Celyad Oncology

• KEYNOTE-B79 Phase 1b trial will evaluate CYAD-101 and KEYTRUDA® (pembrolizumab) in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC)
• ASCO-GI conference abstract accepted that highlights KEYNOTE-B79 clinical trial design

MONT-SAINT-GUIBERT, Belgium, December 15, 2021 – Celyad Oncology SA (Euronext & Nasdaq: CYAD) (“the Company”), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, today announced the first patient was dosed in the KEYNOTE-B79 Phase 1b trial (NCT04991948).

The KEYNOTE-B79 trial is part of a collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, through a subsidiary. The trial will evaluate the Company’s lead developmental candidate, its TCR Inhibitory Molecule (TIM)-based allogeneic NKG2D CAR T cell investigational therapy CYAD-101, with MSD’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with refractory metastatic colorectal cancer (mCRC) with microsatellite stable (MSS)/mismatch-repair proficient disease.

“Dosing the first patient in this Phase 1b trial represents an important step toward understanding any potential role of CYAD-101 for mCRC patients with an MSS background,” said Dr. Charles Morris, Chief Medical Officer of Celyad Oncology. “We are evaluating CYAD-101 in combination with KEYTRUDA in hope of identifying a new option to target patients’ tumors. Preclinical data and translational data from our prior phase 1 study of CYAD-101 suggest that there may be an additive benefit with pembrolizumab as an anti-PD-1 checkpoint inhibitor when combined with CYAD-101 in colorectal cancer and we look forward to studying that in the clinic. We are grateful to MSD for collaborating with us on this trial and expect to share preliminary data next year.”

The Company also reported the KEYNOTE-B79 study will be the subject of a presentation at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium being held in person in San Francisco, California and virtually from January 20-22, 2022.

ASCO GI 2022 Presentation Details:

The following abstract will be available on the ASCO GI website on January 18, 2022 at 5 p.m. EST. Following the presentation at the meeting, the poster will be available in the Scientific Publications section of Celyad Oncology’s website.

Abstract Number: TPS227

Abstract Title: KEYNOTE-B79 phase 1b trial to evaluate the allogeneic CAR T-cells CYAD-101 and pembrolizumab in refractory metastatic colorectal cancer patients.

Session Information: Trials in Progress Poster Session C: Cancers of the Colon, Rectum, and Anus

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Mont-Saint-Guibert, Belgium – 15 December 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 it has received a transparency notification dated December 10, 2021 indicating that CFIP CLYD LLC, an affiliate of Fortress Investment Group LLC, has crossed the statutory threshold of 25%, holding 6,500,000 shares i.e. 28.77% of Celyad Oncology’s shares and 26.04% voting rights as of 8 December 2021.

Content of the Notification:

• Reason of the Notification:

Upward crossing of the 25% threshold

Acquisition of voting securities or voting rights

• Notification by:

A parent undertaking or a controlling person

• Persons subject to the notification requirement:

Fortress Investment Group LLC. – 1345 Avenue of the Americas, 46^th Floor, New York, NY 10105 USA

CFIP CLYD LLC – 1345 Avenue of the Americas, 46^th Floor, New York, NY 10105 USA

• Transaction date

December 8, 2021

• Threshold that is crossed (in %)

25

• Denominator

22,593,956

• Notified details:

A) Voting Rights	Previous notification	After the Transaction
	#of voting rights	# of voting rights	% of voting rights
Holders of voting rights		Linked to the securities	Not linked to the securities	Linked to the securities	Not linked to the securities
Fortress Investment Group LLC		0		0.00%
CFIP CLYD LLC		6,500,000		26.04%
Subtotal		6,500,000		26.04%
	TOTAL	6,500,000		26.04%

Fortress Investment Group LLC indirectly controls 100% of the members of CFIP CLYD LLC, which are various Fortress Funds. Fortress Investment Group LLC has no controlling shareholder.

Miscellaneous

• The Press Release may be consulted on the website of Celyad Oncology via this link.

The notification can be consulted on the website if Celyad Oncology via this link.

• Contact person(s):

By law, any transparency declaration must be sent to our Company by email to the attention of Filippo Petti, Chief Executive Officer (CEO): investors@celyad.com.

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

Mont-Saint-Guibert, Belgium – Celyad Oncology SA (Euronext & Nasdaq: CYAD) (“Celyad” or the “Company”), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, today announced the closing of its previously announced private placement with an affiliate of Fortress Investment Group (such affiliate “Fortress”). The Company issued 6,500,000 ordinary shares at a price of USD 5.00 (about EUR 4.42) for gross proceeds of USD 32.5 million (about EUR 28.7 million).

The Company intends to use net proceeds from the private placement to fund research and development expenses, including the clinical development of its allogeneic CAR T candidates CYAD-101 and CYAD-211, to advance the current pipeline of preclinical CAR T candidates, to discover and develop additional preclinical product candidates using its proprietary non-gene edited short hairpin RNA (shRNA) technology platform, as well as for working capital, other general corporate purposes, and the enhancement of the Company’s intellectual property.

SVB Leerink acted as the exclusive placement agent for the private placement, Goodwin Procter LLP and Harvest acted as legal counsel to the Company. Skadden, Arps, Slate, Meagher & Flom LLP and Eubelius acted as legal counsel to Fortress.

The securities issued in the private placement have not been registered under the Securities Act of 1933 or applicable state securities laws and may not be resold in the United States absent registration under the Securities Act or an applicable exemption from such registration requirements. The Company has agreed to customary registration rights covering the resale of the ordinary shares (in the form of American Depositary Shares) sold in the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be by means of a prospectus.

Mont-Saint-Guibert, Belgium – Celyad Oncology SA (Euronext & Nasdaq: CYAD) (“Celyad” or the “Company”), 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 it has entered into a subscription agreement with an affiliate of Fortress Investment Group (such affiliate “Fortress”) for the private placement of 6,500,000 ordinary shares for gross proceeds of USD 32.5 million (about EUR 28.7 million). The subscription will take place within the framework of the authorized capital and it is expected to close on or about December 8, 2021, subject to satisfaction of customary closing conditions.

Pursuant to the terms of the private placement, the Company will issue the ordinary shares at a price of USD 5.00 (about EUR 4.42) per share, which represents a 18.5% premium to the 30-day volume weighted average price (“VWAP”). The Company intends to use net proceeds from the private placement to fund research and development expenses, including the clinical development of its allogeneic CAR T candidates CYAD-101 and CYAD-211, to advance the current pipeline of preclinical CAR T candidates, to discover and develop additional preclinical product candidates using its proprietary non-gene edited short hairpin RNA (shRNA) technology platform, as well as for working capital, other general corporate purposes, and the enhancement of the Company’s intellectual property.

As a result of the transaction, Fortress will hold 28.8% of the Company’s shares.

Filippo Petti, CEO of Celyad Oncology, commented, “This transformative investment provides an important springboard for the Company and further strengthens our corporate initiatives to advance our novel allogeneic CAR T product candidates. In addition, Fortress’s expertise in the intellectual property domain further validates our robust patent portfolio and emphasizes our position within the allogeneic CAR T field. The growth financing will be essential for us to expand our current allogeneic CAR T pipeline by continuing to exploit our differentiated, non-gene edited technologies and armored CAR T franchise.”

“Celyad Oncology offers a unique optionality around its technology and intellectual property,” said Christopher LiPuma, Director at Fortress. “In particular, the Company’s strong IP position around allogeneic CAR T stands out as a key asset that we believe will provide the foundation for the Company to strategically develop both novel cell therapy candidates and potential partnerships within the exciting off-the-shelf cell therapy landscape.” 

SVB Leerink acted as the exclusive placement agent for the private placement, Goodwin Procter LLP and Harvest acted as legal counsel to the Company. Skadden, Arps, Slate, Meagher & Flom LLP and Eubelius acted as legal counsel to Fortress.

The Company believes that following the close of the private placement, its existing cash and cash equivalents combined with access to the equity purchase agreement established with Lincoln Park Capital Fund, LLC should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into the first half of 2023.

In the framework of this investment, Fortress and the Company have entered into a shareholders’ rights agreement. Pursuant to this agreement, Fortress will be subject to a customary lock-up obligation and standstill obligation, in each case for nine months following the closing of the private placement. Furthermore, as long as Fortress holds 10% of the shares of the Company, it will benefit from a right of first offer on any new indebtedness to be incurred by Celyad and on any new equity securities to be issued, pro-rata its shareholding, as well as of the right to nominate two individuals to Celyad’s board of directors. In addition, as long as Fortress holds 15% or more of the outstanding shares of the Company, certain intellectual property transactions will be subject to a 90% board majority for approval. Celyad will propose an amendment to its articles of association to reflect this qualified right.

The securities to be issued in the private placement have not been registered under the Securities Act of 1933 or applicable state securities laws and may not be offered or sold in the United States absent registration under the Securities Act or an applicable exemption from such registration requirements. The Company has agreed to customary registration rights covering the resale of the ordinary shares (in the form of American Depositary Shares) sold in the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be by means of a prospectus.

• Preclinical data support armoring NKG2D CAR T cells with IL-18 to drive improved anti-tumor activity of the product candidate
• Development continues for second-generation multiplexing shRNA scaffold for novel non-gene edited CAR T candidates with desired phenotypes
• KEYNOTE-B79 Phase 1b trial evaluating CYAD-101 with KEYTRUDA^® (pembrolizumab) in patients with microsatellite stable mCRC set to start in fourth quarter 2021

MONT-SAINT-GUIBERT, Belgium, November 12, 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 three poster presentations on the Company’s allogeneic CAR T therapy programs at the Society for Immunotherapy of Cancer (SITC) Annual Meeting taking place in Washington D.C. and virtually November 10-14, 2021.

“With these presentations, we demonstrate how we continue to execute on our strategic vision to develop differentiated next generation CAR Ts using our non-gene edited allogeneic approaches which are intended to provide multiple real-world benefits to patients,” said David Gilham, Ph.D., Chief Scientific Officer of Celyad Oncology. “We believe our CAR T cells are the only allogeneic CAR T cells currently in human clinical trials that avoid generating double-strand DNA breaks. Combining with multiplexed shRNA and cytokine armoring, we believe this approach provides us with a dynamic platform for the generation of future allogeneic candidates.”

Charles Morris, M.D., Chief Medical Officer of Celyad Oncology said, “In addition to the encouraging preclincal data presented, we are also on the cusp of initiating the KEYNOTE-B79 Phase 1b clinical trial in collaboration with MSD. We believe that KEYNOTE-B79 will be the first clinical trial to evaluate an allogeneic CAR T with an anti-PD-1 therapy in solid tumors. We look forward to evaluating whether the expected highly complementary mechanism of actions of CYAD-101 and KEYTRUDA^® could help to drive important clinical benefit in patients with refractory metastatic colorectal cancer with microsatellite stable disease where a high unmet medical need exists. We look forward to initiating the study in the coming weeks and providing clinical updates to the CYAD-101 program in 2022.”

Key Highlights from SITC Annual Meeting

Poster 107 – Armoring NKG2D CAR T cells with IL-18 improves in vitro and in vivo anti-tumor activity

• This poster demonstrates the key role of Interleukin-18 (IL-18) in driving increased effector function of the NKG2D CAR T cells.
• These data support the ongoing development of the Company’s shRNA-based allogeneic, IL-18-armored CAR T candidate CYAD-203 as well as future allogeneic IL-18-armored CAR T candidates.

Poster 146 – Evolving multiplexed shRNA to generate tailored CAR T cell therapy

• Multiplexing short hairpin RNA (shRNA) within a single vector format ensures co-linked expression of the shRNA with therapeutic transgenes.
• We continue to develop second-generation shRNA scaffold using multiplexed technology to produce novel allogeneic clinical candidates with bespoke, desired phenotypes and function produced using methods that avoid the generation of double strand DNA breaks.

Poster 407 – A Phase 1b KEYNOTE-B79 trial evaluating non-gene edited allogeneic CAR T-cells, CYAD-101, post FOLFOX preconditioning, followed by pembrolizumab, in refractory metastatic colorectal cancer patients

• Clinical and translational results from the alloSHRINK Phase 1 trial evaluating the TCR Inhibitory Molecule (TIM)-based allogeneic NKG2D CAR T-cell product candidate CYAD-101 (NCT03692429) in patients with metastatic colorectal (mCRC) cancer suggest that treatment with sequential checkpoint inhibition following CYAD-101 with FOLFOX preconditioning could drive more durable clinical responses.
• The KEYNOTE-B79 trial will therefore evaluate the safety and clinical activity of multiple infusions of CYAD-101 administered post FOLFOX preconditioning chemotherapy, followed by treatment with KEYTRUDA^® (pembrolizumab) in mCRC patients with microsatellite stable disease, according to a Simon’s two stage trial design.
• The KEYNOTE-B79 clinical trial is expected to begin in fourth quarter 2021.

These ePosters will be available on the SITC website starting today at 1 p.m. CET / 7 a.m. ET and in the Scientific Publications section of Celyad Oncology’s website.

KEYTRUDA^® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.