Immuno-oncology

• Results from ongoing, dose-escalation alloSHRINK Phase 1 trial demonstrate absence of graft-versus-host disease for first-in-class, non-gene edited allogeneic CAR-T candidate,
  CYAD-101, when administered concurrently with FOLFOX chemotherapy
• Best overall response in alloSHRINK trial in refractory metastatic colorectal cancer (mCRC) patients who had previously received prior oxaliplatin-basedchemotherapy, which includes two patients with partial response (PR) and seven patients with stable disease (SD), with 50 percent (6 out of 12) of patients experiencing a decrease in tumor burden
• Enrollment completed in dose-escalation segment of alloSHRINK trial with additional results expected in first half 2020; expansion segment of trial anticipated to begin in mid-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 highlights from the company’s NKG2D-based CAR-T clinical candidates for the treatment of metastatic colorectal cancer (mCRC), including its novel, off-the-shelf cell therapy CYAD-101 and alloSHRINK dose-escalation Phase 1 trial. Results were presented at the Society for Immunotherapy of Cancer (SITC) 34^th Annual Meeting, held in Washington D.C. from November 6-10, 2019.

Dr. Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad, commented, “We are encouraged by the latest results from the alloSHRINK trial in metastatic colorectal cancer patients previously exposed to oxaliplatin- and irinotecan-based chemotherapies, including the tolerability profile and early antitumor activity of CYAD-101 with prior FOLFOX preconditioning chemotherapy. In particular, the lack of clinical and laboratory evidence of graft-versus-host-disease for CYAD-101, which incorporates our proprietary T-cell receptor inhibitory molecule to reduce signaling of the TCR complex, establishes proof-of-concept for this industry-leading, off-the-shelf CAR-T approach. In addition, any host-versus-graft reaction against the allogeneic CAR-T product candidate appears to be controlled by the non-myeloablative FOLFOX chemotherapy. Overall, these encouraging data from the alloSHRINK trial warrant further evaluation of CYAD-101.”

Filippo Petti, CEO of Celyad, stated, “Treatment of advanced metastatic colorectal cancer patients beyond the second line of metastatic chemotherapy remains a high unmet medical need. Our confidence in CYAD-101 has continued to build as data from the alloSHRINK trial have emerged over the past year. We look forward to the planned expansion segment of the alloSHRINK trial to further evaluate the CAR-T product candidate for refractory mCRC patients as we continue to execute on the company’s vision for the treatment of patients with advanced solid tumors with allogeneic CAR-T therapies.”

alloSHRINK Phase 1 Trial Update

Safety and Tolerability

• To date, a total of 12 patients with relapsed/refractory mCRC who progressed after previous treatment with oxaliplatin or irinotecan have been enrolled in the ongoing dose-escalation Phase 1 alloSHRINK trial evaluating three consecutive dose levels of CYAD-101 administered concurrently with FOLFOX chemotherapy. The number of prior therapies received by patients enrolled in the trial ranged from one to six with a mean of three.
• No clinical evidence of graft-versus-host disease (GvHD) has been observed following 35 injections of CYAD-101. These data continue to support the ability of the company’s novel inhibitory peptide T cell receptor (TCR) inhibiting molecule (TIM) to reduce signaling of the TCR complex through a non-gene edited approach.
• Treatment with CYAD-101 in association with FOLFOX chemotherapy was well-tolerated, with no report of dose-limiting toxicity. Six of 12 patients enrolled in the trial reported at least one treatment-related adverse event (AE), however all AEs reported were grade 1 or 2 including one patient who experienced cytokine-release syndrome (grade 1). No patient discontinued treatment due to AEs.

Clinical Activity

• Encouraging anti-tumor activity was observed in the trial with two patients who achieved a confirmed partial response (PR) according to RECIST 1.1 criteria and five patients achieved stable disease (SD) of more than or equal to three months of duration. Tumor burden decrease was observed in six out of 12 patients in total.

Cell Kinetics

• Host-versus-graft (HvG) reaction against the allogeneic CYAD-101 cells appears to be controlled by the non-myeloablative FOLFOX chemotherapy as evidenced by similar levels of CYAD-101 cell engraftment following the second and third infusions of the allogeneic cell product candidate.
• Following administration of FOLFOX chemotherapy, CYAD-101 cells demonstrate similar kinetics as the autologous NKG2D-based CAR-T therapy CYAD-01 as evaluated in the Phase 1 SHRINK trial.

Next Steps

• An additional three patients have been enrolled at dose level three (one billion cells per infusion) of the trial for a total of nine patients in the cohort, as planned per protocol. Preliminary results from the completed dose-escalation segment of the alloSHRINK trial are expected in first half 2020.
• Based on the encouraging data observed to date for the Phase 1 alloSHRINK trial, the Company plans to expand the trial to further evaluate CYAD-101 with prior FOLFOX chemotherapy in refractory mCRC patients. Enrollment in the expansion segment of the trial is expected to begin in mid-2020 following the production of additional CYAD-101 cells planned during first half 2020.

About CYAD-101 and alloSHRINK Trial

CYAD-101 is an investigational, non-gene edited, allogeneic (healthy donor derived) CAR-T therapy engineered to co-express a chimeric antigen receptor (CAR) based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM (T cell receptor [TCR] Inhibitory Molecule). The expression of TIM reduces signalling of the TCR complex, which is responsible for GvHD.

alloSHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of three consecutive administration of CYAD-101 every two weeks administered concurrently with FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) chemotherapy in patients with refractory mCRC.

About Colorectal Cancer

Colorectal cancer is the third most common type of cancer among both men and women worldwide and is the fourth in terms of mortality. In 2018, approximately 1.8 million people were diagnosed with colorectal cancer with about 140,000 and 500,000 diagnoses in the United States and Europe, respectively. According to data from the American Society of Clinical Oncology (ASCO), approximately 40% of patients are diagnosed with early-stage, localized-stage disease. The five-year survival rate of localized disease is approximately 90%. In patients where the cancer has spread to distant parts of the body, as in metastatic colorectal cancer, the five-year survival rate drops to approximately 15%.

• Management to host an analyst and investor event to review data from American Society of Hematology (ASH) on Monday, Dec. 9, at 8:30 p.m. ET

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 three abstracts related to the company’s autologous NKG2D-based CAR-T candidates for the treatment of relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndromes (MDS) have been accepted for presentation at the 61^st Amercican Society of Hematology (ASH) Annual Meeting, which will be held from December 7-10, 2019, in Orlando, Florida. In addition, management will host a live event at ASH for analysts and investors on Monday, December 9, to review the data from the three posters, as well as updates to the company’s development program for r/r AML and MDS and proprietary OptimAb manufacturing process.

Filippo Petti, chief executive officer of Celyad, noted, “We look forward to providing an update at next month’s ASH Annual Meeting on our autologous CAR-T program focused on the treatment of acute myeloid leukemia and myelodysplastic syndromes, including the latest clinical results from the CYAD-01 Phase 1 THINK and DEPLETHINK trials. In addition, we are excited to highlight the latest preclinical data from our next-generation NKG2D-based candidate CYAD-02 and our OptimAb manufacturing process, which underpins both autologous CAR-T assets within the program.”

ASH Investor/Analyst Event and Webcast Information

Celyad will host an event at ASH for investors and analysts on Monday, December 9, 2019, beginning at 8:30 p.m. ET to review data presented, as well as to provide updates on the company’s development program for r/r AML and MDS and its proprietary OptimAb manufacturing process. The event will also be webcast live and can be accessed under Events & Webcasts in the Investors section of the company’s website.Poster Presentation Details:The following abstracts published today are now available on the ASH websitewww.hematology.org.  Following presentation at the meeting, the posters will be available in the library section of Celyad’s website. Publication #3826:         Results from the Completed Dose-Escalation of the Hematological Arm of the Phase I Think Study Evaluating Multiple Infusions of NKG2D-Based CAR T-Cells as Standalone Therapy in Relapse/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome PatientsDate & Time:                      Monday, December 9, 2019, 6 p.m. – 8 p.m. ET Publication #3844:         Interim Results from the Phase I Deplethink Trial Evaluating the Infusion of a NKG2D CAR T-Cell Therapy Post a Non-Myeloablative Conditioning in Relapse or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome PatientsDate & Time:                      Monday, December 9, 2019, 6 p.m. – 8 p.m. ET Publication #3931:         Next Generation NKG2D-based CAR T-cells (CYAD-02): Co-expression of a Single shRNA Targeting MICA and MICB Improves Cell Persistence and Anti-Tumor Efficacy in vivoDate & Time:                      Monday, December 9, 2019, 6 p.m. – 8 p.m. ET Background on THINK Phase 1 TrialThe 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. Background on DEPLETHINK Phase 1 TrialIn October 2018, Celyad initiated the DEPLETHINK Phase 1 trial (NCT03466320). The open-label, dose-escalation trial will 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 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. Background on OptimAb Manufacturing ProcessCelyad’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.

• Management to host webcast on Saturday, Nov. 9, at 12:35 p.m. ET/ 6:35 p.m. CET

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 abstracts highlighting clinical and translational research data from the company’s pipeline of NKG2D-based candidates focused on the treatment of metastatic colorectal cancer (mCRC), including the allogeneic cell therapy CYAD-101, were published today ahead of the Society for Immunotherapy of Cancer’s 34^thAnnual Meeting (SITC).

Filippo Petti, chief executive officer at Celyad, commented, “We are excited to provide additional updates at the upcoming SITC annual meeting from our current CAR-T program in metastatic colorectal cancer, including translational data from multiple approaches we have pursued with our NKG2D-based candidates for the treatment of the disease. Over the past few years, we have treated over thirty metastatic colorectal cancer patients within the program assessing various conditions. We continue to be encouraged by the results and prospects for the program and, in particular, from clinical data of our lead allogeneic candidate CYAD-101 where we have observed an absence of graft versus host disease and preliminary signals of clinical activity in a refractory, difficult to treat patient population.”

SITC Analyst/Investor Event and Webcast Information

Celyad will host an analyst/investor event on Saturday, Nov. 9, 2019, beginning at 12:35 p.m. ET / 6:35 p.m. CET to review both clinical and translational data that will be presented at the SITC 34^th Annual Meeting. The event will be webcast live and can be accessed under Events & Webcasts in the Investors section of the Company’s website.

Poster Presentation Details

The following abstracts published today are now available on the SITC website, www.sitcancer.org/2019.  Following presentation at the meeting, the posters will be available in the library section of Celyad’s website.Abstract P147:  Effect of chemotherapy on cellular kinetics of NKG2D-based CAR T-cells in metastatic colorectal cancer patientsDate & Time:    November 8, 7 a.m. – 8 p.m. ET Abstract P331:  Results from the completed dose-escalation phase I SHRINK study evaluating the autologous NKG2D-based CAR T-cell therapy CYAD-01 in metastatic colorectal cancer patientsDate & Time:    November 8, 7 a.m. – 8 p.m. ET Abstract P330:  Results from the completed dose-escalation of the alloSHRINK phase I study evaluating the allogeneic NKG2D-based CAR T-cell therapy CYAD-101 in metastatic colorectal cancer patientsDate & Time:    November 9, 7 a.m. – 8:30 p.m. ET

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 are planned to receive consecutive cycles of FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) chemotherapy every two weeks concurrently with multiple administrations of CYAD-01.

alloSHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of three consecutive administrations of CYAD-101 every 2 weeks administered concurrently with FOLFOX chemotherapy in patients with refractory mCRC.

• Poster presentations to highlight allogeneic and autologous NKG2D-based CAR-T therapies for the treatment of advanced metastatic colorectal (mCRC) cancers

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 clinical data on the company’s pipeline of candidates will be presented at the 34^th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) being held November 6-10, 2019, in Washington, D.C.

“SITC 2019 remains an important avenue for us to provide updated results of our clinical programs in metastatic colorectal cancer, and in particular, data from the industry’s first trial investigating an ‘off-the-shelf,’ non-gene edited allogeneic CAR-T candidate for the treatment of solid tumors,” commented Dr. Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad. “In addition, disclosing clinical and scientific data from the SHRINK and alloSHRINK dose-escalation Phase 1 trials in parallel will allow the comparison of results obtained with an autologous CAR-T and its equivalent allogeneic version. As such, this comparison highlights our efforts to understand analytical development in CAR-T space and our ongoing mission to get this much-needed therapy to people living with this deadly cancer, for which there are few treatment options”.

Poster Details:Abstract P147:Effect of chemotherapy on cellular kinetics of NKG2D-based CAR T-cells in metastatic colorectal cancer patients.

Date & Time:                     November 8, 7:00 am. – 8:00 p.m. 

Abstract P330:Results from the completed dose-escalation of the alloSHRINK phase I study evaluating the allogeneic NKG2D-based CAR T-cell therapy CYAD-101 in metastatic colorectal cancer patients

Date & Time:                     November 9, 7:00 am. – 8:30 p.m. EDT 

Abstract P331:Results from the completed dose-escalation phase I SHRINK study evaluating the autologous NKG2D-based CAR T-cell therapy CYAD-01 in metastatic colorectal cancer patients

Date & Time:                     November 8, 7:00 am. – 8:00 p.m. EDT

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 refractory 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.

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-01CYAD-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 ProcessThe 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 TrialIn 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.

• Results from the ongoing Phase 1 THINK and DEPLETHINK trials evaluating CYAD-01 for the treatment of relapsed or refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) continue to support the therapeutic clinical development of the NKG2D-based CAR-T therapy product candidate
• Preliminary data from Cohort 10 of the THINK trial evaluating a denser schedule of infusions of CYAD-01 without preconditioning showed better cell engraftment compared to biweekly injections of CYAD-01 without preconditioning
• Initial results from the DEPLETHINK trial evaluating a single infusion of CYAD-01 following preconditioning chemotherapy demonstrated the regimen was well-tolerated with a better time-averaged engraftment of the CAR-T cells compared to the dose-escalation segment of the THINK trial with a cycle of three injections of CYAD-01

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 updated clinical data for the CYAD-01 program in r/r AML and MDS was presented in a poster presentation session on Saturday, June 15 at the 24^th Congress of the European Hematology Association (EHA) in Amsterdam, Netherlands.

Dr. Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad, commented,“Our observations from the Phase 1 THINK clinical trial evaluating CYAD-01 without prior lymphodepletion in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome patients show the cell therapy is generally well tolerated. Encouragingly, this safety and tolerability profile was also demonstrated during the early stages of CYAD-01 treatment intensification where an increased systemic persistence of CAR-T cells is obtained after reduced interval dosing or in combination with preconditioning chemotherapy. As such, we continue to focus our efforts on increasing the aggressiveness of CYAD-01 to potentially deepen the breadth, frequency and duration of clinical responses in this refractory patient population.”

THINK Phase 1 Trial in Hematological Malignancies Update

• As of May 232019, preliminary anti-leukemic activity has been observed in six out of thirteen patients (46%) evaluable per protocol in the THINK Phase 1 trial with four out of thirteen patients (31%) exhibiting objective responses, including one out of the four patients experiencing a duration of response of over 90 days
• Overall, multiple infusions of CYAD-01 without any prior preconditioning chemotherapy continues to show an encouraging tolerability profile with eight patients from over twenty treated experiencing grade 3/4 treatment-related adverse events (AEs). No neurotoxicity AEs have been observed in any patient receiving CYAD-01.
• The denser schedule of infusions in the absence of any bridging or preconditioning chemotherapy without preconditioning chemotherapy evaluated in Cohort 10 showed that of three r/r AML or MDS patients evaluable, one patient experienced disease stabilization and two patients had disease progression following treatment with up to six doses of 1 billion cells of CYAD-01.
• The denser dosing schedule was generally reported to be well-tolerated. Three patients of four patients evaluable for safety in Cohort 10 experienced grade 1/2 cytokine release syndrome (CRS), which showed rapid resolution following the appropriate treatment, including tocilizumab. One patient experienced a grade 4 infusion reaction, which was not considered to be a dose-limiting toxicity of the therapy
• Overall, better time-averaged engraftment (area under the curve) was observed with a reduced interval dosing (Cohort 10) as compared to the equivalent dose of the THINK trial evaluating a cycle of three injections of CYAD-01 administered every two weeks.
• Recruitment in Cohort 11 of the THINK trial evaluating the denser schedule of up to six infusions of three billion cells of CYAD-01 without preconditioning chemotherapy is ongoing and results are expected by the end of 2019.

DEPLETHINK Phase 1 Trial Update

• The initial cohorts of the DEPLETHINK trial enrolled six r/r AML or MDS patients who received a single administration of a safety-precaution low-dose CYAD-01 (100 million cells per infusion) following preconditioning chemotherapy consisting of cyclophosphamide and fludarabine, or CyFlu, at two different time-intervals (three or seven days) between the preconditioning regimen and administration of CYAD-01.
• As of May 23, 2019, three patients experienced grade 1/2 CRS, which showed rapid resolution following the appropriate treatment, including tocilizumab. One patient experienced a grade 4 infusion reaction, which was not considered to be a dose-limiting toxicity of the therapy, during the consolidation cycle without preconditioning.
• Of the five patients evaluable per protocol, two patients experienced disease stabilization following treatment with CYAD-01. 
• Better time-averaged engraftment was observed after a single infusion of low-dose CYAD-01 with prior preconditioning compared to the dose-escalation segment of the THINK trial evaluating a cycle of three injections of CYAD-01.
• Evaluation of higher dose-levels comparable to the Phase 1 THINK trial, including 300 million and 1 billion cells, are ongoing in the dose-escalation trial and preliminary results from these cohorts are expected by year-end 2019.

Background on 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.

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 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 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.