SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the Month of July 2021
Commission File Number: 001-37452
CELYAD ONCOLOGY SA
(Translation of registrants name into English)
Rue Edouard Belin 2
1435 Mont-Saint-Guibert, Belgium
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
Celyad Oncology SA
On July 20, 2021, Celyad Oncology SA (the Company) issued a press release, a copy of which is attached hereto as Exhibit 99.1 and is incorporated by reference herein.
The Company presented a slide presentation at the Companys Research and Development Day on July 20, 2021, a copy of which is furnished to this report as Exhibit 99.2.
The information contained in this Current Report on Form 6-K, including Exhibit 99.1 and 99.2, except for the quotes of Filippo Petti contained in Exhibit 99.1, is hereby incorporated by reference into the Companys Registration Statements on Form F-3 (File No. 333-248464) and Form S-8 (File No. 333-220737).
|99.1||Press release issued by the Company on July 20, 2021|
|99.2||Presentation furnished by Celyad Oncology SA|
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
|CELYAD ONCOLOGY SA|
|Date: July 21, 2021||By:||
/s/ Filippo Petti
Chief Executive Officer and Financial Officer
Celyad Oncology Presents Updates on Allogeneic CAR T Clinical Candidates and shRNA-based Preclinical Concepts at Research & Development Day
Phase 1 IMMUNICY-1 trial evaluating CYAD-211 in relapsed/refractory multiple myeloma (r/r MM) showed dose dependent engraftment up to dose level three (300×106 cells per infusion) with no Graft-versus-Host disease reported to date
Submission of IND application for CYAD-203, a new first-in-class shRNA-based allogeneic, IL-18-armored CAR T candidate, expected in mid-2022
CYAD-101 following FOLFIRI preconditioning in advanced metastatic colorectal cancer (mCRC) was well-tolerated; cell kinetic and activity of alloSHRINK trial support the initiation of the KEYNOTE-B79 Phase 1b trial of CYAD-101 following FOLFOX preconditioning chemotherapy during early fourth quarter 2021
Mont-Saint-Guibert, Belgium Celyad Oncology SA (Euronext & Nasdaq: CYAD) (Celyad Oncology 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, highlighted a new preclinical allogeneic armored CAR T candidate developed from its shRNA platform and data updates to the shRNA-based allogeneic candidate CYAD-211 for r/r MM and allogeneic candidate CYAD-101 for mCRC today during a research and development day hosted by the Companys management team.
We are ushering in a new era of allogeneic CAR T candidates using novel technological advances, including our proprietary shRNA platform for allogeneic CAR T production and now the addition of our armored CAR capabilities with co-expression of the cytokine IL-18, said Filippo Petti, Chief Executive Officer of Celyad Oncology. We believe the advances were making may address many of the current modality limitations and have the potential to provide real-world benefits for patients, including more accessible CAR T cell treatment options, if approved. This continued technological innovation, which is currently being validated in ongoing clinical studies, establishes Celyad Oncology as a leader in this adoptive cell therapy space.
Latest Program Updates
CYAD-211 Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM
CYAD-211 is the Companys first shRNA-based allogeneic CAR T candidate, which co-expresses a BCMA targeting chimeric antigen receptor while using shRNA to knockdown expression of the CD3Î¶ component of theT-cell receptor (TCR)
Currently, CYAD-211 is being evaluated in the Phase 1 IMMUNICY-1 trial in r/r MM following preconditioning with cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) given three consecutive days.
In June, preliminary data from the Phase 1 IMMUNICY-1 trial was presented at the European Hematology Association (EHA) congress demonstrating no dose limiting toxicity (DLT), Graft-versus-Host disease (GvHD) or CAR T-cell-related encephalopathy syndrome (CRES) in the first two dose levels (30×106 and 100×106 cells per infusion) of the trial. Two of the five evaluable patients at the first two dose levels achieved a partial response. In addition, CYAD-211 cells were detected by PCR-based methods in all six patients with evidence of a dose dependent increase in cell engraftment.
Recent data from the first patient at dose level three (300×106 cells per infusion) continues to show dose dependent engraftment with no GvHD reported to date.
Enrollment in the trial is ongoing with plans to explore higher doses of preconditioning regimens in future cohorts.
CYAD-203 Allogeneic shRNA-based, IL-18-armored NKG2D CAR T for Solid Tumors
CYAD-203 is the Companys first armored CAR T candidate engineered to co-express the cytokine interleukin-18 (IL-18) with the NKG2D CAR receptor. To the Companys knowledge, this therapy is on track to be first ever IL-18 secreting allogeneic CAR T candidate.
IL-18 is a proinflammatory cytokine that directly potentiates the anti-cancer activity of CAR T cells while also altering the balance of pro- and anti-inflammatory cells within tumor tissue.
Investigational New Drug (IND)-enabling studies are currently ongoing. Submission of the IND application for CYAD-203 for treatment of solid tumors is expected in mid-2022.
Celyad Oncology SA | Rue Édouard Belin 2, 1435 Mont-Saint-Guibert, Belgium | +32 10 39 41 00
CYAD-101 Allogeneic TIM-based NKG2D CAR T for mCRC
To the Companys knowledge, CYAD-101 is the first investigational allogeneic CAR T candidate to generate evidence of clinical activity for the treatment of a solid tumor indication. This is based on data from the dose-escalation segment of the alloSHRINK Phase 1 trial evaluating CYAD-101 following FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) preconditioning chemotherapy for the treatment of advanced metastatic colorectal cancer (mCRC).
Initial data from the dose expansion cohort evaluating CYAD-101 (1×109 cells per infusion) following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy showed CYAD-101 was generally well-tolerated with no dose limiting toxicities or evidence of GvHD. Overall, nine out of ten evaluable mCRC patients showed stable disease at first tumor assessment.
Data also showed shorter persistence of CYAD-101 cells observed after FOLFIRI preconditioning as compared to FOLFOX preconditioning. Based on better CYAD-101 cell kinetics and clinical activity data from the alloSHRINK FOLFOX cohort, the Company submitted a protocol amendment to regulatory agencies to modify the Phase 1b KEYNOTE-B79 trial to incorporate FOLFOX as preconditioning chemotherapy.
The KEYNOTE-B79 trial to evaluate CYAD-101 with Mercks anti-PD -1 therapy, KEYTRUDA® (pembrolizumab), in refractory mCRC patients with microsatellite stable / mismatch-repair proficient disease is expected to be initiated during the fourth quarter of 2021.
Celyad Oncology has acquired an exclusive license from the Moffitt Cancer Center for an antibody directed to Tumor-associated glycoprotein (TAG-72), which will form the basis of a T cell engager to be used with our proprietary shRNA platform technology. TAG-72 has been shown to be expressed in a wide variety of epithelial malignant tissues including breast, colon and pancreatic cells and will expand the Companys program portfolio in solid tumor targets.
Additional clinical activity data for the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected during second half 2021.
Study initiation for KEYNOTE-B79 Phase 1b is expected early fourth quarter 2021.
Submission of an IND application for CYAD-203 is expected in mid-2022.
Report additional data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome in mid-2021.
About Celyad Oncology
Celyad Oncology is a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer. The Company is developing a pipeline of allogeneic (off-the-shelf) and autologous (personalized) CAR T cell therapy candidates for the treatment of both hematological malignancies and solid tumors. Celyad Oncology was founded in 2007 and is based in Mont-Saint-Guibert, Belgium and New York, NY. The Company has received funding from the Walloon Region (Belgium) to support the advancement of its CAR T cell therapy programs. For more information, please visit www.celyad.com.
This release may contain forward-looking statements, within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the clinical activity and safety and tolerability of CYAD-211, CYAD-203, and CYAD-101; expectations regarding enrollment and the announcement of additional clinical data; outcomes and timelines of the IMMUNICY-1 clinical trial and plans for initiating KEYNOTE-B79 Phase 1b trial; and the timeline for submission an IND application for CYAD-203. Forward-looking statements may involve known and unknown risks and uncertainties which might cause actual results, financial condition, performance or achievements of Celyad Oncology to differ materially from those expressed or implied by such forward-looking statements. Such risk and uncertainty include the duration and severity of the COVID-19 pandemic and government measures implemented in response thereto. A further list and description of these risks, uncertainties and other risks can be found in Celyad Oncologys U.S. Securities and Exchange Commission (SEC) filings and reports, including in its Annual Report on Form 20-F filed with the SEC on March 24, 2021 and subsequent filings and reports by Celyad Oncology. These forward-looking statements speak only as of the date of publication of this document and Celyad Oncologys 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.
Investor and Media Contacts:
Communications & Investor Relations Director
LifeSci Advisors, LLC
Source: Celyad Oncology SA
Research and Development Day Virtual Webinar July 20, 2021 Exhibit 99.2
Forward Looking Statements
Today’s Agenda Topic Speaker Welcome & Introductions Filippo Petti Redefining Allogeneic CAR T Filippo Petti Update on CYAD-211 for r/r MM Charlie Morris, M.D. shRNA Platform Armored CAR T Franchise Introduction to CYAD-203 Optimized for Multiplexed CAR Ts Future programs David Gilham, Ph.D. Update on CYAD-101 for mCRC Charlie Morris, M.D. Final Remarks and Q&A All
Redefining Allogeneic CAR T
Evolution of CAR T Landscape Towards Off-the-Shelf Approaches Allogeneic CAR Ts offer several benefits compared to autologous CAR Ts Quality of Therapy Cost Effective Derived from healthy donor T cells Opportunity to optimize manufacturing process to decrease variability between therapies Speed / Access Faster turnaround time from cancer treatment decision to infusion – days vs. months Improved intent-to-treat metrics given therapy is “on demand” Potential to address larger patient populations with less logistical hurdles Scalability of manufacturing to generate dozens of treatments vs. single patient treatment Potential to improve pharmacoeconomic benefits
Expected Real-World Benefits of Our Approach to Allogeneic CAR T Differentiation Factor Key Characteristics Expected Real-World Benefit(s) All-in-One Vector Single vector for all elements of the CAR T therapy Lower cost of goods sold (COGS) – vector costs are a major contributor to COGS. Using a single vector avoids the costs associated with multi-vector technologies Single transduction / expansion enables shorter manufacturing times T cells age with longer culture times. Short culture times maintain an optimal ‘fit’ T cell phenotype associated with therapeutic potential Multiplex Gene Engineering (Next-Generation Candidates) Ability to potentially knockdown simultaneously multiple gene targets of interest shRNA can target genes that are not suitable for gene editing Opportunity to optimize therapy based on indication / disease of interest
Update on CYAD-211 for r/r MM
Background on CYAD-211 CYAD-211 is our first allogeneic CAR T candidate utilizing our All-in-One vector approach based on the shRNA technology CYAD-211 co-expresses: CAR with a BCMA-specific engager Allogeneic technology – single shRNA targeting CD3ζ component of TCR complex Selection marker – truncated cell surface CD34 tag allows for positive cell enrichment during manufacturing BCMA: B-cell maturation antigen; r/r MM: relapsed/refractory multiple myeloma. CYAD-211 – shRNA-based Allogeneic CAR T Candidate for r/r MM shRNA CD3ζ
Keys to establishing technology proof-of-concept No evidence of GvHD Cell kinetics Initial clinical activity shRNA as a Novel Allogeneic Technology for CAR T
Open-label, Phase 1 dose-escalation trial in relapsed or refractory multiple myeloma patients CYAD-211 – IMMUNICY-1 Phase 1 Trial Study Design (1) Patient Background Primary objective: safety and recommended dose of CYAD-211 Dose escalation: 30x106, 100x106 and 300x106 cells per infusion Standard preconditioning: Cyclophosphamide 300 mg/m² / Fludarabine 30 mg/m² (3 days) Eight patients enrolled across three dose levels Median prior lines of therapy: four Six of eight (75%) patients exposed to all three major MM drug classes (proteasome inhibitors, immunomodulatory drugs, and CD38 specific therapy) 1. NCT04613557 Safety, Activity and Cell Kinetics of CYAD-211 in Patients With Relapsed or Refractory Multiple Myeloma (IMMUNICY-1).
Positive Systemic Cell Engraftment EHA: European Hematology Association; DLT: Dose-limiting toxicity; GvHD: Graft versus Host Disease. | Data from uncleaned database (May 24, 2021). Of the six patients dosed at the first two dose levels (30x106 and 100x106 cells per infusion): No DLTs, no GvHD and no CAR T cell‑related encephalopathy syndrome (CRES) One cytokine release syndrome (CRS) Grade 1 (fever) reported at dose level 1 Favorable Tolerability Profile Five evaluable patients: Two patients achieved partial response (PR) Three additional patients presented with stable disease (SD) Signs of Clinical Activity CYAD-211 – Summary of Initial Clinical Data – EHA June 2021 30x106 100x106
CYAD-211 Case Study – Response in Individual Lesions in Patient 5 1 month prior to infusion (SUV 6.2) D57 post infusion (SUV 5) 1 month prior to infusion (SUV 2.5 – 1.6 x 0.8 cm) D57 post infusion Resolved Left Maxillary Bone Right Lower Lobe (Superior segment)
Cell Kinetics Updated with First Patient at Dose Level 3 Duration and depth of lymphodepletion was variable in dose level 1 patients while patients in dose levels 2 and 3 showed similar lymphodepletion CYAD-211 cell levels detected by PCR-based methods in all patients Consistent with a dose dependent increase in cell engraftment No GVHD reported to date CYAD-211 cell levels detected by PCR-based methods in all patients Peripheral Blood Lymphocyte Count CYAD-211 Cell Engraftment DL: Dose level.
Keys to establishing technology proof-of-concept No evidence of GvHD Cell kinetics Initial clinical activity ü ü ü shRNA as a Novel Allogeneic Technology for CAR T
Enrollment ongoing in dose level 3 (300x106 cells per infusion) Plan to explore higher dose preconditioning regimens after dose level 3 Additional data from the dose escalation trial expected during second half 2021 Next Steps for CYAD-211 IMMUNICY-1 Trial
shRNA Platform – Armored CAR T Franchise
CAR Cytokine Autocrine effect – CAR T function Paracrine effect – Impact the tumor microenvironment Armored CAR Ts to Target the Tumor Microenvironment
Armored CARs Using Interleuken-18 (IL-18)
Expected Mechanism of Action – IL-18 Influence on CAR T Cells Local Environment Strong proliferation and anti-tumor activity in vivo Tbethigh FoxO1low CAR T phenotype through autocrine activity of IL-18 and CAR stimulation Mouse models: IL-18 Increased CD206- M1 macrophages Increased NKG2D+ NK cells Reduced Treg, suppressive CD103+ dendritic cells and M2 macrophages IL-18 binding protein is present in serum (2-3,000 pg/mL) at levels far in excess of IL-18 (80-120 pg/mL) High affinity of IL-18BP for IL-18 (400 pM) Role of IL-18BP is thought to be in controlling excessive pro-inflammatory responses Dinarello et al. (2013) Frontiers in Immunology 4(article 289) 1-10
CYAD-203 – Armored NKG2D Receptor Allogeneic CAR T for Solid Tumors CYAD-203 is a novel allogeneic, armored CAR T candidate using shRNA technology within our All-in-One vector approach. CYAD-203 co-expresses: NKG2D-based CAR Allogeneic technology – single shRNA targeting CD3ζ component of TCR complex Active form of IL-18 Selection marker – truncated cell surface CD19 tag allows for cell purification during manufacturing Background on CYAD-203
IL-18 Secretion Enhances Activity of NKG2D Receptor CAR T Cells Proof-of-principle of IL-18 established in preclinical models NKG2D CAR + IL-18 NKG2D CAR + IL-18 + shRNA CD3ζ
Next Steps for Armored CAR T Franchise Investigational New Drug (IND) enabling studies ongoing Anticipate submission of IND application in mid-2022 To our knowledge, CYAD-203 on track to be first IL-18 secreting allogeneic CAR T candidate Additional Armored CAR Ts CYAD-203 Program Currently evaluating the co-expression of IL-18 in multiple discovery stage next-generation, shRNA-based allogeneic CAR T candidates Opportunity to drive series of differentiated candidates for both solid tumors and hematological malignancies
shRNA Platform – Optimized for Multiplexed CAR Ts
Evolution of shRNA Technology for Next-Generation Allogeneic CAR T CYAD-211 and CYAD-203 employ a single shRNA targeting CD3ζ (CD247) Targeting multiple genes with shRNA to optimize functionality is an obvious next step given the breadth of the technology At ASCO 2020, demonstrated concurrent knockdown of up to four different gene products (multiplexing) in T lymphocyte cell line with our first-generation shRNA scaffold Transition from Single shRNA to Multiplexing ASCO: American Society of Clinical Oncology
Ongoing shRNA Multiplex Research Focused on Key Targets CD3ζ (CD247) Beta-2-microglobulin (β2M) FAS (CD95) Component of the TCR complex Knockdown of TCR designed to prevent Graft versus Host Disease (GvHD) shRNA targeting approach validated through CYAD-211 program Component of the MHC Class I molecules Knockdown of β2M designed to prevent Host versus Graft disease (HvG) allowing for greater cell persistence Cell surface death receptor whose activation leads to apoptosis Knockdown of FAS designed to prevent apoptosis and improve persistence 0.048% TCR+ TCRab staining 99.9% TCR-
Multiplexing with First Generation shRNA Scaffold FAS HLA-I TCRαβ aBCMA CAR shRNA CD3z shRNA B2M shRNA FAS - - - - + - - - + + + - + + - + + + + + First Generation BCMA CAR CD3ζ β2M FAS BCMA: B-cell maturation antigen
First Generation shRNA Scaffold – Transduction Efficiency Targeting multiple genes using first generation shRNA scaffold impacts transduction efficiencies
Multiplexing with Novel Second Generation shRNA Scaffold FAS HLA-I TCRαβ First Generation Second Generation aBCMA CAR shRNA CD3z shRNA B2M shRNA FAS - - - - + - - - + + + - + + - + + + + + + + + - + + - + + + + + CD3ζ β2M FAS BCMA CAR
Second Generation shRNA Scaffold – Transduction Efficiency Broad increase in transduction efficiencies with second generation shRNA scaffold
Next Steps for Multiplexing Research – Illustrative shRNA Targets CD3z TRAC β2M HLAII CD52 MICA/B CD28 PI3Kd PERSISTENCE FAS DGK PD1, TIGIT, LAG3, TIM3, CTL4A, TGFbR ALLOGENICITY FITNESS RESISTANCE to TME RESISTANCE to AICD CD38 CD7 MICA/B THERAPY SPECIFIC Bold/italicized/underlined targets currently evaluated in-house TME: Tumor microenvironment; AICD: Activation induced cell death
shRNA Platform – Future Programs
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development B7H6 5T4 CEA Source: Company disclosures. Includes αβ T cell, γδ T cell and IPSC-derived T cells.
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development Source: Company disclosures. Includes αβ T cell, γδ T cell and IPSC-derived T cells. B7H6 5T4 CEA Currently in clinical development at Celyad Oncology
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development B7H6 5T4 CEA Currently in clinical development at Celyad Oncology Currently in preclinical development at Celyad Oncology Source: Company disclosures. Includes αβ T cell, γδ T cell and IPSC-derived T cells.
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development Source: Company disclosures. Includes αβ T cell, γδ T cell and IPSC-derived T cells 1: Shu R, Evtimov VJ, Hammett MV, Nguyen NN, Zhuang J, Hudson PJ, Howard MC, Pupovac A, Trounson AO, Boyd RL. Engineered CAR-T cells targeting TAG-72 and CD47 in ovarian cancer. Mol Ther Oncolytics. 2021 Jan 16;20:325-341. doi: 10.1016/j.omto.2021.01.002. PMID: 33614914; PMCID: PMC7868933. . B7H6 5T4 CEA Currently in clinical development at Celyad Oncology Currently in preclinical development at Celyad Oncology We recently acquired an exclusive license from the Moffitt Cancer Center for an antibody directed to Tumor-associated Glycoprotein (TAG-72) TAG-72 has been shown to be expressed in a wide variety of epithelial malignant tissues including breast, colon and pancreatic cells and will expand the Company’s program portfolio in solid tumor targets (1)
Update on CYAD-101 for mCRC
Background on CYAD-101 NKG2D receptor-based CAR, TCR Inhibitory Molecule (TIM) and selection marker All-in-One vector approach based on TIM technology Single transduction Avoids multiple genetic modifications and cost associated with additional GMP grade materials TIM inhibits CD3ζ and reduces signaling of TCR complex Believed to reduce potential for Graft versus Host Disease (GvHD) alloSHRINK Phase 1 trial is evaluating CYAD-101 with preconditioning chemotherapy for the treatment of recurrent/progressing mCRC CYAD-101 – Leading Allogeneic CAR T Candidate for mCRC
Patient population mCRC after at least one metastatic treatment line FOLFIRI segment: PD under FOLFIRI Treatment schedule Three CYAD-101 infusions administered Q2W 48 hrs post preconditioning chemotherapy Primary objective: Safety (GvHD, CRS, CRES) Secondary objective: Clinical activity Exploratory evaluation: CYAD-101 engraftment CYAD-101 – alloSHRINK Phase 1 Trial N=3 N=3 N=9 N=10 109 CYAD-101 [FOLFIRI] 1. NCT03692429: Standard Chemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells (alloSHRINK). Study Overview (1) 10 8 CYAD-101 [FOLFOX] 3.10 8 CYAD-101 [FOLFOX] 10 9 CYAD-101 [FOLFOX]
FOLFOX Preconditioning Cohorts Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions alloSHRINK – CYAD-101 Following FOLFOX Showed Encouraging ORR 15 patients were treated at 3 dose-levels Absence of GvHD No treatment-related adverse events ≥ Grade 3 1x109 CYAD-101 cells/infusion defined as the recommended dose PR: Partial response; SD: Stable disease; PD: Progressive disease; UNK: Unknown. (1) Progression of non-target lesions. Best Tumor Burden Response Two partial responses (PRs) mPFS: 3.9 months (range: 1.2‑8.1 months) mOS: 10.6 months (range: 1.9‑18.7 months) mPFS: Median progression free survival; mOS: Median overall survival; PD: Progressive disease; SD: Stable disease; ORR: Overall response rate.
Previous Metastatic Lines and Response Case Study – alloSHRINK Patient 01 (Partial Response, Dose Level 1) Male, 74 years old; ECOG 1 | Left colon | RAS wild type; BRAF wild type; MSS CONFIRMED PARTIAL RESPONSE Responses on CYAD-101 + FOLFOX preconditioning SD FOLFOX CETUXIMAB PR FOLFOX PANITUMUMAB CR SURGERY PD FOLFOX PANITUMUMAB PSEUDOADJUVANT PD FOLFIRI PANITUMUMAB PD REGORAFENIB PD LONSURF PD PHASE I alloSHRINK CONFIRMED PARTIAL RESPONSE CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.
CONFIRMED PARTIAL RESPONSE No better clinical response under FOLFOX alone Male, 62 years old; ECOG 0 | Rectum cancer | RAS mutated; BRAF wildtype; MSS CEA = 10.9 µg/L CEA = 6.3 µg/L Case Study – alloSHRINK Patient 08 (Partial Response, Dose Level 3) Previous Metastatic Lines and Response Responses on CYAD-101 + FOLFOX preconditioning alloSHRINK FOLFOX BEVACIZUMAB PD PD FOLFIRI NAPABUCASIN (BB1608) PD PR LIVER SURGERY CR PR FOLFOX BEVACIZUMAB LIVER SURGERY CR FOLFOX BEVACIZUMAB PSEUDOADJUVANT FOLFOX BEVACIZUMAB PSEUDOADJUVANT CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.
Cell Engraftment following FOLFIRI NKG2D copies/µg DNA Cell Engraftment following FOLFOX Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions Shorter Persistence of CYAD-101 Cells Observed After FOLFIRI vs. FOLFOX
alloSHRINK Expansion Cohort Update Best Tumor Burden Response Cell Engraftment following FOLFIRI NKG2D copies/µg DNA Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions CYAD-101 following FOLFIRI generally well-tolerated No objective response observed with nine of ten patients achieving stable disease (SD) at first tumor assessment
No relevant differences between CYAD-101 batches used CYAD-101 cells may be impacted (lysis) by irinotecan metabolite In vitro testing is ongoing to investigate lead hypothesis Cell Engraftment following FOLFIRI Cell Engraftment following FOLFOX Shorter Persistence of CYAD-101 Cells Observed After FOLFIRI vs. FOLFOX Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions NKG2D copies/µg DNA Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38 RHJ Mathijssen, J Verweij, WJ Loos, P de Bruijn, K Nooster and A parreboom - British Journal of Cancer (2002) 87, 144-150 - ©2002 Cancer Research UK British Journal of Cancer (2002) 87, 144-150 Cancer Research UK. All rights reserved 007-920/02 www.bjcancer.com
mCRC: Metastatic colorectal cancer; MoA: Mechanism of action; TME: Tumor microenvironment KEYNOTE-B79 Trial – CYAD-101 with KEYTRUDA® in Refractory mCRC alloSHRINK Highlights Expected Complementary MoAs Encouraging clinical activity observed in incurable mCRC patients Therapy well tolerated. No evidence of GvHD Evidence of new T-cell clones entering the hyper-expanded TCR repertoire post-treatment with CYAD-101 Modulation of the endogenous immune response NKG2D CAR T cells may convert the TME from immunosuppressive to immunostimulatory Anti-PD1 blocks the co-inhibitory interaction of cancer cells with immune cells and restores the immune response The anti-PD1 therapy, KEYTRUDA® (pembrolizumab), could enhance the CYAD-101-sculpted TME, thereby driving a more durable anti-tumor response KEYNOTE-B79 Trial
KEYNOTE-B79 Phase 1b Trial Design Primary objective: Safety (GvHD, CRS, CRES) Secondary objective: Clinical activity Exploratory evaluation: CYAD-101 engraftment FOLFOX Screening D1 Long-term safety follow-up Y15 D15 D29 D52 D73 M26 D3 D17 D31 FOLFOX FOLFOX CYAD-101 End of treatment phase CYAD-101 CYAD-101 1st Pembro Pembro Q3W max 2 Y Patient population: mCRC with recurrent/progressing disease after at least one line of systemic therapy for metastatic disease which must include FOLFOX chemotherapy Microsatellite stable (MSS) / mismatch-repair proficient (pMMR) tumor status Treatment schedule: Three CYAD-101 infusions administered Q2W 48 hrs post FOLFOX preconditioning chemotherapy Pembrolizumab (200 mg Q3W) initiated three weeks post third (and last) CYAD-101
alloSHRINK Phase 1 KEYNOTE-B79 Phase 1b Next Steps for CYAD-101 Program Continue to monitor patients Analyze SN-38 serum levels in study patients Evaluate sensitivity of CYAD-101 cells to SN-38 in vitro Regulatory process for review of protocol complete in U.S. and Belgium Study initiation by early fourth quarter 2021
Final Remarks and Q&A Company proprietary material – do not copy or distribute
Building Next Generation Allogeneic Candidates MM: Multiple myeloma; mCRC: Metastatic colorectal cancer; MDS: Myelodysplastic syndrome; MSS: Microsatellite stable; pMMR: Proficient mismatch repair; r/r: relapse/refractory. Second Half 2021 2022 CYAD-211 for r/r MM Report additional clinical activity data from dose-escalation IMMUNICY-1 trial CYAD-101 for mCRC Initiate Phase 1b KEYNOTE-B79 trial with KEYTRUDA® in patients with MSS / pMMR disease CYAD-203 for Solid Tumors Submit IND application
Differentiated Pipeline of Allogeneic CAR T Candidates TARGET INDICATION IND ENABLING Phase 1 PHASE 2 PHASE 3 CYAD-101 NKG2DL mCRC CYAD-203 NKG2DL + IL-18 Solid tumors CYAD-211 BCMA r/r MM MM: Multiple myeloma; BCMA: B-cell maturation antigen; IL-18: Interleuken-18; mCRC: Metastatic colorectal cancer; NKG2DL: Natural killer group 2D ligands; r/r: relapse/refractory.
Research and Development Day Virtual Webinar July 20, 2021