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• Celyad grants an exclusive license to ONO for the development and commercialization of Celyad’s unique allogeneic NKR-2 T-cell in Japan, Korea and Taiwan.
• Celyad also grants to ONO an exclusive option to license its autologous NKR-2 T cell product in the above ONO territories.
• Total deal value of up to 31.325 JPY B (€282 million or $311.5 million) plus double digit royalties on net sales in ONO territories.

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of cell therapies, today announced an exclusive license agreement with the leading Japanese immuno-oncology company, ONO Pharmaceutical Co., Ltd. (TSE: 4528), for the development and commercialization of Celyad’s allogeneic NKR-2 T-cell immunotherapy in Japan, Korea and Taiwan. This license agreement opens new markets to Celyad and expands the global footprint of its NKR-2 T-cell cancer immunotherapy treatment and potentially for other disease conditions.

Celyad will receive an upfront payment of 1.25 JPY B (€11.25 million or $12.5 million) and is eligible of up to 30.075 JPY B (€270.75 million or $299 million) in development and commercial milestones. Celyad will also receive double digit royalties based on net sales of the licensed product in ONO’s territories.

Under the terms of the agreement, Celyad will continue developing its allogeneic NKR-2 T-cell immunotherapy in the EU and US territories, and ONO will be responsible for future development and commercialization in ONO’s territories (Japan, Korea and Taiwan). Both companies will also explore the opportunity to collaborate to collectively run global registration trials and combination trials. In addition, Celyad grants to ONO an exclusive option to license for development and commercialization of its autologous NKR-2 T cell product in the above ONO territories.

Dr. Christian Homsy, CEO of Celyad, said: “We are very pleased to collaborate with ONO and to activate the development of our NKR-2 T-cell allogeneic platform in Japan, Korea and Taiwan. This license agreement is a great opportunity for Celyad to expand the scope of its immuno-oncology clinical programs and bring this breakthrough science to numerous patients around the world. Further, this license agreement with ONO, the leader in immuno-oncology in Asia, validates our NKR-2 approach and its tremendous potential.”

Georges Rawadi, VP Business Development of Celyad, said: “Celyad surrounds itself with the best immuno-oncology experts in the world to develop its NKR T-cell platform. This is why we have entered this agreement with ONO. Through this commercial license agreement, Celyad aims to expand the clinical and commercial potential of its allogeneic NKR-2 T-cell immunotherapies worldwide.”

Gyo Sagara, President, Representative Director and CEO of ONO, said: “We are very delighted to collaborate with the leading cell therapy company, Celyad, for its distinct immuno-oncology candidates. Celyad’s NKR-2 is backed by cutting-edge science and we believe that it can be a new therapeutic option for patients who are not cured with existing therapies.”

Conference Call Details

A conference call will be held on Monday, July 11, 2016 at 2:00pm (CEST) / 8:00am (EDT) to review the licensing agreement with ONO Pharmaceutical. Christian Homsy, Chief Executive Officer, will deliver a brief presentation followed by a Q+A session.

Participants are asked to call the assigned numbers approximately five minutes before the conference call begins.

The call can be accessed by dialing the numbers below and using the passcode: 30423803

International:                                +44 (0) 1452 584233
Belgium:                                            024003425
France:                                               0800947325
UK:                                                        08002795994
US:                                                        1 866 629 0057

About Celyad’s NKR Platform

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 mechanism of actions and goes beyond direct killing by signifying that its encoded T-Cells attack the tumor cells, inhibit the mechanisms that enable tumors to evade the immune system, activate and recruit anti-tumor immune cells and disrupt 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 lymphodepleting 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.

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.

NKR-2 is currently being tested in a Phase I trial in acute myeloid leukemia and multiple myeloma patients. The trial is designed to assess the safety and feasibility of NKR-2, with secondary endpoints including clinical activity. Key research investigations include understanding the persistence of NKR-2 cells within the patient.

About ONO PHARMACEUTICAL CO., LTD.
ONO PHARMACEUTICAL CO., LTD., headquartered in Osaka, Japan, is an R&D-oriented pharmaceutical company committed to create innovative medicines in specific areas. It focuses especially on the oncology and diabetes areas. For more information, please visit the company’s website at http://www.ono.co.jp/eng/index.html

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 infusion of the first patient enrolled in the fourth dose level of its Phase I/IIa clinical trial. The study is 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, commented: “We are pleased to have enrolled the first patient in the fourth dose level cohort of this study on track and are encouraged that no adverse safety signals have been observed so far for the nine patients already treated with
NKR-2. We are actively working on the recruitment of the two next patients for this new dose level and we look forward to the data that are expected in the next few months”

Dr. Frédéric Lehmann, Head of Immuno-Oncology at Celyad:«The infusion of the 10^th patient demonstrates good progress in our first-in-human NKR-2 Phase I/IIa study. This technology has great potential in multiple cancer indications and we look forward to completing this Phase I/IIa and moving to the next stage in clinical development.”

About Celyad’s NKR-T program

NKR stands for Natural Killer Cell 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). In contrast to existing CAR-T cells, Celyad’s lead immuno-oncology product candidate, NKR-2, is a T-Cell encoded to express the human Natural Killer activating receptor, NKG2D and the signalling domain of CD3 zeta. Using the human Natural Killer cell receptor, unlike traditional CAR technologies, NKR-2 has the potential to:

• Bind to 8 different ligands that are expressed by a vast majority of cancer cells, both hemaetological and solid malignancies.
• Target and kill tumors as well as the blood vessels that feed them and also express the ligands of the NKG2D receptor.
• Act on the immunosuppressive microenvironment within tumors resulting in the inhibition of the mechanisms which enable tumor to evade the immune system.
• Induce adaptive auto-immune response resulting in the creation of a long term cell memory against the targeted tumor.

The research underlying this technology was originally conducted by Dartmouth College Professor Charles Sentman, and has been published in numerous peer-reviewed publications. NKR-2 has an active Investigational New Drug (IND) application with the FDA for a Phase I clinical trial. The trial is designed to assess the safety and feasibility of NKR-2 in acute myeloid leukemia and multiple myeloma patients, with secondary endpoints including clinical activity.

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 diseases and immuno-oncology, today announced that an oral presentation titled “Validation of Manufacturing NKG2D Chimeric Antigen Receptor T Cells for a First-in Human Trial in AML/MDS and Multiple Myeloma” will be made at the American Society of Gene & Cell Therapy (ASGCT) 19^th Annual Meeting May 4-7 in Washington DC.

Dr. Frédéric Lehmann, Head of Immuno-Oncology at Celyad: “We are pleased that the application to present the validation of our cell manufacturing process was selected for an oral presentation.  It highlights the importance and interest in our NKR-2 clinical program marking a positive step forward.  This technology has great potential and we are looking forward to completing the Phase I.”

About Celyad’s NKR-T program

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 signaling domain of CD3 zeta and one or more co-stimulatory domain(s). In contrast to existing CAR-T cells, Celyad’s lead immuno-oncology product candidate, NKR-2, is a T-Cell encoded to express the human Natural Killer activating receptor, NKG2D. Using the human Natural Killer cell receptor, unlike traditional CAR technologies, has the potential to:

• Bind to 8 different ligands that are expressed by a vast majority of cancer cells, both hemaetological and solid malignancies.
• Target and kill tumors as well as the blood vessels that feed them and also express the ligands of the NKG2D receptor.
• Target and kill the inhibitory mechanisms preventing the tumor from evading the immune system.
• Induces adaptive auto-immune response thanks to the creation of a long term cell memory against the targeted tumor.

The research underlying this technology was originally conducted by Dartmouth College Professor Charles Sentman, and has been published in numerous peer-reviewed publications. NKR-2 has an active Investigational New Drug (IND) application with the FDA for a Phase I clinical trial. The full data readout from the Phase I dose escalation trial is expected in mid-2016. The trial is designed to assess the safety and feasibility of NKR-2 in acute myeloid leukemia and multiple myeloma patients, with secondary endpoints including clinical activity. 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).

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 that the EMA has issued a certification for C-Cure^®non-clinical data.

C-Cure^® (C3BS-CQR-1) is a cardiovascular lineage-committed cell therapy product being developed for the treatment of ischemic heart failure, currently in a pivotal phase III clinical trial in Europe and Israel. The EMA certification announced today is the second of three modules, following the certification of quality data obtained in May 2014, made in preparation for a marketing application. The certification provides confirmation that the Committee for Advanced Therapies (CAT), recognizes that the C-Cure^® development program continues to meet the rigorous standards set by the EMA for a successful development and submission package.

Dr. Jean-Pierre Latere, Head of Cardiovascular Franchise at Celyad, commented: “This certification acknowledges the rigor of our work and we continue to execute on our plans to make C-Cure® available to patients with ischemic heart failure.  We are optimistically awaiting the CHART 1 Phase III results which are expected end of June 2016.”

Dr. Richard Mountfield, Head of Regulatory Affairs and Clinical Operations at Celyad, commented: “Through constructive collaboration with CAT, the issuing of this certification for the non-clinical data for C-Cure^® further reflects the positive Regulatory environment for our Marketing Authorization Application.”

European Regulation on ATMPs

ATMPs (Advanced Therapy Medicinal Product) are at the forefront of biotechnology and medical innovation. Because of their novelty and complexity, evaluating the quality, safety, and efficacy of ATMPs often requires the development of alternative approaches that go beyond what is needed for conventional medicines.

The European Regulation (EC) No 1394/2007 provides a consolidated framework for this innovative class of products, including a procedure allowing SMEs (Small to Medium Enterprises) to voluntarily apply for the certification of the pharmaceutical quality and the pre-clinical data of an ATMP. The aim is to offer an early dialogue with the EMA, to clarify regulatory requirements and provide feedback on the quality and completeness of data submitted. 

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 diseases and immuno-oncology, today announced appointment of Dr. Hinrich Abken, Dr. Scott Antonia, Dr. Marco Davila, Dr. Stéphane Depil, Dr. Marc Ernstoff, Dr. David Edward Gilham, Dr. Sebastian Kobold, Dr. Daniel Olive, Dr. Charles Sentman and Dr. Jeffrey S. Weber to the Company’s Scientific Advisory Board.

Dr. Christian Homsy, CEO of Celyad: “We are proud to have gathered such an accomplished team of international immuno-oncology experts to our Scientific Advisory Board. Each member has dedicated their career to landmark scientific achievements that have advanced the field of immunotherapy for cancer treatment. It is of paramount importance for Celyad to surround itself with thought leaders that will help the Company translate pioneering technology into transformative therapies that will change the lives of cancer patients”.

Dr. Frédéric Lehmann, Head of Immuno-Oncology at Celyad:“We are honored to collaborate with these internationally renowned specialists and to cross-fertilize their scientific expertise in immuno-oncology, in clinical development and in cell therapy to develop our NKR-T platform. Their collective knowledge and guidance will contribute to make the most of Celyad’s unique therapeutic approach and potentially open the path to new treatment options for cancer patients”.

The new members of the Scientific Advisory Board include:

• Dr. Hinrich Abken is Professor for Genetics & Immunology at CMMC (Center for Molecular Medicine Cologne) at the University of Cologne and Dept of Internal Medicine, Oncology?Hematology at the University Hospital Cologne where he is working towards the development of adoptive cell therapy of malignant diseases using engineered
  T-cells. Dr. Abken’s group is internationally leading in pre?clinical research of adoptive therapy with T-cells engineered with chimeric antigen receptors.
• Dr. Scott Antonia is the Department Chair of the Thoracic Oncology Department at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. He is also a Professor of Oncologic Sciences at the University of South Florida College of Medicine in Tampa. 
  Dr. Antonia’s work focuses on translational research. Using his molecular biology and cellular background in the development of immunotherapeutic strategies for the treatment of cancer patients, he has developed strategies designed to thwart the immunosuppressive mechanisms used by tumors to evade T-cell mediated rejection.
• Dr. Marco Davila is a medical oncologist that specializes in both clinical and laboratory research in the treatment of patients with hematologic malignancies.  He is Associate Member in the Blood and Marrow Transplantation and Immunology Departments at the Moffitt Cancer Center, University of South Florida. Dr. Davila’s laboratory develops gene-engineered cell therapies that target and kill cancerous cells in animal models of hematologic malignancies and was the Principal Investigator of a clinical trial using genetically engineered T cells targeted against malignant B cells. 
• Dr. Stéphane Depil is onco-hematologist at Léon Bérard Cancer Center and Associate Professor at University Claude Bernard Lyon I, adjunct Professor at UCBL and CEO of Netris Pharma.  Dr Depil has significant expertise in conducting pre-clinical and clinical development in oncology as the former head of Oncology R&D at Servier.
• Dr. Marc Ernstoff is a medical oncologist, professor and chief of the Division of Hematology/Oncology in the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo (UB). Over the past 30 years, Dr. Ernstoff has focused his research on expanding understanding of the immunobiology of human cancer and the development of new immune therapies for melanoma, renal cell carcinoma and glioblastoma multiforme.
• Dr. David Edward Gilhamis Senior Lecturer Clinical and Experimental Immunotherapy Group Director of the Institute of Cancer Sciences, Manchester.  His group focuses upon developing immunotherapies for the treatment of cancer which include the exploitation of chimeric antigen receptors and recombinant T cell receptors to re-direct the effector functions of T cells, which are then used in adoptive transfer studies.
• Dr. Sebastian Koboldis Professor at the Medical Center of the University of Munich and Senior Academic Assistant. He is also Deputy Head of the Immunopharmacology group at Ludwig-Maximilians University of Munich. His research aims to develop new proteins that are intended to modulate the function of T-cells of the human immune system and enable them to destroy specifically and efficiently cancer cells.
  • Dr. Daniel Olive is Professor of Immunology at Aix Marseille University; he is also in charge of the « Immunity and Cancer » research team of INSERM UMR1068 of Marseille Cancer Research Center (Institut Paoli Calmettes). He is the head of the first IBiSA Platform dedicated to Cancer Immunomonitoring Platform and has been a pioneer and leader in the co-signalling field since 1990. His work is dedicated to tumor immunology with a major emphasis on innate immunity and co-signalling molecules.
  • Dr. Charles L. Sentman is a Professor of Microbiology & Immunology and the Director of the Center for Synthetic Immunity at the Geisel School of Medicine at Dartmouth. In addition to academic research, he is a Scientific Founder for Celdara Medical LLC (Lebanon, NH) and inventor of CM-CS1. He has expertise in natural killer cell biology, T cells, immunotherapy, chimeric antigen receptors, bispecific antibodies, and immuno-oncology.
  • Dr. Jeffrey S. Weber is Deputy Director at the Laura and Isaac Perlmutter Cancer Center at the NYU Langone Medical Center and professor of Medicine at NYU and head of Experimental Therapeutics at the Perlmutter Cancer Center. He is a translational clinician-scientist and clinical trialist with an interest in Immuno-Oncology and the development of new treatment strategies for patients with melanoma. Dr. Weber was the principal investigator of the first trial that demonstrated benefit for PD-1 blocking antibodies in melanoma patients that had failed ipilimumab. He was also the first investigator who demonstrated that PD-1 blocking antibodies had encouraging activity in resected melanoma patients.

CArdio3 BioSciences Reports 2014 Fincancial and Operating Results

Significant Progress Made in Building a Global Specialty Therapeutics Company

Conference Call to Be Held on 26 March 2015 at 2.00 p.m. CET / 9.00 a.m. ET

• Expansion into the CAR T-cell space with rapid development goals leveraging our cell therapy expertise
• Completed enrollment of CHART-1 with top line data in 2016, progressing towards a CHART-2 start in the USA
• Improved financial position following successful capital raises to finance growth
• Establishing our US operations in Rochester MN, and Boston MA

Mont-Saint-Guibert, Belgium, – Cardio3 BioSciences SA (C3BS) (NYSE Euronext Brussels and Paris: CARD), a leader in the discovery and development of engineered cell-therapy treatments, today provided an update on recent business developments and strategic initiatives, and reported consolidated financial results for the twelve-month period ended 31 December 2014, prepared in accordance with IFRS.

Commenting on the 2014 results, Dr Christian Homsy, CEO of Cardio3 BioSciences, said: “We made significant strategic, operational and financial advancements in 2014 as we seek to build C3BS into a global specialty therapeutics company. The momentum built over this period has carried over into the early part of 2015, which has seen us reach important milestones in both of our C-Cure® Phase III programs CHART-1 and CHART-2. C3BS continues to make strong progress in the late stages of C-Cure® development and we look forward to reporting the upcoming futility data.

“Our acquisition of the OnCyte CAR T-Cell portfolio in early 2015 heralds the first major step in our strategy to leverage our unique expertise in cell therapies and drug development to expand beyond the cardiac arena to develop breakthrough treatments to change the outcome of disease. We are excited to be expanding our product offering into the prominent area of immuno-oncology and anticipate the initiation of the Phase I trial of our lead immuno-oncology candidate, CAR-NKG2D in the first half of 2015 and look forward to sharing details of our progress as we evaluate its clinical potential. We intend to leverage our cell therapy know-how and infrastructure to quickly progress those assets into later stage clinical trials in 2016, aiming at more than five trials in liquid and solid tumors in the USA and Europe.

“Overall, 2014 was an exciting and successful year for C3BS, but more importantly, it set the stage for even greater accomplishments in the years to come.”

Conference call details

A conference call will be held on Thursday, March 26, 2015 at 2:00 p.m. CET / 9:00 a.m. EDT to review the financial results. Christian Homsy, Chief Executive Officer, and Patrick Jeanmart, Chief Financial Officer will deliver a brief presentation, which will be available to download from here 15 minutes before the call commences, followed by a Q&A session. Participants are asked to call the assigned number approximately five minutes before the conference call begins.

The call can be accessed by dialing the numbers below and quoting conference ID 10703467.

• Participant International Dial-In: + 44 (0)1452 541003
• Belgium :011500193
• France :0170700780
• United States :1-646-741-2120

A recording of the presentation will be available on the Cardio3 Biosciences website following the call for a period of 15 days.

2014 and recent operational highlights

• Completed enrollment in CHART-1 Phase III clinical trial of lead product candidate, C-Cure®, for the treatment of ischemic heart failure, futility data expected to be reported in the second quarter of 2015
• Received product-specific pediatric waiver for C-Cure® from European Medicines Agency (EMA) – confirming focus on adult population
• Initiated sites for second Phase III trial evaluating C-Cure®, CHART-2, in the U.S. with new protocol for use of injection catheter C-Cathez® to deliver C-Cure,® currently under review by the FDA; pending FDA clearance to initiate the trial expected in the second half of 2015
• Took first major step in strategy to broaden Company’s focus beyond cardiology and entered immuno-oncology arena with acquisition of OnCyte CAR T-cell portfolio from Celdara Medical, LLC
• Initiation of U.S. Phase I trial evaluating lead oncology candidate, CAR-NKG2D, expected in the first half of 2015 with interim results expected to be reported at various times during the trial and full data readout expected in the middle of 2016
• Expanded collaboration with Mayo Clinic, through non-exclusive preferred access agreement, allowing C3BS to regularly review Mayo Clinic’s regenerative medicine portfolio to identify projects of mutual interest
• Confirmed plans to build a new U.S.-based manufacturing facility in Rochester, Minnesota, to support the Company’s current and anticipated manufacturing needs in the United States for C-Cure® CHART-2, and CAR T-cell therapies’ portfolio, and establish a Boston based U.S. headquarters
• Strengthened management team to support Company in its ambitions to become a global leader in specialty therapeutics and reinforce its position in both cardiology and oncology with the appointment of Dr. Georges Rawadi as Vice President, Business Development and Dr. Warren Sherman as Chief Medical Officer

2014 and recent financial highlights

• Completed a €32 million private placement with U.S. and European investors at €44.50 per share in February 2015, representing no discount to previous day market price and a 4% premium to the last 30 days average price preceding the transaction
• Completed a share capital increase of €25 million in June 2014 at €44 per share, a 14% premium to the 30 days average price preceding the transaction
• Completed a secondary placement of 141,800 shares at €43.5 per share with six new Swiss institutional investors in July 2014. This transaction occurred off-market through an exchange of shares between certain historical shareholders of the Company and Swiss professional investors. 
• €30 million in cash and term deposits as of 31 December 2014, sufficient to fund the C-Cure® clinical program until the availability of the read-out of the primary endpoint, anticipated first half of 2016.

Operational review

C-Cure® clinical program update

CHART-1 (Congestive Heart failure Cardiopoietic Regenerative Therapy) Trial

CHART-1 is a Phase III clinical trial evaluating C-Cure®, the Company’s lead cardiac product candidate. The Company successfully met its defined objective of enrolling the 240th patient in CHART-1 by the end of 2014 and completed patient enrolment in March 2015.

At the beginning of May, the European Medicines Agency (EMA) issued a certification of quality data for C-Cure®. The Advanced Therapy Medicinal Products (ATMP) certification recognizes the data generated for C-Cure® in its development program so far as meeting the standards imposed by t he EMA. The ATMP’s certification for quality data will facilitate the EMA’s review of the Company’s anticipated future application for marketing authorization for C-Cure®.

In mid-September, Cardio3 BioSciences announced it had received the unanimous recommendation of the Data Safety and Monitoring Board (DSMB) to continue the CHART-1 trial according to the original protocol. The recommendation was based on a planned analysis performed on all patient safety data available as per mid-August 2014. All the members of the DSMB approved the continuation of the trial having concluded that one month post treatment, C-Cure® and C-Cathez® showed no safety issues that compromise the continuation of the CHART-1 Phase III study.

The Company anticipates publication of the full data set for CHART-1 in mid-2016. However, the Company expects to be able to publish the interim futility data from the CHART-1 trial in the second quarter of 2015. These data, will be independently assessed by the trial’s Data and Safety Management Board (DSMB), which will assess whether efficacy indicators have been met and whether the clinical study can be further completed.

CHART-2

In January 2014, the U.S. Food and Drug Administration (FDA) authorized the Company’s Investigational New Drug (IND) application for clinical testing of C-Cure® as a treatment targeting heart failure using the MyoStar™ injection catheter. CHART-2, the Company’s second Phase III clinical trial to be conducted in the United States, is intended to assess the efficacy of C-Cure®. The primary endpoint of the trial is the “Six Minute Walk Test” nine months post-procedure, a commonly used index of cardiovascular performance. Results of the Phase II trial demonstrated that C-Cure® showed a 25% relative improvement in cardiac function over baseline for treated patients versus 0.7% relative improvement for the control group.

In November, Cardio3 BioSciences announced the nomination of its three Co-principal investigators for its CHART-2 Phase III clinical trial of C-Cure®: Dr Bernard J. Gersh, Professor of Medicine at Mayo Clinic College of Medicine, Rochester, Minnesota; Dr Thomas Povsic, Associate Professor of Medicine at Duke University, Durham, North Carolina; and Dr Gerasimos Filippatos, Head of the Heart Failure Unit at the Athens University Hospital Attikon, President of the Heart Failure Association of the European Society of Cardiology (ESC).

In January 2015, Cardio3 BioSciences submitted an amendment to the protocol to the FDA for the CHART-2 study which included the use of the injection catheter C-Cathez® alongside C-Cure® in the Phase III trial. Final review and FDA decision are expected in the second half of2015.

C-Cure® Pediatric Investigation Plan waiver

In March 2014 Cardio3 BioSciences received from the EMA an official, product-specific pediatric waiver for C-Cure® across all subsets of the pediatric population for the treatment of ischemic heart disease. As medical and surgical treatments exist for this extremely rare condition among pediatric patients, Cardio3 BioSciences has focused its regulatory approach for C-Cure® regenerative therapy on the adult patient population. Subsequently, the EMA delivered the waiver to Cardio3 BioSciences, hence making it official that the clinical studies of C-Cure® would be restricted to the adult population.

Publication in specialized press

During the first quarter of 2014, Cardio3 BioSciences’ lineage-specified cardiac progenitor (Cardiopoietic) technology was referenced in the journal Nature Reviews Cardiology and European Heart Journal as a next generation advancement in the science of regeneration.

Strengthening of Company assets and development strategy

In January 2015, Cardio3 BioSciences entered the immuno-oncology space through the acquisition of OnCyte’s CAR T-Cell portfolio of clinical-stage immuno-oncology assets. The portfolio includes three autologous CAR T-Cell cell therapy products and an allogeneic T-Cell platform, targeting a broad range of cancer indications. CAR T-Cell immuno-oncology represents one of the most promising cancer treatment areas today. We expect to initiate a U.S. Phase I trial evaluating our lead immune-oncology portfolio candidate, CAR-NKG2D, in the first quarter of 2015, with interim results expected at various times during the trial and final results expected by mid-2016. The Company intends to rapidly advance the development all of the OnCyte assets, with a focus on CAR NKG2D, which should move into at least five later stage trials in 2016, in various solid and liquid tumors in both Europe and the USA.

In October 2014, Cardio3 BioSciences announced the signing of a non-exclusive preferred access agreement with the Mayo Clinic. With this agreement, Cardio3 BioSciences agreed to give preferred consideration for Rochester, Minnesota to the U.S. to build a manufacturing facility for the production of C-Cure®, at a facility located adjacent to the campus of the Mayo Clinic, and the Mayo Clinic agreed to periodically review with Cardio3 BioSciences its portfolio of regenerative medicine technologies, including in the areas of cardiology and oncology, with a view towards future potential licensing. Building on its core competencies and unique expertise in cellular therapies and cardiovascular diseases developed with C-Cure®, Cardio3 Biosciences’ potential access to Mayo Clinic Center for Regenerative Medicine technologies has the potential to further strengthen the Company’s long-term plan to bring the best innovative therapeutic response to unmet medical needs.

Also in November, Cardio3 BioSciences successfully acquired CorQuest and its unique heart access platform that could receive CE marking by the end of 2016. The acquisition also included medical devices and implants targeted at mitral valve defects indications. This acquisition bolsters the Company’s strategic position as a leading developer of innovative devices for cardiac surgery and the treatment of cardiovascular indications. Moreover, the CorQuest technology platform is fully complementary with Cardio3 BioSciences’ C-Cathez® and C-Cure® programs.

Strengthening of operational capabilities with additions to the team

At the end of March 2014, the Company announced the appointment of Hanspeter Spek as an Independent director. Mr. Spek represents a major addition to the Board and is expected to contribute significantly to the conclusion of industry partnerships in preparation for the commercialization of the Company’s products. Hanspeter was President Global Operations of Sanofi, prior to his retirement from the Company in mid-2013.

At the beginning of June, the Company appointed Dr. Georges Rawadi as Vice President, Business Development. Leveraging more than 20 years of experience in the healthcare industry, Dr. Rawadi will be responsible for leading Cardio3 BioSciences’ worldwide business development efforts, by identifying avenues for growth, international expansion and managing the company’s business partner relationships.

At the beginning of November 2014, Dr. Warren Sherman joined the Company as Chief Medical Officer to support the continued development of the product pipeline, both in cell therapies and cardiovascular diseases

Financial Review

On 30 June 2014, the Company completed a capital raise of €25 million, which was priced at €44 per share, a 14% premium to the 30 days average price preceding the transaction. In conjunction with the raise, the Company welcomed new investor Medisun International Limited, a Hong Kong-based investment company.

In early July 2014, the Company completed a secondary placement with six Swiss institutional investors. This transaction occurred off-market through an exchange of shares between certain historical shareholders of the Company and Swiss professional investors. The transaction involved the sale of 141,800 shares at €43.5 each. The proportion of shares sold by the existing shareholders did not exceed 25% of their stake in the Company. The share capital and the number of shares of the Company remained unchanged after this secondary transaction.

As of 31 December 2014 Cardio3 BioSciences had €30.3 million in treasury compared to €22.1 million on 31 December 2013.

For the twelve month period ending 31 December 2014, total operating expenses of the Company amounted to €20.9 million compared to €13.0 million for the same period in 2013. Increase of operating expenses of 2013 is in line with Company expectations, and partially offset by non-dilutive funding received over 2014, presented as other operating income. At year-end 2014, the net loss for period was €16.5 million versus a net loss of €14.5 million for same period in 2013.

Cash flow from operating activities represented at year end 2014 a net cash outflow of €17.4 million, or an increase of €6.8 million compared to 2013. This increase primarily resulted from the operational costs associated to the C-Cure® CHART-1 clinical trial, initiated in mid-2013.

Cash flow from investing activities represented a net cash outflow amounting to €1.8 million in 2014 mainly due to the acquisition of CorQuest for €1.5 million. In 2013, most of the cash outflow from investing activities resulted from a €3 million investment in a 3-year short term deposit account.

Cash flow from financing activities represented a net cash inflow €27.8 million in 2014 compared to €31.6 million in 2013. In 2014, the proceeds from issuance of shares amount to €25.3 million (compared to €31.0 million in 2013), whereas the proceeds received from non-dilutive funding (Walloon Region and FP7 programs) amounted to €2.4 million in 2014.

The complete “2014 Annual Financial Report” will be available on the Company’s website on May 5, after the Annual Shareholders’ meeting has taken place.

The Company continues to exercise prudent cash management, ending 2014 with €30.3 million in cash and term deposits. Cardio3 management believes that the current cash balance is sufficient to fund the C-Cure® clinical program until the availability of the read-out of the primary endpoint, anticipated first half of 2016.

Significant events occurring post balance sheet date

In January 2015, we acquired 100% of the membership interests of Oncyte LLC from Celdara Medical LLC in exchange for a total upfront payment of USD 10 million, comprised of cash consideration of $6 million and new shares of Cardio3 BioSciences for a total value of $4 million. The sales price also includes contingent consideration payments based on future outcome of the research and development until market approval of $50 million and potential additional future sales milestones and royalties.

In February 2015, the Company announced that it had successfully raised €32 million through a private placement of ordinary shares to qualified institutional investors in the United States and Europe at a price of €44.50 per share. The proceeds from the private placement will be used by Cardio3 BioSciences to further develop its newly acquired CAR-T cell technology platform; strengthen the leadership of C-Cure® for the treatment of congestive heart failure as well as for general corporate purposes.

Auditor report and restatement of 2013 Financial Statements

PriceWaterhouseCoopers, the new statutory auditor of the Group has not yet issued its audit report on the annual consolidated accounts for the year ended 31 December 2014.

The financial statements of the Group of 2013 were restated to reflect errors in the IFRS accounting treatment of respectively the shareholders convertible loans and the share based payments.

After due consideration with its auditors, we decided that the shareholders convertible loans should have been accounted for as a financial debt instead of equity (previously called ‘quasi equity’) as originally posted in our 2013 financial statements, because the loans were convertible into a variable number of shares. This correction of error in the IFRS accounting treatment triggers the valuation of this financial debt at fair value at inception and at each subsequent reporting date up till conversion in May 2013. The revaluation to fair value of this financial debt led to an additional financial expense of € 1.1 million in the 2013 income statement. Due to the conversion of these convertible loans in May 2013, the amount of the financial liability has been reclassified into equity.

The adjustment of the share based payments is related to the warrant plan issued by the Group in May 2013, initially valued using a share price at €2.64. After due consideration, we decided to increase the fair value of the shares used to determine the share based payment measurements to €16.65 in light of the IPO listing price of €16.65, triggering an increase of the share base payments and an additional noncash expenses in 2013 of €1.0 million.

The total net equity of the Group as of 31 December 2013 remains unchanged. These adjustments have no impact on the cash flow statement neither on the net cash position of the Company as of 31 December 2013 as there are a non-cash adjustment.