UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 6-K

 

 

REPORT OF FOREIGN PRIVATE ISSUER

PURSUANT TO RULE 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the Month of December 2021

Commission File Number: 001-37452

 

 

CELYAD ONCOLOGY SA

(Translation of registrant’s name into English)

 

 

Rue Edouard Belin 2

1435 Mont-Saint-Guibert, Belgium

(Address of principal executive offices)

 

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F  ☒                Form 40-F  ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):  ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):  ☐

 

 

 


Celyad Oncology SA

On December 13, 2021, Celyad Oncology SA (the “Company”) issued a press release, a copy of which is attached hereto as Exhibit 99.1 and is incorporated by reference herein.

The Company presented a slide presentation at 63rd American Society of Hematology Annual Meeting and Exposition on December 13, 2021, a copy of which is furnished to this report as Exhibit 99.2.

The information contained in this Current Report on Form 6-K, including Exhibit 99.1 and 99.2, except for the quotes of David Gilham and Filippo Petti contained in Exhibit 99.1 is hereby incorporated by reference into the Company’s Registration Statements on Form F-3 (File No. 333-248464) and Form S-8 (File No. 333-220737).


EXHIBITS

 

Exhibit   

Description

99.1    Press release issued by the Company on December 13, 2021
99.2    Presentation furnished by Celyad Oncology SA


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

   

CELYAD ONCOLOGY SA

Date: December 13, 2021     By:  

/s/ Filippo Petti

     

Filippo Petti

Chief Executive Officer and Financial Officer

Exhibit 99.1

 

LOGO

Celyad Oncology Presents Updates on shRNA-Based CAR T Programs at the 63rd ASH Annual Meeting and Exposition

 

   

Data continues to support the versatile potential of non-gene edited shRNA technology with updates from the CYAD-02 and CYAD-211 clinical programs

 

   

Management to host conference call today December 13th at 2:30 p.m. CET / 8:30 a.m. EST

MONT-SAINT-GUIBERT, Belgium, December 13, 2021 – Celyad Oncology SA (Euronext & Nasdaq: CYAD), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, today announced that data from the Phase 1 CYCLE-1 trial of CYAD-02 for the treatment of relapsed or refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and the Phase 1 IMMUNICY-1 trial of CYAD-211 for the treatment of r/r multiple myeloma were presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition. The data support the potential and versatility of non-gene edited short hairpin RNA (shRNA) technology for the development of next-generation CAR T therapies.

“Our presentations at this year’s ASH conference continue to support the potential of our shRNA technology platform to have an impact in the CAR T space without the potential risks recently associated with gene-editing technologies,” said Dr. David Gilham, Chief Scientific Officer of Celyad Oncology. “Data from our CYAD-02 program indicate that a single shRNA can target two independent genes to optimize CAR T cell phenotype, a utility that we believe is unique among currently available gene-expression control technologies. Additionally, the initial observations of cell engraftment, lack of GvHD, and initial signs of clinical activity in the early stages of our first-in-human allogeneic CYAD-211 clinical study underpin the broad potential applicability of shRNA as a platform technology. As we continue to explore these individual product candidates and now focus upon evaluating clinical activity, this clinical proof of principle gives us high confidence to develop further novel clinical candidates based upon our novel shRNA platform.”

Filippo Petti, Chief Executive Officer of Celyad Oncology, added, “This is an exciting time for our company as we continue to validate the multifaceted approach of our shRNA technology. Continued progress with the CYAD-02 program demonstrates the power of shRNA in an autologous setting and serves as a strong foundation for any potential partnership with the program. We also have clear direction for our CYAD-211 program, where we plan to initiate enhanced lymphodepleting regimens to increase cell persistence to potentially maximize clinical benefit from the therapy. As we continue to build on our solid foundation in the allogeneic CAR T space, we remain committed to developing a new paradigm of therapy for these patients.”

Key Highlights from the ASH Annual Meeting

CYAD-02 and CYCLE-1 Phase 1 Trial Update

 

   

Data from autologous NKG2D receptor CAR T candidate CYAD-02 using shRNA shows a single shRNA can target two independent genes to enhance the phenotype of the CAR T cells

 

   

A favorable tolerability profile for CYAD-02 with a low rate of Grade ³ 3 cytokine release syndrome in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome (r/r AML / MDS)

 

   

The dual knockdown of genes MICA/MICB with a single shRNA has a positive contribution to the initial clinical activity of CYAD-02 as compared to the first-generation, autologous NKG2D receptor CAR T, CYAD-01

 

  o

Two MDS patients achieved a marrow complete response at dose level 3

 

  o

Of the eight patients with stable disease, four had anti-leukemic activity

 

   

Comparison of cellular kinetics for CYAD-02 and CYAD-01 trend towards increased engraftment and persistence of CYAD-02 versus CYAD-01, potentially associated with the knockdown of MICA/MICB and reduced fratricide in vivo

CYAD-211 and IMMUNICY-1 Phase 1 Trial Update

 

   

Trial observations from allogeneic shRNA-based anti-BCMA CAR T candidate CYAD-211 support the continued development of shRNA-based allogeneic CAR T therapies as a feasible approach to overcome potential drawbacks and risks associated with autologous and gene-edited allogeneic CAR T therapies

 

 

LOGO

Celyad Oncology SA | Rue Édouard Belin 2, 1435 Mont-Saint-Guibert, Belgium | +32 10 39 41 00


   

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

 

   

All patients had detectable CYAD-211 cells in the peripheral blood; preconditioning chemotherapy led to earlier-than-expected recovery of host lymphocytes limiting persistence of CAR T cells

 

   

The next segment of the IMMUNICY-1 trial will evaluate enhanced lymphodepleting regimens with the aim to improve persistence. In addition, the protocol also allows for CYAD-211 redosing in certain patients

 

   

Enrollment in the cohorts evaluating enhanced lymphodepletion is ongoing. Additional data from the CYAD-211 IMMUNICY-1 trial are expected in mid-2022

Conference Call and Webcast Details

Celyad Oncology will host a conference call to discuss the update from ASH on Monday, December 13, 2021 at 2:30 p.m. CET / 8:30 a.m. EST. The conference call can be accessed through the following numbers:

United States: #1 877-407-9208

International: #1 201-493-6784

The conference call will be webcast live and can be accessed here. The event will also be archived and available on the “Events” section of the company’s website. Please visit the website several minutes prior to the start of the broadcast to ensure adequate time for registration to the webcast.

About Celyad Oncology SA

Celyad Oncology SA is a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer. The Company is developing a pipeline of allogeneic (off-the-shelf) and autologous (personalized) CAR T cell therapy candidates for the treatment of both hematological malignancies and solid tumors. Celyad Oncology was founded in 2007 and is based in Mont-Saint-Guibert, Belgium and New York, NY. The Company has received funding from the Walloon Region (Belgium) to support the advancement of its CAR T cell therapy programs. For more information, please visit www.celyad.com.

Forward-looking statements

This release may contain forward-looking statements, within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the clinical activity and safety and tolerability of CYAD-211 and expectations regarding enrollment and the announcement of additional clinical data, and the clinical activity and safety and tolerability of the CYAD-02 and CYAD-101 programs . Forward-looking statements may involve known and unknown risks and uncertainties which might cause actual results, financial condition, performance or achievements of Celyad Oncology to differ materially from those expressed or implied by such forward-looking statements. Such risk and uncertainty can be found in Celyad Oncology’s U.S. Securities and Exchange Commission (SEC) filings and reports, including in the latest Annual Report on Form 20-F filed with the SEC and subsequent filings and reports by Celyad Oncology. These forward-looking statements speak only as of the date of publication of this document and Celyad Oncology’s actual results may differ materially from those expressed or implied by these forward-looking statements. Celyad Oncology expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation.

Investor and Media Contacts:

Sara Zelkovic

Communications & Investor Relations Director

Celyad Oncology

investors@celyad.com

Daniel Ferry

Managing Director

LifeSci Advisors, LLC

daniel@lifesciadvisors.com

 

LOGO

Source: Celyad Oncology SA

SLIDE 0

2021 American Society of Hematology Meeting Update December 13, 2021 Exhibit 99.2


SLIDE 1

Forward Looking Statements


SLIDE 2

ASH 2021 Virtual Webcast – Agenda Topic Discussant Welcome & Introductions Filippo Petti Chief Executive Officer shRNA Background David Gilham, Ph.D. Chief Scientific Officer CYAD-02 CYCLE-1 Phase 1 Trial Results Charles Morris, M.D. Chief Medical Officer CYAD-211 IMMUNICY-1 Phase 1 Trial Results Charles Morris, M.D. Chief Medical Officer Final Remarks Filippo Petti Chief Executive Officer


SLIDE 3

Redefining Next-Generation Allogeneic CAR T Development All-in-One vector approach Two proprietary allogeneic technologies shRNA – short hairpin RNA TIM – TCR Inhibitory Molecule Armored CAR T franchise focused on IL-18 cytokine Potential for non-gene edited shRNA as a viable platform to develop allogeneic CAR Ts shRNA technology offers potential for safer therapies due to no gene cutting Currently being evaluated in multiple clinical trials and preclinical studies $32.5 million private placement with Fortress Investment Group Funding to be used for: Clinical development of allogeneic CAR T candidates Advance current pipeline of preclinical candidates Discover and develop additional preclinical candidates using shRNA platform shRNA and Allogeneic Equals Novel Approach Recent Financing Ushers New Era for Celyad Oncology Pursuing a Differentiated Strategy for Allogeneic CAR Ts IL-18; Interleukin-18.


SLIDE 4

David Gilham, Ph.D. Chief Scientific Officer shRNA Background


SLIDE 5

shRNA – Novel Platform for Allogeneic CAR T Development shRNA: short hairpin RNA; mRNA: messenger ribonucleic acid; TCR: T cell receptor. Generating T cells with desired phenotypic and functional properties Controlling the level of gene knockdown Multiplexing to knockdown multiple genes Celyad is focusing on unlocking the full potential of shRNA by: What is shRNA? Short hairpin RNA (shRNA) is a non-gene editing technology that we are using as a platform to develop allogeneic CAR Ts


SLIDE 6

First-in-Human shRNA Platform Timeline 2018 2022 Today Exclusive agreement with Horizon Discovery (shRNA platform) October 2018 IND clearance for CYCLE-1 study June 2019 First patient treated in CYCLE-1 study January 2020 IND clearance for IMMUNICY-1 study July 2020 First patient treated in IMMUNICY-1 study December 2020 Initial data for CYCLE-1 study December 2020 Initial data for IMMUNICY-1 study June 2021 Updated data for CYCLE-1 study (ASH) December 2021 Additional data for IMMUNICY-1 study (ASH) December 2021 CYAD-02 (autologous candidate) CYAD-211 (allogeneic candidate) 2019 2020 2021


SLIDE 7

Potential Advantages of Non-Gene Edited Allogeneic CAR Ts Using shRNA No double strand breaks – expected minimal risk of genomic instability and translocation Not all allogeneic CAR Ts are created equal All-in-One vector – long clinical history including maintenance of transgenic payload integrity1,2 Level of gene expression can be titrated to the desired level through the choice of specific shRNA No target gene is inaccessible – genes that can be targeted by genetic knockout can be controlled with shRNA Multiplexed shRNA – targeting multiple genes simultaneously in the absence of reported genomic instability issues associated with multiplexed gene editing3 1 Marcucci et al. (2018) Mol Therapy doi:  10.1016/j.ymthe.2017.10.012 2 Scholler et al. (2012). Sci Trans Med. 10.1126/scitranslmed.3003761 3 Bother et al. (2020) The Crispr Journal (http://doi.org/10.1089/crispr.2019.0074)


SLIDE 8

Expected Real-World Benefits of Our Approach to Allogeneic CAR T Gene Knockdown Aims to Optimize Therapy Shorter Manufacturing Time Lower Cost of Goods Sold Ability to potentially simultaneously knockdown multiple gene targets of interest shRNA can target genes that are not suitable for gene editing, thereby potentially expanding therapies based on indication / disease of interest T cells age with longer culture times. Short culture times expected to maintain an optimal ‘fit’ T cell phenotype associated with therapeutic potential Vector costs are a major contributor to Cost of Goods Sold Using a single vector avoids the costs associated with multi-vector technologies


SLIDE 9

Technology continues to show promise as a platform No evidence of GvHD Cell kinetics Initial clinical activity shRNA as a Novel Allogeneic Technology for CAR T


SLIDE 10

Charles Morris, M.D. Chief Medical Officer CYAD-02 CYCLE-1 Trial Results


SLIDE 11

CYAD-02 – Next-Generation Autologous NKG2D CAR T CYAD-02 incorporates shRNA technology to silence the expression of the NKG2D ligands MICA and MICB Targeting MICA and MICB with a single shRNA leads to decrease of ligand expression on T cells and enhanced in vitro expansion compared to first-generation autologous NKG2D candidate, CYAD-01 Background on CYAD-02 NKG2D - natural killer group 2D receptor Building upon our first-generation autologous program


SLIDE 12

Open-label, dose-escalation trial in relapsed or refractory AML and MDS patients CYAD-02 CYCLE-1 – Phase 1 Trial to Determine Recommended Dose Study Design Treatment Schedule Twelve AML and MDS with relapsed or refractory (r/r) disease patients treated Similar patient population as DEPLETHINK Phase I Trial evaluating first-generation CYAD-01 Patient Population Primary objective: Determine the recommended dose of CYAD-02 Study endpoints: Primary endpoint is the occurrence of dose-limiting toxicities Key secondary endpoints include additional safety parameters, objective responses and duration of responses, and CYAD-02 cell kinetics Dose Escalation: 1x108, 3x108 and 1x109 cells per infusion NCT04167696: Study in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients to Determine the Recommended Dose of CYAD-02 (CYCLE-1)


SLIDE 13

+ indicates patient is ongoing. No objective responses observed 5/17 patients with SD including 1 with anti-leukemic activity 2 MDS patients achieved a marrow complete response (mCR) both at dose level 3 (DL3) 8/12 patients with stable disease (SD) including 4 with anti-leukemic activity defined as decrease of at least 50% of the bone marrow blasts CYCLE-1 data from uncleaned database (02 Nov 2021). CYCLE-1 Study (CYAD-02) DEPLETHINK Study (CYAD-01) CYAD-02 vs. CYAD-01 Response in r/r AML and MDS Patients


SLIDE 14

CYAD-02 cells were detected post-infusion in all patients in the CYCLE-1 study Median peak engraftment trending higher for CYAD-02 compared to CYAD-01 Overall, CYAD-02 presents longer persistence compared to CYAD-01 One patient at dose level 3 in the CYCLE-1 study received a delayed infusion of CAR T cells 10 days post CyFlu administration (◄), which negatively impacted the peak engraftment of CYAD-02 compared to other patients at the same dose Kinetics of CYAD-02 vs. CYAD-01 at Dose Level 3 (1x109 cells/dose) Cell kinetics in the peripheral blood were assessed by ddPCR. Black arrowhead indicates CAR T cell infusions, except for patient indicated with blue arrowheads, who received CAR T cells 10 days post-CyFlu instead of 2 days. Values <LOD are set at LOD of the assay (10 copies/µg)


SLIDE 15

CYAD-02 CYCLE-1 Summary Data support the use of shRNA platform for CAR T development Single shRNA can target two independent genes to enhance the phenotype of the CAR T cells Overall good tolerability profile of CYAD-02 post CyFlu preconditioning Two objective responses (mCR) at dose level 3 leading to 33% objective response rate and anti-leukemic activity in 50% of patients The knockdown of MICA/MICB with shRNA appears to have a positive contribution to the initial clinical activity of CYAD-02 as compared to first generation autologous NKG2D CAR T, CYAD-01 Trending higher engraftment of CYAD-02 vs. CYAD-01, potentially associated with the knockdown of MICA/MICB and reduced fratricide in vivo The lack of IL-7/IL-15 induction following preconditioning can be a limiting factor to the homeostatic proliferation of CAR T cells Likely related to the biology of myeloid malignancies A factor for consideration for further clinical development in these specific diseases


SLIDE 16

Charles Morris, M.D. Chief Medical Officer CYAD-211 IMMUNICY-1 Phase 1 Trial Update


SLIDE 17

Background on CYAD-211 First allogeneic CAR T candidate utilizing our All-in-One vector approach based on shRNA technology CYAD-211 co-expresses: CAR with a BCMA-specific engager Allogeneic technology – single shRNA targeting CD3ζ component of TCR complex Selection marker – truncated cell surface tag allows for positive cell enrichment during manufacturing BCMA: B-cell maturation antigen; r/r MM: relapsed/refractory multiple myeloma. CYAD-211 – Novel Allogeneic CAR T Candidate for r/r MM shRNA CD3ζ


SLIDE 18

CYAD-211 – Preclinical Differentiation Among BCMA CAR T Candidates * First experiment performed with one donor. Other donors are currently being investigated to determine whether there is a donor effect. CYAD-211 and peer candidate CAR T cells screened for repeated antigen stimulation After each round, remaining CAR T cells collected and mixed with fresh target cells for the next round Round 1 Round 2 Round 3 Round 4 Only candidate remaining after multiple rounds of antigen stimulation


SLIDE 19

Open-label, Phase 1 dose-escalation trial in r/r multiple myeloma patients CYAD-211 – IMMUNICY-1 First-in-Human Trial Study Design Treatment Schedule Primary objective: Safety and identification of recommended dose of CYAD-211 Secondary objective: Clinical anti-tumor activity and CYAD-211 cell expansion, persistence and trafficking Dose Escalation: 30x106, 100x106 and 300x106 per infusion Preconditioning chemotherapy: Cyclophosphamide: 300 mg/m2 x 3 days Fludarabine: 30 mg/m2 x 3 days NCT04613557: Safety, Activity and Cell Kinetics of CYAD-211 in Patients With Relapsed or Refractory Multiple Myeloma (IMMUNICY-1). IMWG: International Myeloma Working Group; MM: Multiple myeloma; r/r: Relapsed / refractory. Eligibility Criteria At least two prior MM treatment regimens At least 1 complete cycle of treatment At least 1 response to a prior treatment regimen Measurable disease as per the IMWG Response Criteria


SLIDE 20

IMMUNICY-1 – Patient Backgrounds and Safety Data Twelve patients enrolled in three dose levels Most patients had high-risk cytogenetics according to mSMART 25% had extramedullary disease Heavily pre-treated patients: Median prior lines of therapy: four 83% exposed to all three major MM drug classes (Immunomodulatory drugs, proteasome inhibitors and CD38-directed therapies) mSMART: Mayo Stratification of Myeloma and Risk-Adapted Therapy; DLT: Dose limiting toxicities; GvHD: Graft versus Host disease. Continued Favorable Tolerability No DLTs, no GvHD and no CAR‑T‑cell‑related encephalopathy syndrome (CRES) One cytokine release syndrome (CRS) Grade 1 (fever) reported at dose level 1 Three patients experienced adverse event (AE) Grade 3 or 4 possibly or probably related to CYAD-211. These AEs were all blood disorders. Patient Background


SLIDE 21

Three patients achieved partial response (PR), one in each dose-level, while eight patients had stable disease (SD) One patient with SD (4.5 months) showed evidence of reduction in size of plasmacytomas CYAD-211 – Clinical Responses and Duration of Responses to Progression Data from uncleaned database (21 Oct 2021); DL: Dose level; MR: Minimal response; PD: Progressive disease .


SLIDE 22

CYAD-211 – Cell Kinetic Data from IMMUNICY-1 Calls for Further Exploration of Lymphodepletion All patients had detectable CYAD-211 cells in the peripheral blood, although engraftment was short lasting Data suggests expansion and persistence of cells might be more dependent on the depth and period of the lymphodepletion induced by the preconditioning regimen Clearance of CYAD-211 was associated with recovery of endogenous lymphocytes populations as suggested by the averaged absolute lymphocyte counts (ALC) kinetics Key Takeaways


SLIDE 23

Data and observations support the potential of shRNA allogeneic therapies as a feasible approach to CAR T that may overcome challenges associated with autologous and gene edited CAR Ts Three patients achieved partial response (one in each dose level) Eight patients had stable disease One patient with stable disease showed evidence of reduction in plasmacytomas Favorable tolerability profile observed for CYAD-211 across all dose levels CYAD-211 IMMUNICY-1 Summary


SLIDE 24

Filippo Petti Chief Executive Officer Final Remarks


SLIDE 25

Technology continues to show promise as a platform shRNA as a Novel Allogeneic Technology for CAR T No evidence of GvHD Cell kinetics Initial clinical activity ü ü ü


SLIDE 26

Next Steps for shRNA CAR T Candidates and Platform CYAD-211 Enrolling in cohorts 4 and 5 to evaluate enhanced lymphodepletion CYAD-211 redosing also allowed by the protocol CYAD-02 Evaluating potential partnership opportunities for autologous NKG2D franchise shRNA Platform Continue exploring platform for armored CAR franchise Cohort CYAD-211 Cells/Infusion Preconditioning Chemotherapy 1-3 30x106, 100x106 and 300x106, respectively Cy: 300 mg/m2 x 3 days Flu: 30 mg/m2 x 3 days 4 300x106 Cy: 500 mg/m2 x 3 days Flu: 30 mg/m2 x 4 days 5 300x106 Cy: 750 mg/m2 x 3 days Flu: 30 mg/m2 x 4 days Cy: Cyclophosphamide; Flu: Fludarabine.


SLIDE 27

2021 American Society of Hematology Meeting Update December 13, 2021