Celyad's CAR-T Candidate Delivers in Early Stage Study

Celyad recently announced that first data analysis of the NKR-2 Phase I trial shows encouraging results. The NKR-2 Phase I trial is a single infusion, dose escalation study evaluating the safety and feasibility of NKR-2 T-cells in Acute Myeloid Leukemia and Multiple Myeloma patients. This study was completed in September 2016 with a successful safety follow-up for all dose level cohorts. There were no cases of cytokine release syndrome, cell-related neurotoxicity, auto-immunity, or CAR-T related death.

Dr. Christian Homsy, CEO of Celyad, commented “NKR-2 Phase I trial was a safety study with the primary objective of ensuring that there was no on-target, off-tumor toxicity. We are positively surprised at reports of unexpected clinical benefit, while testing just one single infusion dosed between 50 and 1,000 times lower than our expected efficacious dose extrapolated from animal experiments. Our exceptionally strong animal data was obtained with three injections of human equivalent doses of 1 to 2 billion cells per injection, while the highest dose tested in the NKR-2 study was 30 million cells in a single infusion. These results are therefore encouraging, and we look forward to triggering the next phase of our NKR-T program once European agencies and the FDA have approved our THINK trial protocol.”

Dr. Frédéric Lehmann, VP Immuno-Oncology at Celyad, added “We are excited to present these data at ASH and to explore the full potential of our NKR-2 autologous therapy in our next development phase. The THINK trial will evaluate the clinical activity and safety in seven indications, in both hematologic malignancies and solid tumors. It is our hope that this study will be the foundation of a robust approach to treating patients with advanced tumors.”

Dr. David Gilham, VP Research and Development at Celyad, said “NKR-2 CAR T cell therapy was designed to act like a drug with short-term persistence and multiple injections in order to provide a better controlled and more predictable safety profile than that of other traditional CAR-T products. The primary objective is to avoid uncontrolled in-vivo cell expansion and long-term persistence, thereby replacing this paradigm with well controlled pharmacokinetics. We are re-assured to note that the safety outcome of this Phase I study confirms the pre-clinical animal data generated to date.”

Celyad is a clinical-stage biopharmaceutical company focused on the development of specialized cell-based therapies. The company utilizes its expertise in cell engineering to target severe diseases with significant unmet need, including cancer. Celyad’s Natural Killer Receptor based T-Cell (NKR-T) platform has the potential to treat a broad range of solid and liquid tumors. Its lead oncology candidate, NKR-2, has been evaluated in a single dose escalation Phase I clinical trial to assess the safety and feasibility of NKR-2 T-cells in patients suffering from AML or MM. In addition, Celyad has completed a Phase III trial in the EU for its C-Cure cardiovascular disease candidate in ischemic heart failure. Celyad was founded in 2007 and is based in Mont-Saint-Guibert, Belgium, and Boston, MA. Celyad’s ordinary shares are listed on the Euronext Brussels and Euronext Paris exchanges, and its American Depository Shares are listed on NASDAQ Global Market, all under the ticker symbol CYAD.

For more information about Celyad, visit www.celyad.com.

Celyad is developing a unique Natural Killer Receptor (NKR) based T-Cell platform to target a wide range of solid and hematological tumors. Unlike traditional CAR-T cell therapy, which target only one tumor antigen, Natural Killer (NK) cell receptors enable a single receptor to recognize multiple tumor antigens.

Celyad’s lead candidate, NKR-2, is a T-Cell engineered to express the human NK receptor, NKG2D, which is an activating receptor that triggers cell killing through the binding of NKG2D to any of eight naturally occurring ligands that are known to be overexpressed on more than 80% of tumors.

Preclinical results indicate that NKR-2 has multiple mechanisms of actions and goes beyond direct killing by signifying that its encoded T-Cells attack the tumor cells, inhibits the mechanisms that enable tumors to evade the immune system, activates and recruit anti-tumor immune cells and disrupts the blood supply to the tumor. These mechanisms promote the induction of adaptive immunity, meaning the body develops a long-term cell immune memory against specific tumor antigens of the targeted tumor.

In contrast to traditional CAR-T therapeutic approaches, and based on strong preclinical evidence, Celyad’s current NKR-2 program does not employ patient lympho-depleting pre-conditioning, thereby avoiding the toxicities associated with chemotherapy and allowing the immune system to remain intact.

Celyad is developing both autologous and allogeneic NKR-2 administrations. For autologous NKR-2, Celyad collects the patient’s own T-Cells and engineers them to express NKG2D in order to target cancer cells effectively. Celyad’s allogeneic platform engineers the T-Cells of healthy donors, that also express TCR Inhibitory Molecules (TIMs), to avoid having the engineered donor cells be rejected by the patient’s normal tissues (also called Graft vs. Host Disease).

The preclinical research underlying this technology was originally conducted at Dartmouth College by Dr. Charles Sentman and has been published extensively in peer-reviewed publications.