UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 6-K

 

 

REPORT OF FOREIGN PRIVATE ISSUER

PURSUANT TO RULE 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the Month of September 2019

Commission File Number: 001-37452

 

 

CELYAD SA

(Translation of registrant’s name into English)

 

 

Rue Edouard Belin 2

1435 Mont-Saint-Guibert, Belgium

(Address of principal executive offices)

 

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F  ☒            Form 40-F  ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):  ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):  ☐

 

 

 


Celyad SA

On September 4, 2019, Celyad SA (the “Company”) issued a press release, a copy of which is attached hereto as Exhibit 99.1 and is incorporated by reference herein.

The Company will be conducting meetings with investors beginning on September 4, 2019. As part of these meetings, the Company will deliver the slide presentation furnished to this report as Exhibit 99.2 and which is incorporated herein by reference.

The information in this report included as Exhibit 99.1 and Exhibit 99.2 and incorporated herein by reference shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section. It may only be incorporated by reference in another filing under the Exchange Act or the Securities Act of 1933, as amended, if such subsequent filing specifically references the information furnished pursuant to this report.


EXHIBITS

 

Exhibit

  

Description

99.1    Press release issued by the registrant on September 4, 2019
99.2    Investor presentation furnished by Celyad SA


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

    CELYAD SA
Date: September 4, 2019     By:  

/s/ Filippo Petti

     

Filippo Petti

Chief Executive Officer and Financial Officer

     

EXHIBIT 99.1

 

LOGO   

Press Release

4 September 2019

7:00 am CEST

 

Celyad Successfully Doses First Patient with CYAD-01 Produced with OptimAb Manufacturing Process

 

 

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-based therapies, today announced the successful administration of CYAD-01 produced with the OptimAb manufacturing process to a patient enrolled in cohort 3 (300 million cells) of the Phase 1 DEPLETHINK trial.

Jean-Pierre Latere, Chief Operating Officer of Celyad said “The dosing of the first patient with CYAD-01 manufactured with the OptimAb process marks another important milestone for our company. The OptimAb manufacturing process has shown exciting activity in preclinical models and we believe that the integration of the manufacturing process into our autologous relapsed/refractory acute myeloid leukemia program should help us to improve upon the initial signals we have observed to date with CYAD-01. We look forward to reporting preliminary data from patients enrolled in the DEPLETHINK trial treated with CYAD-01 produced with the OptimAb process by the end of the year.”

Background on CYAD-01

CYAD-01 is an investigational CAR-T therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells.

Background on OptimAb Manufacturing Process

The OptimAb manufacturing process utilizes a shortened cell culture and incorporates a selective PI3K inhibitor. This results in a product that is enriched for T cells with a memory-like phenotype. Preclinical data demonstrate that CYAD-01 produced using the OptimAb manufacturing process drives improved anti-tumor activity in an aggressive acute myeloid leukemia (AML) model compared to CYAD-01 produced with the previous mAb manufacturing process.

Background on DEPLETHINK Phase 1 Trial

In October 2018, Celyad initiated the DEPLETHINK Phase 1 trial (NCT03466320). The open-label, dose-escalation trial will evaluate a single infusion of CYAD-01 for the treatment of relapsed/refractory AML and myelodysplastic syndromes (MDS) following preconditioning chemotherapy (cyclophosphamide [300 mg/m²] and fludarabine [30 mg/m²]). The trial will evaluate three dose levels of CYAD-01 including 100 million, 300 million and 1 billion cells per infusion, respectively. The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

***END***

 

www.celyad.com | 1


LOGO   

Press Release

4 September 2019

7:00 am CEST

 

About Celyad

Celyad is a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell-based product candidates and utilizes its expertise in cell engineering to target cancer. Celyad’s CAR-T cell platform has the potential to treat a broad range of solid and hematologic tumors. The company’s lead clinical candidate, CYAD-01, an autologous NKG2D-based CAR-T therapy, is currently being evaluated in several Phase 1 clinical trials to assess safety and clinical activity for the treatment of hematological malignancies, such as acute myeloid leukemia, and solid cancers, such as metastatic colorectal cancer. Celyad is also developing CYAD-101, an investigational, non-gene edited, allogeneic (donor derived) NKG2D-based CAR-T therapy, which is currently being evaluated in a Phase 1 trial for the treatment of patients with metastatic colorectal cancer. Celyad was founded in 2007 and is based in Mont-Saint-Guibert, Belgium, and New York, NY. Celyad’s ordinary shares are listed on the Euronext Brussels and Euronext Paris exchanges, and its American Depository Shares are listed on the Nasdaq Global Market, all under the ticker symbol CYAD.

For more information, please contact:

 

Celyad

Filippo Petti, Chief Executive Officer – investors@celyad.com

Anne Moore, Vice President Corporate Strategy – T: +32(0) 10 39 41 87 – communications@celyad.com

 

For Europe: Ulysse Communication

Bruno Arabian – T.: +33 (0)6 87 88 47 26 – barabian@ulysse-communication.com

 

U.S.: LifeSci Advisors

Investor Relations: Daniel Ferry – T.: +1 (617) 535 7746 – daniel@lifesciadvisors.com

Public Relations: Sara Zelkovic – T.: +1 (646) 876 4933 – sara@lifescipublicrelations.com

Forward-looking statements

This release may contain forward-looking statements, including statements regarding: the safety and clinical activity of CYAD-01, CYAD-101 and CYAD-02; statements regarding the ongoing and planned clinical development of CYAD-01, CYAD-101 and CYAD-02, including the timing of trials, enrolment, data readouts and presentations; the clinical and commercial potential of CYAD-01, CYAD-101 and CYAD-02; and our mAb manufacturing processes. Forward-looking statements may involve known and unknown risks, uncertainties and other factors which might cause actual results, financial condition and liquidity, performance or achievements of Celyad, or industry results, to differ materially from those expressed or implied by such forward-looking statements. In particular it should be noted that the data summarized above are preliminary in nature. There is limited data concerning safety and clinical activity following treatment with the CYAD-01, CYAD-101 and CYAD-02 drug product candidates. Our therapeutic candidates manufactured using our OptimAb process have not yet been evaluated in clinical trials. Prior clinical and preclinical results may not be repeated or observed in ongoing or future clinical studies involving the CYAD-01 and CYAD-101 drug product candidates. These forward-looking statements are further qualified by important factors and risks, which could cause actual results to differ materially from those in the forward-looking statements, including statements about: the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our ability to advance drug product candidates into, and successfully complete, clinical trials; our ability to successfully manufacture drug product for our clinical trials, including with our OptimAb manufacturing process and with respect to manufacturing drug product with the desired number of T cells under our clinical trial protocols; our reliance on the success of our drug product candidates, including our dependence on the regulatory approval of CYAD-01, CYAD-101 and CYAD-02 in the United States and Europe and subsequent commercial success of CYAD-01, CYAD-101 and CYAD-02, both of which may never occur; the timing or likelihood of regulatory filings and approvals; our ability to develop sales and marketing capabilities; the commercialization of our drug product candidates, if approved; the pricing and reimbursement of our drug product candidates, if approved; the implementation of our business model, strategic plans for our business, drug product candidates and technology; the scope of protection we are able to establish and maintain for intellectual property rights covering our drug product candidates and technology; our ability to operate our business without infringing, misappropriating or otherwise violating the intellectual property rights and proprietary technology of third parties; cost associated with enforcing or defending intellectual property infringement, misappropriation or violation; product liability; and other claims; regulatory development in the United States, the European Union, and other jurisdictions; estimates of our expenses, future revenues, capital requirements and our needs for additional financing; the potential benefits of strategic collaboration agreements and our ability to maintain

 

www.celyad.com | 2


LOGO   

Press Release

4 September 2019

7:00 am CEST

 

and enter into strategic arrangements; our ability to maintain and establish collaborations or obtain additional grant funding; the rate and degree of market acceptance of our drug product candidates, if approved; our financial performance; developments relating to our competitors and our industry, including competing therapies and statements regarding future revenue, hiring plans, expenses, capital expenditures, capital requirements and share performance. A further list and description of these risks, uncertainties and other risks can be found in Celyad’s U.S. Securities and Exchange Commission (SEC) filings and reports, including in its Annual Report on Form 20-F filed with the SEC on April 5, 2019 and subsequent filings and reports by Celyad. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document and Celyad’s actual results may differ materially from those expressed or implied by these forward-looking statements. Celyad expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation.

 

www.celyad.com | 3

SLIDE 1

Corporate Presentation September 2019 EXHIBIT 99.2


SLIDE 2

Forward-Looking Statements This presentation may contain forward-looking statements, including statements regarding the safety and efficacy of our drug product candidates and the manufacturing methods used to manufacture these drug product candidates; statements concerning the ongoing and planned clinical development of our drug product candidates, including the timing of trials, enrollment, data readouts and presentations; the clinical and commercial potential of CYAD-01 and CYAD-101 and the adequacy of Celyad’s financial resources; the clinical and commercial potential of technology platforms; Celyad’s financial condition, results of operation and business outlook; and Celyad’s expected cash burn. Forward-looking statements may involve known and unknown risks, uncertainties and other factors which might cause actual results, financial condition and liquidity, performance or achievements of Celyad, or industry results, to differ materially from those expressed or implied by such forward-looking statements. In particular it should be noted that the data summarized above are preliminary in nature. There is limited data concerning safety and clinical activity following treatment with our drug product candidates. These results may not be repeated or observed in ongoing or future studies involving our drug product candidates. These forward-looking statements are further qualified by important factors and risks, which could cause actual results to differ materially from those in the forward-looking statements, including statements about: the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our ability to advance drug product candidates into, and successfully complete, clinical trials; our ability to successfully manufacture drug product for our clinical trials; our reliance on the success of our drug product candidates, including our dependence on the regulatory approval of our drug products in the United States and Europe and subsequent commercial success of our drug products, which may never occur; the timing or likelihood of regulatory filings and approvals; our ability to develop sales and marketing capabilities; the commercialization of our drug product candidates, if approved; the pricing and reimbursement of our drug product candidates, if approved; the implementation of our business model, strategic plans for our business, drug product candidates and technology; the scope of protection we are able to establish and maintain for intellectual property rights covering our drug product candidates and technology; our ability to operate our business without infringing, misappropriating or otherwise violating the intellectual property rights and proprietary technology of third parties; cost associated with enforcing or defending intellectual property infringement, misappropriation or violation; product liability; and other claims; regulatory development in the United States, the European Union, and other jurisdictions; estimates of our expenses, future revenues, capital requirements and our needs for additional financing; the potential benefits of strategic collaboration agreements and our ability to maintain and enter into strategic arrangements; our ability to maintain and establish collaborations or obtain additional grant funding; the rate and degree of market acceptance of our drug product candidates, if approved; our financial performance; developments relating to our competitors and our industry, including competing therapies and statements regarding future revenue, hiring plans, expenses, capital expenditures, capital requirements and share performance. A further list and description of these risks, uncertainties and other risks can be found in Celyad’s U.S. Securities and Exchange Commission (SEC) filings and reports, including in its most recent Annual Report on Form 20-F filed with the SEC and subsequent filings and reports by Celyad. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document and Celyad’s actual results may differ materially from those expressed or implied by these forward-looking statements. Celyad expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation.


SLIDE 3

Clinical-stage Biopharmaceutical Company Focused on the Development of CAR-T Therapies Lead candidate is autologous CAR-T therapy, CYAD-01, which leverages the natural killer receptor, NKG2D, currently in Phase 1 trial for the treatment of r/r AML and MDS First-in-class, non-gene edited allogeneic TIM technology/NKG2D-based CAR-T candidate CYAD-101 currently in Phase 1 trial for the treatment of mCRC Developing novel, non-gene edited allogeneic platform based on shRNA technology with three preclinical candidates from CYAD-200 series targeting BCMA, CD19 and NKG2D/undisclosed membrane protein “All-in-One Vector” approach provides flexibility and versatility to design novel CAR-T therapies Expertise in cell therapy manufacturing with in-house centralized GMP facility and logistical capabilities supporting global CAR-T cell therapy clinical trials Robust intellectual property position with respect to NKG2D receptor-based and allogeneic CAR-Ts CAR-T: Chimeric Antigen Receptor T-cell; AML: Acute myeloid leukemia; mCRC: Metastatic colorectal cancer; BCMA: B-Cell Maturation Antigen; MDS: Myelodysplastic syndrome; r/r: relapsed/refractory; TIM: T cell Inhibitory Molecule.


SLIDE 4

Continuing the Advancement of CAR-T Therapies Accelerate the clinical development program for autologous NKG2D-based CAR-T therapies for the treatment of r/r AML and focus on path to commercialization Today Tomorrow Beyond Leverage our innovative allogeneic approaches including TIM for CYAD-101, novel shRNA platform for CYAD-200 series and broad allogeneic IP to become a leading player in the field “Crack the code” in solid tumors with an NKG2D-based CAR-T therapy through well-established and novel combination regimens to pursue multiple indications


SLIDE 5

Advancing CAR-T Therapy Pipeline Target Product Preclinical IND Submission Design Phase 1 Study AML: Acute myeloid leukemia; mCRC: Metastatic colorectal cancer; MDS: Myelodysplastic syndrome; MM: Multiple myeloma; r/r: relapse/refractory. CyFlu: cyclophosphamide and fludarabine; FOLFOX: leucovorin, fluorouracil, and oxaliplatin. CYAD-01 NKG2D CYAD-101 NKG2D THINK Standalone w/o Preconditioning Concurrent with FOLFOX mCRC alloSHRINK Schedule optimization w/o Preconditioning r/r AML / MDS THINK Cohort 10/11 Preconditioning with CyFlu THINK CyFlu Concurrent with FOLFOX SHRINK Preconditioning with CyFlu r/r AML / MDS DEPLETHINK CYAD-02 NKG2D CYAD-211 BCMA MM CYAD-221 CD19 CYAD-231 NKG2D x Undisclosed ALLOGENEIC CYAD-03 NKG2D B-cell malignancies Hematological malignancies and Solid tumors mCRC mCRC


SLIDE 6

Background on NKG2D Receptor


SLIDE 7

Development of Novel NKG2D-based CAR-T NKG2D is an activating receptor expressed on natural killer (NK) cells which plays an important role in protection against infection and cancer The receptor binds to eight stress induced ligands including: MICA, MICB, ULBPs 1-6 NKG2D ligands are absent or expressed at low levels in normal tissues Expression of NKG2D ligands: Overview of NKG2D Receptor Pancreatic: 90% Triple negative breast: 100% Acute myeloid leukemia: 100% Colorectal: 100% Ovarian: 84% The binding of eight ligands by the NKG2D receptor provides an opportunity to target a broad range of cancers with the novel CAR-T therapy, CYAD-01 NKG2D Receptor DAP10 Costimulatory domain CD3ζ CYAD-01 Source: Company data


SLIDE 8

NKG2D AML / MDS Program


SLIDE 9

CRh CRi mCR SD SD CRi (1) (2) Anti-leukemic activity observed Interim Analysis from THINK Trial Demonstrates Clinical Activity of CYAD-01 Without Preconditioning Chemotherapy Interim results as of January 4, 2019. CRh: Complete response with partial hematological recovery; CRi: Complete response with incomplete marrow recovery; mCR: Marrow complete response; PR: Partial response; SD: Stable disease; DL: Dose-Limiting. Patient 102-507 had relapsing MDS with refractory anemia with excess blasts (RAEB). Patient 202-506 achieved relevant bone marrow blast decrease following second cycle of CYAD-01 without preconditioning chemotherapy (not shown). Clinical activity observed across all three dose levels of CYAD-01 Potential induction of PR post-hematological relapse following second cycle of CYAD-01 in patient 202-506 (2) Bone marrow blasts show no loss of NKG2D ligand expression following treatment with CYAD-01 DL-3 DL-2 DL-1 SD SD


SLIDE 10

r/r AML/MDS Program – Summary of Ongoing Trials CR: Complete response including CRh (Complete response with partial hematological recovery) or CRi (Complete response with incomplete marrow recovery); SD: Stable disease. First three injections of CYAD-01 separated by one-week intervals, while the second cycle of three injections of CYAD-01 separated by two-week intervals. Patients presenting no signs of progression are eligible to receive a second cycle of three CYAD-01 injections without preconditioning. In June 2019, the Food and Drug Administration and Federal Agency for Medicines and Health Products accepted proposal to utilize the OptimAb manufacturing process with CYAD-01 program. In July 2019, one patient was treated with CYAD-01 produced with mAb manufacturing process but died thereafter rapidly due to the progression of AML in the patient.


SLIDE 11

Recent Developments for r/r AML and MDS Program CyFlu: Cyclophosphamide and fludarabine; FDA: U.S. Food and Drug Administration; FAMHP: Federal Agency for Medicines and Health Products. IND: Investigational New Application. Submitted Chemistry, Manufacturing, and Control (CMC) amendments related to CYAD-01’s current IND to the FDA and FAMHP In June 2019, the FDA and FAMHP accepted proposal to utilize the OptimAb manufacturing process with CYAD-01 program Plan to treat first patient with the CYAD-01 OptimAb manufacturing process in cohort 3 of the DEPLETHINK trial by September 2019 Initial clinical data from cohort 3 of the DEPLETHINK trial are expected by year-end 2019 Additional results from patients dosed with OptimAb manufactured product from cohorts 3 and 4 are anticipated in first half 2020 CYAD-01 OptimAb Next-Generation CYAD-02 In June 2019, the FDA accepted the IND application for CYAD-02 CYAD-02 leverages Horizon Discovery’s shRNA SMARTvector technology to target the NKG2D ligands, MICA and MICB, which translates to an encouraging increase in vitro proliferation, in vivo engraftment and anti-tumor activity Utilizes OptimAb manufacturing process Phase 1 dose-escalation trial evaluating the safety and clinical activity of CYAD-02 following preconditioning with CyFlu chemotherapy expected to begin in early 2020 Preliminary data from the Phase 1 trial are expected by mid-2020


SLIDE 12

Highlights of OptimAb Manufacturing Process for r/r AML and MDS Program OptimAb process drives improved survival in an aggressive AML model, where CYAD-01 dose is titrated for minimal activity Enriches for T-cells with Memory-like Phenotype OptimAb manufacturing process maintains an earlier memory phenotype, with higher percentage of central memory cells compared to previous mAb manufacturing process Improved In vivo Anti-tumor Activity Time (Days) Percent survival


SLIDE 13

NKG2D Solid Tumor Program


SLIDE 14

PR: Partial response; SD: Stable disease; RECIST: Response Evaluation Criteria in Solid Tumors. alloSHRINK trial enrolling patients with unresectable metastatic colorectal cancer, refractory to FOLFOX chemotherapy. mCRC Program – Summary of Clinical Data THINK THINK CyFlu SHRINK alloSHRINK (1) Product (Target) CYAD-01 (NKG2D) CYAD-01 (NKG2D) CYAD-01 (NKG2D) CYAD-101 (NKG2D) Monotherapy ü Preconditioning ü (CyFlu) Combination ü (FOLFOX) ü (FOLFOX) Autologous ü ü ü Allogeneic ü Number of injections 3 1 3 3 Dose(s) 3x108, 1x109, 3x109 3x108 1x108, 3x108, 1x109 1x108 3x108 1x109 Patients N=11 N=3 N=9 N=3 N=3 N=9 Data Generally well-tolerated 27% SD in mCRC Generally well-tolerated Translational data suggest an improvement in cell engraftment 1 SD Concurrent treatment with FOLFOX generally well-tolerated Neoadjuvant patients: 1 PR and 2 SD based on RECIST Refractory patients: 4 SD No GvHD in first two dose cohorts (N=6) Generally well-tolerated 1 PR and 3 SD based on RECIST Enrollment ongoing with data expected by YE:2019


SLIDE 15

CYAD-101 – First Non-gene Edited Allogeneic CAR-T Leveraging TIM-mediated Inhibition of TCR Signaling for the Treatment of Solid Tumors Endogenous TCR/CD3 complex CYAD-101 The expression of TIM results in the competitive inhibition of CD3z and reduces signalling of the TCR complex leading to the potential reduction or elimination of GvHD in patients treated with CYAD-101 NKG2D CAR TIM-incorporating TCR/CD3 complex Additional results from the ongoing Phase 1 alloSHRINK trial (1) are expected by year-end 2019 TIM: T cell Inhibitory Molecule; TCR: T-cell receptor; GvHD: Graft versus Host Disease. alloSHRINK: CYAD-101 administered concurrently with standard of care FOLFOX chemotherapy for the treatment of patients with unresectable mCRC (NCT03692429).


SLIDE 16

CYAD-200 Series – Novel, Allogeneic CAR-Ts


SLIDE 17

Celyad Targets CD3ζ to Generate Allogeneic T-cells CD3ζ is the rate-limiting factor to the TCR complex moving to the cell surface and an attractive target (i.e. shRNA, TIM) TCR complex is responsible for GvHD Elimination of the TCR complex is necessary for creating allogeneic CAR-T therapies TCRα (TRAC) is a common target for gene edited approaches (i.e. CRISPR-Cas9, TALENs, ZFNs) TIM: T cell Inhibitory Molecule; TCR: T-cell receptor; GvHD: Graft versus Host Disease; shRNA: short hairpin RNA; TRAC: T Cell Receptor Alpha Constant; TALEN: Transcription Activator-Like Effector Nucleases; ZFN: Zinc Finger Nucleases.


SLIDE 18

Exclusive agreement with Horizon Discovery Group Horizon’s SMARTvector technology mimics endogenous mature microRNA shRNA allows knockdown of gene expression via RNA interference Developing a Novel, Non-gene Edited Allogeneic CAR-T Platform Based on Horizon’s shRNA SMARTvector Technology TCR: T-cell receptor; shRNA: short hairpin RNA. A. Vermeulen et.al. Development of the Dharmacon™ SMARTvector™ Lentiviral shRNA microRNA-adapted scaffold and algorithm for functional shRNAs (2018). microRNA scaffold Optimized for best insertion Pol II promoter To compare in preclinical models the ability of shRNA to modulate the expression levels of the TCR complex from the cell surface of T-cells with that of gene editing technology, we developed a CRISPR-Cas9 control knockout of the CD3ζ to mimic our shRNA approach Comparison of shRNA vs. Gene Editing


SLIDE 19

Cell Surface TCR Complex Intensity of TCRα/β TCR Stimulation Assay shRNA targeting CD3ζ reduces TCR expression and cytokine response shRNA vs. CRISPR-Cas9: Equivalent Knockdown of TCR TCR: T-cell receptor; shRNA: short hairpin RNA.


SLIDE 20

Controlled GvHD of Allogeneic CAR Despite T Cell Expansion Survival Persistence ** Mann-Whitney U -Test p-value of 0.0017; **** Mann-Whitney U-Test p-value of <0.0001. Mean Weight No evidence of major weight loss – a typical characteristic of GvHD induction In vivo protection of GvHD similar to CRISPR-Cas9 knockout Persistence of T cells with shRNA superior to gene editing technologies 16 18 20 22 24 26 < 50% of animals alive -1 1 5 10 15 20 25 30 35 40 45 50 Days Weight (g) CTR (tCD19) (n=22) shRNA CD3z (n=23) CRISPR CD3z (n=17) 0 10 20 30 40 0 50 100 Days Percent survival CTR (tCD19) (n=22) shRNA CD3z (n=23) CRISPR CD3z (n=17) shRNA CD3z CRISPR CD3z Days Frequency of human T-cells (%) 0 7 21 28 34 54 14 0 20 30 10


SLIDE 21

Trio of Disruptive, First-in-Class, Non-Gene Edited Allogeneic CARs BCMA CAR-T for multiple myeloma Evaluate shRNA approach with validated target Potential best-in-class allogeneic approach given increased persistence vs. gene edited candidates Expected to enter the clinic by mid-2020 CYAD-211 CYAD-221 CYAD-231 CD19 CAR-T for B-cell malignancies Despite multiple marketed products for the treatment of B-cell malignancies, many patients fail to receive treatment given manufacturing challenges Expected to enter the clinic by late 2020 Dual specific NKG2D/Undisclosed CAR-T Currently evaluating multiple CARs / targets to pair with NKG2D receptor Expected to enter the clinic by first half 2021 CYAD-200 Series


SLIDE 22

Cell Therapy Manufacturing


SLIDE 23

Proprietary 11,000 sq. ft. facility 94% manufacturing success rate in 2018 vs. 75% in 2017 Capabilities Support Clinical Development and Future Product Launch Streamlined centralized logistics to supply both U.S. and E.U. Over 600 billion cells produced in 2018 33 Patients treated in 2018 vs. 16 in 2017 and 8 in 2016 Cryopreserved products


SLIDE 24

Strategy and Financials


SLIDE 25

Strong Intellectual Property In May 2017, Celyad granted Novartis a non-exclusive license for allogeneic TCR-deficient CAR-T cells patents related to two undisclosed targets Deal terms: Undisclosed upfront payment with $96 million in milestones plus royalties on commercial U.S. sales Celyad retains all rights to grant further licenses to the undisclosed targets Strategic Validation Key U.S. Patents Allogeneic T-Cell Technology (1) T-cell receptor deficient T-cell compositions Method of producing T-cell receptor deficient T-cells expressing a chimeric receptor Chimeric NK receptor and methods for treating cancer (2) Granted U.S. Patents: No. 9,181,527, No. 9,938,497, No. 9,957,480, No. 9,663,763, No. 9,822,340 and No. 9,821,011. Granted U.S. Patent: No. 9,273,283.


SLIDE 26

Upcoming Milestones First Half 2020 CYAD-01 in r/r AML: Enrollment of first patient in cohort 3 of DEPLETHINK trial with OptimAb manufacturing process CYAD-101 in mCRC: Additional data from alloSHRINK trial CYAD-01 in r/r AML: Results from cohort 11 of THINK trial as well as cohort 3 from DEPLETHINK trial * CYAD-01 in r/r AML: Initial OptimAb data from cohort 3 of DEPLETHINK trial CYAD-02 in r/r AML: Initiation of Phase 1 dose-escalation trial CYAD-01 in r/r AML: Report additional OptimAb data from cohorts 3 and 4 of DEPLETHINK trial CYAD-211: Submission of IND application for shRNA-based allogeneic BCMA CAR-T therapy for the treatment of patients with multiple myeloma Second Half 2019 CYAD-02 in r/r AML: Preliminary data from Phase 1 trial CYAD-221: Submission of IND application for shRNA-based allogeneic CD-19 CAR-T therapy for the treatment of patients with B-cell malignancies Second Half 2020 * Cohort 11 of THINK Schedule Optimization and first three patients of Cohort 3 of DEPLETHINK trials utilize mAb manufacturing process.


SLIDE 27

Financial Snapshot Cash, cash equivalents and short-term investments: €33.7 million ($38.3 million) as of second quarter ended June 30, 2019 Current cash expected to support the company’s activities into mid-2020 Basic Shares Outstanding: 11.9 million Ticker: Nasdaq (CYAD) and Euronext Brussels & Paris (CYAD.BR)