CYNK-001 Granted Orphan Drug Designation for Treatment of Malignant Gliomas

The FDA has granted orphan drug designation to CYNK-001, a non-genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, for the treatment of patients with malignant gliomas, according to a press release by Cellularity Inc.¹ 

CYNK-001 is being developed from placental hematopoietic stem cells as a potential therapy for solid tumors, hematologic cancers, and infectious disease, including coronavirus disease 2019 (COVID-19). So far, CYNK-001 has demonstrated a range of biological activities expected of NK cells such as the expression of perforin and granzyme B, cytolytic activity against both hematologic and solid tumor cell lines, and the secretin of immunomodulatory cytokines such as IFN-y in tumor cells. The agent was also found to express NKG2D and CD94 and NK activating receptors DNAM1, NKp30, NKp60, and NKp44.²

The agent is currently being investigated in a phase 1 trial for its effectiveness as a therapy for recurrent glioblastoma multiforme (GBM) (NCT04489420). The non-randomized, sequential assignment, interventional trial has an estimated enrollment of 36 participants and an estimated completion date of February 2024.

The primary outcomes of the study are the number of participants who experience dose-limited toxicities (DLT) within 42 days of treatment and adverse events (AEs) within 1 year of treatment. Secondary outcomes of the study include overall response rate, duration of response rate, progression-free survival, time to progression, and overall survival.

Patients are split into 2 arms. Arm 1 will be made up of several cohorts. In Cohort 1A, which will include up to 6 participants, patients will receive CYNK-001 at a dose of 1.2 x 109 cells intravenous (IV) on days 0, 7, and 14. Patients will be followed for 42 days for DLTs. This ranges from the initial infusion to 28 days after the last dose. No other treatments are planned between the last day of CYNK-001. If there are DLTs, cohort 1C, which is the recurrent GBM dose-de-escalation group, will receive a dose of 00 x 106 cells via IV infusion on days 0, 7, 14. Cohort 1B, the surgical cohort, will receive CYNK-001 at the maximum safe dose at days 0, 7, 14. This cohort will include up to 6 subjects. Tumor resection surgery will occur after the last CYNK-001 infusion.

Arm 2 also contains several cohorts. Cohort 2A or Cohort 2C will begin only after the safety results are deemed acceptable from Cohort 1A or 1C. CYK-001 will be administered on the same schedule as in arm 1, except that it will be administered Intrathecally (IT) as opposed to an IV. Cohort 2A will be treated with CYNK-001 IT at 200 x 10⁶ ± 50 x 10⁶ cells IT. Cohort 2C will received the agent at 200 x 10⁶ ± 50 x 10⁶ cells. Cohort 2B, which is the surgical IT cohort will receive the agent at maximum tolerated dose.

In order to participate, patients must be 18 years old or older and have adequate organ function. Patients who had prior radiation therapy within 12 weeks of screening MRI are not eligible to participate unless this is unequivocal histological confirmation of tumor progression. Patients who have received radiotherapy, chemotherapy, or any other investigation agents within 4 weeks of starting the study are also not eligible to participate. 

“We are very pleased the FDA has granted Orphan Designation in malignant gliomas to continue to develop off-the-shelf therapies for serious unmet clinical needs,” said Robert J. Hariri, MD, PhD, founder, chairperson and chief executive officer of Celularity, in a press release. “Building on the FDA’s recent decision to grant Fast Track status to CYNK-001, we view the Orphan Drug Designation as yet another milestone on our journey to deliver patients a potentially novel treatment. To date, we have observed the potential of CYNK-001 in multiple preclinical models as well as early evidence of activity in the clinic and believe this approach may shift the paradigm in augmenting the body’s natural immune response to diseases such as glioblastoma, other cancer indications and infectious diseases. We are very excited to continue working with the FDA on the development of this exciting therapy.”

In addition to GBM, CYNK-001 is being investigated as a therapy for patients with acute myeloid leukemia (NCT04310592), multiple myeloma (NCT04309084), and coronavirus disease 2019 (NCTO4365101).²

_REFERENCES:

_{1.Celularity receives orphan drug designation for natural killer cell therapy CYNK-001 in the treatment of malignant gliomas. News release. Celularity. April 13, 2021. Accessed April 13, 2021. https://bit.ly/2OOs5Om.}

_{2.NK Cell Program. Celularity. Accessed April 13, 2021. https://bit.ly/3mJyCGn.}