First Patient With Multiple Myeloma Dosed in EsoBiotec's Trial for In Vivo CAR-T ESO-T01

The first patient has been dosed in an early phase 1 investigator-initiated clinical trial (NCT06691685) taking place in China for EsoBiotec's ESO-T01, an investigational BCMA-directed in vivo chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for the treatment of relapsed/refractory multiple myeloma (MM).¹

According to EsoBiotec, this is the first time a patient has been treated with an in vivo BCMA-directed CAR-T therapy in a clinical trial. ESO-T01 is intended to reprogram patients’ own T-cells within their body via the use of EsoBiotec’s ENaBL, a third-generation immune-shielded cell specific lentiviral vector platform, and their collaborator Pregene Biopharma’s BCMA CAR-T transgene. EsoBiotec states that their approach may be able to provide the treatment at a cost 1 order of magnitude lower than the cost of ex vivo CAR-T therapy.

“ESO-T01 has the potential to offer a simplified patient journey, with several benefits over current treatments for MM that are often costly and have unfavorable side effects,” EsoBiotec CEO Jean-Pierre Latere, PhD, said in a statement.¹ “Our treatment does not require lymphodepletion, is immediately available to patients without any waiting time, and is administrated in a single intravenous dose that takes less than 10 minutes. This is why we value our collaboration with Pregene Biopharma to develop ESO-T01, as we share the common goal of making this groundbreaking treatment affordable and available to patients globally. We look forward to sharing initial clinical data in the second half of 2025.”

The multicenter, single arm, open-label trial takes the form of a dose escalation study and is expected to enroll up to 24 patients in total. The incidence and severity of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, dose-limiting toxicities, and other treatment-associated adverse events will serve as primary end points for the trial. According to the clinicaltrials.gov page, which was most recently updates on December 31, 2024, the trial is currently recruiting patients at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, in Wuhan, Hubei, China.

“Initial clinical observations with ESO-T01 indicate a favorable safety profile and promising efficacy already at the first dose level of 0.25x10⁹ transducing unit per patient, with pharmacokinetic characteristics comparable to autologous ex vivo CAR-T therapies,” principal investigator Heng MEI, PhD, MD, a professor at Union Hospital, added to the statement.¹

Notably, several other in vivo CAR-T approaches entered clinical trials last year. In July 2024, Interius BioTherapeutics’ INT2104, an investigational lentiviral vector-based gene therapy that is intended to treat B-cell malignancies through the creation of CD20-directed CAR T-cells and CAR natural killer cells in vivo, received Human Research Ethics Committee approval and clinical trial notification clearance from Australia’s Therapeutic Goods Administration.² INT2104 is specifically targeted at CD7-positive T-cells and NK cells, which it is intended to transduce with the CAR transgene in order to produce effector CAR T-cells and CAR-NK cells. Later that month, the FDA cleared an investigational new drug application for Umoja Biopharma's UB-VV111, a gene therapy product intended to create CD19-directed CAR T-cells within the body, allowing the company to go forward with a phase 1 dose escalation trial in hematologic malignancies.³ UB-VV111 is the first of Umoja’s products based on its VivoVecTM gene delivery platform, which uses third generation lentiviral vectors and a T-cell targeting and activation surface complex, to reach clinical stage development.

“The clinical success of autologous CAR-T in treating hematologic malignancies is well established,” Li Hongjian, the CEO and cofounder of Pregene Biopharma, added to the statement.¹ “With in vivo delivery, more multiple myeloma patients can benefit from CAR-T. Moreover, we anticipate expanding to therapeutic areas such as autoimmune diseases, enabling broader patient access to effective treatment. Through this collaboration, we are pioneering innovative scientific advancements that have the potential to redefine the future of cell therapy”.

REFERENCES
1. EsoBiotec doses first patient in investigator initiated trial of in vivo BCMA CAR-T candidate ESO-T01 for multiple myeloma. News release. EsoBiotec SA. January 8, 2025. Accessed January 9, 2025. https://www.esobiotec.com/esobiotec-doses-first-patient-in-investigator-initiated-trial-of-in-vivo-bcma-car-t-candidate-eso-t01-for-multiple-myeloma/
2. Interius Biotherapeutics receives HREC approval and CTN clearance from the TGA to commence a phase 1 clinical trial for its first-in-class in vivo CAR therapeutic for B cell malignancies. News release. InteriusBioTherapeutics. July 9, 2024. Accessed January 9, 2025. https://interiusbio.com/2024/07/interius-biotherapeutics-receives-hrec-approval-and-ctn-clearance-from-the-tga-to-commence-a-phase-1-clinical-trial-for-its-first-in-class-in-vivo-car-therapeutic-for-b-cell-malignancies-will-initiate/
3. Umoja Biopharma Announces FDA Clearance of IND Application for UB-VV111, a CD19 Directed in situ CAR T for Hematologic Malignancies. News release. Umoja Biopharma, Inc. July 31, 2024. Accessed January 9, 2025. https://www.umoja-biopharma.com/news/umoja-biopharma-announces-fda-clearance-of-ind-application-for-ub-vv111-a-cd19-directed-in-situ-car-t-for-hematologic-malignancies