First Patient with B-cell Lymphoma Dosed With Allogeneic NK CAR T Therapy

Century Therapeutics has dosed the first patient with relapsed or refractory CD19 positive B-cell lymphoma in the first-in-human phase 1 ELiPSE-1 trial (NCT05336409) evaluating the company’s chimeric antigen receptor (CAR) T-cell therapy CNTY-101.¹

“Today’s achievement marks our transition to a clinical-stage company and represents an important milestone for both Century and for patients with relapsed or refractory CD19 positive B-cell lymphomas who are lacking efficacious therapeutic options,” Lalo Flores, PhD, chief executive officer, Century Therapeutics, said in a statement.² “With our vision of a finite multi-dosing regimen combined with core Allo-Evasion™ edits, we are attempting to pave the way for our future product candidates and a new paradigm for allogeneic cell therapies.”

ELiPSE-1 is evaluating the safety, tolerability, and preliminary efficacy of a multi-dosing strategy of CNTY-101. The trial is enrolling up to 75 participants to receive an initial standard dose of cyclophosphamide (300 mg/m2) and fludarabine (30mg/m2) conditioning chemotherapy for 3 days. Schedule A of the trial includes a single-dose escalation of CNTY-101 and subcutaneous IL-2 while schedule B will evaluate a 3-dose schedule per cycle of the therapy. Additional cycles of treatment may be administered to participants that demonstrate a clinical benefit with or without additional lymphodepletion. The trial’s primary endpoints include assessing the maximum tolerated dose of CNTY-101 and the recommended phase 2 dose. Secondary endpoints include complete response rate, overall response rate, duration of response, time to response, progression-free survival, overall survival, adverse events, pharmacokinetics, and pharmacodynamics.

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CNTY-101 is an allogeneic, induced pluripotent stem cell-derived natural killer (NK) cell therapy engineered with a CD19 CAR for tumor targeting, IL-15 support for enhanced persistence, Allo-Evasion technology to prevent host rejection and enhance persistence, and a safety switch that allowselimination of the cells if ever necessary. Century’s allo-evasion technology is designed to allow evasion by the host immune system to enable redosing and increased persistence of the cells and potentially deep and durable responses. The technology knocks out beta-2-microglobulin to prevent CD8+ T cell recognition,Class II Major Histocompatibility Complex Transactivator to prevent CD4+ T cell recognition, and the HLA-E gene to enable higher expression of the HLA-E protein to prevent killing of CNTY-101 cells by host NKcells. The technology has demonstrated efficacy in improving improve functionality and persistence in preclinical studies and the safety switch, activated by administration of cetuximab, also demonstrated quick elimination of CAR T cells. The FDA granted investigational new drug (IND) clearance to CNTY-101 in August 2022.²

“CNTY-101 is the first allogeneic cell product candidate with six genetic modifications incorporated using sequential rounds of CRISPR-mediated homologous recombination and repair that has received IND clearance by the FDA,” Luis Borges, chief scientific officer, Century Therapeutics, added to the statement.² “We believe CNTY-101 will demonstrate the power of Century’s iPSC technology and cell engineering technology platforms. This accomplishment is a testament to the expertise and dedication of our team as we continue to make progress developing our pipeline of iPSC-derived NK and T cell product candidates.”

REFERENCES

1. Century Therapeutics announces first patient dosed in first-in-human phase 1 ELiPSE-1 trial evaluating CNTY-101 in relapsed or refractory CD19 positive B-cell lymphomas. News release. Century Therapeutics. February 8, 2023. https://finance.yahoo.com/news/century-therapeutics-announces-first-patient-123000885.html?guccounter=1&guce_referrer=aHR0cHM6Ly91c2MtZXhjZWwub2ZmaWNlYXBwcy5saXZlLmNvbS8&guce_referrer_sig=AQAAAC_BWSDxe12pnMTAUsIF9O1SVqPiv_LbAUxGOBGgQNSlGSwfETFAauYzS388wGPKFlYYc8uO5Ouod5hiG6h1KtB5BuvsIUtRh63NlN-dyUcd7YCgHACYUmcNEzFPRDkuv_dsMjaQ0ANgyIRaMoRfgse6SF4nLQOhF12WidcLyen3
2. Century Therapeutics receives study may proceed notification from FDA for CNTY-101, the first allogeneic cell therapy product candidate engineered to overcome three major pathways of host vs graft rejection. News release. Century Therapeutics. August 25, 2022. https://finance.yahoo.com/news/century-therapeutics-receives-study-may-113000642.html