• shRNA platform complements Company’s all-in-one-vector approach in the design, discovery and development of next-generation CAR-T candidates
  • Allogeneic T-cells derived by shRNA targeting show distinctive profile compared to CRISPR-Cas9 gene edited cells in preclinical assays
  • Plans to initiate several Phase 1 trials to evaluate lead candidates, including next generation, autologous NKG2D-based CYAD-02 and three first-in-class, shRNA-based, non-gene edited allogeneic CAR-T therapies from the CYAD-200 series

Mont-Saint-Guibert, Belgium - Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, today presented at R&D Day in New York the continued progress of the its pipeline of proprietary CAR-T therapies for the treatment of hematological malignancies and solid tumors, based on its short hairpin RNA (shRNA) platform.

"We are very pleased with the recent progress of our preclinical CAR-T pipeline,” noted Dr. Christian Homsy, CEO of Celyad. “Together with CYAD-101, our next generation allogenic shRNA platform should allow us to leapfrog the competition in the allogeneic CAR-T landscape. In addition, CYAD-02 has shown encouraging preclinical data of increased CAR-T cell expansion, persistence and anti-tumor efficacy. We continue to tap into our deep expertise and knowledge in cell therapy manufacturing and our all-in-one vector approach provides tremendous flexibility, versatility and efficiency in the design of novel, CAR-T therapies."

Corporate Updates

  • Lead asset CYAD-01 continues to advance in clinical trials for the treatment of patients with relapsed/refractory (r/r) acute myeloid leukemia (AML). The Company reported that additional dosing and schedule optimization are under evaluation in the THINK Phase 1 trial. In addition, the Company reported that interim data from the DEPLETHINK Phase 1 trial evaluating CYAD-01 following preconditioning chemotherapy shows the CAR-T cell therapy is well-tolerated at the initial dose levels following preconditioning chemotherapy. Future clinical updates from the Phase 1 THINK and DEPLETHINK trials are anticipated by mid-2019. 
  • Company also highlighted its operational excellence for 2018 including a 94% manufacturing success rate and a twofold increase year-over-year in the number of patients treated.

shRNA Platform

  • In October 2018, Celyad announced it had entered into an exclusive agreement with Horizon Discovery Group for the use of its shRNA technology to generate a novel, next-generation, non-gene-edited allogeneic platform for CAR-T therapies. Horizon Discovery’s SMARTvector technology to express shRNA optimized by Celyad provides an alternate method to knockout the TCR complex in allogeneic CAR-T therapies compared to gene editing techniques as well as the specificity to target a broad range of proteins.
  • Utilization of the shRNA platform allowed the Company to develop the next generation of autologous, NKG2D-based CAR-T candidate, CYAD-02, and the novel, non-gene edited allogeneic CYAD-200 series of CAR-T candidates.
  • In addition, the shRNA platform complements the Company’s strong intellectual property of six U.S. patents related to allogeneic T-cell technology and producing TCR deficient cells expressing a CAR construct.

Autologous CAR-T candidate: CYAD-02

  • CYAD-02 incorporates shRNA technology to target NKG2D ligands MICA/MICB. In preclinical AML models, CYAD-02 shows an encouraging increase in in vitro proliferation and in vivo persistence and anti-tumor activity. The Company plans to generate additional preclinical proof-of-concept data for the program throughout 2019 and plans to submit an Investigational New Drug (IND) application for CYAD-02 in first half 2020.

Non-gene edited allogeneic CAR-T candidates: CYAD-200 series

  • Celyad utilizes two technologies based on non-gene edited approaches to modulate the T-cell receptor (TCR) complex to generate allogeneic CAR-T therapies. The first approach utilizes our TCR-inhibitor molecule (TIM) and is tailored to our NKG2D-based CAR-T clinical candidate CYAD-101. The second approach leverages shRNA technology exclusively licensed from Horizon Discovery to target the CD3ζ component to knockdown the expression of the TCR/CD3 complex on the surface of the T-cell.
  • In vivo data demonstrate that shRNA targeting of CD3ζ effectively protects against Graft-versus-Host Disease (GvHD) to a level equivalent to CRISPR-Cas9 based knock-out.  Furthermore, results from preclinical tests show significant increase in persistence of allogeneic T cells using shRNA targeting when compared to gene editing technologies, such as CRISPR-Cas9.
  • Celyad announced plans to develop three disruptive first-in-class non-gene-edited allogenic CAR-T candidates leveraging the shRNA SMARTvector platform, including:
    • CYAD-211: B-cell maturation antigen (BCMA) targeting CAR-T therapy for the treatment of multiple myeloma, which is expected to enter the clinic by mid-2020.
    • CYAD-221: CD19 targeting CAR-T therapy for the treatment of B-cell malignancies, which is expected to enter the clinic by late 2020.
    • CYAD-231: Dual specific CAR-T targeting NKG2D and an undisclosed membrane protein, which is expected to enter the clinic by early 2021.
  • In addition, the company continues to investigate additional undisclosed targets using the shRNA platform to pair with CARs to develop, differentiated next-generation cell therapies for the treatment of both hematological malignancies and solid tumors.

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