▎Edited by the WuXi AppTec content team

Recently, the global cell and gene therapy (CGT) field has seen a series of advancements. The chimeric antigen receptor (CAR) T-cell immunotherapy product, Purti-lun-sai Injection, developed for CD19-positive B-cell-derived malignant hematological diseases, has received priority review status and is expected to be approved for accelerated market entry in China. In a Phase 1 clinical trial targeting pediatric and adolescent patients with B-cell acute lymphoblastic leukemia (B-ALL), all nine patients achieved complete remission (CR). Roche has invested nearly $2 billion in Alzheimer's disease gene therapy, acquiring Sangamo Therapeutics' new vector STAC-BBB, which has strong blood-brain barrier penetration capabilities. This article will briefly introduce some of these key developments for readers' reference.

Image Source: 123RF

———✦Research Progress✦———

◇ T-Maximum Pharmaceutical announced the progress of its allogeneic CAR-T cell therapy MT027 in the treatment of solid tumors.MT027 is an allogeneic CAR-T cell modified through CRISPR/Cas9 gene editing technology, targeting the tumor antigen B7H3 in recurrent glioblastoma and other solid tumors.As of March 2024, more than 50 adult patients with recurrent high-grade glioma expressing B7H3 have received MT027 treatment.Preliminary safety and efficacy results show that MT027 has good therapeutic potential.

◇ Tr1X announced that the U.S. FDA has approved the IND application for its potential "first-in-class" type 1 Treg (Tr1) cell therapy TRX103. TRX103 is designed to treat refractory Crohn's disease and is currently being evaluated in a Phase 1/2a clinical trial for its efficacy in preventing graft-versus-host disease (GvHD) and improving patient outcomes in blood cancer patients undergoing mismatched hematopoietic stem cell transplantation (HSCT).

TRX103 is generated from CD4+ cells obtained from healthy donors, which are engineered to become cells that mimic the function of Tr1 cells and are referred to as TRX cells.TRX103 possesses the unique characteristics of Tr1 cells, including the ability to migrate to inflamed tissues and lymph nodes, reduce inflammatory cytokines, control harmful T-cell responses, and induce immune tolerance.Unlike other cell therapies, TRX103 is designed to treat autoimmune diseases with fewer side effects and may not require lymphodepletion.These cells are naturally protected from immune system attacks, enhancing their persistence and minimizing potential dangerous immune reactions.Tr1X is developing TRX103 for the treatment of various immune and inflammatory diseases. Multiple preclinical studies have shown that TRX103 has good tolerability and efficacy, with the potential to reset the immune system to a healthy state.

◇ The official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) of China announced that the new drug application for Pucilcelles Injection (pCAR-19B autologous infusion preparation) developed by Chongqing Precision Biotech is proposed.Included in Priority Review, for the treatment of patients aged 3 to 21 with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia. This means that this innovative CAR-T therapy is expected to be approved for marketing in China at an accelerated pace.

Pucelun Injection, independently developed by Precision Biologics, is a CAR-T cell immunotherapy product designed for the treatment of malignant hematological diseases originating from CD19-positive B cells.Data from a Phase 1 clinical trial previously published by Precision Biologics showed,All 9 pediatric and adolescent B-ALL patients enrolled achieved CR, with an overall response rate of 100%.Moreover, minimal residual disease was negative for the first time in patients who achieved CR, and the overall safety and tolerability were good.

◇ Correct Sequence Bio announced that its gene-editing therapy CS-101 for severe β-thalassemia, developed in collaboration with the First Affiliated Hospital of Guangxi Medical University, successfully treated a foreign patient in clinical research.The patient has been free of transfusion dependence for more than two months, with a stable total hemoglobin concentration above 120 g/L, and has returned to normal life.So far, multiple patients with β-thalassemia have been able to摆脱输血依赖 after being treated with CS-101.Two of the patients have been free from transfusion dependence for more than 6 months, with the longest being over 8 months.

According to the press release,CS-101 collects autologous hematopoietic stem cells from patients and utilizes the highly precise deformable base editor tBE (transformer Base Editor) to perform accurate base editing on the HBG1/2 promoter region, simulating the naturally occurring beneficial base mutations found in healthy populations. This reactivates the expression of γ-globin, thereby restoring the oxygen-carrying function of hemoglobin.The edited hematopoietic stem cells are infused back into the patient's body, aiming to increase the patient's hemoglobin concentration to a healthy level and completely eliminate the need for blood transfusions. This therapy has a short preparation cycle, requiring only a few weeks from preparation to infusion treatment. Additionally, the tBE technology does not cause DNA double-strand breaks, effectively avoiding risks such as large DNA fragment loss, chromosomal translocations, and off-target mutations. Meanwhile, the edited target can efficiently activate fetal hemoglobin expression, enabling rapid hematopoietic reconstitution in patients.

◇ According to the public announcement on the CDE official website, the Class 1 new drug SYS6020 Injection submitted by Zhejiang Pharma Group Zhongqi PharmaceuticalApproved for Clinical UseIntended for use in refractory active systemic lupus erythematosus. Public information shows,SYS6020 is an mRNA-lipid nanoparticle (LNP)-based CAR-T cell injection.It is also the first cell therapy candidate in Shiyao Group's pipeline. According to Shiyao Group's press release,SYS6020 expresses a CAR that specifically recognizes the BCMA antigen, thereby targeting and eliminating BCMA-positive cells in patients to achieve the therapeutic purpose.In June this year, SYS6020 was first introduced in China.Approved for Clinical Use, intended for the development of treatment for relapsed or refractory multiple myeloma.

◇ CDE official website announcement: Dingsheng Peptide Source Biotechnology T Cell Receptor (TCR) T cell therapy product DCTY1102 injectionApproved for Clinical Use, intended for the treatment ofKRASPatients with advanced solid tumors who are G12D mutation-positive and have the HLA-A 11:01 genotype.

———✦Financing, Cooperation, M&A✦———

Image Source: 123RF

◇ Sangamo Therapeutics announces that it has reached an agreement with Genentech, a subsidiary of Roche.Authorization AgreementDeveloping gene therapies for intravenous infusion to treat neurodegenerative diseases, including Alzheimer's disease.Genentech Obtains Development Rights for Epigenetic Inhibitors Based on Zinc Finger Proteins Targeting Tau Protein-Encoding GenesMAPTGene.Tau protein plays a crucial role in Alzheimer's disease and other tauopathies. Additionally,Genentech Obtains Rights to Use Sangamo's Proprietary Adeno-Associated Virus (AAV) Capsid STAC-BBB.This AAV capsid demonstrated a strong ability to cross the blood-brain barrier (BBB) in non-human primate models.

Under the agreement, Sangamo will be responsible for technology transfer and certain preclinical research activities, while Genentech will handle all clinical development, regulatory, manufacturing, and commercialization activities. Sangamo will receive a near-term payment of $50 million and is eligible for up to $1.9 billion in development and commercialization milestone payments.

◇ Outpace Bio Announces $144 Million Oversubscribed Series B Financing, Bringing Total Funding to Approximately $200 MillionThe proceeds from the financing will be used to advance the company's multiple candidate programming T-cell products into the early clinical proof-of-concept stage for the treatment of solid tumors.The company's leading project, OPB-101, is a mesothelin-specific CAR-T cell enhanced through its proprietary OUTSMART, OUTLAST, OUTSPACER, and OUTSAFE technologies. It is expected to receive IND approval in 2025 and be first used to treat patients with advanced platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Additionally,This funding will also support the company in expanding its future product lines by leveraging its plug-and-play technology platform.

This round of financing was led by RA Capital Management, with new investors including Qatar Investment Authority (QIA), Surveyor Capital, Sheatree Capital, Black Opal Ventures, Alexandria Venture Investments, and other undisclosed investors. Existing investors in Outpace, such as ARTIS Ventures, Playground Global, Bristol Myers Squibb, Abstract Ventures, Civilization Ventures, Mubadala Capital, Breton Capital Ventures, WRF Capital, and Sahsen Ventures, also participated in this financing.

◇ Shinobi Therapeutics Announces $59 Million Non-Dilutive Funding Awarded by Japan's AMED (Japan Agency for Medical Research and Development),The funding will be used to support Shinobi's lead program—the development of an induced pluripotent stem (iPS) cell-derived iPS-T cell therapy targeting GPC3+ solid tumor cancers.The company also announced an extension of its Series A financing, bringing the total financing amount to $119 million.

Shinobi Therapeutics focuses on developing novel off-the-shelf immune-evasive iPS cell-derived cell therapies.Its comprehensive immune escape technology can not only resist T-cell and innate immunity but also antibody-mediated rejection. The company's CD8 iPS-T cell platform, Katana, can rapidly expand its pipeline by introducing CAR or TCR into non-targeting iPS-T cells.

◇ Ultragenyx Pharmaceutical's subsidiary Amlogenyx has completed a $14 million seed financing round.Amlogenyx is dedicated to developing novel gene therapies for the treatment of Alzheimer's disease and other amyloid protein disorders, with its first candidate drug being a protease capable of effectively degrading the Aβ42 protein.Aβ42 protein is considered one of the main pathological features of Alzheimer's disease and a key target for many Alzheimer's disease studies and treatment developments. This seed round of financing was jointly led by GordonMD Global Investments, affiliated investors, and Ultragenyx.

◇ Huadong Medicine announced a commercial collaboration with Yimiao Shenzhou regarding its CD19-targeted autologous CAR-T candidate product, IM19 Chimeric Antigen Receptor T-Cell Injection (hereinafter referred to as “IM19 Injection”), for the Chinese market.IM19 Injection is the first CAR-T cell therapy product independently developed by Yimiao Zhongshen, and is currently undergoing clinical research in China for three indications: diffuse large B-cell lymphoma, mantle cell lymphoma, and acute B lymphoblastic leukemia.A Phase II confirmatory clinical trial for the end-line treatment of diffuse large B-cell lymphoma is expected to be completed in 2024.

According to the terms of the agreement, Yimiao Zhongshen will receive an upfront payment of 125 million RMB and is eligible to receive registration and sales milestone payments of up to 950 million RMB. Yimiao Zhongshen will continue to be responsible for the development, registration, and production of IM19 injection in mainland China.

◇ Zhenxu Bio announces completion of over 100 million RMB inSeries A+ Financing，The proceeds will further accelerate the clinical research and commercialization of its gene-editing therapy CS-101, and support the clinical translation of subsequent treatment pipelines.This round of financing was led by Shanghai Guotou Futeng Capital, with follow-up investments from existing shareholders such as Lianxin Capital, Boyu Capital, Lilly Asia Ventures, Wanwu Capital, and Sequoia China.

▲To learn more about the application of cutting-edge technologies in the biopharmaceutical industry, please long-press and scan the QR code above to access "WuXi Live Studio" and watch live discussions and exciting replays on related topics.

Copyright Statement: This article is from the content team of WuXi AppTec. Individuals are welcome to share it on their social media circles, but unauthorized reproduction by media or institutions in any form to other platforms is prohibited. For authorization to reproduce, please reply with "reprint" on the WeChat Official Account of "WuXi AppTec" to obtain reprint guidelines.