CYAD-211 / Celyad Oncology - LARVOL DELTA

Clinical Proof-of-Concept of a Non-Gene Editing Technology Using miRNA-Based shRNA to Engineer Allogeneic CAR T-Cells. (PubMed, Int J Mol Sci) - P1 | "We generated allogeneic anti-B-cell maturation antigen CAR T-cells (CYAD-211) that co-express an anti-CD3ζ miRNA-based shRNA within the CAR construct which efficiently inhibited TCR-mediated signaling in vitro and GvHD in vivo...Our data provide proof of concept that a non-gene-edited technology can generate fully functional allogeneic CAR T-cells, without any signs of GvHD. However, further engineering of the CAR T-cells is needed to improve their persistence and long-term activity."

IO biomarker • Journal • Graft versus Host Disease • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology

Celyad Oncology reports third quarter 2023 financial results and recent business highlights (GlobeNewswire) - "Our data provides the proof-of-concept that NKG2DL are valuable targets in a multispecific CAR approach...we showed that CD19/NKG2DL multispecific CAR T-cells, and in particular dual receptors, are highly effective in vitro against CD19+ and CD19- cell lines and against CD19+ primary B-cell acute lymphoblastic leukemia (B-ALL) cells. In vivo, CD19/NKG2DL tandem CAR T-cells outperforms dual CAR T-cells in controlling tumor growth in an aggressive B-ALL relapse model; In vitro data generated with BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells further validate this approach and its application in other hematological and solid indications...More data and evidence in the context of the multi-specific CAR platform and shRNA multiplexing approach will be shared in the first quarter of 2024, with the aim of a clinical evaluation of assets and initiation of clinical trials either by the Company and/or through strategic partnerships afterwards."

Clinical • Preclinical • Hematological Malignancies • Oncology • Solid Tumor

Proof-of-concept of a non-gene editing technology using shRNA down-regulation to engineer and optimize CAR T-cell functionality (SITC 2023) - P1 | "This construct (CYAD-211) was then evaluated in a Phase I clinical trial (NCT04613557) to validate the shRNA technology...This construct (CYAD-02) was also evaluated in a Phase I clinical trial (NCT04167696)...Conclusions Our data provide proof of principle that single shRNA-mediated knockdown can generate fully functional allogeneic CAR T-cells in humans without any signs of GvHD or can improve CAR T-cell characteristics while maintaining a good safety profile and efficacy. We are currently validating the technology to downregulate multiple-genes of interest simultaneously thereby providing a platform approach that could support the future of cell therapy."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Oncology • NKG2D

IMMUNICY-1: Safety, Activity and Cell Kinetics of CYAD-211 in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Celyad Oncology SA | Recruiting ➔ Active, not recruiting | N=12 ➔ 18 | Trial completion date: Feb 2036 ➔ Feb 2037

Enrollment change • Enrollment closed • Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Immunicy-1: Targeting BCMA with Cyad-211 to Establish Proof of Concept of an shRNA-Based Allogeneic CAR T Cell Therapy Platform (ASH 2021) - P1 | "Patients receive non-myeloablative preconditioning (cyclophosphamide 300 mg/m²/day and fludarabine 30 mg/m²/day, for 3 days) followed by a single CYAD-211 infusion in a 3+3 dose escalation design evaluating three dose-levels (DL): 30x10 6 , 100x10 6 and 300x10 6 cells/infusion. The lack of sustained engraftment of CYAD-211 can be explained by rejection of the allogeneic cells by the recovering immune system of the recipient and calls for exploring the role of augmented lymphodepletion. Furthermore, given the ability to include multiple shRNA within the single CAR vector, future strategies will also examine knocking down other molecules that are important in driving immune rejection."

CAR T-Cell Therapy • IO biomarker • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Plasmacytoma • Respiratory Diseases • Transplantation

Celyad Oncology provides an update on its strategic business model, continuing to focus on opportunities to fully harness the true potential of its proprietary technology platforms and intellectual property (GlobeNewswire) - P1 | N=12 | IMMUNICY-1 (NCT04613557) | Celyad Oncology SA | “Based on a strategic and financial review, the Company has decided to discontinue the development of its remaining clinical program CYAD-211...There were no safety concerns leading to this decision and all patients previously treated with CYAD-211 will continue to receive their protocol-defined follow-up. The key data points of the program are as follows: The observed safety profile, including the lack of observed Graft-versus-Host disease, provides proof-of-concept for the use of shRNA technology for allogeneic CAR Ts; Out of 17 evaluable patients, a partial response was achieved in five patients.…The Company will provide updates on the potential proof-of-concept of the dual CAR and multiplexing research programs and on business development in the second quarter of 2023.”

Clinical • Discontinued • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Celyad Oncology Reports First Half 2022 Financial Results and Recent Business Highlights (Businesswire) - "CYAD-211: Additional data updates from the eLD cohorts of the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected during second half of 2022."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Celyad Oncology Reports Full Year 2020 Financial Results and Recent Business Highlights (GlobeNewswire) - “Upcoming Milestones; Additional proof-of-concept data from the initial dose cohorts of the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected by the end of Q2 2021; Preliminary data from the expansion segment of the alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients are expected in Q2 2021; Initiation of the Phase 1b KEYNOTE-B79 trial evaluating CYAD-101 with KEYTRUDA® in mCRC patients with MSS/pMMR disease is anticipated by in the first half of 2021; Additional data from dose level 3 of Phase 1 CYCLE-1 trial of CYAD-02 for r/r AML and MDS are anticipated in the first half of 2021.”

New P1 trial • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Solid Tumor

Celyad Oncology Announces First Quarter 2022 Financial Results and Recent Business Highlights (GlobeNewswire) - "Enrollment in the eLD cohorts of the IMMUNICY-1 trial continues with additional data expected from the program in the second half of 2022."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Celyad Oncology Presents Updates on shRNA-Based CAR T Programs at the 63rd ASH Annual Meeting and Exposition (GlobeNewswire) - P1, N=12; IMMUNICY-1 (NCT04613557); Sponsor: Celyad Oncology SA; "CYAD-211 and IMMUNICY-1 Phase 1 Trial Update...CYAD-211 demonstrated a good tolerability profile and evidence of clinical activity in the dose-escalation segment with three out of 12 total patients with relapsed or refractory multiple myeloma (r/r MM) evaluated for activity achieving partial response, one in each dose-level, while eight patients had stable disease...Enrollment in the cohorts evaluating enhanced lymphodepletion is ongoing. Additional data from the CYAD-211 IMMUNICY-1 trial are expected in mid-2022."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Celyad Oncology Announces Closing of $32.5 Million Private Placement with Fortress Investment Group Affiliate (GlobeNewswire) - "The Company intends to use net proceeds from the private placement to fund research and development expenses, including the clinical development of its allogeneic CAR T candidates CYAD-101 and CYAD-211, to advance the current pipeline of preclinical CAR T candidates, to discover and develop additional preclinical product candidates using its proprietary non-gene edited short hairpin RNA (shRNA) technology platform, as well as for working capital, other general corporate purposes, and the enhancement of the Company’s intellectual property."

Commercial • Oncology

Celyad Oncology Announces $32.5 Million Private Placement with Fortress Investment Group (GlobeNewswire) - "Celyad Oncology SA...announced that it has entered into a subscription agreement with an affiliate of Fortress Investment Group...for the private placement of 6,500,000 ordinary shares for gross proceeds of USD 32.5 million (about EUR 28.7 million)...The Company intends to use net proceeds from the private placement to fund research and development expenses, including the clinical development of its allogeneic CAR T candidates CYAD-101 and CYAD-211, to advance the current pipeline of preclinical CAR T candidates, to discover and develop additional preclinical product candidates using its proprietary non-gene edited short hairpin RNA (shRNA) technology platform, as well as for working capital, other general corporate purposes, and the enhancement of the Company’s intellectual property."

Financing • Oncology

[VIRTUAL] OBJECTIVE RESPONSE AT LOW DOSE IN THE FIRST-IN-HUMAN IMMUNICY-1 TRIAL EVALUATING NON-GENE EDITED ALLOGENEIC CYAD-211 ANTI-BCMA CAR-T PRODUCT IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (EHA 2021) - P1 | "CYAD-211 is administered after a non-myeloablative preconditioning chemotherapy consisting of cyclophosphamide (300 mg/m²/day) and fludarabine (30 mg/m²/day) for 3 days. The observed clinical activity at such low DL of 30x106 cells is encouraging in the allogeneic setting. Clinical and cell kinetics data from the completed first DLs will be presented at the time of the congress.The early stages of this trial continue to support the development of allogeneic CAR T-cell therapy as a feasible approach that may overcome many of the hurdles associated with autologous CAR-T cells."

Clinical • IO biomarker • P1 data • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Multiple Myeloma • Oncology

Celyad Oncology Announces Third Quarter 2021 Financial Results and Recent Business Highlights (GlobeNewswire) - "Upcoming Anticipated Milestones: Additional data from the Phase 1 IMMUNICY-1 trial of CYAD-211 and the Phase 1 CYCLE-1 trial of CYAD-02 are expected at the upcoming ASH meeting in December 2021."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad Oncology to Present Updates from Allogeneic and Autologous CAR T Programs at 63rd ASH Annual Meeting and Exposition (GlobeNewswire) - "The poster will focus on the Company’s shRNA-based anti-BCMA allogeneic CAR T candidate CYAD-211 for the treatment of relapsed/refractory (r/r) multiple myeloma (r/r MM). The oral session will focus on the Company’s autologous NKG2D receptor-based CAR T candidate CYAD-02 for the treatment of r/r acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)."

Clinical data • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad Oncology Presents Updates on Allogeneic CAR T Clinical Candidates and shRNA-based Preclinical Concepts at Research & Development Day (GlobeNewswire) - "Upcoming milestones: (i) Additional clinical activity data for the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected during second half 2021; (ii) Study initiation for KEYNOTE-B79 Phase 1b is expected early fourth quarter 2021; (iii) Submission of an IND application for CYAD-203 is expected in mid-2022; (iv) 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."

IND • New P1 trial • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Microsatellite Instability • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad Oncology Presents Preliminary Data from Phase 1 IMMUNICY-1 Trial of shRNA-based Allogeneic CAR T Candidate CYAD-211 in Relapsed/Refractory Multiple Myeloma at the European Hematology Association Virtual Congress (Businesswire) - P1, N=12; IMMUNICY-1 (NCT04613557); Sponsor: Celyad Oncology SA; "Of the six patients dosed at the first two dose levels (30×106 and 100×106 cells per infusion): No dose limiting toxicity (DLT), Graft-versus Host disease (GvHD) or CAR T-cell-related encephalopathy syndrome (CRES) were observed in the first two dose cohorts. One cytokine release syndrome (CRS) Grade 1 (fever) requiring hospitalization occurred 10 days post CYAD-211 administration in patient 1 (dose level 1) who achieved a partial response (PR)...Additional clinical data from the dose escalation trial are expected during second half 2021."

Cytokine release syndrome • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Celyad Oncology to Present Data From Phase 1 IMMUNICY-1 Trial of Non-Gene Edited Allogeneic CAR T Candidate CYAD-211 in Relapsed/Refractory Multiple Myeloma at the European Hematology Association Virtual Congress (Businesswire) - P1, N=12; IMMUNICY-1 (NCT04613557); Sponsor: Celyad Oncology SA; "No Grade ≥ 3 treatment-related adverse events nor evidence of Graft-versus-Host disease reported from the completed first dose-level (DL1) cohort of Phase 1 dose-escalation IMMUNICY-1 trial evaluating the shRNA-based anti-BCMA CAR T candidate, CYAD-211, for relapsed/refractory (r/r) multiple myeloma. Initial clinical activity observed, with one confirmed partial response (PR) observed in this low dose (30x106 cells per infusion)."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

"$CYAD n=3 / 2 evaluable - 1PR & 1SD w/ their non-gene-edited BCMA allo-CAR-T CYAD-211 #EHA21 #EHA2021 #EHA26" (@BertrandBio)

[VIRTUAL] Clinical Development of a Non-Gene-Edited Allogeneic Bcma-Targeting CAR T-Cell Product in Relapsed or Refractory Multiple Myeloma (ASH 2020) - "IMMUNICY-1 will evaluate three dose-levels of CYAD-211 (3x107, 1x108 and 3x108 cells/infusion) administered as a single infusion after a non-myeloablative conditioning (cyclophosphamide 300 mg/m²/day and fludarabine 30 mg/m²/day, daily for 3 days) according to a classical Fibonacci 3+3 design. We anticipate that subsequent generations of this technology will incorporate multiple shRNA hairpins within a single vector system. This will enable the production of allogeneic CAR T-cells in which multiple genes of interest are modulated simultaneously thereby providing a platform approach that can underpin the future of this therapeutic modality."

CAR T-Cell Therapy • Clinical • IO Biomarker • Graft versus Host Disease • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • IFNG

Celyad Oncology Provides Updates on Allogeneic and Autologous CAR T Programs at 62nd ASH Annual Meeting and Exposition (Businesswire) - "Celyad...today announced updates from the company’s shRNA-based anti-B cell maturation antigen (BCMA) allogeneic CAR T candidate, CYAD-211, and autologous NKG2D receptor-based CAR T candidates, CYAD-01 and CYAD-02....Clinical activity data from the full dose-escalation trial are expected during second half 2021....Based on clinical futility observed to date of CYAD-01 from the Phase 1 THINK trial the company has decided to discontinue the development of CYAD-01 for the treatment of r/r AML / MDS....The dose level 3 cohort of the CYCLE-1 trial is ongoing. Additional safety and efficacy data from the trial are expected during the first half of 2021."

Discontinued • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

IMMUNICY-1: Safety, Activity and Cell Kinetics of CYAD-211 in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Celyad Oncology SA; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Celyad Oncology Announces Dosing of First Patient in Phase 1 IMMUNICY-1 Trial of CYAD-211 for Multiple Myeloma (Businesswire) - "Celyad Oncology...today announced dosing of the first patient of the Phase 1 IMMUNICY-1 trial of CYAD-211, the Company’s novel, short hairpin RNA (shRNA)-based anti-B-cell maturation antigen (BCMA) candidate for the treatment of relapsed/refractory multiple myeloma (r/r MM)...Enrollment in the IMMUNICY-1 trial will continue over the coming months and we expect to report proof-of-concept data from the initial dose cohorts of the trial during the first half of 2021."

P1 data • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

"$CYAD CYAD-211 #ASH20 poster https://t.co/R2qfAgWbFW" (@BertrandBio)

IMMUNICY-1: Safety, Activity and Cell Kinetics of CYAD-211 in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=12; Not yet recruiting; Sponsor: Celyad Oncology SA

Clinical • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology