On July 21, 2021 Celyad Oncology SA (Euronext & Nasdaq: CYAD) (Brussels:CYAD) (Paris:CYAD) (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, reported 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 (Press release, Celyad, JUL 21, 2021, View Source [SID1234585009]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"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) (Free EHA Whitepaper) 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.