Celyad

• First-in-class TIM-based non-gene edited allogeneic CAR-T candidate, CYAD-101, shows encouraging clinical activity with no evidence of graft-versus-host disease in relapsed/refractory metastatic colorectal cancer patients
• Two patients achieved a confirmed partial response and nine patients achieved stable disease, leading to a disease control rate of 73%
• Overall safety and clinical activity data are HLA-independent indicating that CYAD-101 cells can be used in a broad patient population regardless of the HLA haplotype
• Expansion cohort of the alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy is expected to begin in the fourth quarter 2020
• shRNA platform for next-generation allogeneic CAR-T candidates provides proof-of-principle to simultaneously knockdown up to four genes in a single construct
• Management to hold a conference call on Monday, June 1^st, at 2 p.m. CEST/ 8 a.m. EDT

Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell therapies, today announced updates from the company’s allogeneic programs, including additional data from the Phase 1 alloSHRINK trial evaluating the T cell receptor (TCR) inhibitory molecule (TIM)-based, non-gene edited allogeneic CAR-T  candidate, CYAD‑101, for the treatment of metastatic colorectal cancer (mCRC), and the company’s short hairpin RNA (shRNA) platform underpinning the next-generation, non-gene edited CYAD-200 series of CAR-T candidates. These data were presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program from May 29-31, 2020.

Dr. Frédéric Lehmann, VP of Clinical Development at Celyad, commented, “The latest safety and clinical activity data from the alloSHRINK trial in metastatic colorectal cancer patients further demonstrate CYAD-101’s differentiated profile as an allogeneic CAR-T candidate. The absence of clinical evidence of graft-versus-host-disease (GvHD) for CYAD-101, which co-expresses the NKG2D receptor with our novel, TIM technology used to knockdown signalling of the TCR complex, confirms the potential of non-gene edited approaches for the development of allogeneic CAR-T  candidates. Taking these positive clinical data into account, we have decided to broaden the program to include evaluating CYAD-101 following FOLFIRI chemotherapy in refractory patients as an expansion cohort of the alloSHRINK trial. Overall, treatment of advanced metastatic colorectal cancer patients beyond second line regimens remains a high unmet medical need, and we believe CYAD-101 could offer a unique immunotherapeutic approach to treat this incurable disease.”

Dr. David Gilham, CSO of Celyad, stated, “CYAD-101 has pioneered the potential for non-gene edited approaches for the development of allogeneic CAR-T  candidates, and we are excited to build upon this strong position with our shRNA technology platform. Preclinical data reported during ASCO over the past few days confirm the ability of a single shRNA hairpin to provide prolonged TCR knockdown, which our first shRNA-based allogeneic candidate, CYAD-211. In addition, the data demonstrated the breadth and depth of the shRNA platform, including the concurrent knockdown of up to four genes. We believe combining the knockdown potential of the platform with additional construct enhancements provides tremendous therapeutic optionality to our non-gene edited CYAD-200 series of CAR-T candidates.”

• To date, a total of 15 patients with relapsed/refractory mCRC who progressed after previous treatment with oxaliplatin-based or irinotecan-based chemotherapies have been enrolled in the dose-escalation, alloSHRINK Phase 1 trial evaluating three consecutive dose levels of CYAD-101 administered concurrently with FOLFOX chemotherapy. The number of prior therapies received by patients enrolled in the trial ranged from one to six with a mean of three.
• All 15 patients were dosed from a single cell bank of CYAD-101 that was generated in advance from two manufacturing runs each using a fraction of an apheresis from a single healthy donor.

Safety and Tolerability

• No clinical evidence of GvHD has been observed following 44 injections of CYAD-101. We believe these data continue to support the ability of the company’s novel inhibitory peptide TIM to reduce signaling of the TCR complex through a non-gene edited approach.
• Treatment with CYAD-101 following FOLFOX preconditioning chemotherapy was observed to be well-tolerated. Seven of the 15 patients enrolled in the trial reported at least one treatment-related adverse event (AE), however, all AEs reported were grade 1 or 2, including one patient who experienced cytokine-release syndrome (grade 1). No patient discontinued treatment due to AEs.

Clinical Activity

• Encouraging anti-tumor activity was observed in the trial with two patients who achieved a confirmed partial response (PR) according to RECIST 1.1 criteria, including one patient with a KRAS-mutation, the most common oncogenic alteration found in all human cancers. In addition, nine patients achieved stable disease (SD), with seven patients demonstrating disease stabilization lasting more than or equal to three months of duration.
• No correlation was observed between clinical responses and the degree of human leukocyte antigen (HLA) matching between patients and CYAD-101 donor cells, indicating that CYAD-101 can be used in a broad patient population regardless of the HLA haplotype.

Next Steps

• An expansion cohort of alloSHRINK trial will evaluate CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion. Enrollment in the expansion cohort of the trial is expected to begin during the fourth quarter of 2020.

• In October 2018, the company announced an exclusive agreement with Horizon Discovery Group for the use of its shRNA technology to generate a novel, next-generation, non-gene-edited allogeneic platform for CAR‑T therapies. Horizon Discovery’s SMARTvector technology to express shRNA was optimized by Celyad to knockdown the TCR complex in allogeneic CAR-T therapies as well as to target a broad range of proteins.

shRNA Platform

• shRNA platform coupled with company’s all-in-one vector approach is designed to provide flexibility, versatility and efficiency in designing novel, allogeneic CAR-T candidates through single step engineering process.
• Lead shRNA-based allogeneic candidate CYAD-211, targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma, which uses a single hairpin to knockdown the CD3ζ component of the TCR complex, is expected to enter clinical trials by year-end 2020.
• Next-generation candidates exploring two shRNA knockdowns are currently under development.
• Continued preclinical evaluation of the shRNA platform demonstrates proof-of-principle that the concurrent knockdown of four genes using an optimized framework is feasible.
• Combining shRNA knockdown with additional functional components should offer therapeutic optionality to non-gene edited allogeneic CYAD-200 series of product candidates.

• United States: +1 877 407 9208
• International: +1 201 493 6784
• Conference ID: 13703684

The conference call will be webcast live and can be accessed here. The event will also be archived and available on the “Events & Webcasts” 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 CYAD-101 and alloSHRINK Trial

CYAD-101 is an investigational, non-gene edited, allogeneic (healthy donor derived) CAR-T  candidate engineered to co-express a chimeric antigen receptor based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM (TCR Inhibitory Molecule). The expression of TIM reduces signalling of the TCR complex, which is responsible for graft-versus host disease.

alloSHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of three consecutive administrations of CYAD-101 every two weeks administered concurrently with FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) chemotherapy in patients with refractory mCRC. In the expansion cohort of the trial, CYAD-101 will be administered concurrently with FOLFIRI.

About shRNA Platform and CYAD-200 Series

The company is focused on the development of its proprietary non-gene edited allogeneic short hairpin RNA (shRNA) SMARTvector technology platform through the CYAD-200 series of candidates. The company is currently evaluating several shRNA-based allogeneic CAR-T candidates, including CYAD-211, an allogeneic CAR-T candidate targeting B-cell maturation antigen for the treatment of relapsed/refractory multiple myeloma.

About Colorectal Cancer

Colorectal cancer is the third most common type of cancer among both men and women worldwide and is the fourth most common in terms of mortality. In 2018, approximately 1.8 million people were diagnosed with colorectal cancer, with about 140,000 and 500,000 diagnoses in the United States and Europe, respectively. According to data from ASCO, approximately 40% of patients are diagnosed with early-stage, localized-stage disease. The five-year survival rate of localized disease is approximately 90%. In patients where the cancer has spread to distant parts of the body, as in metastatic colorectal cancer, the five-year survival rate drops to approximately 15%.

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Mont-Saint-Guibert, Belgium – Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, today announced that Dr. Maria Koehler and Mr. Dominic Piscitelli have been appointed as independent members to its Board of Directors, effective as of March 24 and May 6, respectively.

“We are delighted to announce the appointment of Dr. Maria Koehler and Mr. Dominic Piscitelli to our Board of Directors given the tremendous industry experience and wealth of knowledge both will offer Celyad as we continue to build an oncology-focused organization rich with expertise,” said Filippo Petti, Chief Executive Officer of Celyad. “We look forward to Maria’s strategic advice as we continue to advance key elements of our developmental pipeline and expand on the clinical evidence supporting our CAR-T programs. In addition, Dominic’s broad financial, operational and strategic experience will provide the company with essential guidance as we look to build a competitive oncology business.”

Dr. Koehler said, “Celyad is at a pivotal moment in its history and I am excited to be joining the Board at this time. I look forward to bringing my experience as an oncologist with a broad understanding of drug development to Celyad and its robust pipeline of CAR-T candidates for the treatment of hematological malignancies and solid tumors.”

Mr. Piscitelli stated, “The advancements that Celyad is making in its clinical and preclinical CAR-T programs has positioned the company as an exciting company to watch throughout the cell therapy landscape. I believe the opportunity to further leverage the company’s underlying technology platforms and intellectual property provides tremendous opportunities to drive long-term shareholder value.”

Dr. Koehler has more than 20 years of experience in oncology drug development. She currently serves as Chief Medical Officer at Repare Therapeutics. Prior to her current role, she was Chief Medical Officer of Bicycle Therapeutics. She previously served as Vice President of Strategy and Innovation for Pfizer Oncology, spearheading major acquisitions and strategic portfolio decisions. As the Pfizer Oncology Integrated Development Leader, she was integral in the development of IBRANCE® (palbociclib) for the treatment of metastatic breast cancer. Her professional experience includes academic clinical work in Poland, Germany and the United States, and executive positions at AstraZeneca, GlaxoSmithKline and Pfizer.

In addition to her extensive pharmaceutical executive experience, Dr. Koehler is also known for a number of accomplishments in academia, including serving as an associate professor at the University of Pittsburgh and the director of Bone Marrow Transplant at St. Christopher’s Hospital in Philadelphia. Her advisory roles included scientific and strategic support for NCI[1], ASCO[2], EORTC[3] and Breast Cancer IMPAKT[4] Scientific Boards, and the Breast Cancer Research Foundation. She received her M.D. and Ph.D. from the Silesian Medical School in Poland.

Mr. Piscitelli brings more than 20 years of industry experience, including debt and equity financings, in-licensing transactions, acquisitions, marketing partnerships and commercial product launches, including playing a part in the commercials launches of XTANDI® (enzalutamide) and Tarceva® (erlotinib).  Since September 2019, Mr. Piscitelli has served as the Chief Financial Officer of ORIC Pharmaceuticals, a publicly traded clinical stage oncology company. Prior to joining ORIC, from 2017 until 2019, he was Chief Financial Officer of AnaptysBio, where he helped raise over $500 million in an IPO and follow-on financings.

From 2012 until 2017, Mr. Piscitelli was Vice President of Finance, Strategy and Investor Relations at Medivation and played a key role in its acquisition by Pfizer Inc. in 2016. Prior to his tenure at Pfizer, he served as Senior Director of Collaborations and Operations Finance at Astellas Pharma. Mr. Piscitelli also served in various roles, and ultimately as the Vice President Treasury & Management Finance, at OSI Pharmaceuticals and played a significant role in their acquisition by Astellas in 2010. Mr. Piscitelli began his career with KPMG and is a certified public accountant. He earned a bachelor’s degree in accounting and an MBA from Hofstra University.