CARsgen Therapeutics has announced promising preliminary clinical data for CT0596, its allogeneic BCMA-targeted CAR-T cell therapy for patients with relapsed/refractory multiple myeloma (R/R MM). The therapy, developed using the company's proprietary THANK-u Plus™ platform, has demonstrated both favorable safety and encouraging efficacy signals in early clinical evaluation.
As of May 6, 2025, eight patients with R/R MM who had received at least three prior lines of therapy were enrolled and treated with CT0596. The therapy was administered following lymphodepletion with fludarabine (22.5-30 mg/m²) and cyclophosphamide (350-500 mg/m²).
Safety Profile Demonstrates Favorable Tolerability
The preliminary safety data from up to four months of follow-up showed no dose-limiting toxicities (DLTs). Importantly, no patients experienced Grade 3 or higher cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GVHD) – complications that have historically been concerns with CAR-T therapies. No patients discontinued treatment due to adverse events, further supporting the therapy's favorable safety profile.
Encouraging Early Efficacy Signals
Among the five patients who completed the first efficacy assessment at Week 4, three patients (60%) achieved stringent complete response/complete response (sCR/CR), and four patients (80%) achieved minimal residual disease (MRD)-negativity in the bone marrow – a critical marker of deep response in multiple myeloma.
Early efficacy data from two additional patients at Day 14 showed substantial reductions in measurable lesions by ≥92% and ≥65%, respectively. One patient had not yet reached the protocol-specified efficacy assessment timepoint.
All patients who achieved sCR/CR maintained ongoing responses throughout the follow-up period, including the first patient who completed the four-month follow-up.
"These preliminary results are quite encouraging for heavily pretreated multiple myeloma patients who have limited treatment options," said a spokesperson from CARsgen Therapeutics. "The combination of favorable safety and promising efficacy signals warrants further investigation of CT0596."
Advantages of Allogeneic Approach
CT0596 represents an important advancement in CAR-T therapy as an allogeneic ("off-the-shelf") product. Unlike autologous CAR-T therapies that require harvesting and engineering a patient's own T cells – a process that can take weeks – allogeneic CAR-T cells are derived from healthy donors, potentially offering more immediate treatment access.
The therapy demonstrated CAR-T expansion across all predefined dose levels, a critical factor for clinical efficacy. This expansion was achieved regardless of varying NKG2A expression levels on NK cells, which has been a challenge for some allogeneic approaches.
THANK-u Plus™ Platform Technology
CT0596 was developed using CARsgen's THANK-u Plus™ platform, an enhanced version of the company's proprietary THANK-uCAR® allogeneic CAR-T technology. The platform was specifically designed to address the potential impact of NKG2A expression levels on therapeutic efficacy.
Preclinical studies have shown that THANK-u Plus™ delivers superior antitumor efficacy in the presence of NK cells compared to the earlier THANK-uCAR® platform. The technology demonstrates sustained expansion regardless of varying NKG2A expression levels on NK cells and exhibits significantly improved expansion compared to its predecessor.
"The THANK-u Plus™ platform represents a significant advancement in our allogeneic CAR-T capabilities," noted the CARsgen spokesperson. "It has broad potential for developing diverse allogeneic CAR-T therapies beyond multiple myeloma."
Future Development Plans
Based on these promising preliminary results, CARsgen plans to expand the investigation of CT0596 not only in R/R MM but also in other plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells.
The company anticipates presenting detailed clinical data at upcoming scientific conferences and plans to submit an Investigational New Drug (IND) application for CT0596 in the second half of 2025.
Multiple Myeloma: A Significant Unmet Need
Multiple myeloma is a hematologic malignancy characterized by the abnormal proliferation of plasma cells in the bone marrow. Despite recent advances in treatment, R/R MM remains challenging to treat, with patients typically experiencing diminishing returns with each subsequent line of therapy.
The disease affects approximately 176,000 people worldwide, with about 34,000 new cases diagnosed annually in the United States alone. The five-year survival rate for multiple myeloma patients is approximately 55%, highlighting the significant need for new therapeutic approaches.
CARsgen's Broader Mission
CARsgen Therapeutics is focused on developing innovative CAR T-cell therapies to address unmet clinical needs in hematologic malignancies, solid tumors, and autoimmune diseases. The company has established end-to-end capabilities for CAR T-cell research and development, covering target discovery, preclinical research, clinical development, and commercial-scale production.
With CT0596 and other candidates in its pipeline, CARsgen aims to overcome challenges faced by existing CAR T-cell therapies, including improving safety profiles, enhancing efficacy in treating solid tumors, and reducing treatment costs.
The company's mission is to become a global biopharmaceutical leader providing innovative and differentiated cell therapies for patients worldwide, with the ultimate goal of making cancer and other diseases curable.
