On June 29, 2016 Selexis SA, a pioneering life sciences company and a global leader in mammalian (suspension-adapted CHO-K1) cell line generation, reported that Symphogen A/S, a private biopharmaceutical company developing recombinant antibody mixtures, has progressed its Sym015 clinical candidate into a Phase 1 dose escalation trial in patients with solid tumors (Press release, Selexis, JUN 29, 2016, View Source!2016jun29-symphogen-cla/c1d4o [SID:1234513619]).

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Symphogen relied upon Selexis SGE (Selexis Genetic Elements) to facilitate the rapid, stable, and cost-effective expression of Sym015, which is a multi-targeting monoclonal antibody (MAb) mixture that targets the MET receptor.

The proto-oncogene c-MET, also called MET, has been recognized as an important mediator of uncontrolled growth of solid tumors. Research has shown that driver mutations that result in activation of the MET receptor tyrosine kinase (RTK) are associated with a wide range of human malignancies including cancers of the kidney, liver, stomach, breast, and brain.

Selexis SGEs are the foundation of the SUREtechnology Platform. SGEs are unique epigenetic DNA-based elements that control the dynamic organization of chromatin in all mammalian cells and allow for higher and more stable expression of recombinant proteins.

"We are pleased that the power of our Selexis Genetic Elements helped Symphogen efficiently produce their next-generation antibody candidate, Sym015, and move it rapidly into clinical development," said Igor Fisch, PhD, chief executive officer and chairman of Selexis. "The goal of our proprietary technology is to help our biopharmaceutical partners advance their discovery development programs into clinical trials and, ultimately, biologics manufacturing, offering patients new and improved treatment options."

In December 2014, Selexis and Symphogen A/S entered into a commercial license agreement and signed the continuation of their R&D license agreement. Symphogen has licensed the rights to the Selexis SUREtechnology Platform and SURE CHO-M Cell Line for the development of recombinant MAb mixtures for the treatment of various cancers and infectious diseases. Symphogen has developed unique technologies for the controlled, reproducible production of highly characterized MAb mixtures manufactured as single drug products.

On June 29, 2016 Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T-cell immunotherapies for the treatment of cancer,reported it has entered into a cooperation agreement with the Max Delbrück Centre for Molecular Medicine in the Helmholtz Association (MDC), Berlin, and the Charité – Universitätsmedizin Berlin (Charité) (Press release, MediGene, JUN 29, 2016, View Source [SID:1234513618]). The partners will collaborate on a research project entitled “MageA1-TCR Gene Therapy of Multiple Myeloma (MAGEA1-TCR)”, which is funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; BMBF). The planned trial is currently the first study in Germany with patients with relapsed or refractory multiple myeloma that will equip a patient’s own T cells with tumor-specific T-cell receptors.

The clinical investigator-initiated phase I trial (IIT) is entitled “A Phase I study of MAGE-A1-specific TCR-transduced T cells in patients with relapsed/refractory multiple myeloma”. As part of the study, the patient’s own T cells are activated and transduced with tumor antigen MAGE-A1-specific T-cell receptors using viral vectors. Following expansion, these modified cells are then re-administered to patients to destroy the cancer cells. The aim of this trial is to investigate the safety and tolerability of this innovative therapy approach.

Charité is responsible as the clinical partner for conducting the clinical trial and is a beneficiary of the public funding along with the MDC, which is in charge of the analytics and ensuring good manufacturing practices (GMP)[1]. Medigene is supporting both the MDC and Charité by handling regulatory affairs matters related to trial approval in addition to advising on the development of the analytics and GMP production. Medigene holds a first right of negotiation for an exclusive license to the study results for the commercial exploitation of the investigated TCR product candidate in multiple myeloma, and is additionally entitled to a undisclosed profit participation in the case of subsequent commercial exploitation by a third party.

Prof. Dr Dolores Schendel, CEO and CSO of Medigene and Project Leader in the collaborative project, comments on the signing of the contract: “We are delighted to be part of this first promising TCR project in Germany. The preparations required for this project will help pave the way for our own product candidates, which are also being developed for the treatment of diseases with a high unmet medical need.”

Prof. Dr Antonio Pezzutto, Medical Director at Charité Campus Benjamin Franklin and Project Lead in the collaborative project, explains: “After signing this contract, we are pleased that the preparations for the clinical trial are in full swing. Our goal is to offer this new, innovative therapy to patients suffering from multiple myeloma with MAGE-A1 expression who do not or no longer respond to traditional chemotherapy.”

Prof. Dr Blankenstein, Head of Molecular Immunology and Gene Therapy at the MDC, Director of the Institute of Immunology at Charité Campus Berlin Buch and Project Coordinator in the collaborative project, adds: “This allocation of funding will now enable us to enter the clinical development phase with our MAGE-A1 T-cell receptor and consequently bring German research in this field up to the highest international level. The MDC is proud to be playing an important role by carrying out the required analytics and ensuring GMP-compliant production of the living cells for this personalized treatment of cancer.”

About TCR technology:
The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex-vivo). A large number of specific T cells to fight the tumor is thereby made available to patients within a short period of time.

Medigene’s technology for T-cell receptor-modified T cells is one of the company’s highly innovative and complementary immunotherapy platforms for adoptive T-cell therapy. The TCR therapy is designed to treat patients with high tumor loads. The clinical development of Medigene has now begun preparing its own TCRs, and developing a library of recombinant T-cell receptors. Moreover, a good manufacturing practice (GMP)-compliant process for their combination with patient-derived T cells is currently being established.

On June 29, 2016 Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T-cell immunotherapies for the treatment of cancer,reported it has entered into a cooperation agreement with the Max Delbrück Centre for Molecular Medicine in the Helmholtz Association (MDC), Berlin, and the Charité – Universitätsmedizin Berlin (Charité) (Press release, MediGene, JUN 29, 2016, View Source [SID:1234513618]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The partners will collaborate on a research project entitled "MageA1-TCR Gene Therapy of Multiple Myeloma (MAGEA1-TCR)", which is funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; BMBF). The planned trial is currently the first study in Germany with patients with relapsed or refractory multiple myeloma that will equip a patient’s own T cells with tumor-specific T-cell receptors.

The clinical investigator-initiated phase I trial (IIT) is entitled "A Phase I study of MAGE-A1-specific TCR-transduced T cells in patients with relapsed/refractory multiple myeloma". As part of the study, the patient’s own T cells are activated and transduced with tumor antigen MAGE-A1-specific T-cell receptors using viral vectors. Following expansion, these modified cells are then re-administered to patients to destroy the cancer cells. The aim of this trial is to investigate the safety and tolerability of this innovative therapy approach.

Charité is responsible as the clinical partner for conducting the clinical trial and is a beneficiary of the public funding along with the MDC, which is in charge of the analytics and ensuring good manufacturing practices (GMP)[1]. Medigene is supporting both the MDC and Charité by handling regulatory affairs matters related to trial approval in addition to advising on the development of the analytics and GMP production. Medigene holds a first right of negotiation for an exclusive license to the study results for the commercial exploitation of the investigated TCR product candidate in multiple myeloma, and is additionally entitled to a undisclosed profit participation in the case of subsequent commercial exploitation by a third party.

Prof. Dr Dolores Schendel, CEO and CSO of Medigene and Project Leader in the collaborative project, comments on the signing of the contract: "We are delighted to be part of this first promising TCR project in Germany. The preparations required for this project will help pave the way for our own product candidates, which are also being developed for the treatment of diseases with a high unmet medical need."

Prof. Dr Antonio Pezzutto, Medical Director at Charité Campus Benjamin Franklin and Project Lead in the collaborative project, explains: "After signing this contract, we are pleased that the preparations for the clinical trial are in full swing. Our goal is to offer this new, innovative therapy to patients suffering from multiple myeloma with MAGE-A1 expression who do not or no longer respond to traditional chemotherapy."

Prof. Dr Blankenstein, Head of Molecular Immunology and Gene Therapy at the MDC, Director of the Institute of Immunology at Charité Campus Berlin Buch and Project Coordinator in the collaborative project, adds: "This allocation of funding will now enable us to enter the clinical development phase with our MAGE-A1 T-cell receptor and consequently bring German research in this field up to the highest international level. The MDC is proud to be playing an important role by carrying out the required analytics and ensuring GMP-compliant production of the living cells for this personalized treatment of cancer."

About TCR technology:
The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex-vivo). A large number of specific T cells to fight the tumor is thereby made available to patients within a short period of time.

Medigene’s technology for T-cell receptor-modified T cells is one of the company’s highly innovative and complementary immunotherapy platforms for adoptive T-cell therapy. The TCR therapy is designed to treat patients with high tumor loads. The clinical development of Medigene has now begun preparing its own TCRs, and developing a library of recombinant T-cell receptors. Moreover, a good manufacturing practice (GMP)-compliant process for their combination with patient-derived T cells is currently being established.

On June 29, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of targeted oncology therapeutics that address major unmet medical needs, reported the recommendation from the Independent Data Monitoring Committee (IDMC) on the interim analysis for Galena’s NeuVax (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) clinical trial (Press release, Galena Biopharma, JUN 29, 2016, View Source [SID:1234513607]). On June 27, 2016, the IDMC recommended that the PRESENT trial be stopped due to futility. The letter is attached to the Form 8-K filed today and available on the Company’s website. This planned safety and futility interim analysis was triggered after 70 qualifying disease free survival (DFS) events were reached, and a total of 71 events were reviewed by the IDMC.

“We are extremely disappointed with the outcome of the PRESENT futility analysis,” said Mark W. Schwartz, Ph.D., President and Chief Executive Officer. “On behalf of our entire company, I would like to thank all of the courageous patients and their families, investigators, study staff and independent committees who participated in the PRESENT study. To date, the trial has not been un-blinded other than by the IDMC, and we need to evaluate the data. We expect to host a conference call next week to provide a preliminary review of the PRESENT trial and an update on all of our immunotherapy and hematology clinical development programs.”

About PRESENT

PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) is an international, Phase 3 study to evaluate NeuVax plus GM-CSF versus placebo plus GM-CSF to prevent cancer recurrence. The trial is being run under a Special Protocol Assessment (SPA) granted by the U.S. Food and Drug Administration (FDA). PRESENT is targeting patients who are node positive, HER2 IHC 1+/2+, and HLA A2+ and/or A3+. The study is double blind, randomized 1:1, and is stratified by stage, type of surgery, hormone receptor status, and menopausal status. Galena enrolled a total of 758 patients, and the primary endpoint for the trial was disease free survival (DFS) upon reaching 141 events with 3 years minimum follow-up. Additional information on the trial can be found here and at clinicaltrials.gov identifier: NCT01479244.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

In addition to PRESENT, Galena has two breast cancer studies ongoing with NeuVax in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.

On June 29, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of targeted oncology therapeutics that address major unmet medical needs, reported the recommendation from the Independent Data Monitoring Committee (IDMC) on the interim analysis for Galena’s NeuVax (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) clinical trial (Press release, Galena Biopharma, JUN 29, 2016, View Source [SID:1234513607]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On June 27, 2016, the IDMC recommended that the PRESENT trial be stopped due to futility. The letter is attached to the Form 8-K filed today and available on the Company’s website. This planned safety and futility interim analysis was triggered after 70 qualifying disease free survival (DFS) events were reached, and a total of 71 events were reviewed by the IDMC.

"We are extremely disappointed with the outcome of the PRESENT futility analysis," said Mark W. Schwartz, Ph.D., President and Chief Executive Officer. "On behalf of our entire company, I would like to thank all of the courageous patients and their families, investigators, study staff and independent committees who participated in the PRESENT study. To date, the trial has not been un-blinded other than by the IDMC, and we need to evaluate the data. We expect to host a conference call next week to provide a preliminary review of the PRESENT trial and an update on all of our immunotherapy and hematology clinical development programs."

About PRESENT

PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) is an international, Phase 3 study to evaluate NeuVax plus GM-CSF versus placebo plus GM-CSF to prevent cancer recurrence. The trial is being run under a Special Protocol Assessment (SPA) granted by the U.S. Food and Drug Administration (FDA). PRESENT is targeting patients who are node positive, HER2 IHC 1+/2+, and HLA A2+ and/or A3+. The study is double blind, randomized 1:1, and is stratified by stage, type of surgery, hormone receptor status, and menopausal status. Galena enrolled a total of 758 patients, and the primary endpoint for the trial was disease free survival (DFS) upon reaching 141 events with 3 years minimum follow-up. Additional information on the trial can be found here and at clinicaltrials.gov identifier: NCT01479244.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

In addition to PRESENT, Galena has two breast cancer studies ongoing with NeuVax in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.