Antibodies to watch in 2018

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody therapeutics (ibalizumab, burosumab, tildrakizumab, caplacizumab, erenumab, fremanezumab, galcanezumab, romosozumab, mogamulizumab) were in regulatory review in the EU or US, and regulatory actions on their marketing applications are expected by the end of 2018. Based on company announcements and estimated clinical study primary completion dates, and assuming the study results are positive, marketing applications for at least 12 antibody therapeutics that are now being evaluated in late-stage clinical studies may be submitted by the end of 2018. Of the 12 candidates, 8 are for non-cancer indications (lanadelumab, crizanlizumab, ravulizumab, eptinezumab, risankizumab, satralizumab, brolucizumab, PRO140) and 4 are for cancer (sacituzumab govitecan, moxetumomab pasudotox, cemiplimab, ublituximab). Additional antibody therapeutics to watch in 2018 include 19 mAbs undergoing evaluation in late-stage studies with primary completion dates in late 2017 or during 2018. Of these mAbs, 9 are for non-cancer indications (lampalizumab, roledumab, emapalumab, fasinumab, tanezumab, etrolizumab, NEOD001, gantenerumab, anifrolumab) and 10 are for cancer indications (tremelimumab, isatuximab, BCD-100, carotuximab, camrelizumab, IBI308, glembatumumab vedotin, mirvetuximab soravtansine, oportuzumab monatox, L19IL2/L19TNF). Positive clinical study results may enable marketing application submissions in 2018. Brief summaries of these antibody therapeutics are provided in this installment of the ‘Antibodies to watch’ article series.     

Antibodies to watch in 2015

The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 6 antibody therapeutics (secukinumab, evolocumab, mepolizumab, dinutuximab, nivolumab, necitumumab) are undergoing a first regulatory review in the EU or US. Of the 39 novel mAbs currently in Phase 3 studies, a marketing application for one (alirocumab) may be submitted in late 2014, and marketing application submissions for at least 4 (reslizumab, ixekizumab, ocrelizumab, obiltoxaximab) are expected in 2015. Other ‘antibodies to watch’ are those in Phase 3 studies with estimated primary completion dates in late 2014 or 2015, which includes 13 for non-cancer indications (brodalumab, bimagrumab, bococizumab, MABp1, gevokizumab, dupilumab, sirukumab, sarilumab, tildrakizumab, guselkumab, epratuzumab, combination of actoxumab + bezlotoxumab, romosozumab) and 2 (racotumomab and clivatuzumab tetraxetan) undergoing evaluation as treatments for cancer. In addition to the novel antibody therapeutics mentioned, biosimilar infliximab and biosimilar trastuzumab are ‘antibodies to watch’ in 2015 because of their potential for entry into the US market and regulatory review, respectively.     

Antibodies to watch in 2015

The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 6 antibody therapeutics (secukinumab, evolocumab, mepolizumab, dinutuximab, nivolumab, necitumumab) are undergoing a first regulatory review in the EU or US. Of the 39 novel mAbs currently in Phase 3 studies, a marketing application for one (alirocumab) may be submitted in late 2014, and marketing application submissions for at least 4 (reslizumab, ixekizumab, ocrelizumab, obiltoxaximab) are expected in 2015. Other ‘antibodies to watch’ are those in Phase 3 studies with estimated primary completion dates in late 2014 or 2015, which includes 13 for non-cancer indications (brodalumab, bimagrumab, bococizumab, MABp1, gevokizumab, dupilumab, sirukumab, sarilumab, tildrakizumab, guselkumab, epratuzumab, combination of actoxumab + bezlotoxumab, romosozumab) and 2 (racotumomab and clivatuzumab tetraxetan) undergoing evaluation as treatments for cancer. In addition to the novel antibody therapeutics mentioned, biosimilar infliximab and biosimilar trastuzumab are ‘antibodies to watch’ in 2015 because of their potential for entry into the US market and regulatory review, respectively.     

Antibodies to watch in 2016

The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016. Commercial late-stage antibody therapeutics development exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to 53 as of late 2015. Of the 53 candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other "antibodies to watch" include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by the antibody therapeutics discussed in this perspective, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future. *See Note added in proof for updates through December 31, 2015.     

Antibodies to watch in 2013

The transitions of antibody therapeutics to late-stage clinical development, regulatory review and the market are proceeding at a rapid pace in 2013. Since late 2012, two monoclonal antibody (mAb) therapeutics (itolizumab, trastuzumab emtansine) received their first approvals, first marketing applications for three mAbs (vedolizumab, ramucirumab, obinutuzumab) were submitted to regulatory agencies, and five mAbs (brodalumab, MABp1, moxetumomab pasudotox, tildrakizumab, rilotumumab) entered their first Phase 3 studies. The current total of commercially-sponsored antibody therapeutics undergoing evaluation in late-stage studies is 30. Recently announced study results for farletuzumab, naptumomab estafenatox, and tabalumab indicate that clinical endpoints were not met in some Phase 3 studies of these product candidates.     

Antibodies to watch in 2014

Since 2010, mAbs has documented the biopharmaceutical industry’s progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the “Antibodies to watch” series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration’s Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed.     

Antibodies to watch in 2019

For the past 10 years, the annual ‘Antibodies to watch’ articles have provided updates on key events in the late-stage development of antibody therapeutics, such as first regulatory review or approval, that occurred in the year before publication or were anticipated to occur during the year of publication. To commemorate the 10th anniversary of the article series and to celebrate the 2018 Nobel Prizes in Chemistry and in Physiology or Medicine, which were given for work that is highly relevant to antibody therapeutics research and development, we expanded the scope of the data presented to include an overview of all commercial clinical development of antibody therapeutics and approval success rates for this class of molecules. Our data indicate that: 1) antibody therapeutics are entering clinical study, and being approved, in record numbers; 2) the commercial pipeline is robust, with over 570 antibody therapeutics at various clinical phases, including 62 in late-stage clinical studies; and 3) Phase 1 to approval success rates are favorable, ranging from 17–25%, depending on the therapeutic area (cancer vs. non-cancer). In 2018, a record number (12) of antibodies (erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), burosumab (Crysvita), lanadelumab (Takhzyro), caplacizumab (Cablivi), mogamulizumab (Poteligeo), moxetumomab pasudodox (Lumoxiti), cemiplimab (Libtayo), ibalizumab (Trogarzo), tildrakizumab (Ilumetri, Ilumya), emapalumab (Gamifant)) that treat a wide variety of diseases were granted a first approval in either the European Union (EU) or United States (US). As of November 2018, 4 antibody therapeutics (sacituzumab govitecan, ravulizumab, risankizumab, romosozumab) were being considered for their first marketing approval in the EU or US, and an additional 3 antibody therapeutics developed by Chinese companies (tislelizumab, sintilimab, camrelizumab) were in regulatory review in China. In addition, our data show that 3 product candidates (leronlimab, brolucizumab, polatuzumab vedotin) may enter regulatory review by the end of 2018, and at least 12 (eptinezumab, teprotumumab, crizanlizumab, satralizumab, tanezumab, isatuximab, spartalizumab, MOR208, oportuzumab monatox, TSR-042, enfortumab vedotin, ublituximab) may enter regulatory review in 2019. Finally, we found that approximately half (18 of 33) of the late-stage pipeline of antibody therapeutics for cancer are immune checkpoint modulators or antibody-drug conjugates. Of these, 7 (tremelimumab, spartalizumab, BCD-100, omburtamab, mirvetuximab soravtansine, trastuzumab duocarmazine, and depatuxizumab mafodotin) are being evaluated in clinical studies with primary completion dates in late 2018 and in 2019, and are thus ‘antibodies to watch’. We look forward to documenting progress made with these and other ‘antibodies to watch’ in the next installment of this article series.     

Marketed therapeutic antibodies compendium

Therapeutic monoclonal antibodies (mAbs) are currently being approved for marketing in Europe and the United States, as well as other countries, on a regular basis. As more mAbs become available to physicians and patients, keeping track of the number, types, production cell lines, antigenic targets, and dates and locations of approvals has become challenging. Data are presented here for 34 mAbs that were approved in either Europe or the United States (US) as of March 2012, and nimotuzumab, which is marketed outside Europe and the US. Of the 34 mAbs, 28 (abciximab, rituximab, basiliximab, palivizumab, infliximab, trastuzumab, alemtuzumab, adalimumab, tositumomab-I131, cetuximab, ibrituximab tiuxetan, omalizumab, bevacizumab, natalizumab, ranibizumab, panitumumab, eculizumab, certolizumab pegol, golimumab, canakinumab, catumaxomab, ustekinumab, tocilizumab, ofatumumab, denosumab, belimumab, ipilimumab, brentuximab) are currently marketed in Europe or the US. Data for six therapeutic mAbs (muromonab-CD3, nebacumab, edrecolomab, daclizumab, gemtuzumab ozogamicin, efalizumab) that were approved but have been withdrawn or discontinued from marketing in Europe or the US are also included.     

Antibodies to watch in 2014

The commercial pipeline of monoclonal antibodies is highly dynamic, with a multitude of transitions occurring during the year as product candidates advance through the clinical phases and onto the market. The data presented here add to that provided in the extensive “Antibodies to watch in 2014” report published in the January/February 2014 issue of mAbs. Recent phase transition data suggest that 2014 may be a banner year for first approvals of antibody therapeutics. As of May 2014, three products, ramucirumab (Cyramza®), siltuximab (Sylvant®) and vedolizumab (Entyvio^TM), had been granted first approvals in the United States, and four additional antibody therapeutics (secukinumab, dinutuximab, nivolumab, pembrolizumab) are undergoing regulatory review in either the US or the European Union. Other notable events include the start of first Phase 3 studies for seven antibody therapeutics (dupilumab, SA237, etrolizumab, MPDL3280A, bavituximab, clivatuzumab tetraxetan, blinatumomab). Relevant data for these product candidates are summarized, and metrics for antibody therapeutics development are discussed.     

Metrics for antibody therapeutics development

A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.     

Bispecific antibodies for cancer therapy

With 23 approvals in the US and other countries and 4 approvals outside US, antibodies are now widely recognized as therapeutic molecules. The therapeutic and commercial successes met by rituximab, trastuzumab, cetuximab and other mAbs have inspired antibody engineers to improve the efficacy of these molecules. Consequently, a new wave of antibodies with engineered Fc leading to much higher effector functions such as antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity is being evaluated in the clinic, and several approvals are expected soon. In addition, research on a different class of antibody therapeutics, bispecific antibodies, has recently led to outstanding clinical results, and the first approval of the bispecific antibody catumaxomab, a T cell retargeting agent that was approved in the European Union in April 2009. This review describes the most recent advances and clinical study results in the field of bispecific antibodies, a new class of molecules that might outshine conventional mAbs as cancer immunotherapeutics in a near future.     

A decade of marketing approval of gene and cell-based therapies in the United States,European Union and Japan: An evaluation of regulatory decision-making

There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management. Product characteristics are very heterogeneous and only three products are marketed in multiple jurisdictions. Almost half of all approved GCTs received an orphan designation. Overall, confirmatory evidence or indications of clinical benefit were evident in US and EU applications, whereas in Japan approval was solely granted based on non-confirmatory evidence. Due to scientific uncertainties and safety risks, substantial post-marketing risk management activities were requested in the EU and Japan. EU and Japanese authorities often took unmet medical needs into consideration in decision-making for approval. These observations underline the effects of implemented legislation in these two jurisdictions that facilitate an adaptive approach to licensing. In the US, the recent assessments of two chimeric antigen receptor-T cell (CAR-T) products are suggestive of a trend toward a more permissive approach for GCT approval under recent reforms, in contrast to a more binary decision-making approach for previous approvals. It indicates that all three regulatory agencies are currently willing to take risks by approving GCTs with scientific uncertainties and safety risks, urging them to pay accurate attention to post-marketing risk management.     

Time required for approval of new drugs in Canada,Australia, Sweden,the United Kingdom and the United States in 1996-1998

BACKGROUND: The timeliness with which national regulatory agencies approve new drugs for marketing affects health care professionals and patients. An unnecessarily long approval process delays access to new medications that may improve patients'' health status. The author compared drug approval times in Canada, Australia, Sweden, the United Kingdom and the United States. METHODS: Application and approval dates of new chemical or biological substances (excluding diagnostic products, and new salts, esters, dosage forms and combinations of previously approved substances) approved for marketing in the 5 countries from January 1996 to December 1998 were requested from the relevant pharmaceutical companies. Data on new drug approvals during the study period were also obtained from the national drug regulatory agencies in Canada, Australia and Sweden and from publications of the US Food and Drug Administration. RESULTS: A total of 219 new drugs were identified as being approved in at least one of the countries during the study period: 23 (10.5%) in all 5 countries, 23 (10.5%) in 4, 27 (12.3%) in 3, 42 (19.2%) in 2, and 104 (47.5%) in 1 country. By individual nation, 97 drugs were identified as being approved in Canada, 94 in Australia, 107 in Sweden, 55 in the UK and 123 in the US. Approval times in Canada and Australia were similar (medians 518 and 526 days respectively), but both countries had significantly longer approval times than Sweden (median 371 days), the UK (median 308 days) and the US (median 369 days). This pattern was consistent across all 3 years and for the 23 new drugs approved in all 5 countries during the 3-year period. Median approval times in Canada were similar in all of the reviewing divisions of Health Canada''s Therapeutic Product Program (539-574 days) except the Central Nervous System Division (428 days) and the Bureau of Biologics and Radiopharmaceuticals (698 days). INTERPRETATION: Median drug approval times during 1996-1998 decreased by varying amounts from the 1995 values in all 5 countries. However, the median approval time in Canada continues to be significantly longer than the times achieved in Sweden, the UK and the US, and it remains considerably longer than Canada''s own target of 355 days for all new drugs.     

Development of membrane-active peptide therapeutics in oncology

Membrane-active peptides play an essential role in many living organisms and their immune systems and counter many infectious diseases. Many have dual or multiple mechanisms and can synergize with other molecules, like peptides, proteins, and small molecules. Although membrane-active peptides have been intensively studied in the past decades and more than 3500 sequences have been identified, only a few received approvals from the US Food and Drug Administration. In this review, we investigated all the peptide therapeutics that have entered the market or were subjected to preclinical and clinical studies to understand how they succeeded. With technological advancement (e.g., chemical modifications and pharmaceutical formulations) and a better understanding of the mechanism of action and the potential targets, we found at least five membrane-active peptide drugs that have entered preclinical/clinical phases and show promising results for cancer treatment. We summarized our findings in this review and provided insights into membrane-active anticancer peptide therapeutics.     

Patient access to and ethical considerations of the application of the European Union hospital exemption rule for advanced therapy medicinal products

Hospital exemption (HE) is a regulated pathway that allows the use of advanced therapy medicinal products (ATMPs) within the European Union (EU) under restrictive conditions overseen by national medicine agencies. In some EU countries, HE is granted for ATMPs with no demonstrated safety and efficacy; therefore, they are equivalent to investigational drugs. In other countries, HE is granted for ATMPs with demonstrated quality, safety and efficacy and for which centralized marketing authorization has not been requested. The Committee on the Ethics of Cell and Gene Therapy of the International Society for Cell & Gene Therapy reflects here on the ethical issues concerning HE application from the perspective of the patient, including risk–benefit balance, accessibility and transparency, while providing evidence that HE must not be regarded as a conduit for unproven and unethical ATMP-based interventions. Indeed, HE represents a legal instrument under which a patient's need for access to novel ATMPs is reconciled with ethics. Moreover, for some unmet medical needs, HE is the only pathway for accessing innovative ATMPs. Nonetheless, HE harmonization across EU Member States and limitations of ATMP use under the HE rule when similar products have already been granted centralized marketing authorization to avoid a parallel regulatory pathway are controversial issues whose political and economic consequences are beyond the scope of this review. Finally, the institution of an EU registry of HE applications and outcomes represents a priority to improve transparency, reduce patient risks, increase efficiency of health systems, facilitate company awareness of business opportunities and boost progressive entry of ATMPs into the therapeutic repertoire of health systems.     

Comparison of regulatory pathways for the approval of advanced therapies in the European Union and the United States

Background aimsRegulatory agencies in the European Union (EU) and in the United States of America (USA) have adapted and launched regulatory pathways to accelerate patient access to innovative therapies, such as advanced therapy medicinal products (ATMPs). The aim of this study is to analyze similarities and differences between regulatory pathways followed by the approved ATMPs in both regions.MethodsA retrospective analysis of the ATMPs approved by EU and US regulatory agencies was carried out until May 31, 2020. Data were collected on the features and timing of orphan drug designation (ODD), scientific advice (SA), expedited program designation (EP), marketing authorization application (MAA) and marketing authorization (MA) for both regions.ResultsIn the EU, a total of fifteen ATMPs were approved (eight gene therapies, three somatic cell therapies, three tissue-engineered products and one combined ATMP), whereas in the USA, a total of nine were approved (five gene therapies and four cell therapies); seven of these were authorized in both regions. No statistical differences were found in the mean time between having the ODD or EP granted and the start of the pivotal clinical trial or MAA in the EU and USA, although the USA required less time for MAA assessment than the EU (mean difference, 5.44, P = 0.012). The MAA assessment was shorter for those products with a PRIME or breakthrough designation.. No differences were found in the percentage of ATMPs with expedited MAA assessment between the EU and the USA (33.3% versus 55.5%, respectively, P = 0.285) or in the time required for the MAA expedited review (mean difference 4.41, P = 0.105). Approximately half of the products in both regions required an Advisory Committee during the MAA review, and 60% required an oral explanation in the EU. More than half of the approved ATMPs (67% and 55.55% in the EU and the USA, respectively) were granted an ODD, 70% by submitting preliminary clinical data in the EU. The mean number of SA and protocol assistance per product conducted by the European Medicines Agency was 1.71 and 3.75, respectively, and only 13% included parallel advice with health technology assessment bodies. A total of 53.33% of the products conducted the first SA after the pivotal clinical study had started, reporting more protocol amendments. Finally, of the seven ATMPs authorized in both regions, the type of MA differed for only two ATMPs (28.6%), and four out of eight products non-commercialized in the USA had a non-standard MA in the EU.ConclusionsThe current approved ATMPs mainly target orphan diseases. Although EU and US regulatory procedures may differ, the main regulatory milestones reached by the approved ATMPs are similar in both regions, with the exception of the time for MAA evaluation, the number of authorized products in the regions and the type of authorization for some products. More global regulatory convergence might further simplify and expedite current ATMP development in these regions.     

Letter from the Editor

mAbs’ September/October 2009 issue highlights the promise and challenges of antibody therapeutics development. Representing promise, our mini-review series on novel antibodies currently undergoing regulatory review or recently approved continues in this issue. Previously published articles include mini-reviews of denosumab and ustekinumab (May/June 2009 issue) and ofatumumab (July/August 2009 issue). The September/October issue features articles on golimumab, tocilizumab and motavizumab. The mini-reviews present overviews of the completed and on-going clinical studies of these molecules. Anti-TNFα golimumab was approved in April 2009 by both the US Food and Drug Administration (FDA) and Health Canada as a treatment for rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis; anti-IL6R tocilizumab is approved in Japan and the European Union (EU), and is currently undergoing FDA review as a treatment for RA. The juxtaposition of these two mini-reviews provides an opportunity to easily compare summaries of the available clinical results. Future issues of mAbs will include mini-reviews of catumaxomab, canakinumab and raxibacumab, as well as any additional antibodies that enter regulatory review in 2009 and beyond.     

Lemon sole Microstomus kitt in the northern North Sea: a multidisciplinary approach to the early life-history dynamics

Lemon sole Microstomus kitt is a commercially valuable flatfish species that occurs in shelf waters around the northeast Atlantic. Only the most basic life-history information is available for the North Sea. Spawning is generally assumed to occur between early May and October, with a peak between May and August. Lemon sole larvae have been found in the water column in the northern North Sea in winter during standard surveys. Larvae captured in November/December 2016 and January/February 2017 using the International Council for the Exploration of the Seas standard 2 m Midwater Ring trawls (MIK) were analysed to gain a better understanding of the pelagic early life-history stages of lemon sole, especially in relation to the timing of spawning and the dispersal of overwintering larvae. Larval age was estimated from sagittal otolith primary increment counts. The larvae caught in November/December ranged in nominal age from 4 to 45 days post-hatching which suggests that spawning continues into late October and November. Most, but not all, of the larvae caught in January/February were post metamorphosis, and the difference in age between the two sampling dates was consistent with the elapsed time between samplings. The estimated hatching dates confirm that lemon sole spawning extends into late autumn in the northern North Sea, with overwintering larvae in all developmental stages. Drift modelling of eggs and larvae released at historically documented spawning grounds in the northern North Sea suggests that these grounds are also the source for all of the larvae sampled during the 2016–2017 surveys.     

Commercializing genetically modified crops under EU regulations: objectives and barriers

Agriculture faces serious problems in feeding 9 billion people by 2050: production must be increased and ecosystem services maintained under conditions for growing crops that are predicted to worsen in many parts of the world. A proposed solution is sustainable intensification of agriculture, whereby yields are increased on land that is currently cultivated, so sparing land to deliver other ecosystem services. Genetically modified (GM) crops are already contributing to sustainable intensification through higher yields and lower environmental impacts, and have potential to deliver further significant improvements. Despite their widespread successful use elsewhere, the European Union (EU) has been slow to introduce GM crops: decisions on applications to import GM commodities are lengthy, and decision-making on applications to cultivate GM crops has virtually ceased. Delayed import approvals result in economic losses, particularly in the EU itself as a result of higher commodity prices. Failure to grant cultivation approvals costs EU farmers opportunities to reduce inputs, and results in loss of agricultural research and development from the EU to countries such as the United States and China. Delayed decision-making in the EU ostensibly results from scientific uncertainty about the effects of using GM crops; however, scientific uncertainty may be a means to justify a political decision to restrict cultivation of GM crops in the EU. The problems associated with delayed decision-making will not improve until there is clarity about the EU's agricultural policy objectives, and whether the use of GM crops will be permitted to contribute to achieving those objectives.     

Antibody Engineering & Therapeutics 2016: The Antibody Society's annual meeting,December 11–15, 2016, San Diego,CA

Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement. The meeting will open with keynote speakers Dennis R. Burton (The Scripps Research Institute), who will review progress toward a neutralizing antibody-based HIV vaccine; Olivera J. Finn, (University of Pittsburgh School of Medicine), who will discuss prophylactic cancer vaccines as a source of therapeutic antibodies; and Paul Richardson (Dana-Farber Cancer Institute), who will provide a clinical update on daratumumab for multiple myeloma. In a featured presentation, a representative of the World Health Organization's INN expert group will provide a perspective on antibody naming. “Antibodies to watch in 2017” and progress on The Antibody Society's 2016 initiatives will be presented during the Society's special session. In addition, two pre-conference workshops covering ways to accelerate antibody drugs to the clinic and the applications of next-generation sequencing in antibody discovery and engineering will be held on Sunday December 11, 2016.