Full Press Release Details
Century Therapeutics
Presents New Preclinical Data Highlighting iPSC-derived Cell Therapy Platform Technology at the 2024 American Association for Cancer
Research (AACR) Annual Meeting
PHILADELPHIA, April 8, 2024
- Century Therapeutics (NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell
(iPSC)-derived cell therapies in immuno-oncology and autoimmune and inflammatory disease, today announced that preclinical data from
the Company's iPSC-derived cell therapy platform was presented at the AACR Annual Meeting 2024. The posters highlight the Company's
end-to-end capabilities in iPSC reprogramming and differentiation, gene editing, synthetic biology, protein engineering and computational
"Together, the promising preclinical
data showcase Century's continued dedication to driving the field of allogeneic cell therapy through the incorporation of a suite
of innovations into next generation product candidates," said Hy Levitsky, M.D., President of Research and Development at Century
Therapeutics. "We presented new data advancing our Allo-Evasion platform through the transgenic expression of HLA-G, which
along with HLA-E can augment the protection against host natural killer cell-mediated rejection of iPSC derived cells also engineered
to resist T cell recognition through the elimination of HLA-I and HLA-II expression. This enhanced protection against rejection is designed
to enable Century's multi-dosing strategy that increases the period of drug exposure, potentially leading to deeper and more durable
responses for patients in need. We also presented new data describing our novel, dual-targeting CAR for B cell mediated malignancies
which demonstrated promising in vitro and in vivo cytotoxicity and resisting antigen loss, and which we believe expands
the potential of allogeneic CAR-T cell therapy beyond currently available options in oncology that only target CD19. Along with other
important preclinical data presented at AACR, the findings to date highlight our unique gene editing, protein engineering, and manufacturing
capabilities that are the foundations of our industry-leading allogeneic cell therapy pipeline and platform."
Details of the posters presented on
Sunday, April 7th and Monday, April 8th are as follows:
The Discovery of a Novel CD19xCD22
Dual-Targeting CAR For the Development of an iPSC-Derived Cell Therapy
Poster Board Number: 4
Session Title: Adoptive
Cell Therapies 2: CAR-T Cells
Session Date & Time: Sunday, April 7, 2024, at 1:30 PM - 5:00 PM
Through its industry leading engineering
capabilities, Century has developed a CD19xCD22 bispecific, CD22 biparatopic chimeric antigen receptor (CAR), which was transduced into
primary T cells and demonstrated cytotoxicity activity against CD19 and CD22-positive tumor cells, as well as CD19 knockout and CD22
knockout cell lines in vitro and in in vivo mouse xenograft models. This novel CAR was engineered and tested in iPSC-derived
gamma-delta T cells, showing in vitro tumor cell cytotoxicity. These findings support the continued examination of a CD19xCD22
bispecific CAR for off-the-shelf allogeneic cell therapy to expand patient access beyond CD19 CAR-T cell therapies.
Engineered Expression Of HLA-E
And HLA-G Protects iPSC-Derived Cells from Killing by Primary NK Cells
Poster Board Number: 3
Session Title: CAR-K, NK Engagers, and NK Modulators
Session Date & Time:
Monday, April 8, 2024, at 9:00 AM - 12:30 PM PT
In this study, the Company showed that
the combination of HLA-E and HLA-G expression was the most effective in protecting allogeneic drug products from elimination of genetically
dissimilar cells. Investigators assessed allo-evasion from natural killer (NK) cells by iPSC-derived cells engineered to express HLA-E
and -G. NK cells across donors expressed heterogeneous combinations of HLA-E and -G ligands. K562 and iPSC-derived cells lacking HLA-I
were susceptible to killing by PBMCs. Overexpression of HLA-E and -G offered protection to K562 and iPSC-derived cells against all tested
donors. HLA-E offered more protection than HLA-G, and the combination of both HLA-E and -G was most potent. When a genetically dissimilar
HLA Class I protein family is deleted to prevent T cell mediated graft rejection, expression of the more-conserved HLA-E and -G
can effectively protect allogeneic drug products from elimination. We believe this data further reinforces the Company's proprietary
Allo-Evasion technology and its potential to evade identification by the host immune system, which would allow for repeat dosing
without rejection, enabling increased persistence of the cells during the treatment period and potentially leading to deeper and more
Screening iPSC Lines for Optimal
Characteristics of Differentiation into Immune Effector Cells for Clinical Programs
Poster Board Number: 19
Session Title: Adoptive Cellular
Session Date & Time:
Monday, April 8, 2024, at 1:30 PM - 5:00 PM PT
Century outlined the genomic characterization
of both its clinical-grade PBMC-derived and its gamma-delta T cell-derived iPSC lines (PiPSCs and TiPSCs, respectively). The Company
successfully reprogrammed these cell lines from multiple donors and analyzed them through its genomic characterization pipeline and tiered
them based on potential genetic liabilities to determine those best suited for clinical development. Multiple lines were then identified
and iPSC and TiPSC were successfully differentiated to immune effector cells. d35 iT cells exhibited diverse phenotypes, yields, and
function. These lines can then be specialized into effector cells exhibiting heightened functionality,
applicable to conditions including autoimmune disorders and oncology indications, among others. Once differentiated, Century further
screened the lines for their in vitro cytotoxicity and post target-engagement persistence, thereby discovering those that were
most suitable for further clinical development.
Discovery of a Novel NECTIN4 iPSC-derived
Cell Therapy for the Treatment of Solid Tumors
Poster Board Number: 27
Session Title: Antibody Drug
Conjugates and Bispecific Antibodies
Session Date & Time:
Monday, April 8, 2024, at 9:00 AM - 12:30 PM PT
Century is developing an iPSC-derived
cell therapy targeting NECTIN4, an established biomarker linked to carcinogenesis, worse prognosis, and disease severity, for the treatment
of NECTIN4 expressing solid tumors. In these preclinical studies, Century identified novel single-domain antibodies (VHH) that bind to
multiple epitopes on the NECTIN4 extracellular domain. The VHH antibodies were engineered into CAR formats and characterized for expression,
cell activation through antigen engagement, and cytotoxicity activity in primary T cells. Selected binders demonstrated efficacy in multiple
CAR formats in primary T cells in a mouse xenograft model using OVCar-3 tumor cells. The lead CARs engineered into primary T cells demonstrated
tumor inhibition similar to a reference CAR using the ASG-5ME antibody (Enfortumab) as the NECTIN4 binder. The CARs were engineered into
Century's iPSC-derived iNK and iT cells and demonstrated cytotoxicity activity against a panel of cell lines with a range of cell
surface expression of NECTIN4. We believe these findings support the advancement of Century's lead NECTIN4 binder for the development
of an iPSC-derived cell therapy to treat NECTIN4 positive solid tumors.
Century will also be sharing two additional
posters at AACR on Tuesday, April 9th and Wednesday, April 10th. Details are as follows:
Discovery Of Inhibitory CAR Target
DSG1 for Damping NECTIN4 On-Target Off-Tumor Toxicity in iPSC-Derived CAR-T Cell Therapy
Poster Board Number: Section 2,
Session Title: Adoptive Cell
Therapies 3: CAR-T Cells
Session Date & Time:
Tuesday, April 9, 2024, at 9:00 AM -12:30 PM PT
Century is developing NECTIN4 targeted
iPSC-derived CAR-T cell therapy. In a NECTIN4 targeted antibody drug conjugate, enfortumab vedotin, severe skin adverse events are seen
in some patients, thought to be driven by on-target off-tumor toxicity against NECTIN4 displaying skin keratinocytes. In this study,
Century compared the expression levels of NECTIN4 to targets associated with tissue and cell-type specific on-target off-tumor toxicity
in primary CAR-T cell clinical trials. These findings support the incorporation of a DSG1-directed inhibitory CAR into NECTIN4 specific
CAR-T cell therapeutic candidates to combat skin related adverse reactions.
CXCR4 Transgene Improves In Vivo
Migration and Efficacy of Engineered iPSC-Derived Natural Killer Cells
Poster Board Number: 7