Non-regulated

• Preliminary data from the Phase 1 CYCLE-1 trial are expected during second half 2020

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 the next-generation, NKG2D-based candidate CYAD-02 to a relapsed/refractory acute myeloid leukemia (r/r AML) patient enrolled in the Phase 1 CYCLE-1 trial.

Dr. Dries Deeren, Head of Clinical Hematology at AZ DeltaHospital Roeselare said, “We are proud to be participating in the CYCLE-1 trial evaluating the novel CAR-T cell therapy, CYAD-02, for the treatment of patients with advanced acute myeloid leukemia. Initial clinical results from Celyad’s AML and MDS program look encouraging. Based on preclinical data, where CYAD-02 has shown a differentiated and more potent profile to the first-generation approach, we’re excited to clinically evaluate the next-generation NKG2D construct in such an extremely challenging patient population.”

Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad, added, “Dosing the first patient with CYAD-02 marks another major milestone to systematically advance our pipeline of proprietary autologous product candidatesin our relapsed/refractory acute myeloid leukemia program. We look forward to investigating this next-generation approach which combines our NKG2D receptor, shRNA technology and OptimAb manufacturing process. Enrollment in the CYCLE-1 trial will continue over the coming months and we expect to report preliminary data from the study during the second half of 2020.”

Background on CYAD-02

CYAD-02 is an investigational CAR-T therapy that engineers an all-in-one vector approach in patient’s T-cells to express both (i) the NKG2D chimeric antigen receptor (CAR), a receptor expressed on natural killer cells that binds to eight stress-induced ligands expressed on tumor cells, and (ii) short hairpin RNA (shRNA) SMARTvector technology licensed from Horizon Discovery to knockdown the expression of NKG2D ligands MICA and MICB on the CAR-T cells. In preclinical models, shRNA-mediated knockdown of MICA and MICB expression on NKG2D CAR-T cells has shown enhanced in vitro expansion, as well as enhanced in vivo engraftment and persistence, of the CAR-T cells, as compared to first-generation NKG2D-based CAR-T cells.

Background on CYCLE-1 Phase 1 Trial

In November 2019, the Company initiated the Phase 1 CYCLE-1 trial (NCT04167696). The open-label, dose-escalation trial will evaluate the safety and clinical activity of a single infusion of CYAD-02 produced with the OptimAb manufacturing process following preconditioning chemotherapy cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu, in patients with r/r AML and myelodysplastic syndromes (MDS). In addition, patients are also eligible to receive bridging therapy, based on physician’s choice, in advance of treatment with CYAD-02. The trial will evaluate three dose levels of CYAD-02, at 100 million, 300 million and one billion cells per infusion.

• Future development of relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) program to be underpinned by proprietary OptimAb manufacturing process
• Enrollment of DEPLETHINK trial evaluating CYAD-01 following preconditioning chemotherapy continues, while THINK trial progresses to expansion segment with plans to evaluate monotherapy CYAD-01 produced with OptimAb manufacturing process
• CYCLE-1 trial evaluating next-generation, NKG2D-based CAR-T therapy CYAD-02 following preconditioning chemotherapy on track to begin enrollment in early 2020
• Preliminary results from the r/r AML and MDS program using the OptimAb manufacturing process are expected by the end of first half 2020

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 updates to the company’s autologous NKG2D-based CAR-T development program for the treatment of relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the American Society of Hematology (ASH) 61^st  Annual Meeting, which is being held from December 7-10, 2019 in Orlando, Florida.

Filippo Petti, CEO of Celyad, commented, “Over the past few months we have worked diligently to transition our proprietary OptimAb manufacturing process to become the cornerstone of our autologous CAR-T program for the treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes. We are encouraged by the body of data generated to date by our lead autologous candidate CYAD-01 for the treatment of AML and MDS, especially given its tolerability profile and anti-leukemic activity.”

“We are excited to further evaluate our NKG2D-based CAR-T approach using our OptimAb manufacturing process, which generates a higher frequency of less differentiated CAR-T cells that exhibit enhanced anti-tumor activity in preclinical studies. Overall, we believe the process gives us the best opportunity for success across both autologous product candidates, CYAD-01 and CYAD-02. Along with our ongoing DEPLETHINK trial, the key next steps for our broad r/r AML and MDS program include the expansion of the THINK trial and initiation of the CYCLE-1 trial as we look to establish NKG2D as an important target for the treatment of difficult-to-treat malignancies”, continued Mr. Petti.   

CYAD-01 THINK Phase 1 Trial

• Sixteen patients have been enrolled to date in the trial evaluating CYAD-01 administered as a multiple injection with a biweekly schedule and an additional nine patients have been enrolled in the dose dense (weekly) schedule in the dose escalation segment of the trial
• CYAD-01 without preconditioning chemotherapy was generally reported to be well-tolerated, with 11 out of 25 patients experiencing grade 3/4 treatment-related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 13 patients, with four grade 3 and two grade 4 events, which showed rapid resolution following the appropriate treatment, including tocilizumab. Two dose-limiting toxicities were reported at dose level 3 (3 billion cells per infusion), including one CRS grade 4 (biweekly) and one CRS grade 3 (dose dense schedule). No treatment-related neurotoxicity AEs were reported
• Overall, eight patients out of 15 evaluable patients treated with CYAD-01 produced with the prior manufacturing process demonstrated anti-leukemic activity. Five out of the eight patients exhibited an objective response. In addition, one patient is exhibiting disease stabilization of over three months
• Patients treated within the CYAD-01 dose-dense (weekly) schedule cohorts of the trial did not demonstrate an improvement in clinical outcome as compared to patients treated with the biweekly dosing schedule. However, patients enrolled in the dose-dense schedule cohorts appeared to have greater bone marrow blasts infiltration and to be more pancytopenic at baseline compared to patients enrolled in the biweekly dose escalation segment of the trial
• Most of the anti-leukemic activity observed in the trial, except for the two patients who bridged to an allogeneic human stem cell transplant, experienced a short durability of response
• To date, anti-leukemic activity appears predominantly observed in patients initially diagnosed with non-adverse (ELN 2017, AML) or non-very high (IPSS-R, MDS) risk stratification categories. Additional patients are needed in the trial to better assess the observation
• Company plans to progress to the expansion segment of the THINK trial to further evaluate CYAD-01 produced with the OptimAb manufacturing process. Enrollment in the expansion segment of the trial is expected to begin in first quarter 2020 with preliminary data anticipated by the end of first half 2020

CYAD-01 DEPLETHINK Phase 1 Trial

• Nine patients have been enrolled in the trial evaluating CYAD-01 produced with the prior mAb manufacturing process following preconditioning chemotherapy cyclophosphamide and fludarabine, or CyFlu, at the first two dose levels of the dose escalation segment of the trial
• CYAD-01 produced with the mAb manufacturing process was generally reported to be well-tolerated following preconditioning chemotherapy. At the first CYAD-01 infusion of the consolidation cycle (3 billion cells per infusion), one patient experienced both grade 4 cytokine release syndrome (CRS) and grade 3 CAR-T cell-related encephalopathy and another patient experienced grade 3 CRS. Both patients recovered following the appropriate treatment, including tocilizumab
• Preconditioning chemotherapy led to improved, dose-dependent engraftment of CYAD-01 cells as compared to cells infused with no preconditioning
• To date, no objective response has been observed at the first two dose levels of the trial in patients treated with CYAD-01 produced with the mAb manufacturing process
• In September 2019, the company announced the successful administration of CYAD-01 produced with the OptimAb manufacturing process to a patient enrolled in cohort 3 (300 million cells per infusion) of the trial
• Enrollment in the trial is ongoing with plans to dose escalate up to one billion cells per infusion in cohort 4. Preliminary data evaluating CYAD-01 produced with the OptimAb manufacturing process from cohorts 3 and 4 are expected by the end of first half 2020

CYAD-02 CYCLE-1 Phase 1 Trial

• In November 2019, the company initiated the dose-escalation Phase 1 CYCLE-1 trial (NCT04167696), which will evaluate the safety and clinical activity of the next-generation, autologous NKG2D-based CAR-T candidate CYAD-02, produced with the OptimAb manufacturing process following preconditioning chemotherapy CyFlu in patients with r/r AML and MDS
• CYAD-02 incorporates shRNA SMARTvector technology licensed from Horizon Discovery to target the NKG2D ligands MICA and MICB. shRNA-mediated knockdown of MICA and MICB expression on NKG2D CAR-T cells has been shown to enhance in vitro expansion of the CAR-T cells and enhanced engraftment and persistence in preclinical models as compared to CYAD-01 produced with the mAb process
• Enrollment in the CYCLE-1 trial is expected to begin in early 2020 with preliminary data anticipated during second half 2020

About THINK Phase 1 Trial

The THINK trial (NCT03018405) is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of multiple CYAD-01 administrations without prior preconditioning.  The dose escalation segment of the trial evaluated three dose levels (300 million, 1 billion and 3 billion cells per infusion) of one cycle of three CYAD-01 administrations with two-week intervals. In 2018, the THINK trial was amended to add two cohorts to assess a more frequent dosing schedule of CYAD-01 for the treatment of r/r AML. The cohorts will evaluate six injections of CYAD-01 without preconditioning over two months of administration. The first cycle includes three infusions of CYAD-01 separated by one-week intervals. The second cycle includes three infusions of CYAD-01 separated by two-week intervals. Patients will either receive 1 billion cells per infusion (Cohort 10) or 3 billion cells per infusion (Cohort 11). The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

About DEPLETHINK Phase 1 Trial

In October 2018, Celyad initiated the DEPLETHINK Phase 1 trial (NCT03466320). The open-label, dose-escalation trial is designed to evaluate a single infusion of CYAD-01 following treatment with the standard preconditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu. The trial includes two different intervals between lymphodepletion and administration of CYAD-01. In addition, the trial is evaluating 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.

About OptimAb Manufacturing Process

Celyad’s proprietary 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 NKG2D-based CAR-T cell therapies produced using the OptimAb manufacturing process drive improved anti-tumor activity in an aggressive AML model compared to alternative manufacturing process.

• Funding will support the advancement of the Company’s autologous and allogeneic
  CAR-T cell therapy programs

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 that the Company has received €8.5 million in grants and non-dilutive funding from the Walloon Region of Belgium. These funds will help support the development of the Company’s CAR-T candidates, including CYAD-01 and CYAD-02 for the treatment of relapsed/refractory acute myeloid leukemia, as well as next-generation approaches currently in preclinical development. The funding for technological innovation received on behalf of the Walloon Region was approved by Mr. Willy Borsus, Vice-President of Wallonia, Minister of Economy, Foreign Trade, Research and Innovation, Digital, Agriculture and Territorial Development.

Filippo Petti, chief executive officer of Celyad, commented, “We are grateful to the Walloon Region, and especially to the SPW-Recherche for their steadfast commitment to Celyad over the past decade. The latest addition of the non-dilutive funding awarded by the Walloon Region will continue to support the innovation of CAR-T cell therapy development and allow for the advancement of several of our autologous and allogenic candidates. Since mid-2016, Celyad has been focused on the development of differentiated candidates within the CAR-T therapy landscape. We believe the additional funds awarded by the Walloon Region will further boost our ability to deliver novel immunotherapies to benefit patients with both hematological malignancies and solid tumors.”

Under the terms of this funding from the Walloon Region of Belgium, the Company was awarded a €2.4 million grant and non-dilutive funding in the form of recoverable cash advances (‘avances récupérables’) for €6.1 million. The regional funding is associated with the Company’s specific research and development programs. Under the applicable conditions, the recoverable cash advance is reimbursable over the economic life of the projects. Thirty percent is refundable based on a fixed reimbursement schedule varying between 20 and 25 years, while the balance is refunded under the form of royalties over the same period. 

The Company also confirms its previous position that its treasury position, based on the current scope of activities and excluding the funding from the Walloon Region, should be sufficient to fund operating and capital expenditure requirements into first half 2021.

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 that management plans to participate at the following investor conferences in October and November 2019.

Conference details:

Investir Day 1^st Edition
Date: Thursday, October 3, 2019
Presentation time:  12:45 p.m. CEDT
Location:  Paris, France

CF&B Communication European Large & Midcap Event 19^th Edition
Date: October 14-15, 2019
Location: Paris, France 

Bryan, Garnier & Co European Healthcare Conference
Date: Wednesday, November 13, 2019
Location: Paris, France 

Finance Avenue 2019
Date: Saturday, November 16, 2019
Presentation Time: 12:55 p.m. CEDT
Location: Brussels, Belgium 

Jefferies 2019 London Healthcare Conference
Date: November 20 – 21, 2019
Location: London, United Kingdom

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 that management plans to participate at the following events in September 2019:

Wells Fargo Healthcare Conference

Date:  Wednesday, September 4, 2019              

Presentation Time:  4:10 p.m. EDT

Location:  Boston, Massachusetts, USA

Webcast:  Celyad’s website, under Events & Webcasts section 

CAR-TCR Summit

Date:  September 10 – 13, 2019            

Location:  Boston, Massachusetts, USA 

International Conference on Lymphocyte Engineering (ICLE)

Date:  September 13 – 15, 2019           

 Location:  London, United Kingdom 

KBC Annual Healthcare Conference

Date:  Thursday, September 26, 2019Location:  Brussels, Belgium