Global Landscape of CAR-M Therapies: In Vivo CAR-M and Autoimmune Indications Emerge as New Trends

November 11, 2023 / eMedClub News /--RecentlyDay, Carisma Therapeutics reported as of this quarterSeptember 202330th DayTheFinancial Status, and emphasizedRecent Business UpdatesIn the third quarter, Carisma's CAR-M program achieved several key advancements and demonstratedPhase 1 Clinical Study of CT-0508、The Unique Design of CT-1119AndCollaborate with Moderna to Develop In Vivo CARClinical Pre-work Data of -MCarisma will continue to developPipeline CT-0508 and CT-0525 Targeting HER2 Overexpression Tumors, further validating Carisma's world-class engineered macrophage platform.

CT-0508 is aHER2-Targeted CAR-M Cell Therapy for the Treatment of Relapsed/Refractory HER2-Overexpressing Solid TumorsCarisma Therapeutics presented the latest results of the Phase 1 clinical trial for its lead pipeline CT-0508 at the 8th Annual CAR-TCR Summit, including data from Group 1 (n=9) and Group 2 (n=5).Supports the mechanism of action of CAR-M, demonstrating the correlation between biomarkers and best overall response.Through a multi-day infusion regimen (Group 1) or through a single-day high-dose infusion (Group 2), where the results of Group 1 indicateCT-0508 Remodels and Activates the Tumor Microenvironment and Stimulates Anti-Tumor T Cell Immunity, the number of exhausted CD8+T cells increased after treatment,The results support the ongoing combination study with K drug.. Both groups showed that CT-0508Well Tolerated, no dose-limiting toxicity has been reported to date.

▲CT-0508 Structure Source: Carisma Therapeutics, Inc. official website

➤Recommended Reading:Infusion within 7 days! Carisma Therapeutics announces Phase 1 data of CAR-M therapy, with new progress in 4 companies in China

CT-1119 is aMSLN-Targeted Chimeric Antigen Receptor CAR-M Therapy, currently in the preclinical research stage. CT-1119 will include two key enhancements: demonstrated in preclinical studies,The next-generation CAR can significantly enhance tumor killing and cytokine release, and combines SIRPα knockdown to overcome the CD47 immune checkpoint.SIRPα knockout was achieved using Carisma's proprietary intronic shRNA platform, which canUsing a Single Vector for CAR Delivery and Gene Knockout. The goal of the company isSubmit a new drug research application (IND) for CT-1119 in 2025.

Recently, Carisma Therapeutics inThe 38thAt the Annual Meeting of the Society for Immunotherapy of Cancer (SITC), new findings from its first collaboration with Moderna were presented. The collaboration aims toCombine Carisma's Chimeric Antigen Receptor Macrophage (CAR-M) platform with Moderna's mRNA and Lipid Nanoparticle (LNP) technology to generate and develop in vivo CAR-M therapies.

At the SITC conference, Carisma delivered an oral presentation titled “In Vivo CAR-M: Redirecting Endogenous Myeloid Cells with mRNA for Cancer Immunotherapy"Displayed inPreclinical Proof-of-Concept Data for the Feasibility, Tolerability, and Early Efficacy of mRNA/LNP In Vivo CAR-M Therapy, successfully utilizing mRNA/LNP to redirect endogenous bone marrow cells against tumor-associated antigens. This novel approach to cancer immunotherapy provides aReady-made solutions, which could potentially increase the accessibility of CAR-based treatments andBecome the foundation for up to 12 oncology programs co-developed by Carisma and Moderna.

➤Recommended Reading:Not Just CAR-T, mRNA In Vivo Production of CAR-M Technology Debuts

Carisma Therapeutics, Inc. recently submitted the IND for CT-0525 to the U.S. FDA. CT-0525 is a HER2-targeted chimeric antigen receptor monocyte therapy.Based on feedback from regulatory authorities, the company expects to treat the first patient in the first half of 2024.

Moreover, the company also expects to do so in the first half of 2024.Submission of Sub-Study Data from the Phase 1 Clinical Trial of CT-0508 in Combination with Pembrolizumab. At the same time, alsoProvide preclinical proof-of-concept data for its initial plan in the field of liver fibrosis outside of oncology.

R&D expenses for the third quarter of 2023 were $19.6 million, an increase of 4 million US dollars compared to 2022, of whichNearly 3/4 of the increase is allocated for the preclinical development of CT-0525.As of September 30, 2023, Carisma Therapeutics' cash, cash equivalents, and marketable securities were$94.1 million, although it was $23 million less than at the end of the second quarter, but alsoSufficient to sustain Carisma's planned operations until the first quarter of 2025.

September 12, 2023Myeloid Therapeutics Completes First Patient Dosing of MT-302 in Phase 1 Study for Advanced or Metastatic Epithelial TumorsMT-302 is amRNA Therapy Targeting TROP2, which uses LNP to specifically express TROP2-targeted CAR in myeloid cells, thereby activating the anti-cancer activity of myeloid cells. Myeloid's approach focuses onProgramming immune cells with ready-made mRNA encoding CAR technology in vivo.In preclinical models, treatment with MT-302 has demonstrated single-agent activity, confirming the ability to reprogram myeloid cells in the absence of T cells.

➤Recommended Reading:First Patient Dosed with LNP-mRNA In Vivo Cell Therapy, Overcoming Solid Tumors Beyond CAR-T, Produced in Just 1 Day

In May 2023, Myeloid announced that it hadCompleted $73 Million Series A2 Financing, The funds will be used to support the research and development of cell therapies.MT-101(It is the companymRNA-Engineered CD5-Targeting CAR Monocyte Therapy CAR-M, has completed the first patient dosing in a Phase 1/2 clinical trial for the treatment of relapsed/refractory peripheral T-cell lymphoma (PTCL)) and the development of MT-302. Previously, the companyCompleted a $50 million Series A financing round in January 2021 and came out of stealth mode, with a total Series A financing amount of $123 million.(Approximately 870 million RMB).

Inceptor Bio, founded in 2020, is committed to developing a diversified next-generation cell and gene therapy platform, including CAR-T, CAR-M, and CAR-NK/NKT, among others.In 2022, Inceptor officially signed a licensing agreement with the University of California, Santa Barbara (UCSB) for the CAR-Macrophage (CAR-M) platform., accelerating the company's research path in refractory cancer. In June 2021, Inceptor Bio had raised $26 million in seed funding.

Thunder Biotech is a spin-off company from Brigham Young University, founded based on MOTO-CAR® technology.MOTO-CAR® can restore TAMs to the M1 tumor-killing state, recruit natural T-cell responses, and activate T cells to destroy tumors.In addition, when activated by MOTO-CAR®, TCells will provide the body with a memory response that can prevent tumor recurrence.

Based on this technology, Thunder has developed multiple pipelines,Currently, the fastest-developing drug targets mesothelin, followed by CAR-M drugs targeting HER2.. It has been previously proven through in vitro experiments,CAR-M targeting mesothelin can shrink tumors in mouse models of triple-negative breast cancer.

October 24, 2023CellOrigin's CAR-M product SY001 cell injection completes first patient dosing, marking the first CAR-M macrophage product clinical trial officially launched in China., aimed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of SY001 in late-stage solid tumor subjects through a single-center, single-arm, dose-escalation study. To date, the clinical research on SY001 injection has yielded preliminary data: all patientsGood safety and tolerability, no dose-limiting toxicity (DLT) was observed, and there were no instances of cytokine storm or related syndromes caused by it.Demonstrated Excellent Safety of Macrophage Immunocyte Therapy。

September 21,Carisma Therapeutics Announces Completion of New Round of Financing Worth Tens of Millions of RMBThis round of financing was led by Zijin Port Capital, with Yuhang State Investment Group participating. The funds will be used to advance the company's next-generation cell therapy drug pipeline into the clinical development stage.

➤Recommended Reading:CellOrigin Completes Tens of Millions in Financing to Advance Clinical Development of iPSC-Derived CAR-M Therapies

At the end of last year,CellOrigin and NeoX Biotech Sign R&D Technology Cooperation Agreement to Develop CAR-M Immune Cells with Specific Tumor Cell Targeting Using mRNA-LNP Technology, and to conduct functional verification of it in vitro and in vivo cell and animal models, with the aim of jointly developing novel therapeutic approaches for solid tumors.

➤Recommended Reading:New SynBio Collaborates with Carisma Therapeutics to Generate CAR-M In Vivo Using mRNA

On October 27, the company Yu Mai Cell independently developedThe CAR-M product MAC001 injection targeting HER2 has completed the first subject dosing.This is an investigator-initiated, single-center, single-arm, dose-escalation clinical study aimed at evaluating the safety, tolerability, and efficacy of MAC-001 injection in treating patients with HER2-positive advanced gastric cancer. As of now,The first subject is in good condition, and no related toxic side effects such as cytokine release storm have been observed so far. The recruitment of subjects for this clinical study is still ongoing.。

➤Recommended Reading:Yuanmai Cell Launches the First Clinical Study of CAR-M Therapeutic Product Targeting Solid Tumors

On September 21, 2023, Kunshi Biotech, Nanjing Drum Tower Hospital, and the Cell Therapy Drug Research Institute of Jiangsu Industrial Technology Research Institute signed an agreement, bringing together their strengths in a tripartite collaboration.Strategic Clinical Collaboration on CAR-M Targeted Therapy for Autoimmune Diseases。This strategic cooperation,Marks the first time that macrophage drugs have entered the field of treating autoimmune diseases globally., bringing new hope for the treatment of autoimmune diseases.In May 2023, Kunshi Bio, a company within BioBAY Park, announced that its submission ofClinical Research on Chimeric Antigen Receptor Macrophages (CAR-M) for the Treatment of Relapsed, Refractory Ovarian Cancer, passed the ethical review of the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University, and obtained the ethical approval,Approved to Conduct Investigator-Initiated Clinical Trials (IIT)。The approval of this project marks that KUNWU Bio's CAR-M pipeline has officially entered the clinical research stage, with the hope of successfully launching two innovative drugs within 5-6 years.In April this year, Kunshi Biotech officially opened in Suzhou Industrial Park.Kunshi Biotech focuses on the development and clinical application of macrophage-based drugs for the treatment of solid tumors.ItsBuildEstablished the "24H-CAR" technology platform, which can complete the preparation of CAR-M on the same day.

In July this year,School of Life Science and Technology, Xidian UniversityAssociate Professor Ning Pengbo's Team JointlyShaanxi Jushi Kangji Biotechnology Co., Ltd.，A "uPA scavenger"-type macrophage (uPAR-MΦ) was constructed using gene reprogramming and loaded with poly(lactic-co-glycolic acid)-encapsulated chemotherapy drug gemcitabine (GEM@PLGA), providing a genetically engineered macrophage-based live-cell drug platform for treating cancer metastasis.The research findings were published in the international authoritative academic journal "Advanced Healthcare Materials".