the safe development of new technologies, such as interpreting current rules to allow for greater flexibility in design and providing limited exemptions to allow for testing of nontraditional vehicle designs in a more timely fashion. Modern Regulatory Tools. This discussion identifies new regulatory tools and statutory authorities that policymakers may consider in the future to aid the safe and efficient deployment of new lifesaving technologies. The 15-point Safety Assessment. The 15-point Safety Assessment outlines objectives on how to achieve a robust design. It allows for varied methodologies as long as the objective is met. The Guidance asks manufacturers and other entities to document how they are meeting each topic area in the guidance. The issues include: Operational Design Domain: How and where the HAV is supposed to function and operate; Object and Event Detection and Response: Perception and response functionality of the HAV system; Fall Back (Minimal Risk Condition): Response and robustness of the HAV upon system failure; Validation Methods: Testing, validation, and verification of an HAV system; Registration and Certification: Registration and certification to NHTSA of an HAV system; Data Recording and Sharing: HAV system data recording for information sharing, knowledge building and for crash reconstruction purposes; Post-Crash Behavior: Process for how an HAV should perform after a crash and how automation functions can be restored; Human Machine Interface: Approaches for communicating information to the driver, occupant and other road users; Consumer Education and Training: Education and training requirements for users of HAVs; Ethical Considerations: How vehicles are programmed to address conflict dilemmas on the road; and Federal, State and Local Laws: How vehicles are programmed to comply with all applicable traffic laws. Proactive. Moving beyond the traditional US auto regulatory approach of reactive, post-sale enforcement of safety standards, the policy is a proactive measure. A March 2016 study by DOT’s Volpe notes that current Federal Motor Vehicle Safety Standards do not directly address automated vehicle technologies. Those standards can take many years to develop and are traditionally only put into force after new technologies have made significant market penetration. Instead, the automated vehicle policy envisions greater transparency as DOT works with manufacturers to ensure that safety is appropriately addressed on the front-end of development. New technologies developed in the 20th century, like seat belts and air bags, were once controversial but have now saved hundreds of thousands of American lives. This is the first in a series of proactive approaches, including the release of a rule on Vehicle to Vehicle communications, which will bring lifesaving technologies to the roads safely and quickly while leaving innovators to dream up new safety solutions. The new policy is a product of public input and stakeholder discussions, including two open public meetings this year and an open public docket for comments. The Department is soliciting additional public comments for the next 60 days on the policy. Through a series of next steps and in response to public comments, DOT intends to update the policy annually. Simultaneously with this policy, NHTSA is releasing a final enforcement guidance bulletin clarifying how its recall authority will apply to automated vehicle technologies. In particular, it emphasizes that semi-autonomous driving systems that fail to adequately account for the possibility that a distracted or inattentive driver-occupant might fail to retake control of the vehicle in a safety-critical situation may be defined as an unreasonable risk to safety and subject to recall.


Napolitano A.,Immuno Inflammation Unit | Miller S.,Quantitative science | Nicholls A.W.,Safety Assessment | Baker D.,Safety Assessment | And 6 more authors.
PLoS ONE | Year: 2014

Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK) activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology. We hypothesized that the pharmacology of metformin includes alteration of bile acid recirculation and gut microbiota resulting in enhanced enteroendocrine hormone secretion. In this study we evaluated T2DM subjects on and off metformin monotherapy to characterize the gut-based mechanisms of metformin. Subjects were studied at 4 time points: (i) at baseline on metformin, (ii) 7 days after stopping metformin, (iii) when fasting blood glucose (FBG) had risen by 25% after stopping metformin, and (iv) when FBG returned to baseline levels after restarting the metformin. At these timepoints we profiled glucose, insulin, gut hormones (glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose-dependent insulinotropic peptide (GIP) and bile acids in blood, as well as duodenal and faecal bile acids and gut microbiota. We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates. These effects reversed when metformin was restarted. Effects on circulating PYY were more modest, while GIP changes were negligible. Microbiota abundance of the phylum Firmicutes was positively correlated with changes in cholic acid and conjugates, while Bacteroidetes abundance was negatively correlated. Firmicutes and Bacteroidetes representation were also correlated with levels of serum PYY. Our study suggests that metformin has complex effects due to gut-based pharmacology which might provide insights into novel therapeutic approaches to treat T2DM and associated metabolic diseases. Trial Registration:: www.ClinicalTrials.gov NCT01357876. © 2014 Napolitano et al.


WILMINGTON, Mass.--(BUSINESS WIRE)--Charles River Laboratories International, Inc. (NYSE: CRL) today reported its results for the fourth-quarter and full-year 2016 and provided guidance for 2017. For the quarter, revenue from continuing operations was $466.8 million, an increase of 31.9% from $353.9 million in the fourth quarter of 2015. Revenue growth was driven primarily by the Discovery and Safety Assessment and Manufacturing Support segments. Research Models and Services revenue also increased. The acquisitions of WIL Research, Agilux Laboratories, Blue Stream Laboratories, and Oncotest contributed 20.9% to consolidated fourth-quarter revenue growth, both on a reported basis and in constant currency. The addition of a 53rd week at the end of 2016, which is periodically required to align to a December 31st calendar year end, contributed approximately 5.1% to reported fourth-quarter revenue growth. The impact of foreign currency translation reduced reported revenue growth by 2.4%. Excluding the effect of these items, organic revenue growth was 8.3%. On a GAAP basis, net income from continuing operations attributable to common shareholders was $44.7 million for the fourth quarter of 2016, an increase of 36.4% from $32.8 million for the same period in 2015. Fourth-quarter diluted earnings per share on a GAAP basis were $0.93, an increase of 34.8% from $0.69 for the fourth quarter of 2015. On a non-GAAP basis, net income from continuing operations was $58.3 million for the fourth quarter of 2016, an increase of 23.3% from $47.3 million for the same period in 2015. Fourth-quarter diluted earnings per share on a non-GAAP basis were $1.21, an increase of 21.0% from $1.00 per share for the fourth quarter of 2015. Both the GAAP and non-GAAP earnings per share increases were driven primarily by the acquisition of new businesses, notably WIL Research, as well as higher revenue for legacy operations. A gain from the Company’s venture capital investments contributed $0.02 per share in the fourth quarter of 2016, compared to a negligible impact for the same period in 2015. James C. Foster, Chairman, President and Chief Executive Officer, said, “Our fourth-quarter results provided a strong finish to an exceptional year in which we met our long-term revenue goals for all of our businesses except Discovery, and our long-term operating margin targets for the three business segments. We were very pleased that three of our businesses, Safety Assessment, Microbial Solutions, and Biologics Testing Solutions, reported low-double-digit organic revenue growth for the full year. Client demand for our unique portfolio of essential products and services remained strong across each of our client segments, particularly for our biotechnology clients, who were the primary driver of our revenue growth in 2016.” “Our continued investments to broaden our early-stage portfolio, the scientific expertise of our staff, our focus on productivity and efficiency initiatives, and our ability to offer flexible partnership structures are the primary reasons that we are the partner of choice for many of our clients. Based on our view of the opportunities in 2017, we believe we will again deliver high single-digit organic revenue growth and earnings per share growth at a faster rate than revenue,” Mr. Foster concluded. Revenue for the RMS segment was $124.7 million in the fourth quarter of 2016, an increase of 9.5% from $113.8 million in the fourth quarter of 2015. Organic revenue growth was 5.7%. Revenue growth was driven primarily by higher sales of research model services, and sales of research models also increased. In the fourth quarter of 2016, the RMS segment’s GAAP operating margin increased to 26.7% from 24.1% in the fourth quarter of 2015. On a non-GAAP basis, the operating margin increased to 27.3% from 25.4% in the fourth quarter of 2015. Both the GAAP and non-GAAP operating margin increases were due primarily to higher sales volume and the benefit of efficiency initiatives. Revenue from continuing operations for the DSA segment was $241.7 million in the fourth quarter of 2016, an increase of 50.6% from $160.5 million in the fourth quarter of 2015. Growth was driven primarily by the acquisitions of WIL Research, Agilux Laboratories, and Oncotest, which contributed 41.6% to DSA revenue growth. Organic revenue growth was 7.9%. Low-double-digit growth in the legacy Safety Assessment business was partially offset by lower revenue for the legacy Discovery Services business, which declined due primarily to softer demand from global clients for Early Discovery services. Robust demand from biotechnology clients continued to drive revenue growth in the DSA segment. In the fourth quarter of 2016, the DSA segment’s GAAP operating margin declined to 18.1% from 23.1% in the fourth quarter of 2015. The margin decline was due to costs associated with the evaluation and integration of acquisitions, including amortization of intangible assets, as well as the benefit from a tax law change in Quebec in the fourth quarter of 2015. On a non-GAAP basis, the operating margin decreased to 23.8% from 27.1% in the fourth quarter of 2015, due primarily to the tax law change in Quebec, which benefited both the GAAP and non-GAAP DSA operating margin by approximately 230 basis points in the fourth quarter of 2015. The acquisition of WIL reduced the fourth-quarter operating margin by approximately 100 basis points, and foreign exchange benefited the DSA operating margin by approximately 80 basis points due primarily to a weaker British pound. Revenue for the Manufacturing segment was $100.3 million in the fourth quarter of 2016, an increase of 26.2% from $79.5 million in the fourth quarter of 2015. The acquisitions of Blue Stream Laboratories and WIL Research’s contract development and manufacturing (CDMO) services contributed 9.2% to Manufacturing revenue growth in the fourth quarter of 2016. Organic revenue growth was 12.9%, primarily driven by robust growth in the Microbial Solutions and Biologics Testing Solutions businesses. In the fourth quarter of 2016, the Manufacturing segment’s GAAP operating margin increased to 31.0% from 23.7% in the fourth quarter of 2015. The GAAP operating margin increase was primarily driven by lower acquisition costs related to Celsis, as well as leverage from higher revenue in the Microbial Solutions business. On a non-GAAP basis, the operating margin increased to 34.2% from 33.8% in the fourth quarter of 2015, driven by operating margin improvement in the Microbial Solutions business as a result of higher revenue and the benefit of efficiency initiatives. For 2016, revenue increased by 23.3% to $1.68 billion from $1.36 billion in 2015. Organic revenue growth was 7.7%. On a GAAP basis, net income from continuing operations attributable to common shareholders was $154.5 million in 2016, an increase of 2.8% from $150.3 million in 2015. Diluted earnings per share on a GAAP basis in 2016 were $3.22, an increase of 2.2% from $3.15 in 2015. On a non-GAAP basis, net income from continuing operations was $218.9 million in 2016, an increase of 22.1% from $179.3 million in 2015. Diluted earnings per share on a non-GAAP basis in 2016 were $4.56, an increase of 21.3% from $3.76 in 2015. For 2016, RMS revenue was $494.0 million, an increase of 5.0% from $470.4 million in 2015. Organic revenue growth was 4.1%. On a GAAP basis, the RMS segment operating margin increased to 27.6% in 2016 from 25.7% in 2015. On a non-GAAP basis, the operating margin increased to 28.4% in 2016 from 27.1% in 2015. For 2016, DSA revenue was $836.6 million, an increase of 36.7% from $612.2 million in 2015. Organic revenue growth was 8.9%. On a GAAP basis, the DSA segment operating margin decreased to 16.5% in 2016 from 19.9% in 2015. On a non-GAAP basis, the operating margin decreased to 22.7% in 2016 from 23.3% in 2015. For 2016, Manufacturing revenue was $350.8 million, an increase of 25.0% from $280.7 million in 2015. Organic revenue growth was 11.3%. On a GAAP basis, the Manufacturing segment operating margin increased to 29.8% in 2016 from 26.6% in 2015. On a non-GAAP basis, the operating margin increased to 33.8% in 2016 from 32.6% in 2015. Charles River completed the divestiture of its CDMO business on February 10, 2017, to Quotient Clinical, a portfolio company of specialist healthcare investment adviser GHO Capital Partners LLP, based in London, England, for $75.0 million in cash, subject to certain post-closing adjustments. The CDMO business, which represented approximately 1% of Charles River’s 2016 consolidated revenue, provides services to support the formulation design and manufacture of oral drug dosages for biopharmaceutical clients, specializing in high-potency compounds. Charles River acquired the CDMO business in April 2016 as part of the acquisition of WIL Research. Following a strategic review, Charles River determined that the CDMO business was not optimized within Charles River’s portfolio at its current scale, and that the capital could be better deployed in other long-term growth opportunities. The Company is providing the following revenue growth and earnings per share guidance for 2017. This guidance reflects the divestiture of the CDMO business. Earnings per share in 2017 are expected to benefit from both higher revenue and operating margin expansion. The benefit is expected to be partially offset by foreign exchange, which is expected to reduce 2017 earnings per share by approximately $0.10, and lower gains from the Company’s venture capital investments. The Company’s 2016 earnings per share included a $0.13 gain on venture capital investments, and 2017 guidance includes an estimated $0.04 gain on these investments, consistent with the Company’s expected return on invested capital. Footnotes to Guidance Table (1) The contribution from acquisitions reflects only those acquisitions which were completed in 2016. (2) Organic revenue growth is defined as reported revenue growth adjusted for acquisitions, the divestiture of the CDMO business, the 53rd week, and foreign currency translation. (3) GAAP earnings per share guidance does not include the expected net gain and tax impact related to the divestiture of the CDMO business because the disposition accounting has not yet been finalized. (4) These charges relate primarily to the Company’s planned efficiency initiatives in 2017, including site consolidation costs, asset impairments, and severance. Other projects in support of the global productivity and efficiency initiatives are expected, but these charges reflect only the decisions that have already been finalized. (5) These adjustments are related to the evaluation and integration of acquisitions and the divestiture of the CDMO business, and primarily include transaction, advisory, and certain third-party integration costs, as well as certain costs associated with acquisition-related efficiency initiatives. Charles River has scheduled a live webcast on Tuesday, February 14, at 8:00 a.m. ET to discuss matters relating to this press release. To participate, please go to ir.criver.com and select the webcast link. You can also find the associated slide presentation and reconciliations of GAAP financial measures to non-GAAP financial measures on the website. Charles River will present at the Leerink 6th Annual Global Healthcare Conference in New York on Thursday, February 16, at 9:30 a.m. ET. Management will provide an overview of Charles River’s strategic focus and business developments. A live webcast of the presentation will be available through a link that will be posted on the Investor Relations section of the Charles River website at ir.criver.com. A webcast replay will be accessible through the same website approximately three hours after the presentation and will remain available for approximately two weeks. The Company reports non-GAAP results in this press release, which exclude often one-time charges and other items that are outside of normal operations. A reconciliation of GAAP to non-GAAP results is provided in the schedules at the end of this press release. In addition, the Company reports results from continuing operations, which exclude results of the Phase I clinical business that was divested in 2011. The Phase I business is reported as a discontinued operation. Use of Non-GAAP Financial Measures This press release contains non-GAAP financial measures, such as non-GAAP earnings per diluted share, which exclude the amortization of intangible assets, inventory purchase accounting adjustments, and other charges related to our acquisitions; expenses associated with evaluating and integrating acquisitions and divestitures, as well as fair value adjustments associated with contingent consideration; charges related to modifications of purchase options on remaining non-controlled equity interests, and re-measurement of previously held equity interests; charges, gains and losses attributable to businesses or properties we plan to close, consolidate or divest; severance and other costs associated with our efficiency initiatives; executive transition costs; a reversal of indemnification assets associated with acquisitions and corresponding interest; write-off of and adjustments to deferred financing costs and fees related to debt financing; gain on bargain purchase; and costs related to a U.S. government billing adjustment and related expenses. This press release also refers to our revenue in both a GAAP and non-GAAP basis: “constant currency,” which we define as reported revenue growth adjusted for the impact of foreign currency translation, and “organic revenue growth,” which we define as reported revenue growth adjusted for foreign currency translation, acquisitions, the divestiture of the CDMO business, and the 53rd week. We exclude these items from the non-GAAP financial measures because they are outside our normal operations. There are limitations in using non-GAAP financial measures, as they are not prepared in accordance with generally accepted accounting principles, and may be different than non-GAAP financial measures used by other companies. In particular, we believe that the inclusion of supplementary non-GAAP financial measures in this press release helps investors to gain a meaningful understanding of our core operating results and future prospects without the effect of these often-one-time charges, and is consistent with how management measures and forecasts the Company's performance, especially when comparing such results to prior periods or forecasts. We believe that the financial impact of our acquisitions and divestitures (and in certain cases, the evaluation of such acquisitions and divestitures, whether or not ultimately consummated) is often large relative to our overall financial performance, which can adversely affect the comparability of our results on a period-to-period basis. In addition, certain activities and their underlying associated costs, such as business acquisitions, generally occur periodically but on an unpredictable basis. We calculate non-GAAP integration costs to include third-party integration costs incurred post-acquisition. Presenting revenue on a constant-currency basis allows investors to measure our revenue growth exclusive of foreign currency exchange fluctuations more clearly. Non-GAAP results also allow investors to compare the Company’s operations against the financial results of other companies in the industry who similarly provide non-GAAP results. The non-GAAP financial measures included in this press release are not meant to be considered superior to or a substitute for results of operations prepared in accordance with GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules and regulations. Reconciliations of the non-GAAP financial measures used in this press release to the most directly comparable GAAP financial measures are set forth in this press release, and can also be found on the Company’s website at ir.criver.com. This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate,” “believe,” “expect,” “intend,” “will,” “may,” “estimate,” “plan,” “outlook,” and “project,” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements also include statements regarding our projected future financial performance including revenue (on both a reported, constant-currency, and organic growth basis), operating margins, earnings per share, the expected impact of foreign exchange rates, and the expected benefit of our life science venture capital investments; the future demand for drug discovery and development products and services, including our expectations for future revenue trends; our expectations with respect to the impact of acquisitions on the Company, our service offerings, client perception, strategic relationships, revenue, revenue growth rates, and earnings; the development and performance of our services and products; market and industry conditions including the outsourcing of services and spending trends by our clients; the potential outcome of and impact to our business and financial operations due to litigation and legal proceedings, including with respect to our ongoing investigation of inaccurate billing with respect to certain government contracts; and Charles River’s future performance as delineated in our forward-looking guidance, and particularly our expectations with respect to revenue, the impact of foreign exchange, and enhanced efficiency initiatives. Forward-looking statements are based on Charles River’s current expectations and beliefs, and involve a number of risks and uncertainties that are difficult to predict and that could cause actual results to differ materially from those stated or implied by the forward-looking statements. Those risks and uncertainties include, but are not limited to: the ability to successfully integrate businesses we acquire; the ability to execute our efficiency initiatives on an effective and timely basis (including divestitures and site closures); the timing and magnitude of our share repurchases; negative trends in research and development spending, negative trends in the level of outsourced services, or other cost reduction actions by our clients; the ability to convert backlog to revenue; special interest groups; contaminations; industry trends; new displacement technologies; USDA and FDA regulations; changes in law; continued availability of products and supplies; loss of key personnel; interest rate and foreign currency exchange rate fluctuations (including the impact of Brexit); changes in tax regulation and laws; changes in generally accepted accounting principles; and any changes in business, political, or economic conditions due to the threat of future terrorist activity in the U.S. and other parts of the world, and related U.S. military action overseas. A further description of these risks, uncertainties, and other matters can be found in the Risk Factors detailed in Charles River's Annual Report on Form 10-K as filed on February 12, 2016, as well as other filings we make with the Securities and Exchange Commission. Because forward-looking statements involve risks and uncertainties, actual results and events may differ materially from results and events currently expected by Charles River, and Charles River assumes no obligation and expressly disclaims any duty to update information contained in this news release except as required by law. Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit www.criver.com. (1) Charles River management believes that supplementary non-GAAP financial measures provide useful information to allow investors to gain a meaningful understanding of our core operating results and future prospects, without the effect of often-one-time charges and other items which are outside our normal operations, consistent with the manner in which management measures and forecasts the Company’s performance. The supplementary non-GAAP financial measures included are not meant to be considered superior to, or a substitute for results of operations prepared in accordance with U.S. GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules, regulations and guidance. (2) This item includes operating losses related primarily to the Company's Shrewsbury, Massachusetts facility. (3) These adjustments are related to the evaluation and integration of acquisitions, which primarily include transaction, third-party integration, and certain compensation costs, and fair value adjustments associated with contingent consideration. (1) Charles River management believes that supplementary non-GAAP financial measures provide useful information to allow investors to gain a meaningful understanding of our core operating results and future prospects, without the effect of often-one-time charges and other items which are outside our normal operations, consistent with the manner in which management measures and forecasts the Company’s performance. The supplementary non-GAAP financial measures included are not meant to be considered superior to, or a substitute for results of operations prepared in accordance with U.S. GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules, regulations and guidance. (2) These amounts represent the reversal of an uncertain tax position and an offsetting indemnification asset primarily related to the acquisition of BioFocus. (3) The amounts relate to the acquisition of Sunrise Farms, Inc. and represents the excess of the estimated fair value of the net assets acquired over the purchase price. (4) The amount represents a $1.5 million charge recorded in connection with the modification of the option to purchase the remaining 13% equity interest in Vital River, partially offset by a $0.7 million gain on remeasurement of previously held equity interest in an entity acquired in a step acquisition. (1) Charles River management believes that supplementary non-GAAP financial measures provide useful information to allow investors to gain a meaningful understanding of our core operating results and future prospects, without the effect of often-one-time charges and other items which are outside our normal operations, consistent with the manner in which management measures and forecasts the Company’s performance. The supplementary non-GAAP financial measures included are not meant to be considered superior to, or a substitute for results of operations prepared in accordance with U.S. GAAP. The Company intends to continue to assess the potential value of reporting non-GAAP results consistent with applicable rules, regulations and guidance. (2) The contribution from acquisitions reflects only those acquisitions which were completed during fiscal year 2016 and 2015. (3) Organic revenue growth is defined as reported revenue growth adjusted for acquisitions, the 53rd week, and foreign exchange.


News Article | May 11, 2016
Site: www.realwire.com

SMi Group reports (2016.05.11, San Diego, California, USA): FDA will provide the latest updates on Pre-Filled Syringes and Combination Products at Pre-Filled Syringes West Coast 2016. SMi are delighted to announce that FDA will be presenting at Pre-Filled Syringes West Coast this June in San Diego. Tina Kiang, Ph.D., Deputy Director, Science and Policy, and Shannon Hoste, Human Factors Engineer, FDA, will be speaking on Day One of the conference on "Safety Assessment and Regulatory Updates on Pre-Filled Syringes and Combination Products". For further information, please visit www.prefilled-syringes-westcoast.com/RealWire Don’t miss the chance in 4 weeks’ to participate in the Q&A session with FDA and meet 100+ leading drug delivery experts from the Pharmaceutical and Biotechnology businesses in the West Coast. Pre-Filled Syringes West Coast 2016 brings together key decision makers in the PFS industry from Biogen, Teva, Pfizer, Boehringer Ingelheim Fremont, Inc., Shire and many more. The two-day conference takes place in San Diego, USA, and will provide the perfect platform to discuss regulatory challenges and analyse device design to drive patient’s safety, usability and delivery excellence. Day one of the conference will address topics on regulatory developments and updates, the rise of complex combination products for PFS, and formative studies of human factor engineering. Day two explores technological advancements in manufacturing, competitiveness of products, and patient concerns. A post-conference workshop on June 8th will focus on Human Factor Engineering for Pre-Filled Syringes and Autoinjectors. Hosted by Core Human Factors, the session will cover the regulatory requirements for human factors work on medical devices, comparisons between the regulatory requirements in the US and the EMEA region, and will discuss when, and how, to go about panning human factors activities. For the full event agenda including all speakers and their topics please visit the event website on www.prefilled-syringes-westcoast.com/RealWire PFS West Coast 2016 will provide delegates with an unrivalled networking platform including a post-conference lunch sponsored by ZebraSci, Inc. The networking lunch will be held at Stone Brewing World Bistro & Gardens and includes beer flight tasting. This is the perfect opportunity to meet and discuss core issues of pre-filled syringes with industry colleagues. This offer is exclusive to the first 40 Pharma and Biotech. For more information please contact Fateja Begum on +44(0)2078276184 or e-mail fbegum@smi-online.co.uk Alongside lead sponsor ZebraSci, Inc., SMi’s Pre-Filled Syringes West Coast 2016 is proudly sponsored by Bosch Packaging Technology, DDL, KBI Biopharma, Mitsubishi Gas Chemical, Noxilizer, Steris, Terumo and Zeon. For tailored sponsorship and exhibition opportunities contact Alia Malick on +44 (0) 20 7827 6168 or email: amalick@smi-online.co.uk. About SMi Group: Established since 1993, the SMi Group is a global event-production company that specializes in Business-to-Business Conferences, Workshops, Masterclasses and online Communities. We create and deliver events in the Defence, Security, Energy, Utilities, Finance and Pharmaceutical industries. We pride ourselves on having access to the world’s most forward thinking opinion leaders and visionaries, allowing us to bring our communities together to Learn, Engage, Share and Network. More information can be found at http://www.smi-online.co.uk


Home > Press > The Sustainable Nanotechnologies Project’s Final Events: Bringing Nano Environmental Health and Safety Assessment to the Wider Discussion on Risk Governance of Key Enabling Technologies Abstract: The EU FP7 Sustainable Nanotechnologies (SUN) Project is coming to its end in March 2017. The project has designed its final events to serve as an effective platform to communicate the main results achieved in its course within the Nanosafety community and bridge them to a wider audience addressing the emerging risks of Key Enabling Technologies (KETs). The series of events include the New Tools and Approaches for Nanomaterial Safety Assessment: A joint conference organized by NANOSOLUTIONS, SUN, NanoMILE, GUIDEnano and eNanoMapper to be held on 7 – 9 February 2017 in Malaga, Spain, the SUN-CaLIBRAte Stakeholders workshop to be held on 28 February – 1 March 2017 in Venice, Italy and the SRA Policy Forum: Risk Governance for Key Enabling Technologies to be held on 1- 3 March in Venice, Italy. Jointly organized by the Society for Risk Analysis (SRA) and the SUN Project, the SRA Policy Forum will address current efforts put towards refining the risk governance of emerging technologies through the integration of traditional risk analytic tools alongside considerations of social and economic concerns. The parallel sessions will be organized in 4 tracks: Risk analysis of engineered nanomaterials along product lifecycle, Risks and benefits of emerging technologies used in medical applications, Challenges of governing SynBio and Biotech, and Methods and tools for risk governance. The SRA Policy Forum has announced its speakers and preliminary Programme. Confirmed speakers include: Keld Alstrup Jensen (National Research Centre for the Working Environment, Denmark) Elke Anklam (European Commission, Belgium) Adam Arkin (University of California, Berkeley, USA) Phil Demokritou (Harvard University, USA) Gerard Escher (École polytechnique fédérale de Lausanne, Switzerland) Lisa Friedersdor (National Nanotechnology Initiative, USA) James Lambert (President, Society for Risk Analysis, USA) Andre Nel (The University of California, Los Angeles, USA) Bernd Nowack (EMPA, Switzerland) Ortwin Renn (University of Stuttgart, Germany) Vicki Stone (Heriot-Watt University, UK) Theo Vermeire (National Institute for Public Health and the Environment (RIVM), Netherlands) Tom van Teunenbroek (Ministry of Infrastructure and Environment, The Netherlands) Wendel Wohlleben (BASF, Germany) The New Tools and Approaches for Nanomaterial Safety Assessment (NMSA) conference aims at presenting the main results achieved in the course of the organizing projects fostering a discussion about their impact in the nanosafety field and possibilities for future research programmes. The conference welcomes consortium partners, as well as representatives from other EU projects, industry, government, civil society and media. Accordingly, the conference topics include: Hazard assessment along the life cycle of nano-enabled products, Exposure assessment along the life cycle of nano-enabled products, Risk assessment & management, Systems biology approaches in nanosafety, Categorization & grouping of nanomaterials, Nanosafety infrastructure, Safe by design. The NMSA conference key note speakers include: Harri Alenius (University of Helsinki, Finland,) Antonio Marcomini (Ca’ Foscari University of Venice, Italy) Wendel Wohlleben (BASF, Germany) Danail Hristozov (Ca’ Foscari University of Venice, Italy) Eva Valsami-Jones (University of Birmingham, UK) Socorro Vázquez-Campos (LEITAT Technolоgical Center, Spain) Barry Hardy (Douglas Connect GmbH, Switzerland) Egon Willighagen (Maastricht University, Netherlands) Nina Jeliazkova (IDEAconsult Ltd., Bulgaria) Haralambos Sarimveis (The National Technical University of Athens, Greece) During the SUN-caLIBRAte Stakeholder workshop the final version of the SUN user-friendly, software-based Decision Support System (SUNDS) for managing the environmental, economic and social impacts of nanotechnologies will be presented and discussed with its end users: industries, regulators and insurance sector representatives. The results from the discussion will be used as a foundation of the development of the caLIBRAte’s Risk Governance framework for assessment and management of human and environmental risks of MN and MN-enabled products. The SRA Policy Forum: Risk Governance for Key Enabling Technologies and the New Tools and Approaches for Nanomaterial Safety Assessment conference are now open for registration. Abstracts for the SRA Policy Forum can be submitted till 15th November 2016. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | November 2, 2016
Site: globenewswire.com

GERMANTOWN, Md., Nov. 02, 2016 (GLOBE NEWSWIRE) -- Neuralstem, Inc. (Nasdaq:CUR), a biopharmaceutical company focused on the development of central nervous system therapies based on its neural stem cell technology, announced poster presentations at two upcoming scientific conferences.  Presentations include preclinical data in both of the company’s stem cell and small molecule platforms at the Society for Neurosciences Annual Meeting, as well as the American College of Toxicology Annual Meeting. Following is a schedule of relevant presentations: Title:  “Comprehensive In Vivo Nonclinical Safety Assessment of NSI-189, a Small Molecule New Chemical Entity for the Treatment of Major Depressive Disorder” Date:  Monday, November 7          Time: 5:30-7 PM EST Presenter: Grace Furman, PhD, CEO Paracelsus, Inc Location:  Baltimore Marriott Waterfront,  Baltimore, MD Title:  "NSI-189, a neurogenic compound enhances short-term and long-term potentiation in C57BL/6 mice and reverses LTP impairment in a mouse model of Angelman Syndrome” Date:  Sunday, November 13        Time:  1-5 PM PT Presenter: Michel Baudry, PhD, Graduate College of Biomedical Sciences, Western University of Health  Location: San Diego Convention Center (San Diego, CA) Title:  “Durable engraftment, neuronal differentiation of human fetal neural stem cell transplants in penetrating ballistic-like brain injury accompanied by amelioration of cognitive deficits.” Date:  Monday, November 14        Time: 8AM-12PM PT Presenter: Shyam Gajavelli, PhD, University of Miami Location:  San Diego Convention Center (San Diego, CA) Title:  “Induction of immune tolerance by short-course immunosuppression after spinal grafting of allogeneic neural precursors in pigs with previous chronic spinal cord traumatic injury” Date:  Monday, November 14        Time: 8AM-12PM PT Presenter: Martin Marsala, MD, University of San Diego School of Medicine  Location:  San Diego Convention Center (San Diego, CA) Title: “Remyelinating human oligodendrocyte progenitors for regenerative treatment of demyelinating diseases and spinal cord injury” Date:  Wed,  November 16        Time: 8AM-12PM PT Presenter: Tom Hazel, PhD, VP of Research, Neuralstem, Inc.  Location:  San Diego Convention Center (San Diego, CA) Neuralstem's patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are being developed as potential therapies for multiple central nervous system diseases and conditions. Neuralstem’s technology enables the generation of small molecule compounds by screening hippocampal stem cell lines with its proprietary systematic chemical screening process.  The screening process has led to the discovery and patenting of molecules that Neuralstem believes may stimulate the brain's capacity to generate new neurons, potentially reversing pathophysiologies associated with certain central nervous system (CNS) conditions. The company has completed Phase 1a and 1b trials evaluating NSI-189, a novel neurogenic small molecule product candidate, for the treatment of major depressive disorder or MDD, and is currently conducting a Phase 2 efficacy study for MDD. Neuralstem's stem cell therapy product candidate, NSI-566, is a spinal cord-derived neural stem cell line. Neuralstem is currently evaluating NSI-566 in three indications: stroke, chronic spinal cord injury (cSCI), and Amyotrophic Lateral Sclerosis (ALS). Neuralstem is conducting a Phase 1 safety study for the treatment of paralysis from chronic motor stroke at the BaYi Brain Hospital in Beijing, China.  In addition, NSI-566 was evaluated in a Phase 1 safety study to treat paralysis due to chronic spinal cord injury, as well as, a Phase 1 and Phase 2a risk escalation, safety trials for ALS.  Patients from all three indications are currently in long-term observational follow-up periods to continue to monitor safety and possible therapeutic benefits. This news release contains "forward-looking statements" made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements relate to future, not past, events and may often be identified by words such as "expect," "anticipate," "intend," "plan," "believe," "seek" or "will." Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Specific risks and uncertainties that could cause our actual results to differ materially from those expressed in our forward-looking statements include risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstem's periodic reports, including the Annual Report on Form 10-K for the year ended December 31, 2015, and filed with the Securities and Exchange Commission (SEC) on March 14, 2016, Form 10-Q for the period ended June 30, 2016, and in other reports filed with the SEC.


News Article | February 23, 2017
Site: motherboard.vice.com

New Jersey is trying a new algorithm to fix its broken bail system, a flashpoint for criminal justice advocates who argue that court-assessed  fines can discriminate against low-income and highly policed communities—most often, people of color. Guidelines for how judges set bail vary across the country, but generally use a combination of a bail schedule, which prices out fees for specific offenses, and their own assessment of whether the defendant will appear at their hearing or commit a crime before their trial. If you can't pay up, you stay in jail until your trial date, sometimes for up to a month. On January 1, New Jersey replaced its bail system with an algorithm designed to mathematically assess the risk of defendants fleeing or committing a crime—particularly a violent one—before their trial date. The algorithm, called the Public Safety Assessment, was designed by the Texas-based Laura and John Arnold Foundation, a nonprofit that tries to fund innovative solutions to criminal justice reform. New Jersey isn't the first state to use algorithms to help judges suss out high-risk defendants. Counties across the country have tried using computer-based techniques to flag those who should continue to be detained until trial, and those who are flight risks. But the algorithms are not without flaws. Last year, investigative reporting by ProPublica revealed that these programs had in-built racial biases, too. The software assessed risk based on data points gleaned from interviews with defendants, including questions about ZIP codes, educational attainment, and family history of incarceration—all of which can serve as proxies for race. This system is different, according to Matt Alsdorf, vice president of the foundation's Criminal Justice Initiative. The initiative assembled a dataset of more than 100,000 individual cases, and looked for factors re-offenders had in common. His team found that the data points that were the most closely correlated with race weren't actually terribly useful. However, the foundation has yet to release the dataset for public analysis. "The strongest predictor of pretrial failure largely has to do with someone's prior conduct," he said. The algorithm uses conviction records instead of arrest records, which are less likely to tip the scales against individuals in heavily policed neighborhoods—studies have found that the arrest rate for black people can be up to ten times higher than for non-blacks. Alsdorf, meanwhile, conceded that conviction records in particular aren't actually race-blind. Advocates contend that there's a significant disparity in conviction rates for black and white defendants, though the Bureau of Justice Statistics doesn't release race data on conviction rates. Cathy O'Neil, former Barnard College math professor and author of Weapons of Math Destruction, says there is still a concern about over-policing of black neighborhoods in general, particularly in the case of nonviolent offenses. And she's not sure how the algorithm will fix the issue. "I'm glad to see that they're making an effort," she said, "but they haven't actually opened up to audit." The Arnold Foundation has released their methodology, but hasn't gone through the kind of rigorous audit ProPublica performed on the COMPAS program by the private company Northpointe, which also used algorithmic risk assessments. There's also a question of whether it's fair to dole out punitive measures—especially ones that could lead to extended pretrial detentions—on predictive policing. Judges are already using their own judgments as a kind of predictive policing, Alsdorf argues, and the results aren't much better. "Those systems are the ones that generate the status quo," he said. "What we see in the status quo is significant disparities in detention rates of white people and people of color." In terms of failure to appear at a trial, O'Neil said that it's possible to set a standard that everyone can live with—and that might involve more innovative solutions. "I think a more humane society would figure out why these people would have trouble getting to their court dates and how to get there," she said.

Loading Safety Assessment collaborators
Loading Safety Assessment collaborators