On November 5, 2024 Century Therapeutics, Inc. ("Century", NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology and autoimmune disease, reported financial results and business highlights for the third quarter ended September 30, 2024 (Press release, Century Therapeutics, NOV 5, 2024, View Source [SID1234647711]).

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"Broadening our strategic focus in autoimmune indications to include idiopathic inflammatory myopathy and diffuse cutaneous systemic sclerosis will give us greater insight into the potential of CNTY-101 in an underserved therapeutic category that we believe is uniquely suited to allogeneic iNK cell therapies. Our confidence in the application of CNTY-101 in autoimmune diseases continues to be reinforced by the Phase 1 ELiPSE-1 trial in patients with r/r B-cell lymphomas where updated interim data shows increased overall response rates at higher doses and observations of deepening responses with additional cycles, alongside a continued favorable safety profile," said Brent Pfeiffenberger, Pharm.D., Chief Executive Officer of Century Therapeutics. "The advancement of our pre-clinical pipeline across multiple cell types is similarly promising, as highlighted by what we believe to be the industry-first presentation of iPSC-derived CD4+ and CD8+ CAR T cells that demonstrate αβ-like T cell function at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Building on this progress, we are conducting a strategic review of Century’s pre-clinical pipeline and expect to announce the outcome in the first quarter of 2025. We have recently refined our organizational structure to enhance ongoing efficiencies and program alignment. On behalf of everyone here at Century, I’d like to thank departing colleagues for their important contributions to building the company’s programs and technology. Supported by extended cash runway from these changes, we remain focused on execution in the period ahead and look forward to delivering our next set of potential catalysts."

Research & Development Highlights

· Consistent with Century’s commitment to expand investigation of autoimmune disease indications during the second half of 2024, the company recently amended the Phase 1 CALiPSO-1 trial of CNTY-101 (NCT06255028) and Investigational New Drug (IND) application to include evaluation of idiopathic inflammatory myopathy (IIM) and diffuse cutaneous systemic sclerosis (dcSSc). This builds upon earlier alignment with the U.S. Food and Drug Administration to expand clinical development to lupus nephritis (LN) in addition to systemic lupus erythematosus (SLE). With the implementation of this amendment, CALiPSO-1 consists of a basket protocol study design, with four arms designed to evaluate the safety and preliminary efficacy of CNTY-101. The study will enroll participants ≥17 years old with refractory B-cell-mediated autoimmune diseases following an inadequate response to at least two lines of prior standard of care immunosuppressive therapies, now including those with moderate to severe IIM and dcSSc with treatment-resistant and active disease alongside those with moderate to severe SLE with or without LN. Century has activated multiple clinical sites in the United States, and expects to activate additional sites in the coming months, with ability to enroll patients across indications. To further facilitate enrollment, the company plans to expand trial sites to select European countries. Century will provide updated timing on initial clinical data from CALiPSO-1 once a clear cadence of patient enrollment has been established across indications.

· Updated interim clinical data from Century’s ongoing Phase 1 ELiPSE-1 study evaluating CNTY-101 (NCT05336409) in relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) has shown increased overall response rates at higher doses and observations of deepening responses with additional cycles alongside a favorable safety profile, building on encouraging interim data previously presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. As of the data snapshot October 15, 2024, eight additional participants have been treated with CNTY-101 for a total of 20 participants evaluable for safety and 19 for preliminary efficacy. Treatment with CNTY-101 continued to be safe and generally well tolerated with no dose-limiting toxicities reported, no additional cases of immune effector cell-associated neurotoxicity syndrome (ICANS), and no Grade 3 or higher cytokine release syndrome (CRS). Consistent with the manageable safety profile observed to date, a majority of participants received CNTY-101 infusions in an outpatient setting. Dose level DL3B (1 billion cells in each of three weekly doses per cycle), which represents the largest single trial cohort (n=6), has shown an overall response rate (ORR) of 83% and a complete response rate (CRR) of 33%, with all participants receiving additional cycles of treatment.

A dose-dependent increase in CNTY-101 exposure was observed as evaluated by a novel pharmacokinetics cell-free DNA (cfDNA) method for detecting total body presence of CNTY-101. Preliminary cfDNA data from Schedule B (three weekly CNTY-101 infusions per cycle) showed that in cycles starting with lymphodepletion, a similar level of exposure was observed between the first and third infusion when the patients’ endogenous T and NK cells had recovered. This supports persistence upon repeated cell dosing, consistent with the anticipated protective activity of Century’s proprietary Allo-Evasion technology.

Efficient B-cell depletion was observed in all participants treated with CNTY-101 who had measurable circulating B cells at baseline. Evaluable re-emergent B cells (N=4 participants) were enriched for naive subtypes with minimal class-switched memory subsets detected. This profile in re-emergent B cells has been associated with SLE responses after CD19 cell therapy treatment, which we believe further supports application of CNTY-101 in the CALiPSO-1 study. Based on favorable safety and encouraging early efficacy data at DL3B, Century is proceeding with DL4B (3 billion cells in each of three weekly doses per cycle), and recently treated the first participant at this dose. The company expects to provide updated clinical data by mid-2025.

Further details pertaining to the ELiPSE-1 data update can be found in Century’s corporate presentation housed on the investor relations section of the website.

· Century separately announced the acceptance of five poster presentations at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held in San Diego, CA from December 7-10, 2024. The presentations include demonstration of pre-clinical function comparable to autologous T cells by allogeneic iPSC-derived CD4+ and CD8+ CAR T cells, alongside additional innovations that highlight the engineerability of the iPSC-derived immune effector cells, a core benefit of the company’s platform. These include data from advanced CAR endo-domains that improved cytotoxicity and persistence, enhanced Allo-Evasion via a novel CD300a TASR that demonstrated universal protection from NK cells, and differentiation stage specific promoters that allow for selective control of gene expression.

Business Highlights

· Following the integration of Clade Therapeutics, Century is conducting a strategic review of the pre-clinical pipeline to leverage the unique capabilities and technologies at Century towards high-value and differentiated programs. The company expects to conclude and communicate the results of this review in the first quarter of 2025. As part of this review, in October, Century implemented changes to the organization structure including elimination of overlapping technical and research capabilities to enhance ongoing efficiencies and alignment with the company’s key programs. With these changes, Century has extended expected cash runway into the second half of 2026.

· In September 2024, Century announced the appointments of Morgan Conn, Ph.D., as Chief Financial Officer and Chad Cowan, Ph.D., as Chief Scientific Officer. The company also announced the transition of Hy Levitsky, M.D., President of Research and Development, from operational duties to serve as an advisor to Century.

Third Quarter 2024 Financial Results

· Cash Position: Cash, cash equivalents, and marketable securities were $244.7 million as of September 30, 2024, as compared to $261.8 million as of December 31, 2023. Net cash used in operations was $85.9 million for the nine months ended September 30, 2024, compared to net cash used in operations of $62.1 million for the nine months ended September 30, 2023.

· Collaboration Revenue: Collaboration revenue generated through the company’s collaboration, option, and license agreement with Bristol-Myers Squibb was $0.8 million for the three months ended September 30, 2024, compared to $0.1 million for the same period in 2023.

· Research and Development (R&D) expenses: R&D expenses were $27.2 million for the three months ended September 30, 2024, compared to $22.8 million for the same period in 2023. The increase in R&D expenses was primarily due to progression of the ELiPSE-1 trial and start-up costs of the CALiPSO-1 trial, increased manufacturing activity for CNTY-101, and the acquisition of Clade Therapeutics.

· General and Administrative (G&A) expenses: G&A expenses were $8.4 million for the three months ended September 30, 2024, compared to $9.0 million for the same period in 2023.

· Net loss: Net loss was $31.2 million for the three months ended September 30, 2024, compared to $32.7 million for the three months ended September 30, 2023.

Financial Guidance

· The company expects full year generally accepted accounting principles (GAAP) operating expenses to be between $150 million and $160 million.

· The company estimates its cash, cash equivalents, and investments will support operations into the second half of 2026.