La Merie
Ulrich Martin

Ulrich Martin

STUTTGART, Germany I March 12, 2015 I The T-Cell Receptor (TCR) has emerged as a means to target peptide antigens derived from intracellular proteins in a major histocompatibility complex (MHC) dependent manner. These peptide antigens are presented on the surface of (tumor) cells by human leukocyte antigen (HLA) molecules and are not druggable by conventional antibody technologies. As the industry is in need of new targets, such a pool of intracellular targets which are validated, disease-specific and intellectual property (IP)-free, has attracted great interest by Big Pharma companies as reflected by several major collaborations.

To make use of the TCR in a therapeutic, the TCR has to be combined with an effector moiety either by recombinant DNA technology or by cellular engineering. Big Pharma has accepted and adopted recombinant antibody technologies over the last one or two decades, but is hesitating to enter the field of personalized (autologous) cell therapy. Thus, a preferred option for a TCR therapeutic is to fuse a monoclonal TCR with a single-chain variable fragment (scFv) against CD3 to recruit T cells in vivo and, thereby, exert the antitumor effect. British biotechnology company Immunocore has developed such a technology called ImmTAC and is employing it to create monoclonal TCR-scFv constructs. The first candidates from collaborations with Big Pharma are now in non-clinical development.

While ImmTACs make indirectly use of T-cells by recruiting them in vivo, the alternative, cellular approach is to transduce ex vivo autologous T-cells with the TCR of choice and additional signaling molecules, expand the selected T cell population and reinfuse the cells to the patient. Several companies are already in early clinical trials with TCR-transduced T cells, but the major differentiating factor between them is the target against which the TCR is directed. A number of intracellular cancer antigens are publicly known and have already been used for antigen-specific cancer immunotherapy. Typical targets are Wilms tumor 1 (WT1), cancer testis antigen NY-ESO-1, MAGE-A3 or PRAME. These targets are not IP protected and, thus, subject to competition. On the contrary, Immunocore and cell therapy sister company Adaptimmune have developed a proprietary TCR target discovery engine which provided them with a pool of novel TCR targets.

Both Immunocre and Adaptimmune have raised substantial funds by partnering and financing rounds to ensure further corporate development.

The power of T cells can also be directed against conventional targets on the surface of tumor cells. Again, there are two alternative therapeutic modalities: a recombinant biologic or a cell therapeutic. One such recombinant molecule has been approved by the US FDA in December 2014 and is directed against the B cell target CD19. Blinatumomab is a recombinant bispecific T cell engaging (BiTE) molecule consisting of two scFv moieties, one directed against the tumor target CD19 and the second directed against CD3 on T-cells to recruit them in a targeted manner to the tumor cells. Blinatumomab (Blincyto) from Amgen is used for treatment of relapsed/refratory (r/r) acute lymphoblastic leukemia (ALL) and will cost US$ 178,000 which includes two therapy cycles.

Leveraging the power of T cells by cellular and recombinant immunotherapeutics

 

Intra-cellular Targets

Cell surface targets

Cellular

TCR T Cells

CAR T Cells
(autologous/allogeneic)

Recombinant

Bispecific TCR-anti-CD3
(e.g. ImmTACs)

Bispecific antibodies
(incl. anti-CD3)

 

A direct way to bring T-cells specifically in contact with tumor B cells, is to transduce ex vivo autologous T-cells with a scFv against CD19 plus additional signaling molecules and transfuse the cells back into the patient. Several such „chimeric antigen receptor“ (CAR) transduced autologous T cell constructs have been evaluated in small clinical trials of r/r ALL with impressing results of 80% or higher response rates. These results have triggered a lot of enthusiasm among investors and have encouraged several leading cancer institutions active in the CAR T-cell field, to spin-off their technology into new companies for further development and commercialization.
However, the early clinical trials also have revealed challenges for the success of further CAR T-cell therapies regarding efficacy, safety and manufacturing.

The report „Engineered TCR and CAR Immunotherapeutics 2015: A comparative analysis of the landscape of and business opportunities with TCR and CAR antibodies, T cells, NK cells, TILs, DLIs & DLIs“ released by La Merie Publishing brings you up-to-date regarding key players, key technologies, TCR and CAR immunotherapeutic projects, business deals and private and public financing rounds. The report analyzes the TCR and CAR immunotherapeutic pipelines and stakeholders in the field, especially among Big Pharma/Biotech and technology companies. This study highlights the value of TCR and CAR immunotherapeutics in terms of partnering economic conditions, private financing rounds and (initial) public offerings with the resulting market capitalization of companies. The report also describes the challenges and limitations and identifies solutions provided by new technologies which offer tremendous business opportunities.

About La Merie

La Merie Publishing is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com and www.PipelineReview.com, the Biologics News Center and Online Store of La Merie Publishing.

SOURCE: La Merie Publishing

STUTTGART, Germany I December 29, 2014 I Since approval of the first recombinant coagulation factors for treatment and prophylaxis of hemophilia A and B about two decades ago, the market of recombinant coagulation factors has constantly grown to a size of US$ 7.4 bln in the year 2013. An oligopoly of five biopharmcaeutical companies essentially shared this sizeable market protected from competition by intellectual property. With the basic patents expiring now, an avenue for innovation has opened. Established key players as well as new stakeholder coming from technology providers or plasma-product companies have taken advantage and develed in a first wave new product candidates with improved properties regarding purity of the recombinant coagulation factor, longer half-life allowing less frequent injections and improved safety regarding immunogenicity.

Within the next two years, the most attractive market of recombinant coagulation factor VIII (rFVIII) with a market size of nearly US$ 5 bln in 2013, could see a total of seven new products if all of them were approved as planned. As a consequence, the rFVIII market will face a reshuffling of market players and market shares with newcomers as winners and established companies at risk to loose if improved rFVIII products or other recombinant coagulation factors cannot compensate for sales loss. The smaller recombinant coagulation factor IX market (US$ 832 mln with one established product) will be shared by five new products with an expected rapid conversion from wild-type rFIX products to novel long-acting versions.

While R&D efforts to discover and develop novel next generation recombinant coagulation factors are successful in that new and improved products are coming to the market, there is still space for improvement. Especially truly long-acting rFVIII molecules have not yet been found, representing a great opportunity for innovators to generate clearly differentiated products.

While the R&D pipeline of classical recombinant coagulation factors is maturing, other approaches are strongly emerging in early clinical development which may become the real thread to the market of classical recombinant coagulation factors. Gene and cell therapy of hemophilia B and A has strongly gained in relevance by improved vectors and transgenes with a potentia total of 14 projects in early clinical trials by the end of 2015. However, gene therapy of hemophilia with the promise of cure by a single treatment course is a long-term plan from which not all patients will benefit due to preformed inhibitors. This problem might be overcome by the second emergent class of potential new treatments of hemophilia. Alternative procoagulants are in early clinicals study which work as coagualation factor mimetics, as downstream coagulation factors or as a switch-off of inhibtors with a re-balance of the coagulation system in favor of a procoagulant state. Among the target profile of such alternative procoagualants are the possibility of subcutaneous administration, an universal use for treatment of hemophilia patients without and with inhibitors as well as reduced dosing frequency. The more of these properties are achived, the more likely such products could become blockbuster candidates.

Furthermore, immune tolerance inducing treatment modalities for hemophilia patients with inhibitors or as a prophylaxis to avoid inhibitor formation are progressing towards clinical evaluation.

With these new and emergent approaches also new stakeholders have entered the scenario of serious bleeding disorders. Among them are not only technology companies from the gene and cell therapy and RNAi field, but also from Big Pharma and rare disease specialist companies giving these new developments sufficient funding and power for determined development.

The report „Recombinant Coagulation Factors 2015: Maturation of recombinant clotting factor pipeline and emergence of gene therapy and alternative procoagulants“ from La Merie Publishing provides an update of recombinant coagulation factors. New sales data are analyzed to evaluate commercial development of the market under the light of a strong pipeline and entry of new competitor products into the market. The profiles of drug candidates in development are presented in detail. The competitve landscape is analyzed. A short- to mid-term outlook into the field is provided and the trends driving the future of this therapeutic segment are identified and described. The report was prepared by an experienced author with an independent view writing the fifth edition of this report series.

About La Merie

La Merie Publishing is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com and www.PipelineReview.com, the Biologics News Center and Online Store of La Merie Publishing.

SOURCE: La Merie Publishing

STUTTGART, Germany I July 16, 2014 I A new business report entitled „Botulinum Neurotoxins: A comparative industry analysis of products, pipelines, technologies and stakeholders has been released by La Merie Publishing. The worldwide market for botulinum neurotoxins has grown with double digit rates over the last years to US$ 2.8 bln in the year 2013 and is expected to reach a size of US$ 4.4 bln in the year 2017. About 54% of the botulinum neutoroxin sales are generated with medical indications, the rest with esthetic indications. The high brand recognition of Botox is one of the factors why Allergan is dominating the global market of botulinum neurotoxins with regional market shares reaching 70-80%. However, patent expiries and the entry of new competitors in the main markets with increasing efforts in development and marketing & sales represents an inflection point in the long-lasting predominance.

Korean companies play an important role in the forthcoming competition as they have specific experience botulinum toxins and have adapted the manufacturing to comply with FDA and EMA guidelines. As a consequence, at least two potential biosimilar versions of botulinum neurotoxin type A are being developed by US and EU companies in partnership with the Korean originators.

As biosimilar products usually go hand in hand with price cuts, the companies with established first generation products are investing in biosuperior product development. Technologies to enable biosuperiors are classical protein formulation to create ready-to-use injectable botulinum toxins, but also more sophisticated pharmaceutical drug delivery technologies to enable, needle- and pain-free transdermal administration. While the first approch may provide advantages for handling of the drug product in the doctor’s office, patients will appreciate topical application of botulinum toxin as a gel, cream or lotion for cosmetic procedures, as market research indicates.

Recombinant DNA technology is also being used to create engineered versions of botulinum toxin which may allow to tap new indications, but also provide a longer-lasting effect with lower side effects in the established indications.

The business report Botulinum Neurotoxins: A comparative industry analysis of products, pipelines, technologies and stakeholders can be acquired at the online store www.pipelinereview.com of La Merie Publishing: http://pipelinereview.com/index.php/therapeuticarea/dermatology/botulinum-neurotoxins-a-comparative-industry-analysis-of-products,-pipelines,-technologies-and-stakeholders-detail

About La Merie Publishing

La Merie Publishing is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com.

About PipelineReview.com

PipelineReview.com is the Biologics News Center and Online Store of La Merie Publishing focused on Research and Development in the Biopharmaceutical Industry. The FREE weekly R&D Newletter La Merie Biologics conveniently brings via e-mail a selection of the most interesting biologics news from biopharmaceutical R&D. For more information visit www.pipelinereview.com

SOURCE: La Merie Publishing

STUTTGART, Germany I January 23, 2014 I The area of antibody-drug conjugates (ADC) is a very fertile area for business ranging from partnerships between pharma and biotech or biotech and biotech up to contract services for conducting research and manufacturing complex ADC products. The field has seen an exponential growth over the last few years. The number of publications has tripled since 2011 and is even 9-times higher in 2013 than during the years before. And the number of stakeholders to be analyzed for La Merie Publishing‘ new report about ADCs was nearly triple that evaluated for the first report in 2011.

First generation ADC technology has matured as evidenced by the regulatory approval and marketing of the first two ADC products against hematologic and solid malignancies with the two main ADC technologies from ImmunoGen and Seattle Genetics. Both companies utilize cell-cycle dependent tubulin polymerization inhibitors (maytansine and auristatin derivatives) conjugated via cleavable or stable linkers to natural lysine or cysteine residues in the targeting antibody. As a result of this conjugation technology, the drug-antibody ratio may be variable and the product heterogenous with potential impact on efficacy, safety and pharmacokinetics. Resistanc of cancer cells to currently employed drug payloads of ADCs adds a further parameter for optimization of ADCs.

Based on the current state of the art, this report describes the emerging next generation ADC technologies regarding target selection, novel antibody and alternative targeting moiety formats, novel drugs and conjugation systems. The report pays special attention to the commercial relevance and value of these technologies and highlights those picked-up by Big Pharma setting a trend for the first wave of new ADCs based on next generation ADC technologies.

The new report Antibody-Drug Conjugates 2014 - a Business, Technology & Pipeline Analysis is based on the evaluation of more than 90 companies. The report analyzes established and new antibody-drug conjugate (ADC) technologies, business activities and opportunities and assesses more than 100 ADC development and research programs. The commercial value of ADC technologies, ADC products and ADC product candidates is described and valued by means of sales, product prices, company market capitalization, initial public offerings, venture capital and private equity financing, infrastructure investments and financial deal terms. Business deal activities in form of acquisitions, licensing and collaboration agreements and joint ventures between pharma, biotech and the service industry serve to identify those technologies of interest for stakeholders in the ADC industry.

About La Merie Publishing

La Merie Publishing is an independent German Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com

About PipelineReview.com

PipelineReview.com is the Biologics News Center and Online Store of La Merie Publishing focused on Research and Development in the Biopharmaceutical Industry. FREE R&D Newletters conveniently bring via e-mail a daily or weekly selection of the most interesting news from biopharmaceutical R&D. For more information visit www.pipelinereview.com

SOURCE: La Merie Publishing

Sunday, 03 November 2013 11:16

Rare Diseases R&D Pipeline

By definition, rare disease are those disorders which affect less than 200,000 patients in the US. A new report lists the more than 450 compounds under development by US companies for treatment of rare diseases.

The study was published by PhRMA, the Pharmaceutical Research and Manufacturers of America and can be downloaded at http://phrma.org/sites/default/files/pdf/Rare_Diseases_2013.pdf The range of rare diseases for which new drugs are being developing, is spanning from cancer (n=105 drug candidates), genetic disorders (n=85), neurological (n=32), infectious (n=28), respiratory (n=20) and autoimmune (n=18) diseases, to name the disease areas with most drug candidates in development.

The drug candidates in development for rare diseases are from all kind of product categories including vaccines, RNA, DNA, proteins, peptides, antibodies and, of course, small molecules.

 

October 24, 2013 I La Merie published in February 2007 for the first time a compilation of the annual sales of therapeutic proteins and antibodies. Since then, we released every year our list of TOP selling antibodies and proteins. You can find these annual reports published in our weekly newsletter R&D Pipeline News as a special edition in our online portal www.pipelinereview.com under FREE Reports.

We thought you might find it useful to have a look how annual sales of antibodies and proteins developed since 2006. We first prepared a table with the data for antibodies and found an amazing average/continuous annual growth rate of 18.9 % from 2006 to 2012. You can download the data at: http://pipelinereview.com/index.php/download?path=antibody%20sales%202006-2012.pdf 


Or go to the menu FREE Reports / FREE Downloads at www.pipelinereview.com

Last year, i.e. 2012, antibody sales summed up US$ 64.6 bln and for the first time were higher than those of recombinant protein therapeutics. Please bear in mind minor errors in accuracy of the data due to currency exchange influences and incomplete publication of some data. But the overall picture is clear: antibodies sell well! And it is not only cancer and anti-TNF antibodies which make out of most of antibody sales. New antibodies are have emerged recently and are gaining in market shares. It can be expected that they will compensate for potential future losses of leading antibodies when biosimilar antibodies come up.  

STUTTGART, Germany I October 22, 2013 I A new report released by La Merie Publishing analyzes the opportunities arising from the use of the T-cell receptor (TCR) in recombinant protein and antibody products as well as in T-cell therapy. The report entitled „The Engineered T-Cell Receptor in Fusion Proteins, Antibodies & Cells: Emerging Opportunities for the Biopharmaceutical Industry“ describes the current state-of-the art of TCR technologies including the monoclonal TCR (mTCR) and single-chain TCR (scTCR) in immunoglobulin and immunocytokine fusion proteins as well as in cytotoxic T-lymphocytes. The unique feature of the T-cell receptor is its ability to target intracellular protein derived peptides presented in the context of the HLA system. This opens up a whole new avenue for targeting in cancer and viral diseases by rendering intracellular antigens so far undruggable to targets accessible for antibodies, proteins and cellular therapies. This approach is becoming validated no only by the first commercial agreements between Big Pharma/Biotech and TCR technology providers, but also by clinical studies with the first TCR-based therapeutics in development.

The report can be found at http://pipelinereview.com/index.php/therapeuticarea/oncology/the-engineered-t-cell-receptor-in-fusion-proteins-antibodies-cells-emerging-opportunities-for-the-biopharmaceutical-industry-detail. This investigation summarizes current activities in the TCR field presents upcoming commercial opportunities for the pharmaceutical and biotechnology industry. As a rather new field of reserach and development in the pharma industry, there are still untapped areas for new entrants regarding platform technologies and products for development.

About La Merie Publising

La Merie Publishing is an independent business information provider for the biotechnology and pharmaceutical industry. We publish reports, offer R&D database access, and provide consulting services in pharmacology and biotechnology. Our products and subscription services are commercialized via our associated biotech portal www.PipelineReview.com  To read more about La Merie Publising, plrase visit our website www.lamerie.com

October 17, 2013 I Undoubtedly, antibodies are a hot area for biotech and pharma companies. Development of antibody therapeutics not only seems to have a lower attrition rate than that of small molecules (at least for toxicity reasons), but antibody products are extremely commercially successful. No wonder, that many companies are „jumping on the wagon" of antibodies. However, only a fraction of the companies is working on antibody molecules directed against new targets. Many, if not the majority is focused on improving antibodies directed against validated and commercially successful targets or directly developing biosimilar versions. Risk aversion cannot be the only reason, but availability of new targets for antibodies seems to be a major bottleneck for industry.

One reason might be that target discovery so far has been focused on extracellular targets (proteins, carbohydrates, glycolipids), because intracellular targets are „not accessable" for antibodies. However, intracellular tumor-associated proteins make out more than 80% of potential cancer drug targets. One company recently has raised considerable interest when it closed within a short periof of time two significant deals with Big Pharma/Biotech companies for intracellular targets and T-cell receptor (TCR) based therapeutics in the field of cancer and viral diseases. This seems to be a kind of proof-of-concept for the attractiveness of the T-Cell Receptor for biopharmaceutical industry.

In light of the potential breakthrough character of the TCR technology, La Merie Publishing has performed a comparative analysis and assessment of TCR technologies, pipelines and companies from an industry perspective. The report can be found in our online store at http://pipelinereview.com/index.php/therapeuticarea/oncology/the-engineered-t-cell-receptor-in-fusion-proteins-antibodies-cells-emerging-opportunities-for-the-biopharmaceutical-industry-detail .

Tuesday, 08 October 2013 09:19

Vaccines in US clinical development 2013

October 8, 2013 I The association of America’s biopharmaceutical companies (the Pharmaceutical Research and Manufacturers of America: PhRMA) recently released the report „Medicines in Development for Vaccines„. The report states that US companies are developing 271 vaccines in clinical stages to prevent or treat a variety of diseases including allergy, neurological diseases, cancer, infectious diseases and some others. The vast majority of vaccines is being developed for infections diseases (51%) followed by cancer vaccines (37%). Among the infectious disease vaccines are e.g. HIV, influneza, hepatitis C virus vaccines, but also vaccines against meningitis, Dengue virus, malaria, cytomegalovirus, herpes simplex virus and many more. The report includes an introduction into and overview of the vaccines field. It can be downloaded at the PhRMA site at http://phrma.org/sites/default/files/pdf/Vaccines_2013.pdf

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