Update on Clinical and Preclinical Programs
CYAD-101 – Allogeneic TIM-based, NKG2D CAR T for Refractory Metastatic Colorectal Cancer with Microsatellite Stable Disease
Celyad Oncology’s first-in-class, non-gene edited clinical candidate CYAD-101, which co-express NKG2D and the novel inhibitory peptide TIM (TCR Inhibitory Molecule), continues to advance in the alloSHRINK Phase 1 trial for the treatment of mCRC. During the American Society of Oncology (ASCO) Virtual Scientific Program, the Company presented data from the first fifteen patients enrolled in the ongoing alloSHRINK trial assessing safety and clinical activity of CYAD-101 administered following FOLFOX chemotherapy in refractory patients with advanced mCRC with microsatellite stable (MSS) disease:
Treatment with CYAD-101 was well-tolerated, with no clinical evidence of Graft-versus-Host Disease (GvHD) observed
In addition, 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 nine patients who achieved stable disease (SD), including two patients with SD through six months
Recent analysis of the dose-escalation segment of the alloSHRINK trial showed median progression free survival (mPFS) was 3.9 months for patients treated with CYAD-101 following FOLFOX chemotherapy
No correlation was observed between clinical responses and the degree of human leukocyte antigen (HLA) matching between patients and CYAD-101 donor cells, indicating that CYAD-101 can be used in a broad patient population regardless of the HLA haplotype
The expansion cohort of the alloSHRINK trial will evaluate CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients with MSS disease, at the recommended dose of one billion cells per infusion. Enrollment in the expansion cohort of the study is expected to begin during the fourth quarter of 2020.
CYAD-211 – Allogeneic shRNA-based, BCMA CAR T for Relapsed or Refractory Multiple Myeloma
CYAD-211 is the lead program from the Company’s CYAD-200 series of proprietary non-gene edited allogeneic short hairpin (shRNA)-based CAR T candidates. CYAD-211 is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3? component of the T-cell receptor (TCR) complex. In July 2020, the IND application for CYAD-211 went into effect with the FDA, and the Company plans to initiate the Phase 1 IMMUNICITY trial evaluating CYAD-211 following preconditioning chemotherapy in r/r MM by year-end 2020.
CYAD-01 – Autologous NKG2D CAR T for Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome
The Company’s first-in-class NKG2D CAR T clinical candidate CYAD-01 continues to advance in the ongoing Phase 1 THINK trial for the treatment of patients with relapsed or refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome (MDS). Based on preliminary clinical activity data from the dose-escalation Phase 1 DEPLETHINK trial, the Company has deprioritized the trial and stopped enrollment. The Company expects to announce preliminary data from CYAD-01 produced with the OptimAb manufacturing process from the expansion cohort of the Phase 1 THINK trial by year-end 2020.
CYAD-02 – Autologous NKG2D CAR T for Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome
In January 2020, the Company announced that the first patient was dosed in the Phase 1 dose-escalation CYCLE-1 trial evaluating CYAD-02 for the treatment of r/r AML and MDS. In July 2020, the Company began enrollment in 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 by year-end 2020.
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 with MSS disease during the fourth quarter of 2020
Report additional data from the CYAD-01 program in r/r AML and MDS, including the dose-expansion cohort of the Phase 1 THINK trial by year-end 2020
Report preliminary data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in r/r AML and MDS by year-end 2020
Expect to initiate the dose-escalation Phase 1 trial evaluating CYAD-211 in r/r MM by year-end quarter 2020
On March 11, 2020, the World Health Organization declared the novel strain of coronavirus (COVID-19) a global pandemic and recommended containment and mitigation measures worldwide. As of the date of our half year report, Belgium and United States, where the Company operates, continues to be impacted by the pandemic. The length or severity of this pandemic cannot be predicted, but the Company anticipates that there may be an additional impact from a prolonged COVID-19 environment on the planned development activities of the Company.
To date, COVID-19 has had no impact on the Company’s financial statements and corporate cash flow, and the Company expects that its existing treasury position will be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into third quarter 2021.
As previously disclosed, the coronavirus pandemic has led to enrollment delays in the Company’s Phase 1 clinical trials within its relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes program. Principally, for several weeks between March and April 2020, the Company experienced a delay in enrollment in the CYAD-01 THINK and DEPLETHINK trials as multiple clinical trial sites, both in Belgium and the United States, paused activities associated with new patient enrollment to prioritize resources to patients with COVID-19. By the end of the second quarter, recruitment in the CYAD-01 THINK and DEPLETHINK trials had recovered. In comparison, enrollment in the CYAD-02 CYCLE-1 dose-escalation trial was less affected by the coronavirus pandemic, partially due to the staggered enrollment associated with the trial.
Operations and timelines associated with the Company’s allogeneic programs, CYAD-101 and CYAD-211, have been insignificantly impacted by the coronavirus pandemic given activities over the first half of 2020 were primarily focused on non-clinical workstreams, including the technology transfer of CYAD-101 into its manufacturing facility in Mont-Saint-Guibert, Belgium and the submission of the IND application for CYAD-211, which in July 2020, the Company announced that the IND application for CYAD-211 is in effect with the FDA.
The long-term impact of COVID-19 on the Company’s operations will depend on future developments, which are highly uncertain and cannot be predicted, including a potential second wave of the pandemic, new information which may emerge concerning the severity of the coronavirus and the actions to contain the coronavirus or treat its impact, among other things, but potential prolonged closures or other business disruptions may negatively affect its operations and the operations of its agents, contractors, consultants or collaborators, which could have a material adverse impact its business, results of operations and financial condition.