Immuno-oncology

Mont-Saint-Guibert, Belgium – Celyad SA/NV (EURONEXT Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of CAR-T cell therapies, today announces the initiation of the SHRINK trial, a third clinical trial with our lead product candidate CYAD-01 (CAR-T NKG2D) targeting metastatic colorectal patients.

• SHRINK study to evaluate the synergetic effect of the concurrent administration of CYAD-01 (CAR-T NKG2D) with standard chemotherapy in patients suffering from metastatic colorectal cancer

SHRINK (Standard CHemotherapy Regimen and Immunotherapy with NKR-2) is an open-label Phase I study evaluating the safety and clinical activity of multiple doses of CYAD-01, administered concurrently with the neoadjuvant FOLFOX treatment in patients with potentially resectable liver metastases from colorectal cancer.

Dr. Christian Homsy, CEO of Celyad commented: “We are happy to start the SHRINK trial as it will allow us to evaluate the efficiency of our promising CYAD-01 therapy in combination with chemotherapy. We are confident that our partnership with key Belgian cancer institutions will provide us with new insights in the treatment of metastatic colorectal cancer. Today’s announcement, in conjunction with our ongoing THINK trial and the upcoming LINK study, reaffirms our commitment and dedication to beat cancer with a strong focus on solid tumors.”

Dr. Frédéric Lehmann, VP Clinical Development and Medical Affairs at Celyad added: “As leaders in our field, it is our task to further develop the potential of our CAR-T treatments. Starting SHRINK is another important milestone for us and for patients worldwide, evaluating the synergetic effect of the concurrent administration of our lead candidate CYAD-01 with standard chemotherapy as first-line treatment for metastatic colorectal cancers. We now look forward to the first infusion of a colorectal patient in the coming weeks and to the registration of other patients. The SHRINK study is one of the new Celyad studies to be initiated in 2017 as part of a global comprehensive clinical program supporting the development of our CYAD-01 candidate.”

SHRINK will be conducted in Belgium in key oncology centers. It contains a dose escalation and an extension stage. The dose escalation design will include three dose levels adjusted to body weight: up to 3×10⁸, 1×10⁹ and 3×10⁹ of CYAD-01. At each dose, the patients will receive three successive administrations, two weeks apart at the specified dose. The dose escalation part of the study will enroll up to 18 patients while the extension phase would enroll 21 additional patients.

The colorectal cancer indication evaluated in the SHRINK trial was selected based on evidence generated in the pre-clinical settings and in the ongoing THINK study.

SHRINK is Celyad’s third clinical trial of its CYAD-01 product candidate, a CAR-T cell therapy using NKG2D ligands as a target. The two other trials are CM-CS1 (completed) and THINK (ongoing).

Mont-Saint-Guibert, Belgium – Celyad SA (EURONEXT Brussels and Paris: CYAD – NASDAQ Global Market: CYAD), a leader in the discovery and development of CAR-T cell therapies, today announces it has published a special report in the peer-reviewed journal “Future Oncology” summarizing pre-clinical work undertaken on NKR-2, the CAR-T cell therapy currently tested in the company’s THINK trial.

• Review of NKR-2 preclinical work published in Future Oncology
• In vitro efficacy on various cancer models
• In vivo evidence of efficacy in a human pancreatic model

Celyad’s special report entitled Exploiting Natural Killer Group 2D Receptors for CAR-T cell therapy discloses new results confirming the potency of CAR-T NKR-2 cells against various human cancer cell lines in vitro including leukemia, colorectal and pancreatic cancer.  Furthermore, new data show the ability of CAR-T NKR-2 cells to effectively challenge established pancreatic cancer xenografts in humanized mouse models.

These pre-clinical studies were performed with Celyad’s long-term collaborator Professor Charles Sentman and further confirm the choice of indications being investigated in the ongoing THINK trial.

Dr. David Gilham, VP of Research & Development at Celyad: “This publication provides important additional pre-clinical evidence supporting the range of cancer indications being explored in the THINK trial. This is an example of our on-going work to further define and understand the mechanisms of action of CAR-T NKR2 cells that will provide greater insight to support our developing clinical program.”

Dr. Christian Homsy, CEO of Celyad: “We are pleased to provide further pre-clinical evidence validating our approach in the THINK trial, in which we aim to demonstrate the potential of CAR-T NKR-2 cells as a disruptive technology in the treatment of cancer.”

Celyad’s special report is available on Future Oncology’s website: http://www.futuremedicine.com/doi/abs/10.2217/fon-2017-0102

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered CAR-T cell therapies, today announces promising early clinical results at the 3-month follow-up of the first dose-level in the solid tumor arm of the THINK trial (THerapeutic Immunotherapy with CAR-T NKR-2).

• Two metastatic colorectal cancer patients reported as Stable Disease at 3-month follow-up
• No toxicity signals reported  up to now

At the first 3 x 10⁸ cell dose-level administered to a total of three patients with metastatic cancer, the two colorectal cancer (mCRC) patients, who were progressing after at least two prior chemotherapy regimens, achieved a confirmed Stable Disease (SD) according to RECIST criteria at three months. According to recent studies conducted on similar patient populations, median progression free survival in these patients under standard of care is between 1.9 and 3.2 months. The third patient, a refractory pancreatic patient, was in progression at the same time point. No toxicity signals were observed in any of the patients.

Christian Homsy, CEO of Celyad comments: “We are pleased to have observed these encouraging preliminary results in such a late stage population. Despite being dosed only at a tenth of the expected efficacious dose based on animal experiments, the results show a stabilization of the disease. We look forward to the next stages of the trial.”

Dr. Frédéric Lehmann, Vice President Clinical Development and Medical Affairs at Celyad adds: “These early results in the two heavily pre-treated mCRC patients are encouraging, considering the dismal clinical outcome of the existing standard of care for this refractory patient population. Based on these preliminary results, we look forward to progressing our clinical development plan, including higher doses and longer follow-up in the THINK study, as well at starting the SHRINK (CAR-T NKR-2 cells in combination with chemotherapy) and LINK (loco-regional administration) clinical trials shortly.”

Patients in the second dose of the solid tumor arm (1 x 10⁹) are currently being enrolled and treated. CAR-T NKR-2 cells have so far showed a safety profile that could allow an outpatient clinical approach.

The hematological cancer dose escalation arm, including relapsing/refractory Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) patients, is progressing. The first dose patients have been registered and are being treated with no toxicity signals to date.

The THINK trial, conducted in the US and in Europe, includes two stages: a dose escalation and an extension stage. The dose escalation is being conducted in parallel in solid cancers (colorectal, pancreatic, ovarian, triple negative breast and bladder) and in hematologic (AML and MM) cancer groups, while the extension phase will evaluate in parallel each tumor type independently. The dose escalation design includes three dose levels adjusted to body weight: up to 3×10⁸, 1×10⁹ and 3×10⁹ NKR-2 CAR T-cells. At each dose, the patients receive three successive administrations, two weeks apart, of NKR-2 CAR T-cells at the specified dose.

NKR-2 CAR T-cell therapy was designed to act as a targeted therapy with short term persistence and multiple injections in order to provide a better controlled and more predictable safety profile. The primary objective is to avoid uncontrolled in vivo cell expansion and long-term persistence thereby replacing this paradigm with well controlled pharmacokinetics. 

Mont-Saint-Guibert, Belgium – Celyad(Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, today announced the issuance of United States Patent No. 9,663,763 relating to Celyad’s method of treating cancer by administering allogeneic primary human T cells that are engineered to be T-Cell Receptor (TCR)-deficient and to express a chimeric antigen receptor (CAR).

US Patent 9,663,763 was examined under the Cancer Immunotherapy Pilot Program, also known as the “Patents 4 Patients” initiative, and is the third patent in Celyad’s allogeneic intellectual property portfolio awarded by the United States Patent and Trademark Office (USPTO). This new patent claims specifically methods of treating cancer patients with allogeneic TCR-deficient CAR-T immunotherapies. Earlier patents were related to the allogeneic TCR-deficient CAR-T cells per se, and to methods of producing them. The combination of these granted patents strengthens Celyad’s position and further 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. TCR-deficient CAR-T cells are aimed at avoiding or greatly reducing adverse immune reactions (such as a graft- versus-hostdisease (GVHD) response) which would greatly benefit patients.

Dr. Christian Homsy, CEO of Celyad: “We are pleased to have obtained this new patent. The combination of this patent with the earlier granted US Patents consolidates our strong IP position in the CAR-T field and strengthens our IP portfolio covering key elements in the allogeneic TCR-deficient CAR-T cells production value chain.”

Dr. Georges Rawadi, VP Business Development & IP at Celyad:“Allogeneic CAR-T cells are of increasing interest to many Pharma and BioPharma companies involved in cell-based cancer immunotherapies. We are looking to maximize the significant value of our allogeneic CAR-T assets through strategic collaborations and partnerships such as the ones we have established with ONO Pharma and Novartis.”

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ:CYAD), a leader in the discovery and development of engineered cell therapies, today announced the dosing of the first patient of the second dose in the solid tumor arm of its THINK trial (THerapeutic Immunotherapy with NKR-2). This first ovarian cancer patient has been dosed at Roswell Park Cancer Institute (Buffalo, New York).

• Initiation of the THINK trial in the US at Roswell Park Cancer Institute
• Dosing of the first patient of the second dose (1×109 ) in solid tumor arm
• Favorable safety profile reported on all patients treated with CAR-T NKR-2 

At the first solid tumor dose-level, one pancreatic and two colorectal cancer patients were successfully dosed. None of these patients experienced dose limiting adverse events. THINK is a multinational open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 T-cells in seven refractory cancers including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma). These cancer indications were selected based on strong preclinical evidence and NKG2D ligand expression. The THINK trial is being conducted in the US and in Europe. It contains a dose escalation and an extension stage. The dose escalation is conducted in parallel in the solid and liquid cancer groups, while the extension phase will evaluate in parallel each tumor independently.

The dose escalation design includes three dose levels adjusted to body weight: up to 3×10⁸, 1×10⁹ and 3×10⁹ NKR-2 T-cells. At each dose, the patients receive three successive administrations, two weeks apart, of NKR-2 T-cells at the specified dose. “The opening of the first U.S. arm of the THINK study is an exciting milestone, and one we are very proud to contribute to”, said Kunle Odunsi, MD, PhD, FRCOG, FACOG, Deputy Director of Roswell Park Cancer Institute and the co-Principal Investigator leading Roswell Park’s involvement in the international basket trial. “NKR-2 represents a unique approach to CAR Tcell therapy, and we hope that our efforts help to establish a new treatment option that will benefit many people with cancer”. Dr. Odunsi is also Chair of Gynecologic Oncology, M. Steven Piver Professor of Gynecologic Oncology and Executive Director of the Center for Immunotherapy at the Buffalo, N.Y., comprehensive cancer center. 

Dr. Frédéric Lehmann, VP Clinical Development and Medical Affairs at Celyad added: “Preliminary results from the first dose-level are encouraging, further reinforcing the favorable safety profile of NKR-2. The THINK study is progressing very well and we look forward to the completion of the dose-escalation stage of the trial and the initiation of the expansion segments to confirm the encouraging clinical signal seen in our previous Phase I study. The active participation of a first key cancer institute in U.S. with the NKR-2 manufacturing in Europe demonstrates the ability of Celyad to conduct a global clinical development.”

Celyad lead compound in development, CAR T NKR-2, is currently being investigated in a second phase I in several oncology indications,  five solid cancers and two hematological malignancies.

This investigational therapy is based on a unique CAR T construct, with a multi-pronged mechanism of action, which is based on a receptor that can binds to ligands that are expressed in 80% of cancer, which makes CAR T NKR-2 applicable to both hematological and solid cancers. 

Before clinical data are available, Celyad experts developed a White Paper that describes the technology and early clinical development of the CAR T NKR-2 platform and elucidates its fundamental differences with classical CAR-T technologies, which could reshape the frontiers of cell-based cancer immunotherapy.

Click here to access the fully referenced White paper

About Celyad
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 cancer. Celyad’s Natural Killer Receptor based T-Cell (NKR-T) platform has the potential to treat a broad range of solid and hematologic tumors. Its lead oncology candidate, the CAR-T NKR-2, has been evaluated in a single dose escalation Phase I clinical trial to assess the safety and feasibility of CAR-T NKR-2 cells in patients suffering from AML or MM. This Phase I study was successfully completed in September 2016. Celyad was founded in 2007 and is based in Mont-Saint-Guibert, Belgium, and Boston, Massachusetts. 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, please visit: www.celyad.com