RNA-Engineered CAR-T Therapy Shows Durable Efficacy in Autoimmune Disease; Johnson & Johnson Licenses Novel Technology to Enhance CAR-T Cell Activity | CGT Weekly Report

▎Edited by the WuXi AppTec content team

Recently, the global cell and gene therapy (CGT) field has seen a series of advancements. Among them: Cartesian Therapeutics' RNA-manufactured CAR-T therapy (rCAR-T) Descartes-08 demonstrated durable efficacy in clinical trials for treating generalized myasthenia gravis (MG). Janssen Biotech, a subsidiary of Johnson & Johnson, reached an agreement with Simcha Therapeutics.Agreement

, will integrate Simcha's decoy-resistant interleukin-18 (DL-18) technology into selected CAR-T cell therapy candidates. This article will provide a brief introduction to some of the key advancements, for readers' reference only.

Image Source: 123RF

———✦R&DProgress✦———

◇Cartesian Therapeutics Announces 12-Month Follow-Up Data from Phase 2a Clinical Trial of Descartes-08, a B-Cell Maturation Antigen (BCMA)-Targeted CAR-T Therapy, in Patients with Myasthenia Gravis. The trial results show,At the 12-month mark of treatment, 5 out of 7 participants maintained clinically significant improvement across four MG disease rating systems. These assessments were conducted approximately 10 months after the final infusion of Descartes-08.

Descartes-08 is a potential "first-in-class" rCAR-T therapy in clinical development that targets BCMA to eliminate antibody-secreting plasma cells.Compared with traditional DNA-based CAR-T cell therapy, rCAR-T does not require chemotherapy to deplete existing lymphocytes, has predictable and controllable pharmacokinetics, and avoids the risk of genomic integration.These features are expected to make Descartes-08 safer than DNA-based cellular therapies. Descartes-08 is an individualized autologous therapy that collects cells from the patient, modifies them with RNA, and then infuses them back into the same individual.

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Indapta Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial of Allogeneic Natural Killer (NK) Cell Therapy IDP-023 for the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma

Indapta Therapeutics’ NK Cell Therapy Platform Comprises a Subset of Natural NK Cells. This subset, named g-NK cells, can significantly enhance the tumor-killing ability of monoclonal antibodies without the need for genetic engineering. The generation of g-NK cells results from epigenetic changes induced after NK cells are exposed to cytomegalovirus (CMV). Indapta’s technology platform enables the preferential expansion of g-NK cells from healthy donors to produce IDP-023. The key differentiating feature of this off-the-shelf cell therapy is that it is a cryopreservable treatment and, compared to conventional NK cells, is capable of releasing more immune-activating cytokines and tumor-killing compounds.

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Taysha Gene Therapies Announces First Pediatric Patient Dosed with TSHA-102, a Gene Therapy for Rett Syndrome, in Phase 1/2 Clinical Trial

TSHA-102 is an intrathecal injection gene therapy based on the adeno-associated virus 9 (AAV9) vector, which uses innovative regulatory technology for control.

Expression of MECP2 transgene in central nervous system (CNS) cells, preventing potential risks associated with overexpression.

◇ GC Cell, a South Korean biotechnology company, announced that its HER2-targeted CAR-NK cell therapy AB-201 has received approval from regulatory authorities in South Korea and Australia to commence clinical trials.

AB-201 demonstrated persistence of over three months in preclinical studies, indicating the potential for long-term treatment of advanced cancer.

Phase 1 clinical trial will evaluate the efficacy and safety of AB-201 in 48 patients with HER2-overexpressing breast cancer, gastric cancer, and gastroesophageal junction cancer.

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Simcha Therapeutics Announces Licensing and Option Agreement with Janssen Biotech, a Johnson & Johnson Company. Johnson & Johnson to Incorporate Simcha’s Decoy-Resistant Interleukin-18 (DR-18) Technology into Selected CAR-T Cell Therapy Candidates.

IL-18 is a key inflammatory cytokine that exerts a potent immune-stimulatory effect on tumor-infiltrating lymphocytes (TILs) and NK cells, which are crucial immune cells for anti-tumor responses.IL-18 can activate both innate and adaptive immune responses, suggesting that it may have broad activity against various types of tumors. However, despite its well-documented immune-stimulatory activity, the clinical therapeutic efficacy of IL-18 has historically been unsatisfactory.

Research led by Dr. Aaron Ring, founder of Simcha Therapeutics, has revealed the reason behind the weak anti-cancer activity of natural IL-18. Tumors often produce large amounts of IL-18 decoy signals through a molecule called IL-18 Binding Protein (IL-18BP), which acts as a decoy receptor. To address this issue, Simcha Therapeutics developed ST-067, the first anti-decoy IL-18 variant, which is completely unaffected by IL-18BP and retains potent immune-stimulating effects within the tumor microenvironment. In preclinical studies, the anti-decoy IL-18 demonstrated robust anti-tumor activity, both as a monotherapy and in combination with immune checkpoint inhibitors such as anti-PD-1 antibodies.

◇Solid Biosciences Announces Completion of $109 Million FinancingThe funds will be used to advance the development of existing pipelines and other corporate operational activities. Solid Biosciences is committed to developing gene therapies for neuromuscular and cardiac diseases. In the R&D pipeline, SGT-003 is a gene therapy for treating Duchenne Muscular Dystrophy (DMD), AVB-401 is for treating BAG3-mediated dilated cardiomyopathy, and AVB-202-TT is for treating Friedreich's Ataxia.

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TG Therapeutics Announces Agreement with Precision BioSciences to Obtain Global Development Rights for Precision’s CD19-Targeted CAR-T Cell Therapy, Azercabtagene Aapreleucel (Azer-Cel), for the Treatment of Autoimmune Diseases and Other Non-Oncology Indications

Azer-cel is an off-the-shelf CAR-T therapy. TG Therapeutics plans to evaluate its efficacy in multiple autoimmune indications and expects to submit an IND application by mid-2024.

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