Press kit. Contact. Nicolas Van Hoecke Director, Investor Relations & Communications t: e:

Transcription

1 Press kit 20 Contact Nicolas Van Hoecke Director, Investor Relations & Communications t: e: 18

2 PRESS KIT JUNE 2018 Table of contents About Celyad...1 Celyad s history... 2 What is cancer?...3 Immunotherapy to treat cancer...5 Celyad s lead drug candidate in immuno-oncology: CYAD Celyad s intellectual property portfolio in immunotherapy...9 Celyad s Senior Leadership Team...10 Appendix: Key Press Releases of Glossary...16

3 About Celyad Celyad, a Belgian biopharmaceutical company, is specialized in the discovery and development of cell therapies aimed at providing therapeutic solutions for patients suffering from severe diseases such as cancer. Active in the field of immuno-oncology, Celyad develops therapies using CAR-T cells, i.e. cells that use the patient s natural immune system to specifically target and destroy cancer cells. The company is currently conducting a Phase I clinical trial (THINK 1 ) to test the dose limiting toxicity of its lead drug candidate CYAD-01 in patients suffering from certain type of solid or hematological tumors. CYAD-01 has a unique cellular construct in which T-cells are genetically engineered to express a receptor of NK cells (the NKG2D receptor) which recognizes 80% of cancers (solid and hematological tumors). CYAD-01 has demonstrated its ability to: Target and destroy cancer cells binding to ligands recognized by the NKG2D receptor Eradicate the tumor s micro-environment and immunosuppressive mechanisms that allow tumors to escape the immune system Create an adaptive cellular memory of the immune system relative to the type of tumor cells eliminated by CYAD-01, thus preventing relapses A first remission has been observed in a patient suffering from Acute Myeloid Leukemia (AML - a type of blood cancer), five months after the first administration of the product and without any other treatment nor preconditioning chemotherapy 2. Celyad has also observed a stabilization of the disease in two patients with colorectal cancer and in a patient with ovarian cancer. Celyad plans to launch two new Phase I clinical trials (SHRINK 3 and LINK 4 ) to explore different approaches (combination with chemotherapy and loco-regional injection) for the treatment of solid tumors. Thanks to a strong portfolio of US patents related to the production and marketing of allogeneic CAR-T cells (from the donor to the patient), Celyad has partnerships with leading players such as Novartis and ONO Pharmaceuticals, and has become a central player actor in the field. Key facts and figures about Celyad As of September 30, 2017, the company had a cash position of 40 million, which should allow the financing of all its programmes through to the first half of Celyad employs 87 people (as of September 30), over whom 84% are dedicated to R&D activities. 1. THINK (THerapeutic Immunotherapy with CAR-T NKG2D) 2. First ever morphologic complete response (MLFS ) with gene-engineered T cells without prior pre-conditioning chemotherapy for a patient with relapsed refractory acute myeloid leukemia (AML). cfr Appendix 1 3. SHRINK (Standard CHemotherapy Regimen and Immunotherapy with CAR-T NKG2D) 4. LINK (Locoregional Immunotherapy with CAR-T NKG2D) CELYAD PRESS KIT JUNE

4 Celyad s history 2007 Creation of Cardio 3 BioSciences, a company specialized in the development of cell therapies to treat ischemic heart failure Cardio 3 BioSciences makes successfully IPO s on Euronext Paris and Euronext Brussels Cardio 3 BioSciences becomes Celyad. The US Patent and Trademark Office (USPTO) grants patent No. 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). Celyad completes IPO on Nasdaq in the US, raising $100.1 m gross proceeds. Acquisition of Oncyte and its portfolio of CAR-T cell therapies using a Natural Killer cell receptor (NK cells) to target several types of cancer The data from the European Phase III trial in cardiology, CHART-1, are published in the European Heart Journal and are presented at the annual congress of the European Society of Cardiology. Celyad signs an exclusive licensing agreement with ONO Pharmaceuticals for the development and commercialization of allogeneic CAR-T NKG2D cells in Japan, Korea and Taiwan January: The Phase I clinical trial THINK (THerapeutic Immunotherapy with CAR-T NKG2D) is initiated in Belgium with the enrollment of a first patient with colorectal cancer. March: The THINK study is initiated in the United States after approval by the Food and Drug Administration (FDA). May: Celyad grants Novartis a non-exclusive license for its patents relating to allogeneic human primary T-Cells that are engineered to be T-Cell Receptor (TCR)-deficient and express a Chimeric Antigen Receptor (CAR). June: Celyad announces first promising clinical results three months after the administration of CYAD-01: the cancer is stabilized in two patients with colorectal cancer and in one patient with ovarian cancer. July: Celyad announces intiation of the SHRINK trial. August: Celyad announces new agreements with Celdara Medical and Dartmouth College. October: Celyad announces a world first by reporting that a complete response has been observed in a patient with acute myeloid leukemia without prior lymphodepletive preconditioning chemotherapy. CELYAD PRESS KIT JUNE

5 Watch the video What is cancer? : our-science/immuno-oncology/ for-non-scientists/cancerimmunotherapy What is cancer? Cancer is a term used to describe a series of more than 200 different but related diseases. Cancer is a disease caused by mutations in the cell DNA. The occurrence of cancer is multifactorial and can be caused by genetic predispositions, exposure to specific environmental hazards, or lifestyle. Cancer cells are abnormal cells that have overcome the barriers that prevent cells from undergoing uncontrolled growth. The immune system can recognize and eliminate such abnormal cells but, occasionally, these cells may develop methods that enable them to escape the immune system. Once cancer cells have defeated our natural immune defenses, they can grow and divide unchecked, spreading into healthy tissues and eventually driving the premature death of the patient. The critical factor for patients is that, while cancer cells - which are abnormal cells - should die, they survive and multiply without control to form tumors. As a tumor grows, some cancer cells can break away from where they first formed and spread to different parts of the body, forming distant tumors (a process that is called metastasis) thereby impacting upon the normal function of affected tissues. Despite significant efforts to improve the ability to detect tumors early in their development, cancer remains one of the leading causes of death worldwide. Key facts and figures about cancer worldwide 5 : February 2017 CELYAD PRESS KIT JUNE

6 Current main therapeutic options for cancer treatment Currently, there are three main treatment options that are used for patients with cancer 6 : Surgery is potentially curative when a tumor can be completely removed. However, for most patients, it is not possible to remove the entire tumor because of infiltration of adjacent tissues, or because the tumor has spread beyond the initial organ. Debulking surgery is sometimes used to reduce the quantity of tumor to relieve specific symptoms but is not curative. Surgery may be used alongside other treatments such as radiation or chemotherapy to reduce tumor bulk before surgery or to reduce the danger of tumor cells escaping to the rest of the body during the surgical process. Chemotherapy is used to kill cancer cells that are growing more rapidly than normal cells of the body. Chemotherapy is used either after surgery ( adjuvant setting ) or to treat cancers that have metastasized to other parts of the body. Typically, combinations of agents are given to enhance the effectiveness of the therapy while combinations with other treatments (such as surgery) are common. Radiotherapy (also called radiation, irradiation or x-ray therapy) uses high-energy particles or waves to destroy cancer cells. Radiotherapy can be used alone or with other treatments. In most instances, chemotherapy or radiotherapy leads to tumor regression although most patients eventually relapse. The genetic instability of the tumor enables it to undergo selection during the treatment process, generally resulting in a relapsing tumor that has increased resistance to the therapy used to treat it initially. Thus, options for patients that relapse after first or second line therapy become increasingly limited. Against this background, the concept of leveraging the immune system to fight cancer or immunotherapy, has emerged. Greater scientific insight into the immune system and the further understanding of the interaction of the immune system with tumor have, in some instances, led to reports of spectacular clinical success. Therapeutic options for patients that relapse after first or second line therapy become increasingly limited. Against this background, the concept of leveraging the immune system to fight cancer or immunotherapy has emerged. Greater scientific insight into the immune system and the further understanding of the interaction of the immune system with tumor have, in some instances, led to reports of spectacular clinical success February CELYAD PRESS KIT JUNE

7 Watch the video: How the immune system fight cancer? : Immunotherapy to fight cancer Reactivating the immune-system to detect and destroy cancer cells with chimeric antigen receptor (CAR) T-cells Immunotherapy is based on the premise that our immune system should recognize and destroy abnormal cells such as cancer cells. However, in some instances, the cancer cells develop mechanisms that allow them to evade the detection of our immune defenses. Immuno-oncology is the field studying the restoration and activation of the immune system s ability to detect and destroy cancers. There are three main types of immunotherapy that are currently being developed: Checkpoint inhibitors: Tumors employ systems to effectively stop immune cell activity or putting brakes upon the immune system. These systems have been called checkpoints. Releasing these breaks by using a checkpoint inhibitor provides an opportunity to restore the function of the immune cells and drive an anti-tumor immune response. Cancer vaccines: focus upon inducing a specific immune response against the tumor. This approach intends to trigger an immune response against specific molecules expressed by the cancer cells in a manner similar to vaccination preventing infections. CAR-T cell therapy: A specific type of white blood cell called the T lymphocytes are genetically modified to allow them to better recognize and destroy cancer cells and are then injected into the patient. This approach is called CAR-T cell therapy, standing for Chimeric Antigen Receptor T-cells. CAR T-cells were born from the idea of arming T-cells with specific fragments of antibodies to target specifically antigens that are present on tumor cells. After just 20 years of development, the CAR-T cell concept has yielded some impressive clinical data with reports of complete remission of advanced chemo-resistant B cell leukemia (a type of blood cancer) in patients receiving CD19 CAR-T cells. Whilst these early clinical studies are driving major interest in CD19 CAR-T cell therapy, this approach is mostly restricted to B cell malignancies. Taking CAR-T cell therapy beyond the B cell cancers, and more specifically into the solid tumor setting, has proven to be highly challenging. Tumors are very effective at blunting the activity of T-cells and solid tumors are particularly apt at eliciting immune suppression. Therefore, a new generation of CAR-T therapy is needed. In some instances, the cancer cells develop mechanisms that allow them to evade the detection of our immune defenses. Immuno-oncology is the field studying the restoration and activation of the immune system s ability to detect and destroy cancers. CELYAD PRESS KIT JUNE

8 Immunotherapy: How does it work? 1. T-cells collection: T-cells are collected via apheresis, a process that withdraws blood from the body and removes one or more blood components (such as plasma or white blood cells). The remaining blood is then returned back into the patient s body. 2. T-cells re-engineering: The selected T-cells are sent to Celyad s laboratory where they are genetically engineered to produce CARs (Chimeric Antigen Receptor) on their surface. 3. T-cells becoming CAR-T cells: CARs are proteins that allow T-cells to recognize an antigen (substance that causes an immune system to produce antibodies against it) on targeted tumor cells (which have the antigen on their surface). 4. CAR-T cells expansion: T-cells are cultured in vitro. Once the required quantity of CAR-T cells has been obtained they are sent to the institute where the patient is being treated. 5. CAR-T cells infusion: Patients are infused with CAR-T cells. Once in the organism, CAR-T cells are multiplying in order to target cancer cells and destroy them. The CAR-T cells are recognizing the cancer cells thanks to the antigen on their surface. CELYAD PRESS KIT JUNE

9 Celyad s lead drug candidate in Immuno-oncology : CYAD-01 CYAD-01 (CAR-T NKG2D) is the lead CAR-T cell approach that is being developed by Celyad. This technology is based upon preclinical work carried out by Professor Charles Sentman at Dartmouth College (USA), who demonstrated that T-cells engineered to express the Natural Killer Receptor Group 2D (NKG2D) receptor fused with the CD3ζ chain of the T-cell receptor complex can drive impressive anti-tumor activity against established tumors in mouse models. CYAD-01 (T-CELLS) CAR-T cells (T-CELLS) NKG2D Receptor scfv DAP10 Costimulatory domain Costimulatory domain (e.g CD28, 4-1BB, etc.) CD3ζ CD3ζ Watch the video: Celyad s CYAD-01 therapy : our-science/immuno-oncology/ for-non-scientists/technologydeveloped-at-celyad CELYAD PRESS KIT JUNE

10 CYAD-01 cells can potentially target 80% of all cancer types Unlike standard CARs that recognize only one target, NKG2D binds to eight different targets (called ligands ). Most tumors express at least one of these NKG2D ligands underscoring the potential of the approach to potentially target 80% of all cancer types (both hematological and solid tumors). Professor Sentman demonstrated the potency of CYAD-01 cell therapy in several tumor models including ovarian, leukemia, myeloma and melanoma. The mechanism of action of CYAD-01 goes beyond direct cell killing Interestingly, Professor Sentman observed that CYAD-01 cells not only targeted tumor cells in those experiments, but also targeted the blood vessels that feed the tumor. A second important mode of action is that CYAD-01 has also an activity on the tumor environment by targeting the cells that drive the immune suppressor activity protecting the tumor from the patient s immune system (the so-called Regulatory T-cells and MDSCs). Because of these combined modalities, CYAD-01 cells induced a long-lasting adaptive immune response that protected the animal against further challenges with the same tumor. This multiplicity of activity by CYAD-01 is indicative of an overall approach that goes beyond that currently described for other standard CAR-T cell therapies. The approach aims at targeting cancer through multiple angles Another key discriminator between CYAD-01 and standard CAR-T cell therapy concerns patient s preconditioning chemotherapy. Classical CAR-T cell therapy requires the patient to be preconditioned using high doses of chemotherapy to eradicate patients own white immune cells prior to infusion of the CAR-T cells. This preconditioning serves many purposes, all aiming at providing conditions where the CAR-T cells can expand massively in the patient and mount a rapid and potent antitumor response to impact upon tumor growth. Celyad s THINK trial has already demonstrated that such preconditioning, which is taxing on the patient, does not seem necessary for CYAD-01 to be effective. CYAD-01 has demonstrated its capability to : Target and destroy cancer cells Eradicate tumor s micro-environment and mechanisms Create an adaptative cell memory preventing relapsed refractory cancer cells CELYAD PRESS KIT JUNE

11 Celyad s intellectual property portfolio in immunotherapy Celyad s intellectual property portfolio includes 4 patent families, including patents issued in the United States and patents pending validation in multiple jurisdictions (in Europe and the United States). In October 2015, the USPTO (United States Patent and Trademark Office) granted patent n relating to allogeneic human primary T-cells that are engineered to be TCR deficient and express a CAR (Chimeric Antigen Receptor). This patent has significantly strengthened the company s CAR-T cell therapies portfolio and leadership in cell therapy since patent claims are not limited to CAR technologies or specific methods for generating allogeneic CAR-T cells (such as genome modification or genetic engineering). The patented products are applicable for the treatment of many human diseases such as cancer, chronic infectious diseases and autoimmune diseases. Allogeneic technology has the potential to expand the therapeutic applications of CAR-T immunotherapies by enabling the development and manufacture with off-the-shelf treatments. Four re-examination requests regarding the validity of this patent were filed with the USPTO, which rejected all of them, thus confirming the validity of the patent held by Celyad. CELYAD PRESS KIT JUNE

12 Celyad s senior leadership team Christian Homsy CHIEF EXECUTIVE OFFICER Patrick Jeanmart CHIEF FINANCIAL OFFICER Frédéric Lehmann VP CLINICAL DEVELOPMENT & MEDICAL AFFAIRS David Gilham VP RESEARCH & DEVELOPMENT Jean-Pierre Latere CHIEF OPERATING OFFICER Philippe Dechamps CHIEF LEGAL OFFICER Philippe Nobels VP HUMAN RESOURCES CELYAD PRESS KIT JUNE

13 Appendix Key press releases in 2018 APPENDIX I - 23/05/18 Celyad announces closing of global offering Mont-Saint-Guibert, Belgium - Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell based therapies, today announced the closing of a global offering of 2,070,000 ordinary shares to purchasers in the United States, Europe and certain countries outside the United States and Europe, comprised of 568,500 ordinary shares in the form of American Depositary Shares (ADSs) at a price per ADS of $26.28, and 1,501,500 ordinary shares at a price per share of (the global offering ). Each ADS represents the right to receive one ordinary share. The number of ADSs and ordinary shares sold in the global offering reflects the full exercise of the underwriters option to purchase additional shares. The gross proceeds to Celyad from the global offering amounted to approximately $54.4 million (approximately 46.1 million), before deducting underwriting commissions and estimated offering expenses. Celyad s ADSs are currently listed on the NASDAQ Global Market under the symbol CYAD and Celyad s ordinary shares are currently listed on Euronext Brussels and Euronext Paris. Wells Fargo Securities, LLC and Bryan, Garnier & Co. acted as joint bookrunning managers for the offering. Bank Degroof Petercam NV acted as a co-manager for the private placement and LifeSci Capital LLC acted as a co-manager for the global offering. Kempen & Co NV was Celyad s advisor in connection with the offering. No stabilization activity was undertaken in connection with the global offering. The securities were offered pursuant to an effective shelf registration statement that was previously filed with, and declared effective by, the U.S. Securities and Exchange Commission (SEC). A final prospectus supplement dated May 17, 2018 relating to and describing the terms of the offering was filed with the SEC on May 18, 2018 and is available on the SEC s website at Copies of the final prospectus supplement and the accompanying prospectus relating to these securities can be obtained for free from Wells Fargo Securities, LLC, Attention: Equity Syndicate Department, 375 Park Avenue, New York, New York, 10152, at (800) or a request to cmclientsupport@wellsfargo.com or Bryan, Garnier & Co., Beaufort House, 15 Saint Botolph Street, London EC3A 7BB, United Kingdom, or by telephone at , or by at info@bryangarnier.com. This press release does not constitute an offer to sell nor a solicitation of an offer to buy, nor shall there be any sale of securities in any state or jurisdiction in which such an offer, solicitation or sale is or would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. ***END*** CELYAD PRESS KIT JUNE

14 APPENDIX II - 17/05/18 Celyad announces pricing of $47.3 million global offering Mont-Saint-Guibert, Belgium - Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell based therapies, today announced the pricing of a global offering of 1,800,000 ordinary shares, comprised of 523,913 ordinary shares in the form of American Depositary Shares (ADSs) offered in the United States, Canada and certain countries outside of Europe at a price per ADS of $26.28, and 1,276,087 ordinary shares in Europe and certain countries outside of the United States and Canada in a concurrent private placement at a price per share of (the global offering ). Each ADS represents the right to receive one ordinary share. The price per ADS was determined based on an exchange rate of $ per euro. The gross proceeds to Celyad from the global offering are expected to be approximately $47.3million (approximately 40.1 million), before deducting underwriting commissions and estimated offering expenses. In addition, Celyad has granted the underwriters a 30-day option to purchase up to an additional 270,000 ordinary shares, which may be in the form of ADSs, on the same terms and conditions. The closing of the global offering is expected to occur on May 22, 2018, and is subject to customary closing conditions. Celyad s ADSs are currently listed on the NASDAQ Global Select Market under the symbol CYAD and Celyad s ordinary shares are currently listed on Euronext Brussels and Euronext Paris. Wells Fargo Securities, LLC and Bryan, Garnier & Co. are acting as joint bookrunning managers for the offering. Bank Degroof Petercam NV is acting as a co-manager for the private placement and LifeSci Capital LLC is acting as a co-manager for the global offering. Kempen & Co NV is Celyad s advisor in connection with the offering. The securities are being offered pursuant to an effective shelf registration statement that was previously filed with, and declared effective by, the U.S. Securities and Exchange Commission (SEC). A preliminary prospectus supplement dated May 15, 2018 relating to and describing the terms of the offering was filed with the SEC on May 16, The final prospectus supplement relating to the offering will be filed with the SEC and will be available on the SEC s website at When available, copies of the final prospectus supplement and the accompanying prospectus relating to these securities can also be obtained for free from Wells Fargo Securities, LLC, Attention: Equity Syndicate Department, 375 Park Avenue, New York, New York, 10152, at (800) or a request to cmclientsupport@wellsfargo.com or Bryan, Garnier & Co., Beaufort House, 15 Saint Botolph Street, London EC3A 7BB, United Kingdom, or by telephone at , or by at info@bryangarnier.com. This press release does not constitute an offer to sell nor a solicitation of an offer to buy, nor shall there be any sale of securities in any state or jurisdiction in which such an offer, solicitation or sale is or would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. ***END*** CELYAD PRESS KIT JUNE

15 APPENDIX III - 15/05/18 Celyad announces launch of proposed global offering Mont-Saint-Guibert, Belgium - Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell based therapies, today announces that it intends to offer and sell, subject to market and other conditions, up to 1,800,000 ordinary shares in a global offering, which is comprised of an offer of ordinary shares in the form of American Depositary Shares (ADSs) in the United States, Canada and certain countries outside of Europe, and an offer of ordinary shares in Europe and certain countries outside of the United States and Canada in a concurrent private placement (the global offering ). Investors other than qualified investors under applicable law will not be eligible to participate in the ordinary share private placement. Each ADS offered represents the right to receive one ordinary share. In connection with the global offering, Celyad intends to grant the underwriters a 30-day option to purchase additional ordinary shares, which may be in the form of ADSs, in an aggregate amount of up to 15% of the total number of ordinary shares (including in the form of ADSs) proposed to be sold in the global offering, on the same terms and conditions. The U.S. offering and the European private placement together constitutes a single offering of securities that will occur simultaneously. The total number of ordinary shares in the U.S. offering and the European private placement is subject to reallocation between them. The closing of the global offering is subject to market and other conditions, and there can be no assurance as to whether or when the global offering may be completed or as to the actual size or terms of the global offering. The size of the global offering and the price per share of the ordinary shares and the ADSs placed in the global offering will be determined following the bookbuilding process. Celyad s ADSs are currently listed on the NASDAQ Global Select Market under the symbol CYAD and Celyad s ordinary shares are currently listed on Euronext Brussels and Euronext Paris. Trading of Celyad s ordinary shares will be suspended on the Euronext Brussels and Euronext Paris pending announcement of the pricing of the global offering. Wells Fargo Securities, LLC and Bryan, Garnier & Co. are acting as joint bookrunning managers for the offering. Bank Degroof Petercam NV and LifeSci Capital LLC are acting as co-managers for the offering. Kempen & Co NV is Celyad s advisor in connection with the offering. The securities are being offered pursuant to an effective shelf registration statement that was previously filed with, and declared effective by, the U.S. Securities and Exchange Commission (SEC). A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC s website at Copies of the preliminary prospectus supplement and the accompanying prospectus relating to these securities, when available, can also be obtained for free from Wells Fargo Securities, LLC, Attention: Equity Syndicate Department, 375 Park Avenue, New York, New York, 10152, at (800) or a request to cmclientsupport@wellsfargo.com; or from Bryan, Garnier & Co., Beaufort House, 15 Saint Botolph Street, London EC3A 7BB, United Kingdom, or by telephone at , or by at info@bryangarnier.com. This press release does not constitute an offer to sell nor a solicitation of an offer to buy, nor shall there be any sale of securities in any state or jurisdiction in which such an offer, solicitation or sale is or would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. ***END*** CELYAD PRESS KIT JUNE

16 APPENDIX IV - 15/05/18 Celyad Announces First Quarter 2018 Business Update Mont-Saint-Guibert, Belgium - Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD) a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell based therapies, today provided an update on key clinical and operational developments for the first quarter ended March 31, FIRST QUARTER 2018 AND RECENT HIGHLIGHTS Robust clinical development plan is foundation for new trials focusing on AML and CRC Steady progress related to ongoing THINK, SHRINK and LINK trials Good safety profile of CYAD-01 confirmed Lead publication Haematologica publishes THINK Study Case Report Dr. Christian Homsy, CEO of Celyad commented: We had a productive first quarter, further defining our strategy that will guide CYAD-01 in becoming the foundation for cancer therapies. Not only have we progressed in the THINK trial, we have also treated our first patients in the SHRINK and LINK trial. The absence of any observed critical on target/off tumor toxicity in our trials is an important signal validating our technology. The next months will be exciting for our company and we look forward communicating results on our clinical trials in scientific congresses. FIRST QUARTER 2017 OPERATIONAL AND FINANCIAL REVIEW In February 2018, Celyad provided a detailed clinical update summarizing the promising results achieved in 2017: the THINK trial resulted in signs of clinical activity ranging from Stable Disease (SD) to Complete Response (CR), despite the absence of preconditioning therapy and the lower doses used at that stage of the trial. The company also announced that it will further evaluate CYAD-01 in a series of additional Phase 1 clinical trials in patients with AML and CRC. Also in February 2018, Celyad organized a Key Opinion Leader meeting on CAR-T therapy in New York, USA. The meeting featured a presentation by Marco Davila, MD, PhD (Moffitt Cancer Center). The numerous attendants received information on the unmet medical need in blood cancers as well as details on Celyad s clinical strategy. On the operation side, during this first quarter, Celyad progressed well in the THINK trial as well as the in LINK trial: The company dosed the three CRC patients in the third dose cohort in the solid arm of the THINK trial, and the two last AML patients in the second dose. Celyad plans to initiate the third dose in the AML arm in May 2018, and complete the recruitement of three additional CRC patients at the higher dose by mid In 2018, all patients were dosed with the our new production process adopted in December The company also treated its first CRC patient in the LINK trial. This patient received three planned injections at the first Dose level (3x108). LINK adopts a loco-regional approach in treating CRC by administering CYAD-01 through multiple hepatic transarterial injections. The company ended the quarter with 25.1 million in cash, cash equivalents and short-term investrments. Use of cash over the first quarter of 2018 amounted to 8.8 million, in line with expectations. The company confirms that existing cash and cash equivalents and short term investments are sufficient to fund operating expenses and capital expenditure requirements, based on the current scope of activities, until the end of Q Events subsequent to quarter-end: In April 2018, Celyad s world s first reported complete response by a CAR-T cell therapy in a patient with refractory and relapsed AML was published as a case report in the leading scientific publication Haematologica. The publication detailed the first objective response related to this patient that is still in remission, more than 9 months after study enrollment. In May 2018, Celyad achieved an important milestone in its CYAD-01 clinical strategy by dosing the first metastatic CRC patients in the LINK and SHRINK trials. No drug related toxicity was observed in the first patients of both SHRINK and LINK trials.,generally, Celyad s progress is the result of the company s clinical development plan aiming at defining the best of three approaches for CYAD-01 in patients with AML and CRC: 1. CYAD-01 as a stand-alone investigational therapy, currently being evaluated in the THINK trial with relapsed refractory AML and CRC patients. Promising results have already been reported including a complete response and stable diseases. CELYAD PRESS KIT JUNE

17 Based on data as of April 5, 2018, the date of Celyad s most recent interim safety report for the THINK trial, Celyad had collected safety data from 20 patients treated with CYAD-01 in the THINK trial. Of the 20 patients included in the interim safety report of the THINK trial (11 solid and nine hematologic cancer patients), Celyad reported the following serious adverse events: Grade 4 serious adverse events occurred in two patients: one patient in the hematologic cohort experienced respiratory failure and other Grade 4 adverse events after administration of dose level one of CYAD-01. The other patient, who was in the solid tumor cohort, experienced cytokine release syndrome and other Grade 4 adverse events after administration of dose level three of CYAD-01, which was adjudicated as a dose limiting toxicity (DLT). Those two patients each experienced a Grade 5 event that was deemed unrelated to administration of CYAD CYAD-01 administered concurrently with standard of care treatments. The SHRINK trial was recently initiated with the dosage of one CRC patient in April No Grade 4 or higher adverse event has been reported so far. This trial evaluates the concurrent administration of CYAD-01 with the standard chemotherapy FOLFOX. We expect that another similar trial aimed at AML patients, EPITHINK trial, will be initiated soon. 3. CYAD-01 administered after preconditioning of the patients using lymphodepletion. We expect trials in AML (DEPLE- THINK AML) and CRC (DEPLETHINK CRC) patients to be initiated in the coming weeks. ***END*** CELYAD PRESS KIT JUNE

18 APPENDIX V - 9/05/18 Celyad Announces Presentations at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting 2018 Mont-Saint-Guibert, Belgium - Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD) a clinical-stage biopharmaceutical company focused on the development of CART-cell therapies, today announced that the company will present recent advances in Celyad s pipeline at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting being held May 16 19, 2018, in Chicago. Poster presentations will highlight the recent developments of Celyad s pipeline in autologous and allogeneic platforms to address cancers. The oral presentation will give updated data of the ongoing THINK Phase 1 trial with the case report of a CYAD-01 associated complete response in one relapsed/refractory AML patient, including observations concerning the modulation of systemic chemokines during the course of treatment. David Gilham, VP of Research and Development at Celyad, commented: Our presentations at the 2018 meeting of the ASGCT will share our increasing knowledge around our lead NKG2D CAR T cell candidate along with discussing our pipeline including the B7H6 CAR T program and our allogeneic platform. These presentations are the culmination of an intensive level of activity within our R&D group. We anticipate that this will lead to a series of assets that will enter clinical stage testing during ***END*** CELYAD PRESS KIT JUNE

19 APPENDIX VI - 03/05/18 Celyad successfully administers CYAD-01 in first patients in SHRINK and LINK trials 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 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 (DEPLE- THINK 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: 1x108, 3x108 and 1x109 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: 3x108, 1x109 and 3x109 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. ***END*** CELYAD PRESS KIT JUNE

20 APPENDIX VII - 27/04/18 Haematologica publishes Celyad THINK Study Case Report of CYAD-01 Induced Complete Remission in Relapsed/Refractory AML Patient 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, announces the publication later today of a patient case study from the hematological arm of its THINK Phase I trial in the journal Case report details first ever reported complete morphologic remission with gene engineered T-cells in a relapsed/refractory AML patient without preconditioning The publication, entitled NKG2D-based Chimeric Antigen Receptor Therapy Induced Remission in a Relapsed/Refractory Acute Myeloid Leukemia Patient is authored by the trial investigators at the Moffitt Cancer Center and Research Institute in Tampa, Fla. and by Celyad s scientific team. The publication details the first objective response to CAR-T in relapsed/refractory AML using CYAD-01, Celyad s Natural Killer Group 2D (NKG2D) chimeric antigen receptor T-cell therapy, without pre-conditioning lymphodepletion. The patient received CYAD-01 infusions at the initial dose level of 3x10 8 cells every 2 weeks for 3 administrations, achieving a morphologic leukemia-free state (MLFS) at 3-months which enabled the patient to benefit from an allo-hematopoietic stem cell transplant (allo-hsct). The patient achieved a complete molecular remission and remains in remission 9 months post study enrollment. CYAD-01 was well tolerated with no significant toxicities. The demonstrated first objective response to any CAR-T in relapsed/refractory AML without preconditioning chemotherapy highlights the potential of CYAD-01 as a treatment for AML. Our results demonstrate the validity of NKG2D as a target, in particular in the context of refractory AML and without other intervening treatments nor preconditioning, commented Frédéric Lehmann, VP Clinical Development and Medical Affairs at Celyad. We look forward to continue our clinical development plan for our NKG2D CAR based platform and explore the various conditions within which this therapy could provide benefits to patients with end stage cancers. Dr. David Sallman, Assistant Member in the Malignant Hematology Department of Moffitt Cancer Center, added: The THINK study case report provides the first clinical validity of CYAD-01 as a tumor-specific antigen-receptor and AML as a disease sensitive to gene-engineered cell therapies. As antigen targeting offers significant challenges in AML, this outcome brings hope for the further use of gene-engineered T-cells for patients with AML that have run out of therapeutic options. It s all the more striking that this outcome was observed without any prior lymphodepletion highlighting the potential of using a physiologic antigen-receptor. ***END*** CELYAD PRESS KIT JUNE

21 Glossary A Acute Myeloid Leukemia (AML) AML is a type of cancer that affects the blood and bone marrow. It is characterized by an overproduction of certain immature white blood cells, called myeloblasts or leukaemic blasts. Allogeneic A situation in which the donor and the recipient are not the same person. Antibody also known as an immunoglobulin is a protein produced mainly by plasma cells that is used by the immune system to identify and neutralize pathogens such as bacteria and viruses. Antigen any substance that causes an immune system to produce antibodies against it Autologous A situation in which the donor and the recipient are the same person. C CAR-T cell A CAR-T cell is a T lymphocyte (a type of white blood cells) in which a DNA construct, coding for a receptor, has been introduced artificially. The result of this engineered cell is that the T lymphocyte express the CAR (Chimeric Antigen Receptor) on its surface and is able to recognize a specific target through new engrafted receptor. CYAD-01 CAR-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. Co-stimulatory molecules During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors Cryopreservation Cryopreservation is a process where cells or whole tissues are preserved by cooling to low sub-zero temperatures. At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, is effectively stopped. Cytokine release syndrome (CRS) CRS is a specific type of infusion reaction that has been most often associated with the use of monoclonal antibodies and T-cell-engaging therapies. Following drug infusion, a high level activation of the immune system and engagement and proliferation of T cells can result in increased cytokine release. Fever is a hallmark of infusion reactions, and therefore, many infusion reactions may mimic symptoms of an infection. G Good Manufacturing Practices (GMP) GMP is part of a quality system covering the manufacture and testing of active pharmaceutical products. GMPs are guidelines that outline the aspects of production and testing that can impact the quality of a product. I In vitro (experiment) Experiments done outside living systems. In vivo (experiment) Experiments done in living systems. L Ligand A ligand is molecule, as an antibody, hormone, or drug, that binds to a receptor Lymphodepletive preconditioning The destruction of lymphocytes and T cells, by irradiation or chemotherapy, prior to immunotherapy. M Multiple Myeloma (MM) MM is a cancer of plasma cells. Plasma cells are mature B lymphocytes, a type of white blood cell, that help to fight infection by producing special proteins called antibodies or immunoglobulins. In myeloma, large numbers of abnormal plasma cells called myeloma cells are made in the bone marrow. N NK cell or Natural Killer cell NK cells are lymphocytes of the innate immune system, which can eliminate targets directly and destroy cells (e.g upon viral infection, or tumor cells) O Off tumor on-target toxicity Toxicity induced when a CAR-T reaches its target (antigens/ligands) that are expressed on cells that are not tumor cells. Open-label study A type of study in which both the health providers and the patients are aware of the drug or treatment being given. P Pivotal trial Usually a Phase III study which presents the data that a regulatory agency uses to decide whether or not to approve a drug. A pivotal study will generally be well-controlled, randomized, of adequate size, and whenever possible, double-blind. Proteomics analysis Proteomics is the large-scale study of proteins, particularly their structures and functions. S Secretome Term used to describe the set of proteins secreted by a cell, a tissue or an organism. T T Lymphocyte (also called T-cell) type of lymphocyte (a subtype of white blood cell) that play a central role in cell-mediated immunity. TCR TCR is a molecule found on the surface of T lymphocytes (or T cells) that is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. CELYAD PRESS KIT JUNE

22 Personal notes CELYAD PRESS KIT JUNE

23 Celyad CELYAD AND THE STOCK EXCHANGE The Company is listed on Euronext Paris and Brussels since July 2013 and on Nasdaq since June Mnemo: CYAD ISIN:BE MORE INFORMATION ON: CONTACT: