Celyad Oncology

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.

• Preliminary data from the Phase 1 trial are expected first half 2021
• Additional €3.4 million in non-dilutive funding from SPW-Recherche of the Walloon Region to support advancement of CYAD-211

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 dosing of the first patient of the Phase 1 IMMUNICY-1 trial of CYAD-211, the Company’s novel, short hairpin RNA (shRNA)-based anti-B-cell maturation antigen (BCMA) candidate for the treatment of relapsed/refractory multiple myeloma (r/r MM).

“Despite the introduction of several new treatment options over the past few years, multiple myeloma remains a devastating disease with a high unmet need for new therapies. We are proud to participate in the IMMUNICY-1 trial which will evaluate CYAD-211 in the treatment of relapsed or refractory multiple myeloma patients,” said professor Dr. Sébastien Anguille, CAR T specialist at the Antwerp University Hospital (UZA), Edegem, Belgium. “Based on the encouraging preclinical data, we believe this new allogeneic CAR T targeting BCMA has the potential to become an important therapy for such a challenging patient population.”

Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad Oncology, added, “Dosing the first patient with CYAD-211 marks another major milestone to systematically advance our pipeline of non-gene edited allogeneic CAR T candidates. BCMA is highly expressed in multiple myeloma patients and we hope to see a positive clinical benefit with our approach of targeting BCMA with our first-in-class CAR T which is underpinned by our shRNA technology. Enrollment in the IMMUNICY-1 trial will continue over the coming months and we expect to report proof-of-concept data from the initial dose cohorts of the trial during the first half of 2021 .”

Financial Update

The Company received €3.4 million in non-dilutive funding from the SPW-Recherche of the Walloon Region, which will support the development of CYAD 211. Under the terms of this funding, the Company was awarded non-dilutive funding in the form of recoverable cash advances (‘avances récupérables’). The regional funding is associated with the Company’s specific research and development programs. Under the applicable conditions, the recoverable cash advance is reimbursable over the economic life of the projects. Thirty percent is refundable based on a fixed reimbursement schedule of 20 years, while the balance is refunded under the form of royalties over the same period.

The Company confirms its previous guidance that its existing treasury position should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into 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 Filippo Petti, Chief Executive Officer, will participate in a fireside chat at the virtual JMP Securities Hematology Summit on Wednesday, December 16, 2020 at 10:00 a.m. ET / 4:00 p.m. CET.

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

• Established a clinical trial collaboration with MSD to evaluate CYAD-101 with KEYTRUDA® in patients with microsatellite stable mCRC
• Expect to initiate the expansion cohort of the Phase 1 alloSHRINK trial for CYAD-101 in mCRC patients following FOLFIRI preconditioning chemotherapy by year-end 2020
• Phase 1 dose-escalation trial for lead shRNA-based allogeneic CAR T candidate, CYAD-211, for r/r MM on track to begin by year-end 2020

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 an update on its operational developments for the third quarter ended September 30, 2020.

“We are pleased with the continued momentum seen across our allogeneic clinical programs over the past few months,” commented Filippo Petti, Chief Executive Officer of Celyad Oncology. “Major milestones during third quarter 2020 include expanding the CYAD-101 clinical program for the treatment of metastatic colorectal cancer through our recent clinical trial agreement with MSD to conduct the KEYNOTE-B79 study which will evaluate the potential synergy of pairing CYAD-101 with KEYTRUDA. We are also steadily progressing towards the initiation of the Phase 1 IMMUNICY-1 study by end of year for our anti-BCMA shRNA-based candidate CYAD-211 for the treatment of relapsed/refractory multiple myeloma. In addition, upcoming data from our autologous NKG2D receptor-based CAR T candidates, which we plan to announce at the annual ASH congress, will help guide next steps for our AML franchise.”

Third Quarter 2020 and Recent Business Highlights

• Announced plans to conduct a Phase 1b KEYNOTE-B79 clinical study of non-gene edited allogeneic CAR T therapy CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy, with MSD’s, a tradename of Merck, anti­PD-1 therapy, KEYTRUDA® (pembrolizumab) in refractory metastatic colorectal cancer (mCRC) patients with microsatellite stable (MSS) / mismatch-repair proficient (pMMR) disease.
• Hosted a Research & Development webinar for investors and analysts on September 29^th, with a replay currently available on the Events page of the Company’s website. Topics covered during the event included:
  • Presentation by Dr. Richard Kim, M.D., Professor of Oncology, Moffitt Cancer Center, on the immuno-oncology and treatment landscapes for mCRC and,
  • Overview of Celyad Oncology’s candidate CYAD-101 for mCRC and CYAD-211 for relapsed / refractory multiple myeloma (r/r MM), and the company’s short hairpin RNA (shRNA) platform and All-in-One vector approach.
• Announced U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application and approval of the Clinical Trial Application (CTA) by the Federal Agency for Medicines and Health Products (FAMHP) of Belgium for the Company’s lead shRNA-based allogeneic candidate CYAD-211, clearing the way to initiate the Phase 1 IMMUNICY-1 clinical trial by the end of 2020.
• Established an Open Market Sale Agreement^SM with Jefferies LLC, pursuant to which the Company may from time to time sell through “an at the market offering” up to $25,000,000 of new American Depositary Shares.

Third Quarter 2020 Financial Review

As of September 30, 2020, the Company ended the quarter with a treasury position of €20.0 million ($23.4 million). Net cash burn during the third quarter of 2020 amounted to €6.7 million ($7.8 million), in line with expectations. The Company confirms its previous guidance that its existing treasury position should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into the third quarter of 2021.

Update on Clinical and Preclinical Programs

CYAD-101 – Allogeneic TIM-based, NKG2D receptor-based CAR T for mCRC

Celyad Oncology’s first-in-class, non-gene edited clinical candidate CYAD-101 continues to advance in the alloSHRINK Phase 1 trial for the treatment of mCRC. CYAD-101 co-expresses the NKG2D receptor and the novel inhibitory peptide TIM (TCR Inhibitory Molecule), whose expression reduces signaling of the TCR complex by interfering with the CD3ζ component of the TCR complex. The Company plans to initiate the expansion cohort of the alloSHRINK trial which will evaluate CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion. Enrollment in this expansion cohort is expected to start by year-end 2020.

Planning is also ongoing to initiate the Phase 1b KEYNOTE-B79 study of CYAD-101, following FOLFIRI preconditioning chemotherapy, with MSD’s KEYTRUDA® in refractory mCRC patients with MSS / pMMR disease during the first half of 2021. The Company believes the mechanism of actions between CYAD-101 and KEYTRUDA® are highly complementary and could help to drive meaningful clinical benefit in patients with advanced mCRC.

CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM

CYAD-211 is an investigational, short hairpin RNA (shRNA)-based allogeneic CAR T candidate for the treatment of r/r MM. CYAD-211 is 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 (TCR) complex. In July 2020, Celyad Oncology announced FDA clearance of its IND application for CYAD-211 and subsequently received CTA approval for CYAD-211 by the FAMHP. The Company plans to initiate the Phase 1 IMMUNICY-1 trial evaluating CYAD-211 following preconditioning chemotherapy in r/r MM by year-end 2020.

CYAD-01 – Autologous NKG2D receptor-based CAR T for r/r AML and MDS

The Company’s first-in-class NKG2D receptor-based CAR T clinical candidate CYAD-01 continues to advance in the ongoing Phase 1 THINK trial for the treatment of patients with r/r acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The Company is scheduled to announce preliminary data from CYAD-01 produced with the OptimAb manufacturing process from the expansion cohort of the Phase 1 THINK trial at the American Society of Hematology (ASH) conference in December 2020.

CYAD-02 – Next-Generation Autologous NKG2D receptor-based CAR T for r/r AML and MDS

CYAD-02 is an investigational CAR T therapy that engineers an All-in-One vector approach in patient’s T cells to express the NKG2D receptor CAR and shRNA to knockdown the expression of NKG2D ligands MICA and MICB on the CAR T cells. The Company is currently conducting the Phase 1 dose-escalation CYCLE-1 trial evaluating CYAD-02 for the treatment of r/r AML and MDS. During the third quarter, the Company initiated the third dose cohort of the trial. The CYCLE-1 trial is assessing the safety and clinical activity of a single infusion of CYAD-02 produced with the OptimAb manufacturing process following preconditioning chemotherapy with cyclophosphamide and fludarabine. Preliminary data from CYCLE-1 trial are expected at the ASH conference in December 2020.

Upcoming Milestones

• Plan to begin enrollment in the expansion cohort of the Phase 1 alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients by year-end 2020.
• Expect to initiate the dose-escalation Phase 1 IMMUNICY-1 trial evaluating CYAD-211 in r/r MM by year-end 2020.
• Expect to initiate the Phase 1b KEYNOTE-B79 clinical study of CYAD-101 following FOLFIRI preconditioning chemotherapy, with KEYTRUDA® in refractory mCRC patients in first half of 2021.
• Three abstracts accepted for presentation at the annual ASH Meeting & Exposition, being held December 5–8, including:
  • Poster presentation of the Company’s anti-BCMA allogeneic CAR T candidate, CYAD-211
  • Poster presentations of the Company’s autologous NKG2D receptor-based CAR T candidates, CYAD-01 and CYAD-02

Upcoming Conferences

Celyad Oncology’s management team is scheduled to participate in the following conferences during the remainder of 2020:

• Bryan, Garnier & Co. Virtual European Healthcare Conference, November 16, 2020
• Jefferies Virtual London Healthcare Conference, November 17, 2020
• SVB Leerink Oncology 1×1 Day, November 19, 2020
• 62^nd American Society of Hematology Annual Meeting & Exposition, December 5 – 8, 2020