Immuno-oncology

Celyad completes 30-day safety follow-up of first patient in NKG2D Phase I Trial. No treatment-related safety concerns reported

• No safety issues related to the investigational treatment reported at 30 days post treatment of the first patient following single dose NKG2D CAR T-cell infusion; triggers enrollment of other two patients in the first cohort. 
• The trial is a dose escalation study evaluating safety and feasibility of a CAR T-cell therapy in patients with acute myeloid leukemia or multiple myeloma.

Mont-Saint-Guibert, Belgique — Celyad SA (Euronext Brussels and Paris: CYAD), today announced the completion of the 30-day safety follow-up of the first patient enrolled in the Company’s Phase I clinical trial evaluating the safety and feasibility of its NKG2D CAR T-cell therapy, in cancer patients suffering from acute myeloid leukemia (AML) or multiple myeloma (MM).

The first patient suffers from AML. This Phase I trial is a dose escalating study. Following the infusion of the first dose of NKG2D CAR T-cell, no safety issues were reported with the treatment over the follow-up period of 30 days. This marks an important step in demonstrating the safety of NKG2D CAR-T cell infusion at that dose and triggers the enrollment of the next two patients in the first dose cohort.

Dr. Christian Homsy, CEO of Celyad, commented, “At 30 days post NKG2D CAR-T cell infusion for this first patient, no safety issues were reported. This is a great milestone in validating our new CAR T-cell platform. We look forward to recruiting of the remaining patients in this first dose cohort.”

The full data readout from the Phase I trial is expected in mid-2016. The trial is designed to assess the safety and feasibility of NKG2D CAR T-cell as primary endpoints, with secondary endpoints including clinical efficacy.

The NKG2D CAR T-cell is an autologous chimeric antigen receptor T lymphocyte (CAR T-cell) therapy constructed using the native sequence of natural killer cell (NK cell) receptors which, unlike traditional CAR technologies such as those targeting the CD19 antigen, has the potential to target a broad range of solid tumors and blood cancers by targeting ligands present on numerous types of cancer cells. The research underlying this technology was originally conducted at Dartmouth College by Professor Charles Sentman, and has been published in numerous peer-reviewed publications such as Journal of Immunology, Cancer Research and Blood. 

Cardio3 BioSciences Announces Infusion of First Patient in NKG2D Phase I Trial with no short term adverse events.

• No short term on-target, off-tumor toxicity observed to date in first patient following single dose NKG2D CAR T-cell infusion; marks an important step in therapy evaluation.
• Staggered enrolment of 2 additional patients to be expected after a 30 day follow-up observation of the initial patient.
• The trial is a dose escalation study evaluating safety and feasibility of a CAR T-cell therapy in patients with acute myeloid leukemia or multiple myeloma.

Mont-Saint-Guibert, Belgium – Cardio3 BioSciences (Euronext Brussels and Paris: CARD), soon to be renamed Celyad, a leader in engineered cell-therapy treatments today announced the infusion of the first patient enrolled in the Company’s Phase I clinical trial evaluating the safety and feasibility of its NKG2D CAR T-cell therapy, in cancer patients suffering from acute myeloid leukemia (AML) or multiple myeloma (MM).

This Phase I trial is a dose escalating study. Following the infusion of the first dose of NKG2D CAR Tcell, there were no short term adverse events observed in that patient. A pre-defined, staggered enrolment of two additional patients at the same dose level is expected to occur after an additional 30-day safety assessment of the first infused patient.

Dr. Christian Homsy, CEO of Cardio3 BioSciences, commented: “The infusion of the first patient enrolled in our initial Phase I trial evaluating NKG2D CAR T-cell marks a significant milestone in developing our immuno-oncology program. Once the preliminary 30 days safety evaluation will have been completed, we expect to continue enrolment in the study to further evaluate the therapy’s safety and hopefully efficacy. We believe NKG2D CAR T-cell could emerge as a new and viable treatment option for patients with a broad range of cancer types, with potential application in patients with haematological malignancies and beyond.”

Dr. Vincent Brichard, Vice President Immuno-oncology of Cardio3 BioSciences, added: “The absence of short term adverse events of NKG2D CAR T-cell observed in the first days following infusion of the first patient is an important step in the initial evaluation of the safety profile of the therapy. According to the trial design, this first patient will be monitored closely over the next 30 days before we expand enrolment to two additional patients at the same dose level, followed by the next dose level with a second cohort of patients. This dose-escalation trial is expected to enrol a total of approximately 24 patients and we look forward to providing updates as the trial advances.”

The Phase I trial, anticipated to be completed in mid-2016, is assessing the safety and feasibility of NKG2D CAR T-cell as primary endpoints, with secondary endpoints including clinical efficacy.

NKG2D CAR T-cell is an autologous chimeric antigen receptor T lymphocyte (CAR T-cell) therapy constructed using the native sequence of natural killer cell (NK cell) receptors which, unlike traditional CAR technologies such as those targeting the CD19 antigen, has the potential to target a broad range of solid tumors and blood cancers by targeting ligands present on numerous cancer types. The research underlying this technology was originally conducted at Dartmouth College by Professor Charles Sentman, and has been published in numerous peer-reviewed publications such as Journal of Immunology, Cancer Research and Blood.

Mont-Saint-Guibert, Belgium – Cardio3 BioSciences (C3BS) (Euronext Brussels and Paris: CARD), a leader in engineered cell-therapy treatments with clinical programs initially targeting indications in cardiovascular disease and oncology, today announced the enrollment of the first patient in a Phase I clinical trial evaluating the Company’s lead CAR T-Cell therapy, NKG2D CAR T-Cell, in blood cancer patients with acute myeloid leukemia (AML) or multiple myeloma (MM). Cell engineering and processing will be followed in the coming days by the infusion of NKG2D CAR T-Cells into the patients.

NKG2D CAR T-Cell is an autologous chimeric antigen receptor T lymphocyte (CAR T-cell) therapy constructed using the native sequence of non-engineered natural killer cell (NK cell) receptors which, unlike traditional CAR technologies such as those targeting the CD19 antigen, have the potential to target a broad range of solid tumors and blood cancers by targeting ligands present on numerous cancer types. We believe that NKG2D CAR T-Cell is a potential new treatment option for patients with solid tumors such as breast, colorectal, lung, liver, ovarian and bladder cancer, in addition to the blood cancers targeted in this trial. The research underlying this technology was originally conducted at Dartmouth College by Professor Charles Sentman, and has been published in numerous peer-reviewed publications such as Journal of Immunology, Cancer Research and Blood.

NKG2D CAR T-Cell received an Investigational New Drug (IND) clearance, under the name CM-CS1, from the U.S. Food and Drug Administration (FDA) in July 2014 for the Phase I clinical trial in hematologic cancers.

Dr. Christian Homsy, CEO of Cardio3 BioSciences, commented: “We are extremely pleased to initiate enrollment of the first Phase I trial of our CAR T-Cell therapy program with lead product candidate NKG2D CAR T-Cell, in-line with our previously disclosed clinical development plan. As AML and MM are two underserved blood cancer subtypes, there is a clear need for new, viable treatment options. To date, NKG2D CAR T-Cell therapies have demonstrated the prevention of tumor development and increased survival in preclinical animal models, suggesting that NKG2D CAR T-Cell has the potential to be one such therapy.”

This trial is assessing the safety and feasibility of NKG2D CAR T-Cell as primary endpoints, with secondary endpoints including clinical efficacy. Cardio3 BioSciences expects to complete the study in mid-2016 and will provide updates as the trial advances.

Cardio3 BioSciences receives USPTO Notice of Allowance for first U.S. patent broadly covering TCR-deficient T-Cells engineered to express a chimeric antigen receptor 

Mont-Saint-Guibert, Belgium – Cardio3 BioSciences (C3BS) (Euronext Brussels and Paris: CARD), a leader in engineered cell therapies with clinical programs initially targeting indications in cardiovascular disease and oncology, today announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for a significant patent application covering T-Cell receptor (TCR)-deficient TCells which are engineered to express a chimeric antigen receptor (CAR). This patent application is the first allowed application in a series of filed patent applications augmenting the Company’s protection for its allogeneic T-Cell technology. The Company has applied for additional patents related to this technology, which are in various phases of USPTO review.

Allogeneic technology has the potential to optimize CAR T-Cell cancer immunotherapies by enabling the manufacturing of off-the-shelf cell products for the treatment of patients without the need for a genetic match.

The allowed patent application complements and directly strengthens Cardio3 BioSciences’ intellectual property portfolio in the CAR T-Cell field. The claims of the allowed application broadly cover isolated TCR-deficient T-Cells (those lacking functional TCRs), which have been further engineered to express a non-TCR receptor, i.e., a ligand binding moiety attached to an immune signalling moiety. We believe the allowed claims will provide valuable protection for the Company as they are not limited to specific methods of generating allogeneic T-Cells, such as genome editing and genetic engineering. The Company believes that this allowed patent application will be an important element of an IP portfolio covering development of allogeneic CAR T-Cells and their use in various immunotherapies.

This allowed patent application, U.S. Application No. 13/502,978, is part of a larger patent portfolio owned by Dartmouth College and exclusively in-licensed by Cardio3 BioSciences through its acquisition of OnCyte, announced on January 6, 2015. 

Dr. Christian Homsy, CEO of Cardio3 BioSciences, commented: “We are extremely pleased to have received the Notice of Allowance from the USPTO for this patent application for TCR-deficient T-Cells engineered to express a CAR, and we are actively pursuing coverage in other countries. To our knowledge, this patent application is the first allowed application regarding TCR-deficient T-Cells suitable for use in allogeneic T-Cell therapies, and we are not aware of any other technology in development for the manufacture of allogeneic T-Cells. Furthermore, the patent provides broad protection because it is not limited to specific methods of generating allogeneic T-Cells, such as genome editing and genetic engineering.”

Dr. Homsy continued: “Our allogeneic T-Cell platform constitutes a high value asset in our portfolio and we look forward to continuing the development of this platform, for which we expect to have our first T-Cell allogeneic CAR T-Cells entering the clinic in late 2016 or early 2017. We believe that with the acquisition of OnCyte, we have the right technology to enter this highly competitive and promising field.”

Cardio3 BioSciences’ pipeline includes autologous CAR T-Cell therapies that have the potential to target a broad range of solid tumours and blood cancers. The Company’s lead oncology product, CAR-NKG2D, is an autologous therapy expected to enter a Phase I clinical trial in certain hematologic cancers in the second quarter of 2015, which follows the receipt by OnCyte of an Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) in July 2014.

The Company’s allogeneic T-Cell platform has the potential for broad-based application, as it not only applies to the Company’s CAR product candidates, but can also be applied to generate allogeneic CAR TCell therapies from external CAR technologies that are currently in development.

Dr. Charles Sentman, Professor of Microbiology and Immunology and Director, Center for Synthetic Immunity, Geisel School of Medicine, Dartmouth College, and lead developer of Cardio3 BioSciences’ allogeneic CAR T-Cell platform technology, remarked: “In developing this allogeneic CAR T-Cell platform, we address a significant unmet medical need by enabling the potential manufacturing of off-the-shelf, ready-to-use immunotherapy cells for the treatment of many cancer patients. In addition, this technology is applicable to both existing and new CAR therapies, meaning that current autologous therapies may be converted to allogeneic treatments and manufactured for broad use.”

The DSMB (Data Safety and Monitoring Board), a committee composed of international independent experts, unanimously recommends continuing the study according to the original protocol, after having analyzed safety data relating to C-Cure® and C-Cathez® in the ongoing Phase III clinical trial conducted in Europe and Israel

Mont-Saint-Guibert, Belgium – Cardio3 BioSciences SA (C3BS) (NYSE Euronext Brussels and NYSE Euronext Paris: CARD), leader in the discovery and development of regenerative, protective and reconstructive therapies for the treatment of cardiac diseases, today announces it has received the recommendation of the Data Safety and Monitoring Board (DSMB) to continue the CHART-1 clinical trial according to the original protocol. The recommendation is based on a planned analysis performed on all patient safety data available as per mid-August 2014.

The Data Safety and Monitoring Board is an independent committee composed of independent international experts in charge of safety evaluation of C-Cure® and C-Cathez® in the CHART-1 Phase III clinical trial currently underway in several countries in Europe and in Israel. The DSMB analyzed safety data 1-month post treatment of all patients randomized in the trial.

The CHART-1 (Congestive Heart failure Cardiopoietic Regenerative Therapy) trial represents the world’s first Phase III trial for a pre-programmed cellular therapy for the treatment of heart failure.

The members of the DSMB approved unanimously the continuation of the trial having concluded that one month post treatment, C-Cure® and C-Cathez® shows no safety issue that compromises the continuation of the CHART-1 Phase III study.

Dr Christian Homsy, CEO of Cardio3 BioSciences, said: “We are very pleased by the unanimous recommendation of the DSMB to continue to pursue CHART-1. This planned analysis is a significant step in our Phase III program and the positive outcome confirms all the confidence placed in the trial by our partners and investors. CHART-1 continues to progress well and the positive view of the DSMB will add further impetus to recruitment which we look forward to completing on schedule by the end of 2014.”

The Phase III trial is a prospective, multi-centre, randomized, sham-controlled, patient-and evaluator-blinded study comparing treatment with C-Cure® to a sham treatment. The trial will recruit a minimum of 240 patients with chronic advanced symptomatic heart failure. The primary endpoint of the trial is a composite endpoint including mortality, morbidity, quality of life, Six Minute Walk Test and left ventricular structure and function at nine months post-procedure.