Celyad Oncology

• Phase 1 IMMUNICY-1 trial evaluating CYAD-211 in relapsed/refractory multiple myeloma (r/r MM) showed dose dependent engraftment up to dose level three (300×10⁶ cells per infusion) with no Graft-versus-Host disease reported to date
• Submission of IND application for CYAD-203, a new first-in-class shRNA-based allogeneic, IL-18-armored CAR T candidate, expected in mid-2022
• CYAD-101 following FOLFIRI preconditioning in advanced metastatic colorectal cancer (mCRC) was well-tolerated; cell kinetic and activity of alloSHRINK trial support the initiation of the KEYNOTE-B79 Phase 1b trial of CYAD-101 following FOLFOX preconditioning chemotherapy during early fourth quarter 2021 

Mont-Saint-Guibert, Belgium – Celyad Oncology SA (Euronext & Nasdaq: CYAD) (Celyad Oncology or the Company), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, highlighted a new preclinical allogeneic armored CAR T candidate developed from its shRNA platform and data updates to the shRNA-based allogeneic candidate CYAD-211 for r/r MM and allogeneic candidate CYAD-101 for mCRC today during a research and development day hosted by the Company’s management team.

“We are ushering in a new era of allogeneic CAR T candidates using novel technological advances, including our proprietary shRNA platform for allogeneic CAR T production and now the addition of our ‘armored’ CAR capabilities with co-expression of the cytokine IL-18,” said Filippo Petti, Chief Executive Officer of Celyad Oncology. “We believe the advances we’re making may address many of the current modality limitations and have the potential to provide real-world benefits for patients, including more accessible CAR T cell treatment options, if approved. This continued technological innovation, which is currently being validated in ongoing clinical studies, establishes Celyad Oncology as a leader in this adoptive cell therapy space.” 

Latest Program Updates

CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM

• CYAD-211 is the Company’s first shRNA-based allogeneic CAR T candidate, which co-expresses a BCMA targeting chimeric antigen receptor while using shRNA to knockdown expression of the CD3ζ component of theT-cell receptor (TCR)
  • Currently, CYAD-211 is being evaluated in the Phase 1 IMMUNICY-1 trial in r/r MM following preconditioning with cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) given three consecutive days.
  • In June, preliminary data from the Phase 1 IMMUNICY-1 trial was presented at the European Hematology Association (EHA) congress demonstrating no dose limiting toxicity (DLT), Graft-versus-Host disease (GvHD) or CAR T-cell-related encephalopathy syndrome (CRES) in the first two dose levels (30×10⁶ and 100×10⁶ cells per infusion) of the trial. Two of the five evaluable patients at the first two dose levels achieved a partial response. In addition, CYAD-211 cells were detected by PCR-based methods in all six patients with evidence of a dose dependent increase in cell engraftment.
• Recent data from the first patient at dose level three (300×10⁶ cells per infusion) continues to show dose dependent engraftment with no GvHD reported to date.
• Enrollment in the trial is ongoing with plans to explore higher doses of preconditioning regimens in future cohorts.

CYAD-203 – Allogeneic shRNA-based, IL-18-armored NKG2D CAR T for Solid Tumors

• CYAD-203 is the Company’s first armored CAR T candidate engineered to co-express the cytokine interleukin-18 (IL-18) with the NKG2D CAR receptor. To the Company’s knowledge, this therapy is on track to be first ever IL-18 secreting allogeneic CAR T candidate.
  • IL-18 is a proinflammatory cytokine that directly potentiates the anti-cancer activity of CAR T cells while also altering the balance of pro- and anti-inflammatory cells within tumor tissue.
  • Investigational New Drug (IND)-enabling studies are currently ongoing. Submission of the IND application for CYAD-203 for treatment of solid tumors is expected in mid-2022.

CYAD-101 – Allogeneic TIM-based NKG2D CAR T for mCRC

• To the Company’s knowledge, CYAD-101 is the first investigational allogeneic CAR T candidate to generate evidence of clinical activity for the treatment of a solid tumor indication. This is based on data from the dose-escalation segment of the alloSHRINK Phase 1 trial evaluating CYAD-101 following FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) preconditioning chemotherapy for the treatment of advanced metastatic colorectal cancer (mCRC).
• Initial data from the dose expansion cohort evaluating CYAD-101 (1×10⁹ cells per infusion) following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy showed CYAD-101 was generally well-tolerated with no dose limiting toxicities or evidence of GvHD. Overall, nine out of ten evaluable mCRC patients showed stable disease at first tumor assessment.
• Data also showed shorter persistence of CYAD-101 cells observed after FOLFIRI preconditioning as compared to FOLFOX preconditioning. Based on better CYAD-101 cell kinetics and clinical activity data from the alloSHRINK FOLFOX cohort, the Company submitted a protocol amendment to regulatory agencies to modify the Phase 1b KEYNOTE-B79 trial to incorporate FOLFOX as preconditioning chemotherapy.
  • The KEYNOTE-B79 trial to evaluate CYAD-101 with Merck’s anti-PD­1 therapy, KEYTRUDA® (pembrolizumab), in refractory mCRC patients with microsatellite stable / mismatch-repair proficient disease is expected to be initiated during the fourth quarter of 2021.

Business Update

• Celyad Oncology has acquired an exclusive license from the Moffitt Cancer Center for an antibody directed to Tumor-associated glycoprotein (TAG-72), which will form the basis of a T cell engager to be used with our proprietary shRNA platform technology. TAG-72 has been shown to be expressed in a wide variety of epithelial malignant tissues including breast, colon and pancreatic cells and will expand the Company’s program portfolio in solid tumor targets.

Upcoming Milestones

• Additional clinical activity data for the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected during second half 2021.
• Study initiation for KEYNOTE-B79 Phase 1b is expected early fourth quarter 2021.
• Submission of an IND application for CYAD-203 is expected in mid-2022.
• Report additional data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome in mid-2021.

Mont-Saint-Guibert, Belgium – Celyad Oncology SA ( Euronext & Nasdaq: CYAD), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, today announced that Chief Scientific Officer, Dr. David Gilham, will participate in a panel discussion titled “Cell Therapies in the Next Decade” to be held on Wednesday, July 14^th, at 08:55 a.m. EST at the William Blair Biotech Focus Conference 2021 taking place virtually from July 14-15, 2021. The management team will participate in one-on-one investor meetings throughout the conference as well.

A live audio webcast of the discussion can be accessed through the Events section of the Company’s website.