London – Another UK biotech company was taken over when Novartis signed a recommended all-cash offer worth Euro435 million for the antibiotics specialists Neutec pharma. The Swiss pharma giant paid more than twice of the Manchester-based company’s market capitalization before the takeover approach. Buying Neutec gives Novartis access to two advanced stage antibody products for serious hospital-acquired infections: Mycograb, for treating systemic fungal infections and Aurograb, for treating methicillin-resistant Staphylococcus aureus. Daniel Vasella, CEO of Novartis, said the products “promise to dramatically improve treatments in the area and will also enable Novartis to strengthen its biologics pipeline and anti-infective drug portfolio.” Mycograb has been filed in Europe and has been approved for compassionate use, while Aurograb is in phase III. NeuTec has retained 100% ownership of its products. The buyout is a big payday for the founders Ruth Mathews and James Burnie, who still own a 7% stake. During the takeover negotiations the founders secured NeuTecs operations at the current facility in Manchester for at least two years. The sale of the company came just three weeks after AstraZeneca agreed to buy Cambridge Antibody for Euro1.1 billion. Besides the Neutec deal the antibiotics market has seen amany known players disappear. One of the most prominent was the US-based Vicuron, bought by Pfizer for $1.9 billion. New companies have nevertheless emerged as Roche (Basilea), Sanofi-Aventis (Novexel), Sandoz (Nabriva) and Bayer (Aicuris) span out their infectious disease businesses.
Dutch biotech firm Mucosis B.V. (Groningen) has appointed Thomas Johnston as its Chief Business Officer. Johnston, who comes in from Novavax Inc, will have global responsibility for the licensing and marketing of the company’s...
Dutch biotech firm Mucosis B.V. (Groningen) has appointed Thomas Johnston as its Chief Business Officer. Johnston, who comes in from Novavax Inc, will have global responsibility for the licensing and marketing of the company’s platform, as well as in negotiating strategic alliances. Prior to his engagement at Novavax, Johnston served as a strategic consultant in a number of industries, and held various senior-level positions with several world-class organisations, including Comcast, Microsoft, and Schlumberger.
London – In mid-May, the EMA adopted two guidelines concerning the centralised market authorisation that is relevant for all biologics. One is on pre-submission procedural advice, the other on post-authorisation procedural...
London – In mid-May, the European Medicines Agency was under pressure from the European Parliament, which postponed signing off on its accounts for the financial year 2009. The decision came on the heels of a critical report from...
London – In mid-May, the European Medicines Agency was under pressure from the European Parliament, which postponed signing off on its accounts for the financial year 2009. The decision came on the heels of a critical report from the EU’s Budgetary Control Committee complaining that there was no guarantee ensuring the independence of experts hired to carry out scientific evaluations of human medicines at the agency. More eyebrows were raised when – just two weeks after he left the EMA – former chief Thomas Lönngren took a position as a strategic consultant with the UK-based NDA Group that advises pharmaceutical companies on developing new medications and reducing the length of time to market introduction. Lönngren also joined the board of the Australian drug developer CBio, and took on a post as a strategic advisor to VC specialist Essex Woodlands. In March, the EMA then stated that Lönngren will have to wait at least two years before taking other positions in the pharmaceutical industry. However, the conflict-of-interest policy seems to have loopholes in not defining exactly what kinds of post-EMA activities in the pharma sector or industry associations are acceptable. The agency has now been asked by the European Parliament to provide a report by June 30th listing all “comparable cases” of (ex)staff associations with pharma companies that have occurred since the creation of the agency, explaining in detail the management board’s decision in each case. The move came at the right time to draw attention from the revelation that some MEPs might sell their votes. A recent operation showed that some MEPs were willing to sell votes to British journalists pretending to be lobbyists who asked them what a vote would cost. In May, the European Parliament greenlighted the establishment of a transparency register aimed at monitoring any payments from lobbyists to MEPs or European Commission staff. Although a step forward, the move is not legally binding.
Parma – The EU’s food watchdog EFSA published two biotech-relevant guidelines in May – one on gut and immune system related health claims, and one on GMO food and feed safety assessments.The update on risk assessments of food and...
Parma – The EU’s food watchdog EFSA published two biotech-relevant guidelines in May – one on gut and immune system related health claims, and one on GMO food and feed safety assessments. The update on risk assessments of food and feed made from GM plants covers the latest scientific developments in allergenicity and toxicology testing, design of field trials, animal feeding studies and analysis of stacked events such as multiple insect resistance and herbicide tolerance. The long-awaited guidance document on gut and immune system-related health claims gives more information on appropriate study groups (for example people with irritable bowel syndrome or functional constipation). It also looks at which parameters or clinical outcomes for health claims covering bowel function, allergy-reduction, and maintenance of normal immune function may be accepted by the authority’s NDA panel. While industry representatives complain that the new guidance isn’t significantly different than the EFSA’s draft document, Nutrialpha Europe said it was the first time the agency had provided clear recommendations regarding the choice of target populations for human studies and on R&D strategies to substantiate health claims. Prior to the publication, a group of probiotics experts led by Ger Rijkers (Univ. Utrecht) had criticised EFSA’s reluctance to publish a list of definitive markers and study populations for substantiation of health claims. EFSA says it will continue to evaluate claims on a case-by-case basis.
Increasing evidence suggests that the cellular response to ligand-induced receptor activation is influenced by receptor expression levels and downstream signaling components that can be different amongst various cell types. There...
Increasing evidence suggests that the cellular response to ligand-induced receptor activation is influenced by receptor expression levels and downstream signaling components that can be different amongst various cell types. There is therefore increasing interest in measuring drug target activity and the effects of target-modulating principles, such as synthetic compounds, in assays that reflect native and disease-relevant cellular environments. Sensitive label-free technologies have been recently developed for cellular applications, including optical waveguide grating, live-cell imaging or impedance (reviewed by Xi et al. 2008 and Nayler et al. 2010). Compared to standard readout technologies, one of the major advantages of these approaches is that cellular processes are measured in real-time kinetics in a non-invasive manner, and this makes them particularly suitable for the development of assays using primary cells. The impedance-based xCELLigence RTCA System from Roche Applied Science, which was co-developed with ACEA Bioscience, uses gold electrodes at the bottom surface of microplate wells as sensors to which a low-voltage alternating current is applied. Cells that are grown as adherent monolayers on top of such electrodes influence the alternating current at the electrodes by changing the electrical resistance (impedance). The degree of change is primarily determined by the number of cells, strength of the cell-cell interactions, interactions of the cells with the microelectrodes and the overall morphology of the cells. Importantly, GPCR activation translates into quantitative changes in impedance due to induction of morphological changes, and these highly reproducible impedance changes are well-suited for the quantitative pharmacological characterization of GPCR agonists and antagonists.
Integration of RTCA HT Stations in the BioCel1200 system
Our dual BioCel1200 System from Agilent Technologies (Santa Clara, US) is an automated high-throughput screening platform with two central robots (of the “Asyst” type) and additional devices located in a radial configuration around the robots in a modular way (see Fig. 1). Agilent’s event-driven scheduler VWorks 4 is used for automation control. An updated VWorks 4 version with a newly developed driver for the RTCA HT Instrument was written and installed by Agilent. With the current set-up, test compounds and agonist were added off-line, causing a time lag of 40 seconds prior to the first impedance measurement. Due to the geometry of the E-Plate 384 lids and the grippers of the Asyst robot, the plate lids had to be removed before the impedance measurement. The overall performance and process stability of the system was tested in two reference experiments (data not shown).
Validation of Ox1 hits in
secondary impedance assays
The Ox1 receptor selectively binds and is activated by the neuropeptide orexin A (for reviews, see Gatfield et al. 2010, Tsujino et al. 2009). A high-throughput calcium flux-based screen was performed with a Fluorometric Imaging Plate Reader (FLIPR, Molecular Devices, US). 71,063 compounds were tested at 10 μM to identify potential inhibitors of orexin A-induced Ox1 receptor activation using recombinant CHO-K1 cells expressing the human Ox1 receptor. With a cutoff of >50 % inhibition, 570 initial primary hits were found, of which 263 were subsequently confirmed in the same assay. These 263 compounds were randomly placed in adjacent duplicates in a set of 1,258 compounds on eight microplates. This compound set was then measured at 10 μM in the RTCA HT assay, using the same Ox1 receptor expressing CHO-K1 cells that had been used for the FLIPR screening. In the automated workflow, cells were seeded in the E-Plates 384 and incubated overnight in a controlled environment incubator (Cytomat, Thermo) at 37°C and 5% CO2. During this time, impedance was recorded at regular intervals by shuttling the E-plates out of the Cytomat onto the RTCA HT stations. The following morning, cells were washed with serum-free medium and equilibrated for 50 minutes in the Cytomat. Baseline impedance measurements were taken, compounds were then added, and impedance was recorded for five minutes before addition of 10 nM orexin A agonist. Subsequently, impedance was recorded for 25 minutes at 30 second intervals. Traces were normalized to the time point of agonist addition; data reduction was performed 25 minutes after agonist addition, and the results were exported as text files via the RTCA bridge server software (installed on the RTCA HT Control Unit). For the final analysis, said text files were imported into an Actelion proprietary HTS software suite.
Data quality obtained in the RTCA HT Instrument screen was assessed in several ways (see also Fig. 2): First we looked at the quality of the E-Plates 384: within the whole test phase, a total of 101 E-Plates 384 were screened. 39 wells failed electronically, corresponding to a single-well failure rate of 0.4 well/plate (0.1%). Second, on the basis of 16 high controls (with 10 nM agonist) and 16 low controls (no agonist) on each E-Plate 384 of the Ox1 screen, the Z’ factor and coefficient of variation (CV) values were calculated. At an average window size of 1.38, the average Z’ factor was 0.46±0.09; CV values were 3.4% for high and 3.4% for low controls (Fig. 2). Third, as a further control, a dilution series of the agonist and a reference antagonist were added to each plate. There was very little variation across plates in the EC50 and IC50 values (9.5nM±4.0nM and 13.3nM±3.2nM, respectively). The correlation coefficient (Bravais-Pearson) of adjacent duplicates – a measure of intra-assay reproducibility – was calculated as 0.96. Finally, the same screen was repeated on a different day under identical conditions. The correlation coefficient of 0.87 was calculated for the average of the duplicates in the two independent runs (Fig 2). In summary, the RTCA HT Instrument delivered a high-quality data set with very high intra-assay and inter-assay reproducibility.
Hit confirmation rates in RTCA HT Instrument assays
It is important to note that the calcium flux FLIPR assay and the RTCA HT Instrument assay produced very similar EC50 values for orexin A and IC50 values for a reference antagonist (data not shown). It therefore appeared reasonable to apply a similar inhibition threshold for the RTCA assay (40%). In addition, an upper threshold of <120% inhibition for impedance data was used, as inhibition >120% might be due to cytotoxicity. 170 compounds of the 263 FLIPR hits were confirmed in the RTCA HT Instrument assay, corresponding to a confirmation rate of 65% (Fig. 3). The remaining 93 compounds were then investigated in more detail, and were measured in a calcium flux FLIPR using an unrelated G protein-coupled receptor. 40 of the 93 compounds (43%) showed >30% inhibition in this specificity assay, and are therefore considered false positive FLIPR hits.
The integration of two RTCA HT Stations into an automated dual BioCel1200 system from Agilent Technologies was successfully performed in a single day. Fully automated runs worked well: on average, less than 0.5 wells per E-Plate 384 failed electronically to deliver data. During this pilot study, Z’ factors around 0.5 and coefficients of variation (CV) below 5% were obtained. Intra-assay and inter-assay data reproducibility were high. Consistent with this, the EC50 and IC50 values of reference substances showed very little variation from plate to plate or screen to screen. 170 compounds of 263 calcium flux FLIPR hits were confirmed with RTCA HT Instrument assays as secondary assays (65%). Compounds that were non-specific in the FLIPR assay were not confirmed by impedance technology, so that impedance was able to distinguish between specific and non-specific hits. In the set-up with two RTCA HT Stations and with our assay protocol, the throughput was about 20 plates per day. We conclude that the RTCA HT Instrument is well suited as a secondary screening technology and complements classical GPCR assay formats.D
References 1 Abassi et al. (2009). Chem Biol. 16 (7): 712-23. 2 Atienza et al. (2006). Assay Drug Dev Technol. 4(5): 597-607. Review. 3 Gatfield et. al. (2010). ChemMedChem. 5(8):1197-214. Review. 4 Nayler, Birker-Robaczewska, Gatfield (2010). Integration of label-free detection methods in GPCR Drug Discovery. GPCR Molecular Pharmacology and Drug Targeting. Wiley&Sons. Edited by Annette Gilchrist. Chapter 11. 5 Tsujino et al. (2009). Pharmacol Rev. 61(2):162-76. Review. 6 Xi et al. (2008). Biotechnol J. 3(4):484-95. Review.
Bethesda – VEGF-A blockers Lucentis and Avastin have shown similar efficacy in patients with age-related macular degeneration (AMD), according to one-year results from the CATT study performed on more than 1,000 AMD patients....
Bethesda – VEGF-A blockers Lucentis and Avastin have shown similar efficacy in patients with age-related macular degeneration (AMD), according to one-year results from the CATT study performed on more than 1,000 AMD patients. This is bad news for Novartis AG, which markets Lucentis in Europe. While the antibody fragment is 40 times more expensive than the full antibody, Roche’s Avastin has been used extensively off-label by ophthalmologists. Roche remains reluctant to file an MAA for Avastin in AMD, however, saying there were more side effects observed with Avastin in the CATT study. However, CATT investigators said it was still too early to comment on safety issues, because any statement wouldn’t be backed up by statistically significant data.
Ireland’s ICON plc (Dublin) has named Elizabeth Thomas as Vice President and General Manager of the company’s Bioanalytical Operations in Manchester (UK). Thomas, who comes in from AstraZeneca, brings ICON over 30 years’...
Ireland’s ICON plc (Dublin) has named Elizabeth Thomas as Vice President and General Manager of the company’s Bioanalytical Operations in Manchester (UK). Thomas, who comes in from AstraZeneca, brings ICON over 30 years’ experience in bioanalysis.
Swedish Medivir AB (Huddinge) and Belgian Tibotec BVBA (Beerse) have reported positive data from an ongoing Phase IIb study (48 weeks) with Tibotec’s hepatitis C virus protease blocker TMC435 in patients that responded poorly to...
Swedish Medivir AB (Huddinge) and Belgian Tibotec BVBA (Beerse) have reported positive data from an ongoing Phase IIb study (48 weeks) with Tibotec’s hepatitis C virus protease blocker TMC435 in patients that responded poorly to prior treatment with ribavirine or PEG-interferon. The companies say that addition of TMC 435 to either of the antiviral therapies “substantially” improved the so-called SV4 rates, making the virus “undetectable…four weeks after the end of treatment.” At that point, the EoT (92%, 83% and 71% of relapser patients, partial responder patients and null responder patients respectively) taking 150 mg of TMC435 once daily and placebo, achieved undetectable HCV RNA levels compared to 70%, 17% and 25% in the placebo, PegIFN/RBV groups. Four weeks after cessation of treatment (SVR4), 88%, 77% and 57% of prior relapser patients, partial responder patients and null responder patients taking 150 mg of TMC435 once daily and placebo (respectively), achieved undetectable HCV RNA levels. That compared to 50%, 11% and 23% in the placebo groups. According to the companies, TMC435 was also safe and well-tolerated at all doses.
Hamburg/Ingelheim: Evotec AG’s second oral compound against neuropathic pain has reached clinical development stage. The progress triggered a EUR 2 million milestone from Boehringer Ingelheim that will pay all clinical...
Hamburg/Ingelheim: Evotec AG’s second oral compound against neuropathic pain has reached clinical development stage. The progress triggered a EUR 2 million milestone from Boehringer Ingelheim that will pay all clinical development and commercialisation costs of compounds co-developed within the ongoing strategic alliance the companies initially signed in 2004. Neuropathic pain, which is estimated to affect up to 8% of the world’s population, is a type of pain caused by damage to or dysfunction of the nervous system. This March, Boehringer Ingelheim prematurately terminated a first-in-man dose escalation study (NCT01145014) of its compound BI 660848, intended to be developed in neuropathic pain, due to „new embryotoxicology data but not for safety reasons“. The transition of the new back-up compound into clinical stage triggered the 13th milestone for Evotec within the alliance with Boehringer Ingelheim that includes several unnamed compounds „working on multiple high priority targets across key therapeutic areas“. Following the end of the collaboration with Roche on EVT 101, Evotec which increased its Q1/2011 revenues by more than 50% (EUR15.1m) compared to Q1/2010, requires a positive newsflow.
Vienna-based Intercell AG replaced former CEO Gerd Zettlmeissl with the company’s former COO Thomas Lingelbach in May. Lingelbach, who joined Intercell in 2006 after executive positions at the German branches of both Chiron and...
Vienna-based Intercell AG replaced former CEO Gerd Zettlmeissl with the company’s former COO Thomas Lingelbach in May. Lingelbach, who joined Intercell in 2006 after executive positions at the German branches of both Chiron and Novartis, was already the Managing Director of Intercell Biomedical Ltd. and President and CEO of Intercell USA, Inc.
7th Berlin Conference on IP in Life Sciences: Big Data, Big Drugs
The health care industry faces significant transformation, driven by a boom in knowledge within biomedical sciences and breakthrough technologies such as gene sequencing. The management of "big data“ will change the understanding of diseases, development of drugs and treatment of patients. more