Annual Report 2024 ENG

2024 Annual Report

2024 ANNUAL REPORT

0

2024 Annual Report

3

2024 Annual Report

ANNUAL REPORT 2024

This Annual Report (the "Report") is dated April 4, 2025, and contains all required information as per the Belgian Code of the Companies and Associations (the "BCCA").

The affiliates included in this Report are Celyad Oncology SA, Celyad Inc. and CorQuest Medical Inc.

Celyad Oncology SA and its affiliates will be collectively referred to as "the Company", "the Group", "Celyad", "we" or "us".

LANGUAGE OF THE REPORT

The Company publishes this Report in French, in accordance with Belgian laws. The Company also provides an English translation. In case of a difference of interpretation, the French version will prevail.

AVAILABILITY OF THE REPORT

A printed copy of the Report is available free of charge upon request to:

Celyad Oncology SA

Investor Relations

Rue André Dumont 9,

B-1435 Mont-Saint-Guibert, Belgium

Tel: +32 10 394100

E-mail: investors@celyad.com

An electronic version of this Report is available on the Company website: http://www.celyad.com/investors/regulated-information

FORWARD LOOKING STATEMENTS

This Report may contain forward-looking statements, including, without limitation, statements regarding beliefs about and expectations for the Company's updated strategic business model, including associated potential benefits, transactions and partnerships, statements regarding the potential value of the Company's IP, statements regarding the Company's financial statements and future fundraising plans, and statements regarding the continuation of the Company's existence. The words "will," "believe," "potential," "continue," "target," "project," "should" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this Report are based on management's current expectations and beliefs and are subject to a number of known and unknown risks, uncertainties and important factors which might cause actual events, results, financial condition, performance or achievements of Celyad Oncology to differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks related to the Company's ability to realize the expected benefits of its updated strategic business model; the Company's ability to develop its IP assets and enter into partnerships with outside parties; the Company's ability to enforce its patents and other IP rights; the possibility that the Company may infringe on the patents or IP rights of others and be required to defend against patent or other IP rights suits; the possibility that the Company may not successfully defend itself against claims of patent infringement or other IP rights suits, which could result in substantial claims for damages against the Company; the possibility that the Company may become involved in lawsuits to protect or enforce its patents, which could be expensive, time-consuming, and unsuccessful; the Company's ability to protect its IP rights throughout the world; and the potential for patents held by the Company to be found invalid or unenforceable. 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.

4

2024 Annual Report

Shareholder Letter

Dear Shareholder,

Today, Celyad Oncology (the "Company") operates as a highly efficient and focused entity within the life sciences sector. The value and opportunity provided by our cellular therapy technology platforms are key areas of focus. Our overall ambition is to advance human therapeutics by acquiring and enhancing proprietary technologies, which we then integrate with strategic alliances and partnerships to form or support cutting-edge treatments.

Importantly, this means that the Company no longer independently develops and finances its own therapeutics through costly and time-consuming human clinical trials. Instead, Celyad works behind the scenes to provide select partners with the technologies and intellectual property required to deliver best-in-class treatments to patients in need. This innovative model allows the Company to avoid taking concentrated, multi-year risks with any single program and enables it to collaborate with numerous companies across multiple therapeutic areas while retaining potential long-term value creation within each partnership.

Over the past year, we have advanced this new business model by engaging in partnership discussions with numerous companies in the life sciences, advancing our technologies, filing new patent applications, and evaluating several technologies for potential acquisition.

Encouragingly, Celyad's scientists have made significant progress in our core strategic areas of focus in 2024. We are confident that these key advancements will enhance our partnering efforts by further clarifying the utility of our proprietary technologies as they address some of the challenges in current cancer and other disease areas.

Several of these advancements are detailed below.

• We progressed our proprietary, multi-plex miRNA technology by expanding the platform to a 5-plex system. The novel chimeric cluster demonstrated high efficiency in knocking down five highly relevant genes in T-cells simultaneously. Furthermore, each target gene could be adjusted to a specific level of expression allowing for fine-tuning of the target independently of the other targets. This demonstrates multiple advantages over gene editing approaches such as CRISPR by avoiding the need to break the cell's DNA, or make any change to the underlying DNA sequence.
• We demonstrated the feasibility and effectiveness of our multiplex approach in three separate contexts:
• 1st improving allogeneic (or donor-derived) Chimeric Antigen Receptor (CAR) T cells by avoiding Graft versus Host disease (knocking down CD3zeta), while avoiding Host versus Graft (knocking down B2M and CIITA) and avoiding CD95L- mediated apoptosis (knocking down CD95).

5

2024 Annual Report

• 2nd improving CAR T cell resilience to the tumor microenvironment by targeting immune checkpoint inhibitors PD-1, LAG3, TIM3 and CD95.
• 3rd combatting cytokine related toxicities and enhancing CAR T-related safety by targeting IFN-g, GM-CSF and TNFa.
• We developed and validated our multi-specific CAR T cell platform by generating a PSMA/NKG2D tandem CAR T-cell to specifically target the potential loss of the PSMA antigen in prostate cancer. Thus, creating a CAR that can potentially overcome antigen heterogeneity and provide enhanced efficacy against prostate cancer.
• We provided in vivo proof-of-concept of our CD19/NKG2DL tandem CAR T cell candidate in a B-ALL relapse model, showing that our multi-specific CAR T cell candidate has an enhanced anti-tumor efficacy in a lymphoma model of antigen- loss.
• Two manuscripts were published during 2024. The first details non-gene edited technologies for allogeneic CAR T-cell therapies (Cells) and the second on the topic of engineering strategies to safely drive CAR T-cells into the future (Front Immunol).

The leadership team was also enhanced with the full time CEO role filled by an industry veteran with deep expertise in advanced, cellular therapy drug development and extensive partnering experience across gene and cell therapy. More recently, the Company successfully reached an agreement that simplified and removed certain obligations in its foundational license with Dartmouth. Further, the Company and majority shareholders are fully committed to support our innovative new partnering strategy and believe it promotes the best interests of all Celyad stakeholders with the aim of creating significant shareholder value in the coming years.

6

2024 Annual Report

1. Activity Report

1.1 Who we are - Business Overview

We are a cutting-edge biotechnology company dedicated to pioneering the discovery and advancement of revolutionary technologies for chimeric antigen receptor (CAR) T-cells. Our primary objective is to unlock the potential of proprietary technology platforms and intellectual property, enabling us to be at the forefront of developing next-generation CAR T-cell therapies. By fully leveraging our innovative technology platforms, we aim to maximize the transformative impact of our candidate CAR T-cell therapies and redefine the future of CAR T-cell treatments.

Our differentiated strategy includes the development of technology platforms and CAR T-cell candidates to broaden the range of cancer indications and tackle the main limitations of current CAR T-cell therapies.

Overview of the CAR T-cell landscape and current main limitations

Over the past decades, immunotherapy has become the main approach for novel cancer treatment options with several approved blockbuster products that saved the lives of thousands of patients with cancer indications. Within the field of immuno-oncology, chimeric antigen receptor (CAR) T-celltherapy is now a realistic treatment paradigm for patients with advanced disease. In this strategy, T-cells are genetically reprogrammed in the lab to express a gene coding for a receptor (called CAR), aiming to help the T-cells to specifically recognize, attack, and destroy tumor cells via binding to proteins that are mainly expressed by tumor cells (called antigens).

As of the date of this Report, a total of twelve autologous CAR T-cell therapies for the treatment of hematological malignancies have been approved by different regulatory authorities. These include seven CAR T-cell products directed against the cluster of differentiation 19 (CD19) or the B-cell maturation antigen (BCMA) which are approved in the United States, in Europe and in other countries, and five CD19-specific or BCMA-specific CAR T-cell products which are only approved in China or India. In addition, one CD19- specific CAR T-cell product has received approval in Spain under the "hospital exemption" approval pathway. All these approvals were based on impressive overall response rates and durable remissions observed with CD19 and BCMA-specific CAR T-cell therapies in patients with non-Hodgkin lymphoma, B-cell acute lymphoblastic leukemia (B-ALL), or multiple myeloma who had failed under standard therapies. These CAR T-cell therapies have profoundly altered the treatment landscape in those indications.

Despite this success and continued progress in the CAR T-cell field, many challenges remain including: i) antigen modulation and heterogeneity, ii) tumor microenvironment (TME), and iii) cell source of CAR T-cells.

1. Antigen modulation and heterogeneity are major causes of CAR T-cell resistance in B-cell malignancies. In pediatric B-ALL, 50% of relapses are associated with CD19 antigen loss, and, in large B- cell lymphoma, 30% of relapses are CD19-negative and an additional 30% has CD19 expression levels that are too low to allow for CAR T-cell activation.

To overcome tumor antigen escape, reduction in antigen expression levels, or mutational changes within the single antigen, platforms with CAR T-cells targeting multiple antigens rather than a single antigen need to be created. It is likely that antigen modulation poses an even greater challenge in solid tumors, where antigens show significant heterogeneity due to the heterogenous nature of the components that make up the TME, than in hematological malignancies.

1. The TME contains a variety of cells (such as: cancer cells, cancer-associated fibroblasts, and immune cells including but not limited to tumor-associated macrophages, myeloid progenitor cells, and myeloid- derived suppressor cells), matrix proteins, secreted proteins as well as an extracellular matrix comprised of stromal cells, fibrous proteins, glycoproteins, proteoglycans, and polysaccharides. The presence of each of

7

2024 Annual Report

these cells and proteins varies depending on the tumor location and cancer type, but all contribute to the very complex and immunosuppressive TME.

In order for CAR T-cells to exert their function against the tumor cells, the first challenges are to navigate through the ecosystem of the TME and to reach the tumor. Once there, they need to bypass the strong immunosuppressive and complex TME that downregulates their activity, expansion, and persistence at the tumor site. To face those challenges, additional engineering of CAR T-cells to endow them with novel attributes and functionalities necessary to overcome the TME is required.

1. Another limitation is related to the source of CAR T-cells. The majority of CAR T-cell therapies in clinical testing worldwide, including the marketed products, are autologous in nature which means that the CAR T- cells are produced from patient-derived T-cells. Specifically, T- cells are harvested from the patient's blood using a procedure known as leukapheresis, after which the cells are genetically modified and then administered back to the patient via intravenous infusion in the bloodstream. This custom-made cell production is very expensive, requires complex patient-specific manufacturing with a failure rate between 2- 10% in the commercial setting, has limited scalability, and shows a large variability in quality between patients due to the patient's prior treatment and disease history which makes it difficult to predict the potency of the T-cells. Additionally, the delay in treatment initiation due to the time needed for the manufacturing process (weeks to months) can be particularly problematic in patients with rapidly progressing disease. Moreover, there is a logistical challenge in shipping cells back and forth between the treatment site and cell production facilities, which usually follows a centralized manufacturing model, meaning that patients with advanced diseases have a significant possibility of disease progression before they receive the CAR T-cells. The development of allogeneic, 'off-the-shelf' CAR T- cells allows to overcome many of these limitations, contributing to scalability and direct access to CAR T-cell therapies.

Allogeneic CAR T-cells are manufactured from blood collected from healthy donors after which the cells can be stored frozen until a patient requires treatment. Hence, allogeneic CAR T-cells are available on demand and lack the variability inherent in autologous CAR T-cells. Whilst attractive, the main downside of the allogeneic approach is the risk of potential life-threatening toxicity called "graft-versus-host disease" (GvHD) that is mediated by recognition of the patient's healthy tissues by the T-cell receptor (TCR) present on the surface of allogeneic CAR T-cells. To minimize this risk, the manufacturing process of allogeneic CAR T-cell therapies include an engineering step that aims to eliminate or blunt the signaling or the expression of the TCR using specific technology. As a result, the engineered allogeneic CAR T-cells fail to recognize the patient's healthy tissue as foreign, preventing GvHD.

Of late, current research efforts to prevent GvHD have been focused on gene editing technologies to enable the genome-level ablation of components of the TCR. Several gene-edited allogeneic CAR T-cell candidates are currently being evaluated in human clinical trials in B-cell malignancies, with some preliminary success. However, off-target editing remains a concern for developers and regulators because the safety risks associated with genetic disruptions that may lead to unintended, irreversible off-target genetic alterations (i.e. off-target DNA cleavages, mutations, or chromosomal rearrangements) are significant. Moreover, practical hurdles (i.e. lengthy and difficult technical process to engineer multiple gene editing, an inefficient production characterized with lower yield as the number of edits increase, etc.) to delivering a gene-edited T-cell product remain.

1.2 Our Strategy

Our activities are based on three main pillars:

• The development of CAR T-cells based on targets expressed in a vast majority of tumor indications aims to provide a treatment option to a broad patient population. Celyad Oncology has developed several CAR T-cellproduct candidates based on the natural killer group 2D (NKG2D), a receptor that is expressed on natural killer (NK) and T-cellsand binds to eight stress-inducedligands broadly expressed on tumor cells in most solid tumors and hematological malignancies. Two autologous product candidates, CYAD-01and CYAD-02,and the allogeneic counterpart of

8