On June 29, 2016 Xcovery, a developer of targeted therapeutics for cancer, reported the initiation of its Phase 3 trial of X-396 in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) (Press release, Xcovery, JUN 29, 2016, View Source [SID:1234513622]). The eXalt3 trial is an open-label, randomized study designed to evaluate the efficacy and safety of X-396, the Company’s lead ALK inhibitor drug candidate, versus crizotinib in over 400 patients with ALK+ NSCLC.

“The initiation of our Phase 3 eXalt3 trial represents an important step forward in Xcovery’s advancement of our lead candidate, X-396,” said Michael Webb, Chief Executive Officer and President of Xcovery. “The recently released data from our ongoing Phase 1/2 study of X-396 showed promising activity with durable responses noted in both treatment-naïve patients as well in patients resistant to current standard-of-care. These results, coupled with a favorable tolerability profile, support the continued development of X-396 as a potential new treatment option for patients with ALK+ NSCLC. Xcovery will now focus on actively recruiting additional patients and new clinical sites across the globe.”

About the Phase 3 eXalt3 Study

The Phase 3 eXalt3 study is an open-label, randomized study that will evaluate the efficacy and safety of the ALK inhibitor X-396 compared to crizotinib in patients with ALK+ NSCLC. The primary efficacy endpoint being measured is progression-free survival (PFS) as assessed by an independent radiology review based on RECIST v. 1.1 criteria. The study will also allow the Company to obtain additional pharmacokinetic data on X-396 in select patients and samples for exploratory biomarkers research to be compared against the clinical outcomes. The company expects to enroll approximately 400 patients who have received up to one prior chemotherapy regimen and no prior ALK tyrosine kinase inhibitor (TKI) treatments. The trial is designed so patients either receive a 225 mg daily dose of X-396 or a 250 mg dose twice a day of standard-of-care crizotinib over a 28-day schedule.

About X‐396 (Ensartinib)

Xcovery’s lead asset is X‐396, a small molecule, anaplastic lymphoma kinase (ALK) inhibitor. It is being studied in the eXalt2 and eXalt3 studies, Phase 2 and Phase 3 trials for the treatment of ALK‐positive non‐small cell lung cancer (NSCLC). Both studies are currently enrolling patients. To learn more, visit: www.xalt2study.com or ClinicalTrials.gov.

About NSCLC and ALK

Lung cancer is the second most common type of cancer identified in the United States with an estimated 221,000 new diagnoses expected in 2015. Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for an estimated 85‐90% of the lung cancer cases. The anaplastic lymphoma kinase (ALK) gene is located on chromosome 2 and rearrangement of the ALK gene can lead to its activation or expression, therefore increasing a person’s chance of developing certain types of cancer, including NSCLC. Between three and seven percent of patients with NSCLC have the ALK rearrangement, making this a molecular target warranting investigation for NSCLC patients.

On June 29, 2016 Xcovery, a developer of targeted therapeutics for cancer, reported the initiation of its Phase 3 trial of X-396 in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) (Press release, Xcovery, JUN 29, 2016, View Source [SID:1234513622]). The eXalt3 trial is an open-label, randomized study designed to evaluate the efficacy and safety of X-396, the Company’s lead ALK inhibitor drug candidate, versus crizotinib in over 400 patients with ALK+ NSCLC.

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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

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"The initiation of our Phase 3 eXalt3 trial represents an important step forward in Xcovery’s advancement of our lead candidate, X-396," said Michael Webb, Chief Executive Officer and President of Xcovery. "The recently released data from our ongoing Phase 1/2 study of X-396 showed promising activity with durable responses noted in both treatment-naïve patients as well in patients resistant to current standard-of-care. These results, coupled with a favorable tolerability profile, support the continued development of X-396 as a potential new treatment option for patients with ALK+ NSCLC. Xcovery will now focus on actively recruiting additional patients and new clinical sites across the globe."

About the Phase 3 eXalt3 Study

The Phase 3 eXalt3 study is an open-label, randomized study that will evaluate the efficacy and safety of the ALK inhibitor X-396 compared to crizotinib in patients with ALK+ NSCLC. The primary efficacy endpoint being measured is progression-free survival (PFS) as assessed by an independent radiology review based on RECIST v. 1.1 criteria. The study will also allow the Company to obtain additional pharmacokinetic data on X-396 in select patients and samples for exploratory biomarkers research to be compared against the clinical outcomes. The company expects to enroll approximately 400 patients who have received up to one prior chemotherapy regimen and no prior ALK tyrosine kinase inhibitor (TKI) treatments. The trial is designed so patients either receive a 225 mg daily dose of X-396 or a 250 mg dose twice a day of standard-of-care crizotinib over a 28-day schedule.

About X‐396 (Ensartinib)

Xcovery’s lead asset is X‐396, a small molecule, anaplastic lymphoma kinase (ALK) inhibitor. It is being studied in the eXalt2 and eXalt3 studies, Phase 2 and Phase 3 trials for the treatment of ALK‐positive non‐small cell lung cancer (NSCLC). Both studies are currently enrolling patients. To learn more, visit: www.xalt2study.com or ClinicalTrials.gov.

About NSCLC and ALK

Lung cancer is the second most common type of cancer identified in the United States with an estimated 221,000 new diagnoses expected in 2015. Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for an estimated 85‐90% of the lung cancer cases. The anaplastic lymphoma kinase (ALK) gene is located on chromosome 2 and rearrangement of the ALK gene can lead to its activation or expression, therefore increasing a person’s chance of developing certain types of cancer, including NSCLC. Between three and seven percent of patients with NSCLC have the ALK rearrangement, making this a molecular target warranting investigation for NSCLC patients.

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]). 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 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]).

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!

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.