Full Press Release Details
Therapeutics Presents Initial Data from CNTY-101 Phase 1 ELiPSE-1 Trial Supporting the Potential
for a Multi-Dosing Strategy for CAR iNK Enabled by Allo-Evasion Edits
- Data presented at 65th ASH
Annual Meeting show CNTY-101 was generally well tolerated at Dose Level 1 (100 million cells) in a high-risk, heavily pretreated R/R B-cell
Preliminary clinical data demonstrate six-month durable complete response in Dose Level 1 in a single patient following
multiple cycles of CNTY-101 without lymphodepletion -
Pharmacokinetic data suggests CNTY-101 exposure may be maintained upon administration of additional cycles without lymphodepletion
due to lack of observed allo-rejection -
Company to host conference call on Monday, December 11 at 7:30 AM PT/10:30 AM ET to review ASH data including additional
clinical results from Dose Level 1 (100 million cells) and Dose Level 2 (300 million cells), as well as clinical plans for CNTY-101 in
systemic lupus erythematosus -
December 9, 2023 - 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
the presentation of initial clinical data from a single-patient case study which Century believes support the potential for a multi-dosing
strategy for CAR iNK enabled by Allo-Evasion edits at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition,
being held December 9-12 in San Diego. The poster, titled, "Multiple Doses of CNTY-101, an iPSC-Derived Allogeneic CD19 Targeting
CAR-NK Product, are Safe and Result in Tumor Microenvironment Changes Associated with Response: A Case Study", is available on
the Scientific Resources page of the Company's website.
"We are thrilled that the initial clinical
evidence for CNTY-101 provides support for the potential for Allo-Evasion to enable a multi-dosing regimen without the need for
continued lymphodepletion. This is highly encouraging in advancing our goal to increase persistence of the cells during the treatment
period and potentially lead to deeper and more durable responses," said Brent Pfeiffenberger, Pharm.D., Chief Executive Officer
of Century Therapeutics. "We look forward to advancing the study at both higher and more frequent doses of CNTY-101, and plan to
present additional clinical data in mid-2024."
the first cell therapy product candidate engineered with six precision gene edits aimed at providing selectivity and persistence, CNTY-101
is positioned to potentially fill a high unmet need among heavily pretreated non-Hodgkin lymphoma patients," said Krish Patel, M.D.,
Director of Lymphoma Program, Director of Hematologic Malignancies and Cellular Therapy, Swedish Cancer Institute, Seattle. "The
encouraging initial data presented today from this patient who received low
doses of CNTY-101 exhibits signals of persistence of CNTY-101 cells out of circulation and supports testing at higher doses. I look forward
to the continuation of the study and to further investigating the full therapeutic potential of CNTY-101."
Data featured in a single-patient case study presented
at ASH involves a 63-year-old patient with relapsed/refractory (R/R) progressive follicular lymphoma previously treated with four prior
lines of therapy who was enrolled at Dose Level 1 (100 million cells). As of a data cutoff date of November 13, 2023, the patient
has received seven 28-day cycles of a single infusion of CNTY-101 at Dose Level 1. Cycles one and two included three days of lymphodepletion
(LD), whereas cycles three through seven were given with no LD. Interleukin-2 (IL-2) was administered for all cycles except for the first.
The patient maintained a complete response with a duration of six months before subsequently progressing.
Data from the single-patient case study indicated
that CNTY-101 was generally well tolerated in this patient at Dose level 1 (100 million cells). No dose-limiting toxicities, cytokine
release syndrome or immune effector cell-associated neurotoxicity syndrome were observed, and no adverse events related to treatment
with CNTY-101 were detected in this patient, to date. Additionally, no concerted changes in inflammatory cytokines and mediators associated
with cytokine release syndrome or neurotoxicity have been detected in this patient.
Following administration of two cycles with and
three cycles without LD, serum assessments from available data of the first five cycles of CNTY-101 treatment in this patient showed no
evidence of functional pre-existing or induced humoral immunogenicity against CNTY-101. Importantly, tumor microenvironment initial analyses
demonstrated a vigorous increase in T cells within 8 days of the 1st CNTY-101 cell infusion. Increases in proliferating cytotoxic
T cells and TNF and IFN -secreting cells were observed, suggestive of induction of adaptive immune responses within the tumor.
Additionally, ddPCR analysis of CNTY-101 genomic DNA and cell-free DNA from Dose Level 1 patient (n=4) samples suggest that CNTY-101 cells
were able to traffic out of circulation shortly after infusion and showed persistence in tissues for at least 3 days.
In addition to the preliminary clinical data presented
today, the Company will also present additional results from patients treated at Dose Level 1 (100 million cell dose), as well as preliminary
data from three patients treated at Dose Level 2 (300 million cell dose) during a conference call and webcast on Monday, December 11
at 7:30 AM PT/10:30 AM ET. In addition, the Company will discuss its planned Phase 1 trial, including supporting preclinical data, for
CNTY-101 in systemic lupus erythematosus, the Company's first autoimmune and inflammatory disease indication.
Conference Call and Webcast
live audio webcast and accompanying slides may be accessed through the Events & Presentations page in
the Investors section of the Company's website. Alternatively, the conference call may be accessed through the following:
those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company's website
at www.centurytx.com approximately 24 hours after the conference call and will be available for 90 days following
Century's proprietary Allo-Evasion
technology is used to engineer cell therapy product candidates with the potential to evade identification by the host immune system so
they can be dosed multiple times without rejection, enabling increased persistence of the cells during the treatment period and potentially
leading to deeper and more durable responses. More specifically, Allo-Evasion 1.0 technology incorporates three gene edits designed
to avoid recognition by patient/host CD8+ T cells, CD4+ T cells and NK cells. Knockout of beta-2-microglobulin or 2m, designed to
prevent CD8+ T cell recognition, knock-out of the Class II Major Histocompatibility Complex Transactivator, or CIITA, designed to
prevent CD4+ T cell recognition, and knock-in of the HLA-E gene, designed to enable higher expression of the HLA-E protein to prevent
killing of CNTY-101 cells by host NK cells. Allo-Evasion technology may allow the implementation of more flexible and effective
repeat dosing protocols for off-the-shelf product candidates.
Phase 1 ELiPSE-1 trial (NCT05336409) is intended to assess the safety, tolerability, pharmacokinetics, and preliminary
efficacy of CNTY-101 in adult patients with relapsed or refractory CD19-positive B-cell lymphomas. All patients will receive an initial
standard dose of conditioning chemotherapy consisting of cyclophosphamide (300 mg/m2) and fludarabine (30mg/m2) for 3 days. Schedule
A of the trial includes a single-dose escalation of CNTY-101 and subcutaneous IL-2. Schedule B will evaluate a three-dose schedule per
cycle of CNTY-101. Patients who demonstrate a clinical benefit are eligible for additional cycles of treatment with or without additional
CNTY-101 is an investigational off-the-shelf immunotherapy
product candidate that utilizes iPSC-derived natural killer (NK) cells with a CD19-directed chimeric antigen receptor (CAR) and includes
Century's core Allo-Evasion edits designed to overcome the three major pathways of host versus graft rejection - CD8+ T cells,
CD4+ T cells and NK cells. In addition, the product candidate is engineered to express IL-15 to provide homeostatic cytokine support,
which has been shown pre-clinically to improve functionality and persistence. Further, to potentially improve safety, the iNK cells were
engineered with an EGFR safety switch, and proof-of-concept studies have demonstrated that the cells can be quickly eliminated by the
administration of cetuximab, an antibody against EGFR approved by the U.S. Food and Drug Administration for certain cancers. Century is
currently assessing CNTY-101 in patients with relapsed or refractory CD19-positive B-cell lymphomas in its Phase 1 ELiPSE-1 clinical trial
and intends to initiate its second Phase 1 clinical trial assessing CNTY-101 in patients with moderate to severe systemic lupus erythematosus.
About Century Therapeutics
Therapeutics (NASDAQ: IPSC) is harnessing the power of adult stem cells to develop curative cell therapy products for cancer and autoimmune
and inflammatory diseases that we believe will allow us to overcome the limitations of first-generation cell therapies. Our genetically
engineered, iPSC-derived cell product candidates are designed to specifically target hematologic and solid tumor cancers, with a broadening
application to autoimmune and inflammatory diseases. We are leveraging our expertise in cellular reprogramming, genetic engineering,
and manufacturing to develop therapies with the potential to overcome many of the challenges inherent to cell therapy and provide a significant
advantage over existing cell therapy technologies. We believe our commitment to developing off-the-shelf cell therapies will expand patient
access and provide an unparalleled opportunity to advance the course of cancer and autoimmune and inflammatory disease care. For more
information on Century Therapeutics please visit www.centurytx.com.
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