Update on Clinical and Preclinical Programs
CYAD-101 – Allogeneic TIM-based, NKG2D receptor-based CAR T for mCRC
Celyad Oncology’s first-in-class, non-gene edited clinical candidate CYAD-101 continues to advance in the alloSHRINK Phase 1 trial for the treatment of mCRC. CYAD-101 co-expresses the NKG2D receptor and the novel inhibitory peptide TIM (TCR Inhibitory Molecule), whose expression reduces signaling of the TCR complex by interfering with the CD3z component of the TCR complex. The Company plans to initiate the expansion cohort of the alloSHRINK trial which will evaluate CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion. Enrollment in this expansion cohort is expected to start by year-end 2020.
Planning is also ongoing to initiate the Phase 1b KEYNOTE-B79 study of CYAD-101, following FOLFIRI preconditioning chemotherapy, with MSD’s KEYTRUDA® in refractory mCRC patients with MSS / pMMR disease during the first half of 2021. The Company believes the mechanism of actions between CYAD-101 and KEYTRUDA® are highly complementary and could help to drive meaningful clinical benefit in patients with advanced mCRC.
CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM
CYAD-211 is an investigational, short hairpin RNA (shRNA)-based allogeneic CAR T candidate for the treatment of r/r MM. CYAD-211 is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3z component of the T-cell receptor (TCR) complex. In July 2020, Celyad Oncology announced FDA clearance of its IND application for CYAD-211 and subsequently received CTA approval for CYAD-211 by the FAMHP. The Company plans to initiate the Phase 1 IMMUNICY-1 trial evaluating CYAD-211 following preconditioning chemotherapy in r/r MM by year-end 2020.
CYAD-01 – Autologous NKG2D receptor-based CAR T for r/r AML and MDS
The Company’s first-in-class NKG2D receptor-based CAR T clinical candidate CYAD-01 continues to advance in the ongoing Phase 1 THINK trial for the treatment of patients with r/r acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The Company is scheduled to announce preliminary data from CYAD-01 produced with the OptimAb manufacturing process from the expansion cohort of the Phase 1 THINK trial at the American Society of Hematology (ASH) conference in December 2020.
CYAD-02 – Next-Generation Autologous NKG2D receptor-based CAR T for r/r AML and MDS
CYAD-02 is an investigational CAR T therapy that engineers an All-in-One vector approach in patient’s T cells to express the NKG2D receptor CAR and shRNA to knockdown the expression of NKG2D ligands MICA and MICB on the CAR T cells. The Company is currently conducting the Phase 1 dose-escalation CYCLE-1 trial evaluating CYAD-02 for the treatment of r/r AML and MDS. During the third quarter, the Company initiated the third dose cohort of the trial. The CYCLE-1 trial is assessing the safety and clinical activity of a single infusion of CYAD-02 produced with the OptimAb manufacturing process following preconditioning chemotherapy with cyclophosphamide and fludarabine. Preliminary data from CYCLE-1 trial are expected at the ASH conference in December 2020.
Upcoming Milestones
| • | | Plan to begin enrollment in the expansion cohort of the Phase 1 alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients by year-end 2020. |
| • | | Expect to initiate the dose-escalation Phase 1 IMMUNICY-1 trial evaluating CYAD-211 in r/r MM by year-end 2020. |
| • | | Expect to initiate the Phase 1b KEYNOTE-B79 clinical study of CYAD-101 following FOLFIRI preconditioning chemotherapy, with KEYTRUDA® in refractory mCRC patients in first half of 2021. |
| • | | Three abstracts accepted for presentation at the annual ASH Meeting & Exposition, being held December 5–8, including: |
| • | | Poster presentation of the Company’s anti-BCMA allogeneic CAR T candidate, CYAD-211 |
| • | | Poster presentations of the Company’s autologous NKG2D receptor-based CAR T candidates, CYAD-01 and CYAD-02 |
Upcoming Conferences
Celyad Oncology’s management team is scheduled to participate in the following conferences during the remainder of 2020:
| • | | Bryan, Garnier & Co. Virtual European Healthcare Conference, November 16, 2020 |
| • | | Jefferies Virtual London Healthcare Conference, November 17, 2020 |
| • | | SVB Leerink Oncology 1x1 Day, November 19, 2020 |
| • | | 62nd American Society of Hematology Annual Meeting & Exposition, December 5 – 8, 2020 |