Celyad Oncology

• Median overall survival and median progression free survival from the dose-escalation segment of the trial were 10.6 months and 3.9 months, respectively
• Tumor burden decrease observed in eight of 15 refractory unresectable mCRC patients, including six of nine patients at the highest dose level of 1×10⁹ cells per infusion
• Emergence of new T cell clones in the peripheral blood T cell repertoire four months after therapy was observed in patients analyzed from the highest dose level who experienced either a confirmed partial response or stable disease suggesting that modulation of the endogenous immune response may be an important mechanism of action of CYAD‑101 in mCRC patients
• Preliminary data from the ongoing expansion cohort of the Phase 1 alloSHRINK expected in the first half of 2021

Mont-Saint-Guibert, Belgium – 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 updates from the  Phase 1 alloSHRINK trial evaluating CYAD-101, the Company’s allogeneic NKG2D-receptor and T cell receptor (TCR) inhibitory molecule (TIM)-based, non-gene edited CAR T candidate administered concurrently with FOLFOX chemotherapy for the treatment of refractory metastatic colorectal cancer (mCRC), presented at the American Society of Clinical Oncology 2021 Gastrointestinal Cancers Symposium (ASCO-GI), held virtually from January 15-17, 2021.

“We continue to build on the promise of CYAD-101, a highly differentiated cell therapy investigational candidate which has delivered preliminary evidence of clinical benefit for an allogeneic CAR T in solid tumors,” said Filippo Petti, Chief Executive Officer of Celyad Oncology. “At ASCO-GI, we highlighted the encouraging median progression free-survival data from alloSHRINK which complements the previously reported tolerability, objective response rate for CYAD-101 in patients with mCRC. Moreover, translational data from the trial suggests that immune modulation underpins the clinical responses observed in the alloSHRINK trial and supports further development of CYAD-101 with therapies with complementary mechanisms of action including checkpoint inhibitors. We’re excited about the next steps for the CYAD-101 program for the treatment of advanced colorectal cancer and we look forward to future updates from the alloSHRINK trial as well as initiating the upcoming Phase 1b KEYNOTE-B79 trial.”

Phase 1 alloSHRINK Trial Update

Background

• A total of 15 patients with relapsed/refractory mCRC who progressed after previous treatment with oxaliplatin-based or irinotecan-based chemotherapies were treated in the dose-escalation segment of the alloSHRINK trial evaluating three dose levels of CYAD-101 (1×10⁸, 3×10⁸, 1×10⁹ cells per infusion) administered concurrently with FOLFOX as preconditioning chemotherapy. The number of prior therapies received by patients enrolled in the trial ranged from one to six with a mean of three.
• Previously reported data for primary and secondary safety and clinical activity endpoints include:
• Two patients achieved a confirmed partial response (PR) according to RECIST 1.1 criteria, including one patient with a KRAS-mutation
• Nine patients achieved stable disease (SD), with seven patients demonstrating disease stabilization lasting more than or equal to three months of duration
• Median progression free survival (mPFS) for the dose-escalation segment of the trial was 3.9 months
• No clinical evidence of Graft-versus-Host Disease (GvHD)
• Treatment was observed to be well-tolerated with no treatment-related adverse events greater than Grade 3
• The recommended dose of 1×10⁹ CYAD-101 cells per infusion will be further evaluated in the expansion cohort of the alloSHRINK trial concurrently with FOLFIRI chemotherapy

Updated Clinical and Translational Data

• Recent analysis of the dose-escalation segment of the alloSHRINK trial showed median overall survival (mOS) was 10.6 months
• Tumor burden decrease was observed in eight of 15 patients, including six of nine patients at dose level 3 (1×10⁹ cells per infusion)
• Of four patients treated at the highest dose level of 1×10⁹ CYAD-101 cells per infusion available for analysis, three patients who achieved either a confirmed PR or SD also showed hyper-expanded TCR repertoire post-treatment through the emergence of new T cell clones in the peripheral blood T cell repertoire, while the patient with progressive disease displayed no evidence of new T cell clones
• Cytokine modulation was also observed after the first and second infusions of CYAD-101 in the patient who achieved a confirmed PR from the highest dose level

Next Steps

• Preliminary data from the expansion cohort of the Phase 1 alloSHRINK trial are expected during the first half of 2021
• Initiation of the Phase 1b KEYNOTE-B79 trial of CYAD-101 following FOLFIRI, with Merck’s KEYTRUDA® in refractory mCRC patients with microsatellite stable (MSS) / mismatch-repair proficient (pMMR) disease is expected to be initiated during the first half of 2021

Mont-Saint-Guibert, Belgium – 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 Marina Udier, Ph.D., has been appointed to its Board of Directors.

“I am very pleased to welcome Marina to our Board of Directors,” stated Filippo Petti, CEO of Celyad Oncology.  “As a highly regarded leader in the biopharmaceutical industry, we look forward to benefiting from Marina’s wealth of experience as we continue to advance key elements of our pipeline with the goal of developing innovative cell therapies against cancer.”

Dr. Marina Udier said, “Celyad Oncology is at a pivotal moment in its company history with multiple candidates in the clinic and a promising array of significant milestones expected in 2021. I am honored to be part of the Celyad Oncology Board and look forward to working with the talented team to execute on the company’s strategic vision of establishing itself as an industry leader in the CAR T space.”

Dr. Udier currently serves as CEO of Nouscom, a private oncology company developing next-generation immunotherapies, after joining as Chief Operating Officer in 2016 from Versant Ventures, where she was Operating Principal. Prior to Versant, she held various senior development and commercial roles at Novartis Pharma in Basel. As the Global Commercial Head, she developed the global strategy for a point of care diagnostics platform. Her experience in molecular diagnostics includes In Vitro Diagnostics development; she led development of a Companion Diagnostics for RYDAPT^TM, the first approved AML drug in over three decades. Marina managed the Global Neurodegeneration portfolio for Novartis driving her brands to a blockbuster status. She spent five years with McKinsey & Company in Chicago, working with Healthcare Fortune 500 companies in areas of marketing, strategy and pricing. Dr. Udier received her Ph.D. in Organic Chemistry from Yale University. She authored peer-reviewed publications covering HIV/AIDS research.

Mont-Saint-Guibert, Belgium – 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 it has entered into a committed equity purchase agreement (“Purchase Agreement”) for up to $40 million with Lincoln Park Capital Fund, LLC (“LPC”), a Chicago-based institutional investor.

Over the 24-month term of the Purchase Agreement, the Company will have the right to direct LPC to purchase up to an aggregate amount of $40 million American Depositary Shares (“ADSs”), each of which represents one ordinary share of the Company. LPC’s maximum obligation under any single regular purchase will not exceed $2.5 million, unless both parties mutually agree to increase the maximum amount of such purchase. The purchase price for the ADSs to be purchased by LPC under a regular purchase will be the equal to the lower of (i) the lowest sale price for ADSs on the applicable purchase date, and (ii) the average of the three lowest closing sale prices for ADSs during the ten business days prior to the purchase date. There are no upper limits to the price LPC may pay to purchase common stock from the Company. Celyad Oncology controls the timing and amount of any future sales of ADSs to LPC. As part of the Purchase Agreement, LPC has agreed not to cause or engage in any manner whatsoever any direct or indirect short selling or hedging of Celyad Oncology’s shares of common stock. The Purchase Agreement may be terminated by Celyad Oncology at any time, at its sole discretion, without any additional cost or penalty.

In consideration for entering into the Purchase Agreement, at the signing of the Purchase Agreement, LPC received a commitment fee of $1 million comprised of $600,000 in cash and $400,000 in the form of a discount on the initial purchase of $2 million of ADSs under the equity facility.

Celyad Oncology currently intends to use the net proceeds from sales of ADSs under the Purchase Agreement with LPC for general corporate purposes, including but not limited to the research and development of Company’s clinical and preclinical CAR T cell therapy candidates.

“We are thrilled to announce today’s agreement with Lincoln Park, as the committed equity facility is expected to strengthen our current balance sheet while also providing us with access to future capital on an as needed basis,” commented Filippo Petti, Chief Executive Officer of Celyad Oncology. “In addition, the Company now has greater flexibility to further advance our pipeline of clinical and preclinical next-generation CAR T candidates for the treatment of cancers through several potential value-creating milestones over the next several quarters.”

This press release does not constitute an offer to sell or a solicitation of an offer to buy the securities in this offering, nor will there be any sale of these securities in any jurisdiction in which such offer solicitation or sale are unlawful prior to registration or qualification under securities laws of any such jurisdiction. Additional information regarding the Purchase Agreement with LPC is available in Celyad Oncology’s Form 6-K filed with the SEC on January 7, 2021. The ADSs covered by the Purchase Agreement are being offered pursuant to a shelf registration statement on Form F-3 (File No. 333-248464) that was declared effective by the SEC on September 4, 2020. A prospectus supplement relating to the offering was filed by Celyad Oncology with the SEC on January 7, 2021 and is available on the SEC’s website at www.sec.gov or by request from Celyad Oncology S.A., Rue Edouard Belin 2, 1435 Mont-Saint-Guibert, Belgium.

Financial Update

As of December 31, 2020, the Company ended the year with an unaudited treasury position of €17.2 million ($21.2 million). The Company confirms its previous guidance that its existing treasury position, without proceeds from the LPC purchase agreement, should be sufficient to fund operating expenses and capital expenditure requirements, based on the current scope of activities, into the third quarter of 2021.

In addition, the Company expects that the net proceeds from the $40 million purchase agreement with LPC should help to extend the Company’s cash runway beyond the third quarter of 2021.

Mont-Saint-Guibert, Belgium – 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 the company plans to participate at the following conferences in January 2021:

H.C. Wainwright BioConnect Conference

Date: January 11 – 14, 2021

Time: On-demand, January 11 at 6:00 a.m. (EST) / 12:00 p.m. CET

Webcast: A live and archived webcast of the presentation will be available in the Events section of the Celyad Oncology website

Keystone eSymposia

Date: Monday, January 25, 2021

Time: 10:00 a.m. ET / 4:00 p.m. CET

A live and archived webcast of available presentations will be on the Events section of the Celyad Oncology website

• Preliminary data from the expansion cohort are expected during first half 2021

December 15, 2020 10:01 p.m. CET

Mont-Saint-Guibert, Belgium – 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 the successful dosing of the first patient in the expansion cohort of the Phase 1 alloSHRINK trial for CYAD-101, the Company’s allogeneic T cell receptor (TCR) inhibitory molecule (TIM)-based, non-gene edited CAR T candidate for the treatment of refractory metastatic colorectal cancer (mCRC).

“CAR T therapies historically had little success in treating solid tumors, including advanced metastatic colorectal cancer,” said Dr. Eric Van Cutsem, Professor of Internal Medicine at University of Leuven. “Based on the encouraging response rate we’ve observed from the dose escalation segment of the alloSHRINK trial, we believe that this expansion study using FOLFIRI as preconditioning chemotherapy will provide a more robust data set and clinical benefit for these patients.”

Dr. Anne Flament, Director of Clinical Development at Celyad Oncology, commented, “The expansion cohort in our ongoing alloSHRINK trial will provide valuable data on the effectiveness of the highest dose level of CYAD-101 following preconditioning therapy in mCRC patients. Over the past year, we have presented what we believe to be the first-ever evidence of clinical benefit using an allogeneic CAR T in solid tumors with the CYAD-101 program and we look forward to building upon that data to continue to validate our position as an industry leader in CAR T cell therapies for the treatment of solid tumors.”

• First patient dosed in the CYAD-211 Phase 1 IMMUNICY-1 trial. Preclinical results for CYAD-211 for multiple myeloma showed robust antitumor activity with no demonstrable evidence of Graft-versus-Host Disease
• Company discontinues the development of first-generation, autologous CAR T candidate CYAD-01 based on clinical futility observed to date from the Phase 1 THINK trial
• Preliminary data from CYCLE-1 trial evaluating next-generation autologous CYAD-02 in r/r AML / MDS patients showed encouraging clinical signals, including a high-risk MDS patient treated at dose level 3 who achieved an objective marrow complete response; dose level 3 cohort of the CYCLE-1 trial is ongoing
• Management to hold a conference call later today, December 7, at 1 p.m. CET/ 7 a.m. ET

Mont-Saint-Guibert, Belgium – 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 updates from the company’s shRNA-based anti-B cell maturation antigen (BCMA) allogeneic CAR T candidate, CYAD-211, and autologous NKG2D receptor-based CAR T candidates, CYAD-01 and CYAD-02. These updates were virtually presented at the 62^nd American Society of Hematology (ASH) Annual Meeting and Exposition, held from December 5-8, 2020.

“The recent announcement of the dosing of our first patient with CYAD-211 in the IMMUNICY-1 trial was a major milestone for the organization as we continue to strategically focus on next-generation allogeneic CAR T cell therapies underpinned by our innovative shRNA technology platform that we took from concept to clinic in just two years,” said Filippo Petti, Chief Executive Officer of Celyad Oncology. “With IMMUNICY-1, we’re not only looking to offer patients with refractory multiple myeloma an option where few exist, but also to use this as an opportunity to validate the use of our shRNA platform as a novel allogeneic technology in what we believe could greatly expand our potential to develop best-in-class, off-the-shelf CAR T cell therapies.”

Mr. Petti added, “While we are disappointed by the latest update from the Phase 1 THINK trial for CYAD-01, we are encouraged by the initial clinical results from our next-generation CYAD-02 candidate for the treatment of patients with relapsed or refractory AML and MDS and look forward to future updates from the CYCLE-1 trial. With greater perspective on our autologous programs, the organization will remain steadfast in our commitment to patients with cancer by continuing to concentrate on the discovery and development of novel, allogeneic CAR T candidates.”

CYAD-211 and IMMUNICY-1 Phase 1 Trial Update

Background

• CYAD-211 is a first-in-class, allogeneic CAR T candidate engineered to co-express a BCMA targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3ζ component of the T cell receptor complex.
• IMMUNICY-1 will evaluate the safety and clinical activity of a single infusion of CYAD-211 following preconditioning chemotherapy cyclophosphamide and fludarabine in patients with relapsed/refractory multiple myeloma (r/r MM).
• The trial seeks to determine the recommended dose of CYAD-211 in r/r MM patients for further development as well as to establish proof-of-principle that single shRNA-mediated knockdown can generate allogeneic CAR T cells in humans without inducing Graft-versus-Host Disease (GvHD).
• On December 4, 2020, the company announced dosing of the first patient in the CYAD-211 Phase 1 IMMUNICY-1 trial.

Preclinical Results

• CYAD-211 demonstrated robust anti-tumor activity in vitro and in vivo concurrent with lack of alloreactivity in preclinical MM models.
• No demonstrable evidence of GvHD was observed with CYAD-211 in preclinical models confirming efficient inhibition of alloreactivity.

Study Design

• The IMMUNICY-1 trial is a first-in-human, open-label dose-finding study evaluating three dose levels of CYAD-211, including 3×10⁷, 1×10⁸ and 3×10⁸ cells per infusion, in patients with r/r MM.

Next Steps

• Proof-of-principle data from the initial dose cohorts are expected during first half 2021.
• Clinical activity data from the full dose-escalation trial are expected during second half 2021.

CYAD-01 and THINK Phase 1 Trial Update

Background

• The company’s first generation NKG2D receptor-based CAR T clinical candidate CYAD-01 was evaluated for the treatment of patients with r/r acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in the Phase 1 THINK trial.
• In 2019, the company implemented the OptimAb manufacturing process within the CYAD-01 program, to be evaluated in the study expansion cohort of the THINK trial. The trial intended to assess the safety and clinical activity of CYAD-01 when produced with the OptimAb process following no preconditioning chemotherapy.

Latest Clinical Data

• Overall, eight of the eleven patients planned per protocol in the THINK trial were treated with OptimAb-produced CYAD-01 cells.
• No dose-limiting toxicities were reported from patients treated with OptimAb-produced CYAD-01 cells.
• Stable disease (SD) was achieved in two of eight patients treated with OptimAb-produced CYAD-01 cells (one MDS and one AML patient); an additional MDS patient became eligible for an allogeneic stem cell transplantation after treatment with CYAD-01 and achieved a complete response. No objective responses were observed following treatment with OptimAb-produced CYAD-01 cells.

Next Steps

• Based on clinical futility observed to date of CYAD-01 from the Phase 1 THINK trial the company has decided to discontinue the development of CYAD-01 for the treatment of r/r AML / MDS. No additional patients will be enrolled in the CYAD-01 program.

CYAD-02 and CYCLE-1 Phase 1 Trial Update

Background

• In November 2019, the company initiated the dose-escalation Phase 1 CYCLE-1 trial, evaluating the safety and clinical activity of the next-generation, autologous NKG2D receptor-based CAR T candidate CYAD-02 following preconditioning chemotherapy in patients with r/r AML / MDS.
• The next-generation, NKG2D receptor-based CAR T candidate CYAD-02 incorporates shRNA to target the NKG2D ligands MICA and MICB. In preclinical models, shRNA-mediated knockdown of MICA and MICB expression on NKG2D receptor-based CAR T cells has shown enhanced in vitro expansion, as well as enhanced in vivo engraftment and persistence of the CAR T cells, as compared to first-generation NKG2D receptor-based CAR T cells.

Preliminary Clinical Data

• To date, nine patients have received treatment with CYAD-02: three patients at dose level 1, three patients at dose level 2 and three patients at dose level 3.
• CYAD-02 was generally well-tolerated, with one grade 4 infusion reaction (dose level 1) and one grade 3 cytokine release syndrome (dose level 3). Both patients recovered rapidly following the appropriate treatment.
• To date, seven patients were evaluable for clinical activity:
• Of the five very high-risk MDS patients: (i) three patients demonstrated anti-leukemic activity (at least 50% bone marrow blasts decrease) with the single patient evaluated at dose level 3 achieved a marrow complete response (mCR) at first assessment (ongoing); (ii) two additional patients exhibited a durable SD of more than five months (one of two ongoing).
• Of the two adverse AML patients, one patient demonstrated anti-leukemic activity with a SD of four months (ongoing).

Next Steps

• The dose level 3 cohort of the CYCLE-1 trial is ongoing. Additional safety and efficacy data from the trial are expected during the first half of 2021.

Conference Call and Webcast Details

Celyad Oncology will host a conference call to discuss the update from ASH on Monday, December 7, 2020 at 1 p.m. CET / 7 a.m. ET. The conference call can be accessed through the following numbers:

United States: +1 877 407 9716

International: +1 201 493 6779

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.