Immuno-oncology

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, with clinical programs in cardiovascular disease and immuno-oncology, today announced the issuance of United States Patent No. 9,273,283 (“US Patent 9,273,283”) relating to a method of producing allogeneic primary human T cells that are engineered to be T-Cell Receptor (TCR)-deficient and express a Chimeric Antigen Receptor (CAR).

The US Patent 9,273,283 is the second patent of Celyad allogeneic intellectual property portfolio that is awarded by the United States Patent and Trademark Office (USPTO). The first US patent (9,181,527) – that was granted to Celyad in November 2015 – was related to TCR deficient CAR T cells, regardless of the method used to generate them. This new patent strengthens Celyad’s coverage for its proprietary CAR T cells by adding broadly protecting methods for making these modified allogeneic T cells, and providing them as medicines. The resulting products may benefit patients with various human disease conditions and particularly cancer. By this reinforcement of the Company’s patent portfolio in the CAR-T field, Celyad confirms its leadership in engineered cell therapy, and in the allogeneic CAR T space.

Allogeneic technology has the potential to broaden the therapeutic applications of CAR T-Cell immunotherapies as it does not depend on cells derived from the patient.

Dr. Christian Homsy, CEO of Celyad: “We are pleased to have obtained this new patent. To our knowledge, this is the first patent covering a method of producing allogeneic TCR-deficient CAR T-cells and administering them to patients. Thanks to the combination of this patent with the US Patent 9,181,527 that we received a few months ago, we have a strong patent portfolio covering key elements in the allogeneic TCR-deficient CAR T-cells production value chain. We intend to maximize the significant potential of our allogeneic CAR T-cells platform internally and externally through strategic collaborations and partnerships”.

Dr. Peter de Waele, VP R&D and Intellectual Property at Celyad: “Obtaining this patent once again illustrates not only the innovative approach of our NKR-T cell platform, but also our proprietary independence. It provides support for our continuous efforts developing promising allogeneic effective therapies, improving process efficiency and broadening availability significantly”.

Celyad currently has pre-clinical studies underway to develop allogeneic cancer therapies by using a TCR Inhibitory Molecule, or “TIM^TM”, in combination with a next generation CAR construct that incorporates a Natural Killer Receptor, or “NKR”. This proprietary process results in a TCR-deficient NKR T-Cell aimed at eliciting no or a greatly reduced graft- versus-host-disease (GVHD) response.

• The trial is a dose escalation study evaluating safety and feasibility of T-cell Natural Killer Receptor NKG2D in patients with acute myeloid leukemia or multiple myeloma.
• No dose limiting toxicity reported of the last patient of the second dose level.
• First patient of third dose level (10^7 cells) started cell processing.

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, with clinical programs in cardiovascular disease and immuno-oncology, today announced the completion of the 21-day safety follow-up of the last patient enrolled in  the second dose level in the Phase I/IIa clinical trial evaluating the safety and feasibility of its NKR-2 T-cell therapy using T-cells with NKG2D receptor in cancer patients suffering from acute myeloid leukemia (AML) or multiple myeloma (MM).

Dr. Christian Homsy, CEO of Celyad, said: “The NKR-2 Phase I trial is progressing well. No product related safety issue were reported since the beginning of the trial. We look forward to treating the next patient who will be the first of the third dose cohort”.

Dr. Frédéric Lehmann, Head of Immuno-oncology at Celyad, added: “We are pleased of the progression of this study which remains encouraging so far with no safety issue reported and a good enrolment of patients along the first two cohorts. We are grateful to our Phase 1 investigators at the Dana Farber Cancer Institute for their work to achieve this milestone”.

NKR stands for Natural Killer Receptor. NKG2D CAR T-cells are now called NKR-2 T-cells and the product development name is NKR-2.  

Existing CAR-T cells are engineered using constructs encoding an antibody single chain variable fragment, the signalling domain of CD3 zeta and one or more co-stimulatory domain(s).  While very favourable outcomes have been presented using CD19 based constructs, current CAR-T target a limited set of cancers.  NKR-2 was generated by fusion of the native human NKG2D receptor gene with the human CD3 zeta cytoplasmic signalling domain and uses the natural co-stimulatory molecule DAP10. This new generation construct allows the targeting of a much broader set of cancers via the recognition of eight well characterized NKG2D ligands, MICA, MICB and ULBP 1-6. Those ligands are expressed on most blood and solid tumors.

The Phase I trial is designed to assess the safety and feasibility of NKR-2, in two different haematological indications.  The safety follow-up period post-infusion has been decreased to 21 days after approval by the U.S. Food and Drug Administration (FDA) and Institutional Review Board (IRB).  Data readouts from the first 12 patients treated in the Phase I portion are expected in mid-2016, once a recommended dose is determined.

• No dose limiting toxicity related to the investigational treatment reported at 30 days post treatment of the first patient of the second dose-level;
• 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 – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, with clinical programs in cardiovascular disease and immuno-oncology, today announced the completion of the 30-day safety follow-up of the first patient enrolled in  the second cohort in the 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).

Dr. Christian Homsy, CEO of Celyad, said: “The NKG2D CAR T-Cell Phase I trial is progressing well. No safety issue were reported since the beginning of the trial. We look forward to recruiting the next patients in this second dose cohort”.

Dr. Frédéric Lehmann, Head of Immuno-oncology at Celyad, added:“Our NKG2D CAR T-Cell Phase I study is advancing at a nice pace and according the initial plans. No safety issue were reported after the first dose cohort and the second one knows a good start. I am grateful to our Phase 1 investigators who have positioned us so well for this milestone”.

The Phase I/IIa trial is designed to assess the safety and feasibility of NKG2D CAR T-Cells, with secondary endpoints including clinical activity in two different haematological indications.  Data readouts from the first 12 patients treated in the Phase I portion are expected in mid-2016. Once the recommended dose is determined, the IIa phase of the trial will enroll 12 additional patients.

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, with clinical programs in cardiovascular disease and immuno-oncology, today announced the infusion of the first patient of the second cohort of its Phase I clinical trial evaluating the Company’s NKG2D CAR T-Cell therapy in acute myeloid leukaemia (AML) and multiple myeloma (MM) indications.  

Dr. Christian Homsy, CEO of Celyad, said: “The treatment of the first patient enrolled in the second cohort of our first-in-man Phase I trial evaluating NKG2D CAR T-Cells demonstrates continued progress in developing our lead immune-oncology program. Once the safety evaluation is complete, we expect to continue enrolment in the study to further evaluate the therapy’s safety and to determine an appropriate dose. Due to its unique ability to target ligands present on most cancers, we believe our NKG2D CAR T-Cells have potential as a new treatment option for patients with a broad range of cancer types, including haematological malignancies and various solid tumours.”

Dr. Frédéric Lehmann, Vice President of Immuno-Oncology at Celyad, added: “We are proud to have advanced our first NKG2D CAR T-Cell Phase I study so rapidly. I am grateful to our dedicated investigators at Dana Farber Cancer Institute and look forward to completing enrolment in this important trial. Celyad continues to be committed to developing immune-oncology CAR-T programs that should provide clinically meaningful benefit for patients.

The Phase I/IIa trial is designed to assess the safety and feasibility of NKG2D CAR T-Cells, with secondary endpoints including clinical activity.  Data readouts from the first 12 patients treated in the Phase I portion are expected in mid-2016. Once the recommended dose is determined, the IIa phase of the trial will commence, with 12 additional patients treated at the recommended dose.

• No treatment-related safety issues reported at 30 days post-treatment of all patients in first cohort of the trial following single dose NKG2D CAR T-Cell infusion
• Triggers enrolment of first patient of the second cohort
• Expanding trial to include sites at renowned cancer research centers in U.S.

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, with clinical programs in cardiovascular disease and immuno-oncology, today announced the completion of the 30-day safety follow-up of the final patient enrolled in the first cohort of 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 aims to assess the infusion of four escalating doses of NKG2D CAR T-Cells in four consecutive patients cohorts of three patients each. Following infusion of the first dose of NKG2D CAR T-cells to the three patients of the first cohort (2 AML and 1 MM), no treatment related safety issues were reported with the treatment over the follow-up period of 30 days.

Dr. Christian Homsy, CEO of Celyad, commented, “These data mark an important step in demonstrating the safety of NKG2D CAR T-Cells infusion at single dose levels and allows us to initiate the enrolment of new patients for the second cohort of the trial. In order to boost enrolment of these new patients and also enable an extensive evaluation of this innovative approach, Celyad is extending the trial network to additional sites at renowned clinical sites in the U.S.

“These results, in addition to the positive outcome of the 30-day safety follow-up of the first patient reported last June and the recent completion of important milestones in Celyad’s
C-Cure^® and NKG2D CAR T-Cell programs, give us further confidence in our ability to achieve our clinical development objectives for our novel pipeline.”

Dr. Frédéric Lehmann, VP Immuno-Oncology of Celyad,added: “This is the first time that our technology platform, which Celyad acquired in January 2015, has been tested in human subjects. The safety results to-date are encouraging for the future of the NKG2D CAR T-Cell program and we believe we are well positioned to continue our clinical programs in immuno-oncology on schedule.”

The full data readout from the Phase I trial focusing on 12 patients 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.

Fundamental IP has potential broad applicability for development of TCR deficient CAR-T therapies 

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, with clinical programs in cardiovascular disease and immune-oncology today announced the issuance of United States Patent No. 9,181,527 (“US Patent 9,181,527”) relating to allogeneic human primary T-Cells that are engineered to be T-Cell Receptor (TCR)-deficient and express a Chimeric Antigen Receptor (CAR).

The US 9,181,527 Celyad Allogeneic Patent significantly strengthens Celyad’s patent portfolio in the CAR T-Cell field and its leadership in engineered cell therapy since the granted product claims are not limited to specific CARs or specific methods of generating allogeneic CAR T- Cells, such as genome editing or genetic engineering. The patented products are applicable for use in treating various human disease conditions such as cancer, chronic infectious diseases, and autoimmunity.

Allogeneic technology has the potential to broaden the therapeutic applications of CAR T-Cell immunotherapies by enabling the development and manufacturing of “off-the-shelf” treatments.

Dr. Christian Homsy, CEO of Celyad, commented: “We are pleased to have obtained the 9,181,527 Patent from the United States Patent and Trademark Office (USPTO) for allogeneic T-Cells engineered to express a CAR, and we are pursuing patents in other geographies as well. To our knowledge, this is the very first patent covering TCR-deficient CAR T-Cells. The Company intends to maximize the significant therapeutic potential of our allogeneic CAR-T technology platform, either on our own or potentially through one or more strategic collaborations.”

Dr. Frederic Lehmann, VP Immuno-Oncology, added: “Our current autologous NKG2D oncology clinical trial is going well and we look forward to potentially following this with an allogeneic platform into the clinic. This technology has applications beyond cancer and allows us to explore other diseases such as autoimmune disorders and chronic infections.” 

Celyad currently has pre-clinical studies underway to develop allogeneic cancer therapies by using a TCR Inhibitory Molecule, or “TIM”, in combination with a next generation CAR construct that incorporates a natural killer receptor. This proprietary process results in an off-the-shelf “weaponized” TCR-deficient NK CAR T-Cell aimed at eliminating or greatly reducing graft- versus-host-disease (GVHD).