On December 7, 2020 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a pioneer in T-cell immunotherapy, leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with serious diseases including solid tumors, hematologic cancers and autoimmune disease, reported the presentation of the first preclinical evaluation of ATA3219, a next-generation, off-the-shelf, allogeneic CAR T-cell therapy targeting CD19, as well as data supporting its multicohort Phase II study with tab-cel (tabelecleucel) for the treatment of rare EBV-driven diseases (ATA129-EBV-205) (Press release, Atara Biotherapeutics, DEC 7, 2020, View Source [SID1234572347]). These data are being featured in five poster presentations at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 5-8, 2020.

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"Though the current generation of CD19 CAR T immunotherapies has transformed how we treat hematologic malignancies, a significant opportunity remains to improve outcomes and make the power of CAR T accessible to more patients using allogeneic cells with our differentiated EBV T-cell platform," said Jakob Dupont, M.D., Executive Vice President and Global Head of Research and Development at Atara. "As a leader in allogeneic CAR T-cell therapy, Atara is developing ATA3219 to be best-in-class, improving upon established CD19 targeting by leveraging both our EBV T-cell platform and novel 1XX co-stimulation signaling technology. We are pleased to share, for the first time, preclinical data demonstrating the antitumor activity, persistence, polyfunctional phenotype and safety of ATA3219."

Preclinical results presented at ASH (Free ASH Whitepaper) detail findings from in vitro and in vivo evaluations of ATA3219. Specifically, in vitro functional studies demonstrate potent antitumor activity of ATA3219 against CD19-expressing target lines, with durable CD19 antigen-specific and HLA-independent killing of CD19 targets. In addition, both in vivo and in vitro assessments of ATA3219 alloreactivity support a potentially favorable safety profile that would be required for an allogeneic, off-the-shelf CAR-T therapy.

Furthermore, in vivo, ATA3219 demonstrates potent antitumor activity in an established disseminated tumor model of acute lymphoblastic leukemia and is associated with long-term persistence and survival benefit. No treatment-related toxicities were observed in this animal model. Together, these findings support advancing ATA3219 to clinical evaluation.

ATA3219 combines an allogeneic EBV T-cell approach with a CAR signaling domain designed to improve upon current and clinically validated CD19 targeted CAR therapies without the need for gene editing. ATA3219 utilizes next-generation 1XX co-stimulatory domain technology, designed to extend functional persistence without compromising potency.

Following a successful pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration (FDA) in early Q4 2020, Atara plans to submit an IND for ATA3219 in 2021.

Additionally, Atara will report several data sets related to lead product candidate tab-cel including the first-ever presentation of data on patients with life-threatening complications associated with EBV viremia.

In this heterogeneous group of patients with life-threatening complications stemming from EBV viremia including some with hemophagocytic lymphohistiocytosis (HLH), a condition with poor prognosis for which treatment options are limited, 80 percent (n=4/5) of patients in the EAP-201 study with persistent EBV viremia (not HLH or chronic active EBV (CAEBV) were responders, and 50 percent (n=2/4) of the patients in EAP-901 with EBV viremia and HLH were responders. The overall survival (OS) rate at one year in patients with EBV viremia treated in the EAP-201 study was 100 percent for a median follow-up of 14.6 months (min 12.2, max 17.8).

Tab-cel was generally well-tolerated with no new safety signals in this study and data support the continued overall safety profile of the product. The EAP-901 study reported a fatal SAE of chronic hepatic failure that was assessed as unrelated to treatment; one patient experienced a grade 3 TESAE of facial nerve disorder that was assessed as possibly related to treatment and recovered in one month. There were no other fatal or treatment-related TESAEs reported in this patient population.

The Company has now presented clinical data for tab-cel in all six of the patient populations of the multi-cohort study, showing meaningful efficacy and consistent favorable safety profile.

In a poster evaluating the Healthcare Resource Utilization (HRU) and cost for patients with post-transplant lymphoproliferative disease (PTLD) following kidney transplant, it was found that PTLD is associated with substantial HRU and cost (>$200k PPY in the year diagnosed), regardless of the year diagnosed post-transplant, while patients without PTLD and patients who haven’t developed PTLD had a cost of ~$83k per-person year (PPY) in year one, and ~$26k PPY for year two and three post-transplant. Patients who developed PTLD continued to incur higher healthcare costs than patients who did not develop PTLD in years beyond the PTLD diagnosis year.

"We are pleased to see the growing body of evidence showing that tab-cel was well-tolerated and demonstrated strong objective response rates and overall survival in patients with life-threatening EBV-driven diseases beyond EBV+ PTLD," said AJ Joshi, M.D., Senior Vice President and Chief Medical Officer at Atara. "These data support the continued study of tab-cel in the multicohort trial aligned with our mission of bringing potentially transformative therapies to patients with serious diseases of high unmet medical need. Additionally, the characterization of the significant cost burden of PTLD begins to clarify important aspects of the significant value that a transformative treatment could provide to patients and the healthcare system."

Atara Poster Presentations at ASH (Free ASH Whitepaper):

Title: ATA3219: A Potent Next-Generation Allogeneic Off-the-Shelf CD19-CAR T Therapy without the Need for Gene-Editing
Abstract #: 3259
Session: 703. Adoptive Immunotherapy: Mechanisms and New Approaches: Poster III
Time and Location: Monday, December 7, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: Clinical Experience of Tabelecleucel in Patients with Life-Threatening Complications of Epstein-Barr Virus Viremia
Abstract #: 2554
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster II
Time and Location: Sunday, December 6, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: Clinical Experience of Tabelecleucel in Patients with EBV+ Primary (PID) or Acquired Immunodeficiency (AID) Associated Lymphoproliferative Disease
Abstract #: 1658
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster I
Time and Location: Saturday, December 5, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: High Healthcare Resource Utilization and Cost for PTLD Patients Following Kidney Transplants
Abstract #: 3482
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster III
Time and Location: Monday, December 7, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: A Multicenter, Multicohort, Open-Label, Single-Arm per Cohort, Phase II Study to Assess the Efficacy and Safety of Tabelecleucel in Patients with EBV-Associated Diseases Using an Adaptive Two-Stage Study Design
Abstract #: 2551
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster II
Time and Location: Sunday, December 6, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

On December 7, 2020 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that it will hold a conference call on Wednesday, December 9, 2020 at 10:00 a.m. ET to discuss clinical data from ongoing studies evaluating eganelisib in triple negative breast cancer (TNBC) which will be presented during the San Antonio Breast Cancer Symposium (SABCS) being held virtually, December 8-11, 2020 (Press release, Infinity Pharmaceuticals, DEC 7, 2020, View Source [SID1234572346]).

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Conference Call Information

A live webcast of the conference call can be accessed in the "Investors/Media" section of Infinity’s website at www.infi.com. To participate in the conference call, please dial (877) 316-5293 (domestic) and (631) 291-4526 (international) five minutes prior to start time. The conference ID number is 2088322. An archived version of the webcast will be available on Infinity’s website for 30 days.

Presentation Details:

Title: MARIO-3 phase II study initial data evaluating a novel triplet combination of eganelisib (IPI-549), atezolizumab (atezo), and nab-paclitaxel (nab-pac) as first-line (1L) therapy for locally advanced or metastatic triple-negative breast cancer (TNBC)

Presenter: Erika Hamilton, M.D., Tennessee Oncology

Date: Wednesday, December 9, 2020, 8:00 a.m. CT

Abstract: PS11-32

Poster Session: 11

Title: ARC-2: Efficacy and safety of etrumadenant (AB928) + pegylated liposomal doxorubicin (PLD) ± eganelisib (IPI-549) in participants with metastatic ovarian and triple negative breast cancer

Date: Wednesday, December 9, 2020, 8:00 a.m. CT

Abstract: PS12-12

Poster Session: 12

On December 7, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported updated results from a dose expansion study of tebotelimab, an investigational, bispecific PD-1 × LAG-3 DART molecule, in patients with diffuse large B-cell lymphoma (DLBCL) (Press release, MacroGenics, DEC 7, 2020, View Source [SID1234572345]). The data were presented at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 5-8, 2020.

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LAG-3 has been shown to be highly expressed in DLBCL and has emerged as a therapeutic target of interest in this population, while PD-1-targeted therapy has yielded modest efficacy. There remains significant unmet need for patients with relapsed/refractory (R/R) DLBCL.

In one of the tebotelimab monotherapy dose expansion cohorts, 20 DLBCL patients were enrolled, half of whom were CAR T cell therapy experienced. As of the October 23, 2020 data cut-off, there were 13 response-evaluable patients.

A preliminary objective response rate (ORR) of 53.8% (7 of 13 patients) was observed, including responses in five of seven CAR T cell-naïve patients and in two of six CAR T cell experienced patients, the latter of whom both had complete responses. A preliminary duration of response of up to 168 days was observed, with six of seven ongoing responses as of the cut-off date. In the study, baseline LAG-3 expression appeared to associate with clinical response, with additional analyses ongoing.

Tebotelimab was generally well-tolerated among heavily pre-treated R/R DLBCL patients, with manageable infusion-related reactions and no evidence of tumor lysis syndrome. The most common TRAE was pyrexia, which occurred in three (15%) patients. A single Grade 3 TRAE of anemia was observed.

"Although early, the preliminary ORR observed in relapsed/refractory DLBCL patients treated with tebotelimab is promising," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "Beyond our continued enrollment of patients in the combination study of tebotelimab in solid tumors, we look forward to presenting data from the full cohort of the 20 enrolled DLBCL patients, as well as potentially defining a future registration path for this DART molecule."

About Diffuse Large B-Cell Lymphoma

DLBCL is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 25 percent of NHL cases globally. According to published research, the incidence in the U.S. and England is approximately 7 cases per 100,000 persons per year, with a median age at presentation of 64 years. DLBCL represents a heterogeneous group of tumors consisting of large, transformed B cells with prominent nucleoli and basophilic cytoplasm, a diffuse growth pattern, and a high proliferation fraction. While DLBCL is curable in approximately half of cases with current therapy, particularly those who achieve a complete remission with first-line treatment, significant unmet medical need remains for patients with relapsed or refractory disease.

About Tebotelimab

Tebotelimab (previously known as MGD013) is an investigational, first-in-class bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab has been engineered to concomitantly or independently bind to PD-1 and LAG-3 and disrupt these non-redundant inhibitory pathways to further restore exhausted T-cell function. Tebotelimab is being evaluated in a Phase 1 dose expansion study as monotherapy in several tumor types, including both solid tumors and hematological malignancies, and in combination with margetuximab, an investigational Fc-engineered monoclonal antibody targeting HER-2, in three cohorts of patients with advanced HER2-positive cancers (NCT03219268). Tebotelimab will also be evaluated in combination with margetuximab and chemotherapy as part of the ongoing Phase 2/3 MAHOGANY study in patients with HER2-positive gastric or gastroesophageal junction cancer (NCT04082364). MacroGenics’ regional partner in Greater China, Zai Lab, participates in the MAHOGANY study and is also evaluating tebotelimab independently in Phase 1 combination studies with niraparib, a PARP inhibitor, and brivanib, a dual target tyrosine kinase inhibitor of the VEGF and FGF receptors, for the study of advanced gastric cancer and hepatocellular carcinoma, respectively.

On December 7, 2020 ADC Therapeutics SA (NYSE:ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, reported updated clinical data from its two lead programs, loncastuximab tesirine (Lonca) and camidanlumab tesirine (Cami), which were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, ADC Therapeutics, DEC 7, 2020, View Source [SID1234572344]).

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"The encouraging data presented at the 2020 ASH (Free ASH Whitepaper) Annual Meeting reinforce the significant progress we have made with our PBD-based ADCs for patients with hematological malignancies," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "The U.S. Food and Drug Administration recently accepted our Biologics License Application for Lonca for the treatment of relapsed or refractory diffuse large B-cell lymphoma and granted priority review status with a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2021, based on the data from our pivotal LOTIS 2 clinical trial. As we rigorously prepare for potential approval and launch in 2021, we look forward to continuing to evaluate the potential of Lonca, as a single agent and in combination, in heavily pretreated patients, in earlier lines of therapy and in additional indications such as follicular lymphoma. As for Cami, our pivotal Phase 2 trial in Hodgkin lymphoma is now more than 50 percent enrolled, and the preliminary data presented at ASH (Free ASH Whitepaper) highlight its potential to address an unmet need in heavily pretreated Hodgkin lymphoma patients."

Lonca LOTIS 2 Subgroup Analysis (Abstract 1183)

In LOTIS 2, a single-arm, open-label, 145-patient Phase 2 clinical trial in patients with relapsed or refractory DLBCL who had failed ≥2 established therapies, Lonca demonstrated substantial antitumor activity and an acceptable safety profile. Updated results, including analysis of response in subgroups with high risk of poor prognosis, were presented in a poster at ASH (Free ASH Whitepaper) 2020 by Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University.

Key data at the August 6, 2020, data cut include:

Overall response rate (ORR) was 48.3% and complete response rate (CRR) was 24.8%
Median duration of response (mDoR) of 12.58 months for the 70 responders, and mDoR of 13.37 months for patients achieving a complete response
Durable responses in high-risk patient groups, including:
Those who had progression after prior CAR-T therapy: ORR was 46.2% (6/13 patients)
Double or triple hit: ORR was 33.3% (5/15 patients)
Transformed DLBCL: ORR was 44.8% (13/29 patients)
No new safety concerns were identified during the study and no increase in toxicity was observed in patients aged ≥65 years compared with younger patients
Lonca LOTIS 3 Interim Results (Abstract 2099)

LOTIS 3, a Phase 1/2, two-part, open-label, single-arm clinical trial that is intended to support the submission of a Biologics License Application, is evaluating Lonca in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL). Updated interim data for patients receiving the 60 µg/kg Phase 2 dose of Lonca every three weeks and ibrutinib 560 mg/day were presented in a poster at ASH (Free ASH Whitepaper) 2020. As of the data cut-off date of August 20, 2020, 37 patients had received the Phase 2 dose and 35 were evaluable for efficacy.

Key data include:

ORR in all patients was 62.9%
In non-germinal center B-cell DLBCL patients, ORR was 66.7% (16/24 patients) and CRR was 37.5% (9/24 patients)
In germinal center B-cell DLBCL patients, ORR was 20% (1/5 patients)
In all DLBCL patients, ORR was 58.6% (17/29 patients)
In all MCL patients, ORR was 83.3% (5/6 patients)
Lonca in combination with ibrutinib had manageable toxicity, with the most common grade ≥3 treatment-emergent adverse events (TEAEs) in ≥5% of patients being anemia (10.8%), neutropenia (10.8%), thrombocytopenia (5.4%), and fatigue (5.4%)
Pharmacokinetic profiles demonstrated good Lonca exposure coverage throughout the dosing interval
"The need for a later line of therapy that is both effective and tolerable is underscored by the significant number of patients with DLBCL or MCL who relapse after treatment and have a poor prognosis," said Julien Depaus, MD, Department of Hematology, CHU UCL Namur. "It is very encouraging to see that Lonca in combination with ibrutinib, at the Phase 2 dose identified as the maximum tolerated dose in the initial Phase 1 portion of the clinical trial, continues to demonstrate antitumor activity and manageable toxicity in patients with relapsed or refractory DLBCL and MCL."

Cami Pivotal Phase 2 Preliminary Results (Abstract 474)

Cami is being evaluated in a multicenter, open-label, single-arm, 100-patient Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL) who have received ≥3 prior lines of treatment (≥2 lines if ineligible for hematopoietic stem cell transplantation, HSCT) including prior treatment with brentuximab vedotin and a checkpoint inhibitor. Preliminary efficacy and safety data were reported in an oral presentation at ASH (Free ASH Whitepaper) 2020. As of the data cut-off date of August 24, 2020, 51 patients had been treated with Cami and the median number of Cami cycles was five.

Key data include:

ORR was 83% (39/47 patients) and CRR was 38.3% (18/47 patients)
Five patients (10.6%) went on to consolidation with HSCT
No new safety signals have been identified and the most common grade ≥3 TEAEs in ≥5% of patients were hypophosphatemia (11.8%), gamma-glutamyltransferase increased (9.8%), alanine aminotransferase increased (5.9%), and maculopapular rash (5.9%)
Three cases of Guillain-Barré syndrome have been reported
"Patients with relapsed or refractory HL who do not respond, or experience disease progression after initial response, to treatments such as brentuximab vedotin and PD-1 blockade have limited therapeutic options," said Alex Herrera, MD, Assistant Professor, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope Medical Center. "The encouraging antitumor activity Cami has demonstrated as a single agent and its safety profile, which has been consistent with the Phase 1 trial, warrant the continued evaluation of this CD25-targeted ADC in relapsed or refractory HL patients."

ADC Therapeutics anticipates reporting interim results from the pivotal Phase 2 trial of Cami in HL in the first half of 2021. A Phase 1b clinical trial of Cami as monotherapy or in combination with pembrolizumab is currently enrolling patients with selected advanced solid tumors.

Conference Call and Webcast

ADC Therapeutics will host a live conference call and webcast today, December 7, 2020, at 8 a.m. ET, to highlight the Lonca and Cami data presented at ASH (Free ASH Whitepaper). The event will feature presentations from ADC Therapeutics management and key opinion leader Mehdi Hamadani, MD, Professor of Internal Medicine at the Medical College of Wisconsin, Division of Hematology and Oncology. To access the conference call, please dial (833) 303-1198 (domestic) or +1 914 987-7415 (international) and provide the pin number 1486164. A live webcast of the presentation will be available on the Investors section of the ADC Therapeutics website at www.adctherapeutics.com. The archived webcast will be available on the ADC Therapeutics website after the completion of the event.

About Loncastuximab Tesirine (Lonca)

Loncastuximab tesirine (Lonca, formerly ADCT-402) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Once bound to a CD19-expressing cell, Lonca is designed to be internalized by the cell, following which the warhead is released. The warhead is designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, thus disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death. CD19 is a clinically validated target for the treatment of B-cell malignancies.

A Biologics License Application for Lonca for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is currently under review with the U.S. Food and Drug Administration (FDA) and has been granted priority review status. The FDA has set a Prescription Drug User Fee Act target date of May 21, 2021. Lonca is being evaluated in LOTIS 3, a Phase 1/2 clinical trial in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma, and LOTIS 5, a Phase 3 confirmatory clinical trial in combination with rituximab in patients with relapsed or refractory DLBCL.

About Camidanlumab Tesirine (Cami)

Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, Cami is internalized into the cell where enzymes release the PBD-based warhead killing the cell. This applies to CD25-expressing tumor cells, and also to CD25-expressing Tregs. The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells and PBDs have also been shown to induce immunogenic cell death. All of these properties of Cami may enhance immune-mediated anti-tumor activity. Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL), as well as in a Phase 1a/1b clinical trial in patients with relapsed or refractory HL and non-Hodgkin lymphoma and a Phase 1b clinical trial as monotherapy and in combination with pembrolizumab in solid tumors.

On December 7, 2020 Celyad Oncology SA (Brussels:CYAD) (Paris:CYAD) (NASDAQ:CYAD) (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, reported 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 (Press release, Celyad, DEC 7, 2020, View Source [SID1234572341]). These updates were virtually presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held from December 5-8, 2020.

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"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 (Free ASH Whitepaper) 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.

About CYAD-211

CYAD-211 is an investigational, short hairpin RNA (shRNA)-based allogeneic CAR T candidate for the treatment of relapsed or refractory multiple myeloma (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.

About CYAD-01

CYAD-01 is an investigational CAR T therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells.

About CYAD-02

CYAD-02 is an investigational CAR T therapy that engineers an all-in-one vector approach in patient’s T cells to express both (i) the NKG2D chimeric antigen receptor (CAR), a receptor expressed on natural killer cells that binds to eight stress-induced ligands expressed on tumor cells, and (ii) short hairpin RNA (shRNA) SMARTvector technology licensed from Horizon Discovery to knockdown the expression of NKG2D ligands MICA and MICB on the CAR T cells. In preclinical models, shRNA-mediated knockdown of MICA and MICB expression on NKG2D 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.