Clinical

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD) a clinical-stage biopharmaceutical company focused on the development of CAR-T cell therapies, today announced the successful injection of the first patients in the SHRINK trial and the LINK trial, both targeting metastatic colorectal patients.

Celyad achieves important milestone in CYAD-01 treatment evaluation of metastatic colorectal cancer: ​

• No toxicity observed to date in first patient enrolled in the SHRINK[1] trial (concurrent administration of CYAD-01 with standard chemotherapy)
• No toxicity observed to date in first patient enrolled in the LINK[2] trial (hepatic transarterial administrations)

Dr. Christian Homsy, CEO of Celyad commented: “The infusion of a first patient in a new trial is always an important moment. CYAD-01, concurrently administered with standard chemotherapy FOLFOX in SHRINK, or administered through hepatic transarterial injections in LINK appears to have been well–tolerated to date. We are particularly satisfied with the lack of on-target/off-tumor toxicity observed to date in the context of the combination of CYAD-01 with chemotherapy. This bolstered our belief that, based on a careful and exhaustive clinical development plan, our product candidate will lead the path towards a therapy for cancer patients.”

After the promising signals of clinical activity of CYAD-01 reported in 2017 and validation of the use of the NKG2D receptor, Celyad designed a clinical development plan which aims at defining the best of the following approaches for CYAD-01 in patients with Acute Myeloid Leukemia (AML) and colorectal (CRC) cancers:

– CYAD-01 as a stand-alone investigational therapy, currently being evaluated in the THINK trial with relapsed refractory AML and CRC patients. Results have already been reported: the world’s first complete response by a CAR-T cell therapy in a patient with refractory and relapsed AML as well as stable diseases reported in colorectal and ovarian cancer patients.

– CYAD-01 administered concurrently with standard of care treatments. The SHRINK trial was initiated with CRC patients earlier in 2018. We expect that the EPITHINK trial will be initiated soon with AML patients.

– CYAD-01 administered after preconditioning of the patients using lymphodepletion. We expect trials in AML (DEPLETHINK AML) and CRC (DEPLETHINK CRC) patients to be initiated in the coming weeks.

Our objective is to continue with the above approach that offers the best observed safety/efficacy profile and to move forward in later phase clinical trials in both AML and CRC indications.

Dr. Frédéric Lehmann, VP Clinical Development and Medical Affairs at Celyad added: “Today’s announcement reflects Celyad’s commitment to develop the potential of CYAD-01 and is the result of our strong collaborations with key academic institutions in both the USA and Europe. Our clinical strategy aims to build on the favorable tolerability profile of CYAD-01 observed to date, and evaluate CYAD-01 in multiple settings to find the best approach for cancer patients. We are making good progress and look forward to sharing further results on SHRINK, LINK and other trials.“

SHRINK is an open-label Phase I trial evaluating the safety and clinical activity of multiple doses of CYAD-01, administered concurrently with the neoadjuvant FOLFOX treatment in patients with resectable liver metastases from colorectal cancer. The dose escalation design of SHRINK includes three dose levels: 1×10⁸, 3×10⁸ and 1×10⁹ of CYAD-01. At each dose, the patients will receive three successive administrations, two weeks apart at the specified dose. No adverse events have been reported in the first injection of the first patient enrolled.

LINK is an open-label Phase I trial evaluating the safety and clinical activity of multiple doses of CYAD-01, adopting a loco-regional approach in treating patients with CYAD-01 administration through multiple hepatic transarterial injections to colorectal cancer patients diagnosed with unresectable liver metastases. The dose escalation design of LINK includes three dose levels: 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. No  adverse events have been reported in the first patient enrolled, who has received his three consecutive CYAD-01 administrations at the first dose level.

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[1] Standard CHemotherapy Regimen and Immunotherapy with NKG2D

[2] Loco-regional Immunotherapy with NKG2D

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell therapies, today announces that first data analysis of the NKR-2 Phase I trial shows encouraging results which will be presented during a poster session at the 58th American Society of Hematology (ASH) Annual Meeting, taking place on December 3-6, 2016, in San Diego, CA.

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. 

Based on recent analysis, encouraging clinical update and correlative analysis, including post-infusion immunophenotyping, will be presented at the poster session of the ASH Annual Meeting:

• Title: Safety Data from a First-in-Human Phase 1 Trial of NKG2D Chimeric Antigen Receptor-T Cells in AML/MDS and Multiple Myeloma (Poster Presentation)
• Abstract: 4052
• Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
• Presentation: Monday, December 5, 2016, 6:00pm – 8:00pm PST
• Location: San Diego Convention Center, Hall GH

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: “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: “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.”

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.”