CT-0508 / CARISMA Therap - LARVOL DELTA

CAR-macrophage therapy for HER2-overexpressing advanced solid tumors: a phase 1 trial. (PubMed, Nat Med) - P1 | "These findings demonstrate the preliminary safety, tolerability and manufacturing feasibility of CT-0508 for HER2+ tumors. ClinicalTrials.gov registration: NCT04660929 ."

Journal • P1 data • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD8 • HER-2

A Phase 1, First-in-Human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2 overexpressing solid tumors (SABCS 2024) - P1 | "The anti-HER2 CAR-Macrophage cell therapy product, CT-0508, was evaluated in a Phase 1 trial as a monotherapy and in combination with pembrolizumab...CT-0525 is an autologous anti-HER2 CAR-Monocyte cell therapy based on CD14+ monocytes engineered with an Ad5f35 adenoviral vector to express an anti-HER2 CAR...Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation...Nature Biotechnology. 2020; 38: 947-953"

IO biomarker • P1 data • Breast Cancer • Oncology • Solid Tumor • CD14

A phase 1, first-in-human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2 overexpressing solid tumors (SITC 2024) - "We previously developed human chimeric antigen receptor macrophages (CAR-Macrophage) and have shown potent anti-tumor activity in pre-clinical solid tumor models.1 The anti-HER2 CAR-Macrophage cell therapy product, CT-0508, was evaluated in a Phase 1 trial as a monotherapy and in combination with pembrolizumab...Methods This Phase 1, first-in-human study evaluates the preliminary safety, feasibility, tolerability, trafficking, TME activation, and initial evidence of efficacy of the investigational CAR-Monocyte product CT-0525 in pts with locally advanced unresectable/metastatic solid tumors overexpressing HER2...Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation...Correlative assessments include pre- and post-treatment biopsies and blood samples for safety, immunogenicity, pharmacokinetics, tumor trafficking, TME modulation, epitope spreading, and other translational biomarkers. Ethics Approval The..."

P1 data • Oncology • Solid Tumor • CD14

Carisma Therapeutics Reports Second Quarter 2024 Financial Results and Recent Business Highlights (PRNewswire) - P1 | N=48 | NCT04660929 | Sponsor: Carisma Therapeutics Inc | "The study met its primary endpoints of safety, tolerability and manufacturing feasibility of CT-0508. The pembrolizumab sub-study data from Regimen Level 1 and RL2 (n=6 patients) demonstrate that the combination therapy was generally well-tolerated with no dose-limiting toxicities. The best overall response was stable disease (n=1/6 patients), with corticosteroid administration and / or loss of human leukocyte antigens (HLA) expression being key limitations to potential efficacy in three of the patients who experienced progressive disease...Carisma expects to nominate a development candidate for its liver fibrosis program in the first quarter of 2025."

P1 data • Pipeline update • Fibrosis • Oncology • Solid Tumor

Carisma Therapeutics Reports Second Quarter 2024 Financial Results and Recent Business Highlights (PRNewswire) - "Second Quarter 2024 Highlights and Upcoming Milestones...GPC3+ solid tumors (CAR-M + mRNA/LNP; Moderna Collaboration)...The Company expects to present preclinical data from the development candidate at an upcoming medical meeting...Research and development expenses for the three months ended June 30, 2024 were $15.3 million....The decrease of $3.2 million was primarily due to a $2.9 million decrease in our facilities and other expenses associated with a decrease in sponsored research agreement fees, a $1.7 million decrease in direct costs associated with CT-0508, a $0.2 million decrease in direct costs associated with the pre-clinical development related to CT-1119, a $0.1 million decrease in costs associated with a reduction in pass through studies, partially offset by a $1.2 million increase in direct costs associated with pre-clinical development of CT-0525 and a $0.5 million increase in personnel costs due to severance costs related to the revised operating plan."

Commercial • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Oncology • Solid Tumor

A phase 1, first-in-human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2-overexpressing solid tumors. (ASCO 2024) - P1 | "The anti-HER2 CAR-M cell therapy product, CT-0508, is currently being evaluated in a Phase I trial as a monotherapy and in combination with pembrolizumab...Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation...CT-0525 will be administered without conditioning chemotherapy. Primary endpoints include assessment of safety and tolerability, as well as manufacture feasibility. Correlative assessments include pre- and post-treatment biopsies and blood samples for safety, immunogenicity, pharmacokinetics, tumor trafficking, TME modulation, epitope spreading, and other translational biomarkers."

P1 data • Oncology • Solid Tumor • CD14

Harnessing the Power of Engineered Macrophages to Treat Solid Tumours (IO-SUMMIT EUROPE 2024) - "The first applications of the platform, are CAR-macrophages for the treatment of solid tumours and have the potential to transform the treatment of cancer and other serious illnesses. We will present data from our ongoing Phase 1 study of an anti-HER2 CAR-Macrophage and discuss next steps for our platform and programs."

Oncology • Solid Tumor

CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Carisma Therapeutics Inc | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jul 2023 ➔ Dec 2024

Enrollment closed • Trial primary completion date • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • HER-2

Carisma Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2023 Financial Results (PRNewswire) - P1 | N=48 | NCT04660929 | Sponsor: Carisma Therapeutics Inc | "In Study 101, CT-0508...was well-tolerated, remodeled the tumor microenvironment (TME), and induced anti-tumor T cell immunity in patients with HER2 3+ tumors that achieved stable disease, despite suboptimal dose and a patient population with exhausted T cells; In late March 2024, Carisma made the decision to prioritize CT-0525, a chimeric antigen receptor monocyte (CAR-Monocyte), as the development candidate in its anti-HER2 program due to the potential for a CAR-Monocyte to have an approximately 2,000-fold increase in total exposure compared to a CAR-Macrophage. As a result, the Company believes that CT-0525 will be able to build on CT-0508's observed clinical anti-tumor activity....The Company expects to treat the first patient in the CT-0525 Phase 1 clinical study in the second quarter of 2024 and to report initial data from the study by year-end 2024."

P1 data • Pipeline update • Trial status • Oncology • Solid Tumor

Carisma Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2023 Financial Results (PRNewswire) - "Company to prioritize CT-0525 as its anti-HER2 CAR-M product candidate and will cease further development of CT-0508...The Company has also enrolled six patients in a Study 101 substudy evaluating the co-administration of CT-0508 and pembrolizumab, a programmed cell death protein 1 (PD-1) checkpoint inhibitor, evaluating the safety and tolerability of the co-administration, along with several customary secondary endpoints; While the Company will continue all study operations for subjects enrolled in Study 101, it plans to stop recruitment of new patients into the study and its substudies, and expects to report data from the substudy evaluating the co-administration of CT-0508 and pembrolizumab in the second quarter of 2024....The Company has elected to pause further development of CT-1119 as part of its reprioritization plan, pending additional financing."

Discontinued • Enrollment status • P1 data • Oncology • Solid Tumor

Carisma Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2023 Financial Results (PRNewswire) - "The increase of $17.5 million year-over-year was primarily due to a $8.4 million increase in direct costs associated with pre-clinical development of CT-0525, a $4.4 million increase in personnel costs due to growth in research and development employee headcount, a $2.7 million increase in the Company's facilities and other expenses resulting from increased laboratory space and laboratory supplies from expanded clinical and pre-clinical work, a $1.3 million increase due to costs associated with growth and expansion of pre-clinical activities towards submission of an IND for CT-0525, and a $0.9 million increase in direct costs associated with the pre-clinical development related to CT-1119, partially offset by a $0.2 million decrease in direct costs associated with CT-0508. The Company expects its research and development expenses to decrease in 2024 as it implements the revised operating plan, including a reduction in workforce, prioritization of CT-0525..."

Commercial • Oncology • Solid Tumor

Harnessing the Power of Engineered Macrophages to Treat Solid Tumours (IO-SUMMIT EUROPE 2024) - "The first applications of the platform, are CAR-macrophages for the treatment of solid tumours and have the potential to transform the treatment of cancer and other serious illnesses. We will present data from our ongoing Phase 1 study of an anti-HER2 CAR-Macrophage and discuss next steps for our platform and programs."

Oncology • Solid Tumor

Translational insights from a phase 1, first-in-human (FIH) clinical trial of the anti-HER2 CAR macrophage CT-0508 in participants with HER2 positive metastatic breast cancer and other HER2 overexpressing solid tumors. (SABCS 2023) - P1 | "CT-0508 was feasible to manufacture and had acceptable safety and tolerability. Early correlative data demonstrate trafficking, TME modulation, and induction of anti-tumor T cell immunity in participants with HER2 overexpressing solid tumors including metastatic breast cancer. The study is actively enrolling (NCT04660929)."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Carisma Therapeutics Reports Third Quarter 2023 Financial Results and Recent Business Highlights (PRNewswire) - "Upcoming Milestones: (i) The Company recently submitted an IND to the U.S. Food and Drug Administration (FDA) for CT-0525. Subject to regulatory feedback, the Company expects to treat the first patient in the first half of 2024; (ii) The Company expects to present data from the sub-study of its Phase 1 clinical trial of CT-0508 in combination with pembrolizumab in the first half of 2024; (iii) The Company is targeting an IND for CT-1119 in 2025."

IND • New trial • P1 data • Solid Tumor

A phase 1, first in human (FIH) study of autologous macrophages engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants (pts) with HER2 overexpressing solid tumors (SITC 2023) - "Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, without the need for lymphodepleting chemotherapy, followed by manufacturing and cryopreservation. Additional cohorts include: CT-0508 co-administered with pembrolizumab and CT-0508 monotherapy administered intraperitoneally in pts with peritoneal predominant disease. Correlative assessments include pre- and post-treatment biopsies and blood samples for safety (immunogenicity), trafficking (PCR, RNA scope), CT-0508 persistence in blood and tumor, target antigen engagement, TME modulation (single cell RNA sequencing), immune response (TCR sequencing) and others."

Clinical • IO biomarker • P1 data • Oncology • Solid Tumor • CD14 • CD8

Carisma to Present First Results From in vivo CAR-M Collaboration with Moderna at SITC 2023 (PRNewswire) - "Carisma Therapeutics Inc...announced that new pre-clinical data leveraging an mRNA platform to develop in-vivo chimeric antigen receptor macrophage ('CAR-M') will be presented as a late-breaking abstract (#LBA1514) at the upcoming Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting held from Wednesday, November 1, to Sunday, November 5, 2023, in San Diego, California. Two posters highlighting next-generation enhancements to Carisma's CAR-M platform, including a custom intronic shRNA approach and data on Engineered Microenvironment Converters (EM-C), will also be presented. Additionally, Carisma will share a trial-in-progress poster overviewing its Phase 1 first-in-human (FIH) study design of its lead program, CT-0508, sharing objectives and eligibility criteria."

P1 data • Preclinical • Oncology • Solid Tumor

Carisma Announces Latest Data from Phase 1 Clinical Trial of CT-0508 at 8th Annual CAR-TCR Summit (PRNewswire) - P1 | N=48 | NCT04660929 | Sponsor: Carisma Therapeutics Inc | "Carisma Therapeutics Inc...will present findings today at the 8th Annual CAR-TCR Summit from its Phase 1 clinical trial of the Company's lead product candidate, CT-0508, a human epidermal growth factor receptor 2 ('HER2') targeted chimeric antigen receptor macrophage ('CAR-M') for the treatment of advanced/metastatic HER2 overexpressing cancers. The presentation includes data from group 1 (n=9) and group 2 (n=5)....In the presentation...will present data demonstrating that, in both groups, CT-0508 was successfully manufactured for patients and that the administration of CT-0508 was well-tolerated after infusion with no dose-limiting toxicities reported to date."

P1 data • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

Carisma Therapeutics Reports Second Quarter 2023 Financial Results and Recent Business Highlights (PRNewswire) - "Anticipated Upcoming Milestones: Data from Group 2 of Phase 1 clinical trial of CT-0508 expected in the second half of 2023; Initial data from Phase 1 clinical trial of CT-0508 in combination with KEYTRUDA^® (pembrolizumab) expected in the second half of 2023; Submission of Investigational New Drug (IND) application to the U.S. Food and Drug Administration for CT-0525, Carisma's first anti-HER2 CAR-Monocyte product candidate, expected in the second half of 2023; Selection of next-generation candidate for CT-1119 expected in the first half of 2024."

IND • P1 data • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor

Carisma Therapeutics Announces First Patient Dosed in Phase 1 Study of CT-0508 in Combination with KEYTRUDA (pembrolizumab) in Patients with HER2 Overexpressing Solid Tumors (PRNewswire) - "Carisma Therapeutics Inc...announced that the first patient has been dosed in its Phase I clinical trial that will test the safety and tolerability of the Company's lead product candidate, CT-0508, a human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M) in combination with Merck's anti-PD1 therapy KEYTRUDA^® (pembrolizumab) for the treatment of HER2 overexpressing cancers....The clinical trial sub-study of CT-0508 in combination with KEYTRUDA^® has been initiated at multiple site locations in the U.S. and will enroll patients with different types of recurrent or metastatic cancers with HER2 overexpressing solid tumors."

Trial status • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor

A phase 1, first-in-human (FIH) study of autologous macrophages engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants (pts) with HER2-overexpressing solid tumors. (ASCO 2023) - P1 | "Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation...Additional cohorts include: CT-0508 co-administered with pembrolizumab and CT-0508 monotherapy administered intraperitoneally in pts with peritoneal predominant disease. Correlative assessments include pre- and post-treatment biopsies and blood samples for safety (immunogenicity), trafficking (PCR, RNA scope), CT-0508 persistence in blood and tumor, target antigen engagement, TME modulation (single cell RNA sequencing), immune response (TCR sequencing) and others. Clinical trial information: NCT04660929."

Clinical • IO biomarker • P1 data • Oncology • Solid Tumor • CD14 • CD8

CAR-M: Driving Anti-Tumor Immunity with Chimeric Antigen Receptor Macrophages (IO-SUMMIT EUROPE 2023) - "The first applications of the platform, are CAR-macrophages for the treatment of solid tumors and have the potential to transform the treatment of cancer and other serious illnesses. We will present data from our ongoing Phase 1 study of an anti-HER2 CAR-Macrophage and discuss next steps for our platform and programs."

Oncology • Solid Tumor

Carisma Therapeutics to Present at Upcoming Healthcare Industry Conferences in June 2023 (PRNewswire) - "Carisma Therapeutics...announced that the Company will present at several healthcare industry conferences in June 2023....Yara Abdou, MD, will present trials in progress poster during the...2023 American Society of Clinical Oncology (ASCO) Annual Meeting."

Trial status • Oncology • Solid Tumor

A Phase 1, First in Human (FIH) Study of Autologous Anti-HER2 Chimeric Antigen Receptor Macrophage (CAR-M) in Participants (pt) with HER2 Overexpressing Solid Tumors (ASGCT 2023) - "Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation. Additional cohorts include: CT-0508 co-administered with pembrolizumab and CT-0508 monotherapy administered intraperitoneally in pt with peritoneal predominant disease. Correlative assessments include pre- and post-treatment biopsies and blood samples for safety (immunogenicity), trafficking (qPCR, RNA in situ hybridization), CT-0508 persistence in blood and tumor, target antigen engagement, TME modulation (single cell RNA sequencing), immune response (TCR sequencing) and others."

IO biomarker • P1 data • Oncology • Solid Tumor • CD14 • CD8

Pre-Clinical Development of CT-1119, a Mesothelin-Targeting Chimeric Antigen Receptor Macrophage (ASGCT 2023) - "Previously, we developed CT-0508, a HER2-targeted CAR-M, which showed efficacy in a variety of pre-clinical models and is currently in a Phase I clinical trial for patients with HER2+ solid tumors. In addition, Ad5f35 was utilized to generate functional anti-mesothelin CAR monocytes in a rapid single day process, yielding a population of myeloid progenitors restricted to M1-macrophage differentiation. In summary, these results show that the autologous human anti-mesothelin CAR-M are a targeted cell therapy capable of inducing a multi-modal anti-tumor mechanism of action."

Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • HER-2 • MSLN • TNFA

A phase 1, first-in-human (FIH) study of autologous anti-HER2 chimeric antigen receptor macrophage (CAR-M) in participants (pt) with HER2 overexpressing solid tumors (AACR 2023) - "Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation. Additional cohorts include: CT-0508 co-administered with pembrolizumab and CT-0508 monotherapy administered intraperitoneally in pt with peritoneal predominant disease. Correlative assessments include pre- and post-treatment biopsies and blood samples for safety (immunogenicity), trafficking (qPCR, RNA in situ hybridization), CT-0508 persistence in blood and tumor, target antigen engagement, TME modulation (single cell RNA sequencing), immune response (TCR sequencing) and others."

IO biomarker • P1 data • Oncology • Solid Tumor • CD14 • CD8