On August 4, 2021 Celyad Oncology SA (Euronext & Nasdaq: CYAD) (the "Company") (Brussels:CYAD) (Paris:CYAD) (NASDAQ:CYAD), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, reported an update on its financial results and recent business developments for the fiscal quarter ended June 30, 2021 (Press release, Celyad, AUG 4, 2021, View Source [SID1234585708]).
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"We continue to blaze a path forward by developing new technologies to advance allogeneic CAR T therapies, including our proprietary shRNA platform for allogeneic CAR T production and ‘armored’ CAR capabilities with co-expression of secreting cytokines, starting with IL-18. The innovations we are making through our clinical development pipeline and new technologies were the focus of our R&D day last month. This is an exciting time in our Company’s history as we plan for a steady stream of milestones in the second half of 2021," commented Filippo Petti, Chief Executive Officer of Celyad Oncology. "We plan on announcing multiple clinical updates in the next six months that are expected to help further the progress of our lead programs and proprietary shRNA platform for the development of next-generation allogeneic CAR Ts."
Second Quarter 2021 and Recent Business Highlights
Dr. Charles Morris was appointed as Chief Medical Officer in April 2021.
Preliminary data from the Phase 1 IMMUNICY-1 trial of CYAD-211 for the treatment of r/r MM were announced at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress.
Research & Development Day held on July 20, 2021, during which the management team provided:
Updates on the allogeneic CAR T clinical candidates CYAD-211 and CYAD-101.
Highlights from the latest research from its proprietary shRNA platform, including the introduction of CYAD-203 – a novel allogeneic, IL-18-armored CAR T candidate for solid tumor now in IND-enabling studies.
Acquisition of 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 shRNA platform technology.
Pipeline Update
CYAD-101 – Allogeneic TIM-based NKG2D CAR T for mCRC
CYAD-101 is the Company’s first-in-class, allogeneic CAR T candidate engineered to co-express a chimeric antigen receptor (CAR) based on the NKG2D receptor and the novel inhibitory peptide TCR Inhibitory Molecule (TIM).
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 reported 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).
CYAD-101 following FOLFOX preconditioning chemotherapy was observed to be well-tolerated with no evidence of Graft-versus-Host Disease (GvHD). In addition, two of 15 patients from the dose-escalation segment of the alloSHRINK trial achieved a confirmed partial response (PR). Median progression-free survival (mPFS) and median overall survival (mOS) from the dose-escalation segment was 3.9 months and 10.6 months, respectively. In addition, tumor burden decrease based on RECIST 1.1 criteria was observed in eight of 15 patients, including six of nine patients at the recommended dose of 1×109 CYAD-101 cells per infusion.
In September 2020, the Company entered a clinical trial collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ., USA, through a subsidiary. The Company will conduct the Phase 1b KEYNOTE-B79 clinical trial, which will evaluate CYAD-101 following FOLFOX preconditioning chemotherapy, with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in refractory mCRC patients with microsatellite stable (MSS) / mismatch-repair proficient (pMMR) disease. Initiation of the KEYNOTE-B79 trial is expected in the fourth quarter of 2021.
CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM
CYAD-211 is an investigational, shRNA-based allogeneic CAR T candidate for the treatment r/r MM. CYAD-211 is engineered to co-express a B cell maturation antigen (BCMA) targeting CAR and a single shRNA, which interferes with the expression of the CD3ζ component of the T-cell receptor (TCR) complex.
The Company recently announced preliminary data from the dose-escalation Phase 1 IMMUNICY-1 trial, evaluating the tolerability and clinical activity of a single infusion of CYAD-211 following preconditioning with cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) given for three consecutive days.
In June 2021, preliminary data from the Phase 1 IMMUNICY-1 trial was presented at the EHA (Free EHA Whitepaper) congress that demonstrated 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 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.
In July 2021, the Company reported data from the first patient at dose level three (300×106 cells per infusion) which continues to show dose dependent engraftment of CYAD-211 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 the first 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 in-progress for the program. Submission of the IND application for CYAD-203 for treatment of solid tumors is expected in mid-2022.
CYAD-02 – Autologous NKG2D CAR-T for r/r AML and MDS
CYAD-02, the Company’s autologous CAR T candidate with shRNA technology that targets the NKG2D ligands MICA and MICB, is currently being evaluated for the treatment of r/r acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in the Phase 1 CYCLE-1 dose-escalation trial.
To date, eleven patients have received treatment with CYAD-02 in the CYCLE-1 trial, with an enrollment of five patients at dose level three (1×109 cells per infusion).
Preliminary data from the dose level three cohort demonstrated that CYAD-02 was generally well-tolerated. One dose-limiting toxicity was reported at dose level three (cytokine release syndrome, grade 4), leading to expansion of that cohort to six patients. In addition, initial clinical activity has been observed which appears greater than that previously reported from the first-generation autologous NKG2D candidate consistent with a positive contribution from the shRNA-mediated reduction in MICA/B production.
Dose level three cohort of the CYCLE-1 trial is ongoing. Additional safety and efficacy data from the trial are expected by year-end 2021.
Upcoming Anticipated Milestones
Initiation of Phase 1b KEYNOTE-B79 trial evaluating CYAD-101 with KEYTRUDA for advanced mCRC patients with MSS / pMMR disease in fourth quarter of 2021.
Report additional data for the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM by year-end 2021.
Submission of an IND application for CYAD-203 for solid tumors in mid-2022.
Report additional data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in r/r AML and MDS by year-end 2021.
First Half 2021 Financial Results
Key financial figures for the first half of 2021, compared with the first half of 2020 and full year 2020, are summarized below: