* 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
Mont-Saint-Guibert,
Dr.
Dr.
alloSHRINK Phase 1 Trial Update
BackgroundTo 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 TolerabilityNo 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.
shRNA Platform and CYAD-200 Series
Background
* In
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 CD3? 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.
Conference Call and Webcast Details
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* 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
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