La Merie
Ulrich Martin

Ulrich Martin

STUTTGART, Germany I May 13, 2016 I Immunotherapy of cancer with direct or indirect use of T-cells is one of the most exciting fields in cancer research. Direct T-cell therapy implies the ex vivo engineering of autologous or allogeneic T-cells for tumor targeting by chimeric antigen receptors (CAR) or T-cell receptors (TCR). Despite stunning clinical results with CD19-targeted CAR T-cells, many major pharmaceutical companies have not embarked on adoptive cell therapy, probably because cell products are a world completely different from that of small molecules or recombinant proteins and antibodies.

Tremendous progress in bispecific antibody technologies during the last decade and the clinical success of a first generation bispecific T-cell engager (BiTE) antibody molecule directed against CD19 lead to an explosion of T-cell redirecting bispecific antibodies in clinical development. Within 18 months, the number of clinical stage T-cell or natural killer (NK) cells redirecting bispecific antibodies has increased from 4 to 21 and further 16 molecules could enter clinical development within the next 12 months. Data from these clinical studies in the next years will give valuable feedback for the further design of T-cell redirecting bispecific constructs.

In a new report released by La Merie Publishing, the competitive T-cell redirecting bispecific antibody stakeholders, technologies, pipelines and deals is described and analyzed.

This report „T-Cell Redirecting Bispecific Antibodies 2016: A competitive landscape analysis of stakeholders, technologies, pipelines and deals“ provides up-to-date information about and analysis of 34 corporate players, 22 key technologies, 47 T-cell and NK-cell redirecting bispecific antibody profiles, business deals and private and public financing rounds.

The report analyzes the pipeline of T-cell and NK-cell redirecting bispecific antibody molecules regarding preferred targets, molecular constructs, dosing schedules, clinical experience, combination study plans, competition with other treatment modalities and the next wave of T-cell and NK-cell redirecting antibodies.

Preferences in bispecific antibody technologies are evaluated regarding drug candidate output, partnering, technological features and impact on clinical administration regimens.

The report highlights the commercial value of T-cell redirecting bispecific antibody immunotherautics in terms of drug prices, sales, company acquisition prices, economic terms of partnering deals, and private or public financing rounds.

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 May 13, 2016 I Immunotherapy of cancer with direct or indirect use of T-cells is one of the most exciting fields in cancer research. Direct T-cell therapy implies the ex vivo engineering of autologous or allogeneic T-cells for tumor targeting by chimeric antigen receptors (CAR) or T-cell receptors (TCR). Despite stunning clinical results with CD19-targeted CAR T-cells, many major pharmaceutical companies have not embarked on adoptive cell therapy, probably because cell products are a world completely different from that of small molecules or recombinant proteins and antibodies.

Tremendous progress in bispecific antibody technologies during the last decade and the clinical success of a first generation bispecific T-cell engager (BiTE) antibody molecule directed against CD19 lead to an explosion of T-cell redirecting bispecific antibodies in clinical development. Within 18 months, the number of clinical stage T-cell or natural killer (NK) cells redirecting bispecific antibodies has increased from 4 to 21 and further 16 molecules could enter clinical development within the next 12 months. Data from these clinical studies in the next years will give valuable feedback for the further design of T-cell redirecting bispecific constructs.

In a new report released by La Merie Publishing, the competitive T-cell redirecting bispecific antibody stakeholders, technologies, pipelines and deals is described and analyzed.

This report „T-Cell Redirecting Bispecific Antibodies 2016: A competitive landscape analysis of stakeholders, technologies, pipelines and deals“ provides up-to-date information about and analysis of 34 corporate players, 22 key technologies, 47 T-cell and NK-cell redirecting bispecific antibody profiles, business deals and private and public financing rounds.

The report analyzes the pipeline of T-cell and NK-cell redirecting bispecific antibody molecules regarding preferred targets, molecular constructs, dosing schedules, clinical experience, combination study plans, competition with other treatment modalities and the next wave of T-cell and NK-cell redirecting antibodies.

Preferences in bispecific antibody technologies are evaluated regarding drug candidate output, partnering, technological features and impact on clinical administration regimens.

The report highlights the commercial value of T-cell redirecting bispecific antibody immunotherautics in terms of drug prices, sales, company acquisition prices, economic terms of partnering deals, and private or public financing rounds.

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 March 13, 2016 I 2015 was another year of record sales of recombinant therapeutic proteins and antibodies despite the beginning commercialization of biosimilar antibodies and proteins. Global sales of originator antibodies and proteins reached USD 154 bln, a growth of 9.2% compared with the previous year. While sales of anti-TNF antibodies slowed down, the strong growth was mainly due to antibodies (+11.3%) driven by sales of cancer antibodies and other anti-inflammatory antibodies. The commercially most successful class of protein products were insulin and insulin analogs with growth of 11.9% from 2014 to 2015. On the contrary, the successful lauch and market uptake of oral antivirals to treat hepatitis C cut interferon alpha sales by 50%

A total of 39 biologic therapeutics reached blockbuster status with 2015 sales exceeding US$ 1 bln: 21 antibodies and 18 proteins. Nine biologics reached global sales in 2015 of more than US$ 5 bln. Four biologics were new in the blockbuster biologics list and one dropped out. Six biopharmaceutical companies posted combined biologics sales of more than US$ 10 bln in the year 2015.

Quite a number of new therapeutic antibodies and proteins were launched in the year 2015 and will contribute to the further growth of biologics sales, but also to compensate for expected losses of blockbuster biologics by biosimilar antibodies and proteins or by new competitors.

The report „Blockbuster Biologics 2015: Sales of Recombinant Therapeutic Antibodies & Proteins“ can be acquired at La Merie Publishing’s News Center and Online Store www.PipelineReview.com: http://pipelinereview.com/index.php/store-online/blockbuster-biologics-2015-sales-of-recombinant-therapeutic-antibodies-proteins-detail

The report provides a compilation of the sales data of recombinant therapeutic proteins and antibodies in the calendar year 2015. Sales data were obtained from company publications and refer to branded products originating from companies based in regulated markets. All sales data were converted from their original, published currency into US$. Sales figures represent the sum of revenues in all territories where the products were marketed. Growth rates usually are listed as reported (not based on constant exchange rates).

Sales data are presented for each product within the respective class of biologics. The data were analyzed to establish a ranking list of blockbuster biologics with 2015 sales higher than US$ 1 bln. Another ranking list was prepared for companies according to biologics sales in 2015 and the percentage of antibody sales vs protein sales.

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 March 14, 2016 I 2015 was another year of record sales of recombinant therapeutic proteins and antibodies despite the beginning commercialization of biosimilar antibodies and proteins. Global sales of originator antibodies and proteins reached USD 154 bln, a growth of 9.2% compared with the previous year. While sales of anti-TNF antibodies slowed down, the strong growth was mainly due to antibodies (+11.3%) driven by sales of cancer antibodies and other anti-inflammatory antibodies. The commercially most successful class of protein products were insulin and insulin analogs with growth of 11.9% from 2014 to 2015. On the contrary, the successful lauch and market uptake of oral antivirals to treat hepatitis C cut interferon alpha sales by 50%

A total of 39 biologic therapeutics reached blockbuster status with 2015 sales exceeding US$ 1 bln: 21 antibodies and 18 proteins. Nine biologics reached global sales in 2015 of more than US$ 5 bln. Four biologics were new in the blockbuster biologics list and one dropped out. Six biopharmaceutical companies posted combined biologics sales of more than US$ 10 bln in the year 2015.

Quite a number of new therapeutic antibodies and proteins were launched in the year 2015 and will contribute to the further growth of biologics sales, but also to compensate for expected losses of blockbuster biologics by biosimilar antibodies and proteins or by new competitors.

The report „Blockbuster Biologics 2015: Sales of Recombinant Therapeutic Antibodies & Proteins“ can be acquired at La Merie Publishing’s News Center and Online Store www.PipelineReview.com: http://pipelinereview.com/index.php/store-online/blockbuster-biologics-2015-sales-of-recombinant-therapeutic-antibodies-proteins-detail

The report provides a compilation of the sales data of recombinant therapeutic proteins and antibodies in the calendar year 2015. Sales data were obtained from company publications and refer to branded products originating from companies based in regulated markets. All sales data were converted from their original, published currency into US$. Sales figures represent the sum of revenues in all territories where the products were marketed. Growth rates usually are listed as reported (not based on constant exchange rates).

Sales data are presented for each product within the respective class of biologics. The data were analyzed to establish a ranking list of blockbuster biologics with 2015 sales higher than US$ 1 bln. Another ranking list was prepared for companies according to biologics sales in 2015 and the percentage of antibody sales vs protein sales.

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 February 4, 2016 I Targeting the proinflammatory cytokine interleukin-17 (IL-17) produced by T helper cells has become a clinically validated strategy of successfully treating psoriasis, psoriatic arthritis and ankylosing spondylitis. The first approved and marketed antibody secukinumab from Novartis also shows great commercial promise as evidenced by sales of US$ 261 mln in the first year of market launch. The success is due to superior efficacy of anti-IL17 over established psoriasis antibodies targeting TNFα and interleukin-12/23 with a multi-billion dollar market only for psoriasis. However, neutralizing IL-17 with antibodies has proved ineffective and possibly deleterious in patients with inflammatory bowel disease. Given that T helper 17 (TH17) cells express IL-17 together with many other proinflammatory cytokines (IL-17F, IL-22, IL-26, and granulocyte-macrophage colony-stimulating factor), targeting the Th17 cell lineage may be superior to blocking a single effector cytokine.

Th17 cells specifically express the DNA-binding transcription factor retinoic-acid-receptor-related orphan receptor gamma T (RORγT). The activity of RORγT is required for the proliferation and functionality of immune Th17 cells.. Active RORgammaT is a prerequisite for the differentiation of T cells into Th17 cells. Small-molecule inhibition of RORγT has therefore emerged as a novel strategy for the treatment of autoimmune diseases while stimulation of RORγT by agonists holds promise in immune-oncology. Orally bioavailable RORgamma agonists have demonstrated single agent therapeutic activity in multiple in vivo animal models of cancer. Ex vivo treatment with RORgamma agonist compounds has been shown to enhance the therapeutic benefit of adoptive T-cell therapy by improving both immune cell persistence and activation.

In a new report released by La Merie Publishing, the landscape of drug discovery and development of novel small molecule antagonists (inverse agonists) and agonists of RORγ is described and analyzed. Nuclear receptors are „difficult-to-drug“ targets, and, thus, represent a high entry barrier, which requires specific expertise in structure-based drug discovery.

The report entitled “RORgamma Modulators 2016: A comparative analysis of the landscape of RORgamma antagonists and agonists“ outlines the scientific rationale for discovering antagonists of RORgamma for treatment of autoimmune and inflammatory diseases, but also of agonists of RORgamma for treatment of cancer. Clinical as well as non-clinical data for validation of RORgamma as target are provided and lead and up-side indications for development including the key product profile are discussed. Potential safety concers for novel RORgamma modulators were identified. Drug discovery approaches of more than 30 technology and pharmaceutical companies are shown regarding strategies in partnering as well as in applied technologies.

Based on the experience in the past, estimates of the required time from start of a discovery program of RORgamma modulators until entry into human studies are calculated. The competitive landscape of RORgamma modulator development and discovery projects is analyzed and the profiles of companies are presented, separately for unpartnered technology or pharmaceutical companies and for partnerships between technology and pharmaceutical companies.

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 February 4, 2016 I Targeting the proinflammatory cytokine interleukin-17 (IL-17) produced by T helper cells has become a clinically validated strategy of successfully treating psoriasis, psoriatic arthritis and ankylosing spondylitis. The first approved and marketed antibody secukinumab from Novartis also shows great commercial promise as evidenced by sales of US$ 261 mln in the first year of market launch. The success is due to superior efficacy of anti-IL17 over established psoriasis antibodies targeting TNFα and interleukin-12/23 with a multi-billion dollar market only for psoriasis. However, neutralizing IL-17 with antibodies has proved ineffective and possibly deleterious in patients with inflammatory bowel disease. Given that T helper 17 (TH17) cells express IL-17 together with many other proinflammatory cytokines (IL-17F, IL-22, IL-26, and granulocyte-macrophage colony-stimulating factor), targeting the Th17 cell lineage may be superior to blocking a single effector cytokine.

Th17 cells specifically express the DNA-binding transcription factor retinoic-acid-receptor-related orphan receptor gamma T (RORγT). The activity of RORγT is required for the proliferation and functionality of immune Th17 cells.. Active RORgammaT is a prerequisite for the differentiation of T cells into Th17 cells. Small-molecule inhibition of RORγT has therefore emerged as a novel strategy for the treatment of autoimmune diseases while stimulation of RORγT by agonists holds promise in immune-oncology. Orally bioavailable RORgamma agonists have demonstrated single agent therapeutic activity in multiple in vivo animal models of cancer. Ex vivo treatment with RORgamma agonist compounds has been shown to enhance the therapeutic benefit of adoptive T-cell therapy by improving both immune cell persistence and activation.

In a new report released by La Merie Publishing, the landscape of drug discovery and development of novel small molecule antagonists (inverse agonists) and agonists of RORγ is described and analyzed. Nuclear receptors are „difficult-to-drug“ targets, and, thus, represent a high entry barrier, which requires specific expertise in structure-based drug discovery.

The report entitled “RORgamma Modulators 2016: A comparative analysis of the landscape of RORgamma antagonists and agonists“ outlines the scientific rationale for discovering antagonists of RORgamma for treatment of autoimmune and inflammatory diseases, but also of agonists of RORgamma for treatment of cancer. Clinical as well as non-clinical data for validation of RORgamma as target are provided and lead and up-side indications for development including the key product profile are discussed. Potential safety concers for novel RORgamma modulators were identified. Drug discovery approaches of more than 30 technology and pharmaceutical companies are shown regarding strategies in partnering as well as in applied technologies.

Based on the experience in the past, estimates of the required time from start of a discovery program of RORgamma modulators until entry into human studies are calculated. The competitive landscape of RORgamma modulator development and discovery projects is analyzed and the profiles of companies are presented, separately for unpartnered technology or pharmaceutical companies and for partnerships between technology and pharmaceutical companies.

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 2, 2015 I Only a few years ago, before the times of immuno-oncology and chimeric antigen receptor (CAR) T-Cell Therapeutics, antibody-drug conjugates (ADC) were the most exciting investment opportunity in oncology which nobody wanted to miss. Since then, the exaggerated expectations have waned because the early successes with Kadcyla and Adcetris could not be repeated as quickly as investors had hoped. Antibody-drug conjugates as a class, i.e. therapeutic antibodies empowered by intracellular delivery of cytotoxic drugs, so far did not prove as a money-making machine.

Some of the technological obstacles encountered on the way of maturation of antibody-drug conjugates were inappropriate patient selection, a narrow therapeutic window, drug resistance, and the heterogeneity of ADCs generated by conventional ADC technologies. Numerous technology as well as some major pharmaceutical companies have successfully worked on finding next generation ADC technology solutions to these problems.

In a brand-new report released by La Merie Publishing the field of antibody-drug conjugates was analyzed in depth by profiling more than 90 companies, more than 100 ADC drug candidates and more than 26 ADC technologies and components. The report entitled „Antibody-Drug Conjugates 2016: Perspectives & Opportunities - a Pipeline, Technology, Stakeholder & Business Analysis“ also described and analyzed business deals in the ADC field, e.g. collaboration and license agreements, mergers and acquisitions, financial transactions (divestments, public offerings, private equity and venture capital fund-raising).

The prospects for success of ADC drug candidates remain good and are based on a well-filled pipeline, increasing adoption of next generation ADC technologies, lessons learned from failures, a balanced mixture of stakeholders and a variety of options for funding of ADC developments. About 70 ADCs are in clinical and pre-IND stages of development and at least the same number of ADC programs are in preclinical R&D. However, targets are still a bottleneck with the attractive consequence that companies with successful target identification capabilities are highly rewarded by investors and business partners.

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 2, 2015 I Only a few years ago, before the times of immuno-oncology and chimeric antigen receptor (CAR) T-Cell Therapeutics, antibody-drug conjugates (ADC) were the most exciting investment opportunity in oncology which nobody wanted to miss. Since then, the exaggerated expectations have waned because the early successes with Kadcyla and Adcetris could not be repeated as quickly as investors had hoped. Antibody-drug conjugates as a class, i.e. therapeutic antibodies empowered by intracellular delivery of cytotoxic drugs, so far did not prove as a money-making machine.

Some of the technological obstacles encountered on the way of maturation of antibody-drug conjugates were inappropriate patient selection, a narrow therapeutic window, drug resistance, and the heterogeneity of ADCs generated by conventional ADC technologies. Numerous technology as well as some major pharmaceutical companies have successfully worked on finding next generation ADC technology solutions to these problems.

In a brand-new report released by La Merie Publishing the field of antibody-drug conjugates was analyzed in depth by profiling more than 90 companies, more than 100 ADC drug candidates and more than 26 ADC technologies and components. The report entitled „Antibody-Drug Conjugates 2016: Perspectives & Opportunities - a Pipeline, Technology, Stakeholder & Business Analysis“ also described and analyzed business deals in the ADC field, e.g. collaboration and license agreements, mergers and acquisitions, financial transactions (divestments, public offerings, private equity and venture capital fund-raising).

The prospects for success of ADC drug candidates remain good and are based on a well-filled pipeline, increasing adoption of next generation ADC technologies, lessons learned from failures, a balanced mixture of stakeholders and a variety of options for funding of ADC developments. About 70 ADCs are in clinical and pre-IND stages of development and at least the same number of ADC programs are in preclinical R&D. However, targets are still a bottleneck with the attractive consequence that companies with successful target identification capabilities are highly rewarded by investors and business partners.

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 April 1, 2015 I This year’s systematic comparison of the US$ sales of recombinant therapeutic antibodies and proteins in the year 2014 based on standardized currency exchange rates as of March 17, 2015 suffered from the strong rise of the US$ relative to other currencies, mainly the EURO. The review, conducted by La Merie Publishing, reveals that overall biologics sales in 2014 OS US$ 141 bln were virtually identical to those of US$ 140 in the year 2013. However, the relative weight of antibody sales increased by 8.6% and compensated the decrease of therapeutic proteins by 8.4%. European companies such as Sanofi, Novo Nordisk and Merck Serono lost positions in the ranking list of companies with biologics sales due to their strong exposure to currency exchange influencies.

The decrease of protein sales not only was influenced by currency effects, but also by lack of introduction of new therapeutic proteins into the market, i.e. innovation, increasing competition with other treatment modalities, e.g. in hepatitis C (interferon alpha) and cost contaiment pressures of healthcare payers. On the other hand, a number of new therapeutic antibodies have been launched in the recent years and now are strongly driving the increase of antibody sales. While overall 2014 sales of cancer antibodies remained nearly the same, antibodies to treat inflammatory and autoimmune diseases strongly gained momentum with an increase of 12.9% for anti-TNF antibodies, but even more with an increase of 20.1% for other anti-inflammatory antibodies. More than US$ 47 bln (33% of all biologics sales) were earned by the total of all anti-inflammatory antibodies in 2014.

Thirty-eight biologics achieved blockbuster status in 2014 with annual sales of more than US$ 1 bln. The top three blockbuster biologics were the anti-TNF antibodies Humira, Remicade and Enbrel. The best selling therapeutic protein was insulin glargine from Sanofi. New in the Blockbuster Biologics list was the anti-CTLA-4 antibody ipilimumab.

The report „2014 Sales of Recombinant Therapeutic Antibodies & Proteins“ can be acquired at La Merie Publishing’s News Center and Online Store www.PipelineReview.com: http://pipelinereview.com/index.php/store-online/2014-sales-of-recombinant-therapeutic-antibodies-proteins-detail

The report provides a compilation of the sales data of recombinant therapeutic proteins and antibodies in the calendar year 2014. Sales data were obtained from company publications and refer to branded products originating from companies based in regulated markets. All sales data were converted from their original, published currency into US$. Sales figures represent the sum of revenues in all territories where the products were marketed.

Sales data are presented for each product within the respective class of biologics. The data were analyzed to establish a ranking list of blockbuster biologics with 2014 sales higher than US$ 1 bln. Another ranking list was prepared for companies according to biologics sales in 2014 and the percentage of antibody sales vs protein sales.

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 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

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