Non-regulated

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 the Company will report first half 2019 financial results and business highlights on the evening of Thursday, August 22, 2019.

Following the press release, Celyad management will host a conference call on Friday, August 23 at 2pm CEDT / 8am EDT to discuss first half 2019 results and provide an update on the Company’s recent progress and upcoming milestones.

Participants may access the conference call by dialing any of the following numbers:

Belgium, Brussels       +32 (0) 24 01 70 35

France, Paris                 +33 (0)1 76 72 89 28

United States:             +1 917 720 0181

International:               +44 (0) 2071 928501

Conference ID:            3547725

To access the subsequent archived recording, visit the “Events & Webcasts” section of the Celyad website.

• Preliminary interim results from the alloSHRINK Phase 1 trial demonstrate no evidence of GvHD for first-in-class, non-gene edited allogeneic NKG2D-based CAR-T candidate CYAD-101 when administered concurrently with FOLFOX chemotherapy for the treatment of metastatic colorectal cancer (mCRC)
• Initial observations of disease control, including partial response and stable disease, were observed with CYAD-01 and CYAD-101, in relapsed or refractorymCRC patients who have received prior FOLFOX chemotherapy
• At the same dose levels, allogeneic CYAD-101 appears to provide increased levels of relative cell engraftment as compared to autologous NKG2D-based CAR-T candidate, CYAD-01
• Management to hold a conference call on Friday, July 5^th, at 2 p.m. CEDT/ 8 a.m. EDT

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 Professor Dr. Eric Van Cutsem from the University Hospital of Leuven (Universitair Ziekenhuis Leuven, UZ Leuven) presented preliminary interim data from the ongoing SHRINK and alloSHRINK Phase 1 trials assessing safety and clinical activity of the NKG2D-based CAR-T therapies CYAD-01 (autologous) and CYAD-101 (allogeneic) for the treatment of metastatic colorectal cancer (mCRC) at the European Society for Medical Oncology (ESMO) 21^st World Congress on Gastrointestinal Cancer (WCGIC). Following the oral and poster presentations at WCGIC, Celyad’s management team will host a conference call to discuss the initial clinical results from the SHRINK and alloSHRINK trials.

“We are encouraged by these initial results showing increased levels of cell engraftment of the non-gene edited allogeneic CAR-T candidate CYAD-101, and that following treatment with CYAD-101 we did not observe any evidence of graft versus host disease, our foremost concern with the  allogeneic therapy” commented Professor Dr. Eric Van Cutsem, Gastrointestinal Oncologist at the University Hospital of Leuven. “In addition, anti-tumor activity has been observed with both the autologous CYAD-01 and allogeneic CYAD-101 candidates, in heavily pre-treated metastatic colorectal cancer patients who have received prior FOLFOX chemotherapy, providing confidence into this potential combination approach of CAR-T therapy with standard-of-care chemotherapy.”

Dr. Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad, commented “We are excited to share data on the first-in-class non-gene edited allogeneic CAR-T therapy CYAD-101 in metastatic colorectal cancer at ESMO GI in Barcelona. Professor Dr Van Cutsem gave us the great honor to share compelling clinical data for this novel class of NKG2D-based CAR-T therapies and the ability of the company’s novel T cell receptor Inhibiting Molecule, TIM, to reduce signalling of the TCR complex”. 

SHRINK Phase 1 Trial Update

• To date, nine mCRC patients (three in each dose level (DL): DL-1: 1×10⁸cells, DL-2: 3×10⁸ cells and DL-3: 1×10⁹ cells) have been enrolled as part of the dose-escalation, SHRINK Phase 1 trial evaluating CYAD-01 administered concurrently with FOLFOX chemotherapy. Patient enrollment included four neoadjuvant first-line treatment CRC patients with resectable liver metastasis (no prior FOLFOX treatment) and five non-resectable mCRC patients with prior multiple chemotherapy lines including FOLFOX and/or FOLFIRI chemotherapy. The mean number of prior therapies received for the relapsed/refractory mCRC patients enrolled was three
• Treatment with CYAD-01 with standard FOLFOX chemotherapy was generally well-tolerated, with no reports of cytokine syndrome release (CRS) grade 2 or higher, related serious adverse events (SAEs), dose-limiting toxicities (DLTs), nor on-target off-tumor toxicity
• Preliminary data show a dose–dependent effect on the kinetics of cells with higher levels of cell engraftment at higher doses of CYAD-01 doses
• Of the nine mCRC patients, one neoadjuvant patient experienced a partial response (PR) according to RECIST 1.1 criteria and a total of six patients experienced stable disease (SD) at month 3 including two neoadjuvant and four relapsed/refractory mCRC patients

alloSHRINK Phase 1 Trial Update

• To date, a total of six patients with relapsed/refractory mCRC have been enrolled in the two first dose-levels (three each at DL-1 (1×10⁸ cells) and DL-2 (3×10⁸ cells)) of the alloSHRINK trial evaluating CYAD-101 administered concurrently with FOLFOX chemotherapy. The mean number of prior therapies received for the patients enrolled was four
• No clinical evidence of Graft-versus-Host Disease (GvHD) have been observed. These initial data support the ability of the company’s novel inhibitory peptide TIM (T cell receptor (TCR) Inhibiting Molecule to reduce signaling of the TCR complex
• Host-versus-Graft (HvG) response against the allogeneic CYAD-101 cells appears to be controlled as evidenced by similar levels of CYAD-101 cell engraftment following the second and third infusions of the allogeneic cell therapy 
• At the dose levels evaluated, the treatment with CYAD-101 in association with FOLFOX chemotherapy was well-tolerated, with no reports of CRS, related SAEs, DLTs, nor on-target off-tumor toxicity
• Encouraging anti-tumor activity was observed in one patient experiencing a partial response (PR) and three patients experiencing stable disease (SD) at month 3
• CYAD-101 appears to provide better relative cell engraftment as compared to CYAD-01, at the same dose levels
• Recruitment in DL-3 (1×10⁹ cells) of the alloSHRINK trial is ongoing and preliminary results from the cohort are expected by year-end 2019

THINK CyFlu Phase 1 Cohort Update

• Three mCRC patients were enrolled in the THINK CyFlu cohort of the Phase 1 THINK trial and received a single injection of 300 million cells of CYAD-01 following preconditioning chemotherapy of cyclophosphamide and fludarabine, or CyFlu
• Treatment with CYAD-01 following CyFlu was well tolerated with no reports of CRS grade 2 or higher, related SAEs, DLTs, nor on-target off-tumor toxicity
• Translational data from the cohort also suggest an improvement in cell engraftment of CYAD-01 induced by the CyFlu preconditioning as compared to the same dose of CYAD-01 without preconditioning chemotherapy
• Of the three patients enrolled, one patient achieved stable disease (SD), while two patients experienced disease progression

Conference Call / Webcast Details 

A conference call including a Q&A session will be held by the Company on Friday July 5, 2019 at 2:00 pm CEDT / 8:00 am EDT.

The conference call can be accessed using the details below:

United States:     +1 877 407 9208

International:      +1 201 493 6784

Conference ID:   13692101

Alternatively, participants may also access an audio webcast of the event using the link below:  http://public.viavid.com/index.php?id=135092

Background on CYAD-01 and CYAD-101 

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. CYAD-101 is an investigational, non-gene edited, allogeneic (healthy donor derived) CAR-T therapy that co-expresses the NKG2D CAR of CYAD-01 and the novel inhibitory peptide TIM. The expression of TIM reduces signalling of the TCR complex, which is responsible for GvHD.

Background on SHRINK and alloSHRINK Trials

SHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and activity of CYAD-01 administered concurrently with FOLFOX chemotherapy in patients with metastatic colorectal cancer (mCRC). Patients will receive six cycles of FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) chemotherapy every two weeks and three administrations of CYAD-01 every two weeks.

alloSHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of CYAD-101 administered concurrently with FOLFOX chemotherapy in patients with unresectable mCRC. Similar to the SHRINK trial for CYAD-01, patients will receive six cycles of FOLFOX chemotherapy every two weeks and three administrations of CYAD-101 every two weeks.

Background on THINK CyFlu Cohort

In February 2018, the THINK trial was amended to include a cohort known as THINK CyFlu. The cohort evaluated a single injection of CYAD-01 following treatment with the standard preconditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu.

***END***

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 Professor Dr. Eric Van Cutsem from Universitair Ziekenhuis Leuven (UZ Leuven) will present data from the NKG2D-based autologous and allogeneic CAR-T candidates, CYAD-01 and CYAD-101, respectively, at the upcoming European Society for Medical Oncology (ESMO) 21^st World Congress on Gastrointestinal Cancer (WCGIC) to be held on July 3-6, 2019, in Barcelona, Spain. Following the oral and poster presentations at WCGIC, Celyad’s management team will host a conference call to discuss the initial clinical results from the SHRINK and alloSHRINK trials.

Filippo Petti, CEO of Celyad noted “We are honored to have Professor Dr. Van Cutsem present preliminary data from our SHRINK and alloSHRINK trials, including an initial glimpse of data from the industry’s first off-the-shelf investigational non-gene edited CAR-T candidate, CYAD-101. The comparable trial designs investigating similar NKG2D-based CAR-T therapies should provide for a unique comparison of an autologous and allogeneic engineered cell therapy approach for the treatment of metastatic colorectal cancer.”

Poster Oral Presentation 

Title: Phase 1 studies assessing the safety and clinical activity of autologous and allogeneic NKG2D-based CAR-T therapy in metastatic colorectal cancer

Abstract: SO-009

Presenter: Eric Van Cutsem, M.D., Universitair Ziekenhuis Leuven (UZ Leuven)

Date: Friday, July 5, 9:00 a.m. CEST

Location: Auditorium B, Level 0

The poster (same title, same number) will be presented in the Exhibit Hall, Level 0 on Friday, July 5, 2019 from 10:35am – 11:05am CEST and 04:35pm – 05:05pm CEST.

Conference Call / Webcast Details 

A conference call including a Q&A session will be held by the Company on Friday July 5, 2019 at 2:00 pm CEST / 8:00 am EDT.

The conference call can be accessed using the details below:

United States:   +1 877 407 9208

International:     +1 201 493 6784

Conference ID:  13692101

Alternatively, participants may also access an audio webcast of the event using the link below:  http://public.viavid.com/index.php?id=135092

Background on CYAD-01 and CYAD-101

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. CYAD-101 is an investigational, non-gene edited, allogeneic (donor derived) CAR-T therapy that co-expresses the NKG2D CAR of CYAD-01 and the novel inhibitory peptide TIM (T cell receptor [TCR] Inhibiting Molecule). The expression of TIM reduces signalling of the TCR complex, which is responsible for Graft versus Host Disease (GvHD).

Background on SHRINK and alloSHRINK Trials

SHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and activity of CYAD-01 administered concurrently with FOLFOX chemotherapy in patients with metastatic colorectal cancer (mCRC). Patients will receive six cycles of FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) chemotherapy every two weeks and three administrations of CYAD-01 every two weeks.

alloSHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of CYAD-101 administered concurrently with FOLFOX chemotherapy in patients with unresectable mCRC.  Similar to the SHRINK trial for CYAD-01, patients will receive six cycles of FOLFOX chemotherapy every two weeks and three administrations of CYAD-101 every two weeks.

• Regulators accept proposal to utilize OptimAb manufacturing process, which enriches for T cells with memory-like phenotype, with CYAD-01 under current IND application
• FDA accepts IND application, including OptimAb manufacturing process, for CYAD-02—next-generation NKG2D-based CAR-T therapy focused on improved persistence. CYAD-02 Phase 1 trial scheduled to start in early 2020
• Today’s updates to our r/r AML and MDS program are built on the clinical profile seen to date for CYAD-01 and focus on increasing the potency of NKG2D-based CAR-Ts in order to drive towards Phase 2 clinical development
• Management to hold a conference call on Tuesday, July 2^nd, at 2 p.m. CEDT/ 8 a.m. EDT

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 several strategic updates to its relapse/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) program, including its lead autologous NKG2D-based CAR-T therapy, CYAD-01, as well as the next-generation NKG2D-based CAR-T candidate, CYAD-02. The Company’s management team will host a conference call tomorrow, July 2^nd, at 2 p.m. CEDT / 8 a.m. EDT, to discuss each of the updates and future milestones for the program.

Filippo Petti, CEO of Celyad noted “Over the past few years Celyad has made great strides in evaluating our NKG2D-based CAR-T therapy for the treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome. We have observed that targeting NKG2D ligands with our lead CAR-T candidate CYAD-01 drives anti-leukemic activity and is well tolerated. Today marks a milestone event as we announce that the FDA has accepted our Investigational New Drug application to commence clinical trials for our next-generation, CAR-T candidate, CYAD-02, and that the FDA and FAMHP have accepted our proposal to utilize our new, proprietary ‘OptimAb’ manufacturing process for both CYAD-01 and CYAD-02. Given the recent updates to our relapsed/refractory AML program, we believe we are well-positioned to improve upon the initial signals we’ve observed to date for CYAD-01 in this difficult to treat and rapidly progressing patient population.”

Overview of CYAD-01 r/r AML and MDS Clinical Program

To date, results from the Phase 1 THINK trial evaluating CYAD-01 without prior preconditioning chemotherapy for the treatment of r/r AML and MDS have shown the NKG2D-based CAR-T to be well tolerated with encouraging preliminary anti-leukemic activity in six of thirteen patients (46%) evaluable per protocol.

The company is currently evaluating the potential for CYAD-01 in the treatment of r/r AML and MDS in multiple clinical trials including the Schedule Optimization cohorts of the THINK trial, which is assessing a more frequent dosing schedule of CYAD-01, and in the Phase 1, dose-escalation DEPLETHINK trial, which is assessing CYAD-01 following the preconditioning chemotherapy cyclophosphamide and fludarabine, or CyFlu. CyFlu is the preconditioning therapy typically used with other hematological malignancies evaluating CAR-T cell therapies.

In June 2019, preliminary data presented at the European Hematology Association (EHA) meeting demonstrated that a denser schedule of infusions of CYAD-01 without preconditioning in Cohort 10 (Schedule Optimization) of the THINK trial and a single infusion of low dose (1×10⁸ cells) CYAD-01 following preconditioning chemotherapy in the DEPLETHINK trial was well tolerated and led to better time-averaged engraftment of the CAR-T cells.

Strategic Drivers Aimed to Enhance NKG2D-based CAR-T for r/r AML and MDS

Based on the initial clinical data and tolerability profile for CYAD-01 from the r/r AML and MDS clinical program, Celyad aims to increase the potency of the NKG2D-based CAR-T therapy to potentially deepen the breadth, frequency and duration of clinical responses in this patient population. In particular, Celyad is focused on: 1) the optimization of treatment conditions, including denser dosing schedule or exploiting preconditioning chemotherapy; 2) optimization of the manufacturing process, including enrichment of T cells with memory-like phenotype; and 3) improving the persistence of CAR-T cell therapies through RNA interference using short hairpin RNA (shRNA) technology.

Recent Developments for r/r AML and MDS Program

CYAD-01 – Enriching Early Memory T cells in our First-in-Class, NKG2D-based CAR-T Candidate by Leveraging the OptimAb Manufacturing Process

Celyad recently submitted Chemistry, Manufacturing, and Control (“CMC”) amendments to the U.S. Food and Drug Administration (FDA) and Belgium’s Federal Agency for Medicines and Health Products (FAMHP) related to “OptimAb”, a modified manufacturing process for CYAD-01.

OptimAb, is designed as an iterative improvement of Celyad’s first two manufacturing processes for CYAD-01 (the LY and mAb processes) and builds upon key characteristics of both. OptimAb utilizes a shortened eight-day cell culture and incorporates a selective PI3K inhibitor. Combined with the manufacturing optimizations previously developed by the company, the OptimAb process results in a product that is enriched for T cells with a memory-like phenotype while maintaining the high level of manufacturing reliability required to support clinical development. The amendment filed with the regulatory agencies is based upon our in-house research focused on the development of a manufacturing process to enrich for T cells with memory-like phenotype.

Preclinical data based on conditions where the dose of CYAD-01 produced with the mAb manufacturing process is reduced to have minimal activity indicate that cells produced using the OptimAb manufacturing process drive improved anti-tumor activity in an aggressive AML model.

Following feedback from the FDA and FAMHP, the CMC amendments were accepted and now in effect with regulators under the current Investigational New Drug (IND) application for CYAD-01. Celyad expects to treat the first patient using the recently accepted OptimAb manufacturing process for CYAD-01 in cohort 4 (1×10⁹ cells) of the Phase 1 DEPLETHINK trial in August 2019. Based on regulatory feedback, Celyad expects to stagger treatment of the first three subjects treated with CYAD-01 cells manufactured by OptimAb.

CYAD-02 – Next-Generation, NKG2D-based CAR-T Candidate

At the company’s R&D Day held in March 2019, management unveiled its novel shRNA platform to develop next-generation autologous and allogeneic CAR-T cell therapies, including CYAD-02, a next-generation, autologous NKG2D-based CAR-T candidate that incorporates shRNA technology to target the NKG2D ligands MICA and MICB. The single shRNA modulates the expression of both ligands which translates to encouraging increases in in vitro proliferation, in vivo engraftment and anti-tumor activity. CYAD-02 also incorporates the OptimAb manufacturing process thereby enriching for T cells with memory-like phenotype.

In late June 2019, the FDA accepted the IND application for CYAD-02 and permitted it to go into effect. The company plans to begin enrollment of a Phase 1 dose-escalation trial evaluating the safety and clinical activity of CYAD-02 with the preconditioning chemotherapy CyFlu for the treatment of r/r AML and MDS in early 2020.

The CYAD-02 Phase 1 trial will be the first CAR-T cell therapy clinical trial employing the optimized shRNA SMARTvector technology licensed from Horizon Discovery and represents the output of a strong collaboration with the company’s partner.

Upcoming Milestones for r/r AML and MDS Program based on OptimAb Manufacturing Process

• Initial clinical data from cohort 4 of the Phase 1 DEPLETHINK trial for CYAD-01 using the OptimAb manufacturing process are expected by year-end 2019. Full results from cohort 4 of the DEPLETHINK trial are anticipated in first quarter 2020.
• Initiate the Phase 1 dose-escalation trial evaluating CYAD-02, following preconditioning chemotherapy for the treatment of r/r AML and MDS in early 2020. Preliminary data from the Phase 1 trial are expected by mid-2020.

Conference Call and Webcast Details

Celyad will host a conference call to discuss the update to the r/r AML and MDS program on Tuesday, July 2^nd, 2019 at 2 p.m. CEDT / 8 a.m. EDT. The conference call can be accessed through the following numbers:  

United States:   +1 877 407 9208

International:     +1 201 493 6784

Conference ID:  13692100

The conference call will be webcast live and can be accessed here. The event will also be archived and available on the “Events & Webcasts” section of the Company’s website. Please visit the website several minutes prior to the start of the broadcast to ensure adequate time for registration to the webcast.

Background on Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS)

Acute myeloid leukemia (AML) is an aggressive (fast-growing) form of leukemia characterized by the abnormal growth of myeloid cells, that spread in the bone marrow, blood stream and occasionally to other organs. AML is most commonly diagnosed in males aged 65-74 years old.

With about 40,000 new cases diagnosed each year in aggregate in the United States and Europe, AML is the most common type of aggressive leukemia in adults. The five-year survival rate for people 20 and older with AML is approximately 24%. For people younger than 20 diagnosed with AML, the survival rate is 67%. It has one of the lowest survival rates of all types of leukemia.

AML can develop either de novo in a healthy individual or in patients with a predisposing disease called myelodysplastic syndrome (MDS). Myelodysplastic syndrome (MDS) can be considered a premalignant disease that affects myeloid cells. Approximately 1,400 individuals in the United States are diagnosed each year with MDS.

Standard therapies for AML include chemotherapy (cytarabine) or hypomethylating agents (azacytidine or decitabine). If these therapies fail patients will receive a blood stem cell transplant. In addition, some patients are not eligible for transplant due to a poor general health condition. Despite these treatments, most patients relapse. As such, new or improved therapies for the treatment of AML are urgently needed.

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 attend the following events in June 2019:

Conference details:

BIO International Convention 

Date: June 3 – 6, 2019

Location: Philadelphia, PA 

William Blair 39th Annual Growth Stock Conference

Date: Wednesday, June 5, 2019

Presentation time: 8:40 – 9:10 a.m. CDT

Location: Chicago, IL 

HealthTech Investor Days, France Biotech

Date: June 24 – 25, 2019

Location: Paris, France

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 selection of three abstracts for poster presentation at the upcoming 24^th Congress of the European Hematology Association (EHA) in Amsterdam, The Netherlands, on June 13-16, 2019, including updated data from the THINK and DEPLETHINK Phase 1 trials evaluating the company’s autologous NKG2D-based CAR-T therapy CYAD-01 for the treatment of relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome (MDS).

Clinical Presentation

Title:          Updated Results from the Phase 1 Trials Assessing a NKG2D CAR T-Cell Approach in Relapsed/Refractory Acute Myeloid Leukimia and Myelodysplastic Syndrome Patients. Download the poster 

Abstract:    PS1212

Session:     Gene therapy, cellular immunotherapy and vaccination – Clinical

Date:         Saturday, June 15^th

Time:         5:30 – 7:00 p.m. CEST (Poster Area)

Preclinical Presentations

Title:          Development of a Next Generation Allogeneic CAR-T Cell Platform Without Gene Editing. Download the poster.

Abstract:    PS1210

Session:     Gene therapy, cellular immunotherapy and vaccination – Biology & Translational   Research

Date:          Saturday, June 15^th

Elevator pitch:   4:30 – 4:45 p.m. CEST (Hall G106)

Time:          5:30 – 7:00 p.m. CEST (Poster Area)

Title:           Modeling NKG2D-based CAR-T Cell Therapy in Animals with Acute Myeloid Leukemia. Download the poster

Abstract:     PS974

Session:      Acute myeloid leukemia – Biology & Translational Research

Date:          Saturday, June 15^th

Time:          5:30 – 7:00 p.m. CEST (Poster Area)