On February 1, 2018 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company reported about an update on its ongoing Phase 1 clinical trial, called THINK (THerapeutic Immunotherapy with NKG2D), to assess the safety and clinical activity of its lead drug product candidate, CYAD-01, in seven refractory cancers, including both solid and hematologic cancers (Press release, Celyad, FEB 1, 2018, View Source [SID1234523680]). As of December 31, 2017, Celyad had treated 15 patients with CYAD-01 in the THINK trial. In six of the 10 patients treated at the per-protocol intended dose, Celyad observed signs of clinical activity ranging from Stable Disease (SD) to Complete Response (CR). In all cases, CYAD-01 was administered as a monotherapy without chemotherapy preconditioning. Based on the promising interim results of the THINK trial, the company plans to further evaluate CYAD-01 in a series of additional Phase 1 clinical trials in patients with acute myeloid leukemia (AML)and colorectal cancer (CRC).
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Celyad also announced that drug product manufactured using an improved manufacturing process designed to significantly increase the yield of T cells in the drug product that is produced, is now in the clinic. The first patient in the THINK trial to be administered drug product manufactured using the new manufacturing process was treated in late January 2018.
Christian Homsy, CEO of Celyad commented: "We are very pleased with our progress in the clinic during 2017, especially the observations of Stable Disease and Complete Response achieved at the lower doses and without chemotherapy preconditioning. Encouraged by these results, we are rapidly developing a robust clinical development plan for this product candidate in both AML and CRC. We are likewise excited to see drug product produced using our improved manufacturing process in the clinic. We anticipate that this process will enable us to significantly increase the yield of T cell expansion in the drug product we produce, while at the same time reducing process complexity and cost. We look forward to advancing our clinical development efforts in 2018, as we see to leverage our expertise in cell therapy technology for the benefit of critically ill patients in need."
The company also reported that, based on preliminary unaudited information and management estimates, at December 31, 2017, it had cash and cash equivalents and short term investments of approximately €34 million and is reconfirming guidance of a cash run rate into the first half of 2019.
THINK Trial Update (all data is as of December 31, 2017)
As of December 31, 2017, Celyad had treated 15 patients with CYAD-01 drug product in the THINK trial. Patients have been treated at the first and/or second dose level in both the solid and hematological tumor cohort of the dose escalation part of the trial. The company is currently enrolling patients for the third dose level phase in the solid tumor cohort and completing the second dose level phase in the hematological arm.
As of December 31, 2017, Celyad had not observed the same Grade 4 or above adverse event in two or more patients and no patient experienced a Grade 5 adverse event. No patient experienced an adjudicated Grade 4 or higher CRS adverse event or neurotoxic adverse event.
Of the 15 patients treated as of December 31, 2017, 10 were dosed at the per-protocol intended dose and five were treated at a dose lower than the per-protocol intended dose using drug product manufactured using a prior manufacturing method. In six of the 10 patients treated at the per-protocol intended dose Celyad observed signs of clinical activity ranging from Stable Disease (SD) to Complete Response (CR). Signs of clinical activity were observed in patients with AML, CRC and ovarian cancer. No signs of clinical activity were observed in patients treated with a dose lower than the per-protocol intended dose.
In all three AML patients treated at the per-protocol intended dose Celyad observed signs of clinical activity. A fourth AML patient was treated at a dose lower than the per-protocol intended dose and did not show signs of clinical activity. In two of four CRC patients treated at the per-protocol intended dose, Celyad observed signs of clinical activity. These two patients showed SD at the three-month follow-up date, both receiving the first dose level. A fifth CRC patient was treated at a dose lower than the per-protocol intended dose and did not show signs of clinical activity.
Manufacturing Update
Until recently, CYAD-01 drug product was manufactured using a process which did not consistently produce the required number of T cells in the drug product for the higher doses, resulting in some cases in an inability to manufacture drug product consistent with the protocol for the THINK trial. All 15 patients treated in the THINK trial as of December 31, 2017 were treated with drug product manufactured using this process. Of these 15 patients, 10 were dosed at the per-protocol intended dose and five were treated at a dose lower than the per-protocol intended dose due to an inability to obtain sufficient cell numbers in the drug product using this manufacturing method.
In response to these manufacturing challenges, Celyad modified the manufacturing process to include a monoclonal antibody (mAb) that inhibits NKG2D expression on the T cell surface during production. This method has the potential to yield significantly higher cell numbers. The THINK protocol has been amended for this new approach, and in the first three patient lot produced since this process was implemented, a very high cell yield was obtained.
The first patient in the THINK trial to be administered drug product manufactured using the mAb process was treated in late January 2018. The data from this patient is still emerging, but based on a preliminary review, the patient experienced an adverse event consistent with those observed in patients treated with drug product manufactured using the prior method, specifically hypoxia, which may or may not be adjudicated to be the result of CRS. Given that the drug product was administered in late January, it is too early to assess signs of clinical activity in this patient.
C-Cure
Until mid-2016, Celyad was focused on the development of a cardiovascular drug product candidate called C-Cure, an autologous cell therapy for the treatment of patients with ischemic heart failure. This program was funded in part through various research programs from the Walloon Region of Belgium. In June 2016, Celyad reported topline results from a Phase 3 clinical trial for this drug product candidate. Following the announcement of these results, the company explored strategic options to further develop and commercialize C-Cure, while the company focused on its CAR-T oncology drug product candidates. In December 2017, Celyad notified the Walloon Region of its decision not to exploit the results of this program in exchange for a cancellation of the loans of the Region to the Company.