MCY-M11 IP / Johns Hopkins University, MaxCyte - LARVOL DELTA

[VIRTUAL] MCY-M11, a CAR-PBMC cell product transiently expressing a mesothelin targeted mRNA CAR, exhibits desirable functional and immune phenotype attributed to sustained antitumor immunity in vitro (SITC 2020) - P1 | "These phenotypic changes in cell subsets of MCY-M11 transpired with simultaneous secretion of potent immunostimulatory molecules and chemokines facilitating an extended antitumor response through epitope spreading. Conclusions We demonstrated that MCY-M11 is a unique cell product possessing a complete built-in immune cellular machinery with favorable phenotype and enhanced functions specialized in mediating an effective and long-term antitumor response."

IO Biomarker • Preclinical • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • CD27 • CD8 • MSLN • NKG2D

Single-day CAR manufacturing platform using mRNA and Flow Electroporation Technology (SITC 2019) - P1; "The CARMA one-day manufacturing process using cGMP grade mRNA has the potential to revolutionize cell therapy strategies by significantly reducing the wait time for patients receiving treatment. MCY-M11 is currently being tested in a first-in-human clinical trial for advanced epithelial ovarian cancer and peritoneal mesothelioma (ClinicalTrials.gov Identifier: NCT03608618)."

UPDATED RESULTS FROM ZUMA-4: A PHASE1/2 STUDY OF KTE-C19 CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY IN PEDIATRICAND ADOLESCENT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2017) - P1/2; "...Pediatric and adolescent patients (aged 2-21 y) with high burden R/R ALL (>25% marrow blasts), adequate renal, hepatic, pulmonary and cardiac function received 2 × 106 CAR T cells/kg after low-dose conditioning chemotherapy consisting of cyclophosphamide (900 mg/m2 once) and fludarabine (25 mg/m2/d for 3 days) (CyFlu)...All cytokine release syndrome events resolved with tocilizumab, corticosteroids, and/or siltuximab plus other supportive care with a median duration of 8.5 (range, 4–16) days...KTE-C19 after low-dose CyFlu has been tolerable and appears safe for further analysis in pediatric and adolescent patients with R/R ALL. No dose-limiting toxicities were observed with KTE-C19 at the 2 × 106 cells/kg dose in patients despite high leukemic burden. All patients receiving KTE-C19 achieved a minimal residual disease-negative remission."

Biomarker • CAR T-Cell Therapy • Clinical • P1/2 data • Acute Lymphocytic Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Modulation of CD22 Antigen Density Improves Efficacy of CD22 Chimeric Antigen Receptor (CAR) T Cells Against CD22lo B-Lineage Leukemia and Lymphoma (ASH 2017) - P1; "We further demonstrate that increased CD22 CAR affinity does not seem to improve CD22 CAR activity against CD22lo ALL. Bryostatin1-mediated CD22 modulation can improve CD22 CAR response against leukemia and lymphoma providing a potential rational combination to rescue CD22 CAR activity and remission durability."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • Biosimilar • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Indolent Lymphoma

A phase 1 study of intraperitoneal MCY-M11 therapy for women with platinum resistant high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube, or subjects with peritoneal mesothelioma with recurrence after prior chemotherapy (AACR 2019) - P1; "The study is being conducted at two centers, and the first patient was dosed in October 2018. Recruitment in dose level 1 cohort continues."

Clinical • P1 data • Gynecologic Cancers • Hematological Malignancies • Leukemia • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer

Clinical trial of P-BCMA-101 T stem cell memory (Tscm) CAR-T cells in relapsed/refractory (r/r) multiple myeloma (MM) (AACR 2018) - P1; "...Patients are apheresed to harvest T cells, then P-BCMA-101 CARTyrin T cells are manufactured and administered to patients as a single dose after a standard cyclophosphamide/fludarabine conditioning regimen.Preliminary Two heavily pretreated patients are thus far evaluable at a dose of 0.75 x 106 CARTyrin+ cells / kg... Two heavily pretreated patients are thus far evaluable at a dose of 0.75 x 106 CARTyrin+ cells / kg. P-BCMA-101 manufactured for patients were primarily Tscm, and demonstrated robust and specific in vitro killing and cytokine production against BCMA+ tumor cells. Both patients MM was BCMA+."

CAR T-Cell Therapy • Clinical • IO biomarker • Multiple Myeloma

[VIRTUAL] MCY-M11, a CAR-PBMC cell product transiently expressing a mesothelin targeted mRNA CAR, exhibits desirable functional and immune phenotype attributed to sustained antitumor immunity in vitro (SITC 2020) - P1 | "These phenotypic changes in cell subsets of MCY-M11 transpired with simultaneous secretion of potent immunostimulatory molecules and chemokines facilitating an extended antitumor response through epitope spreading. Conclusions We demonstrated that MCY-M11 is a unique cell product possessing a complete built-in immune cellular machinery with favorable phenotype and enhanced functions specialized in mediating an effective and long-term antitumor response."

IO Biomarker • Preclinical • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • CD27 • CD8 • MSLN • NKG2D

A phase 1 multicenter study evaluating KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. (ASCO 2018) - P1; "...After leukapheresis and manufacturing, pts undergo lymphodepleting chemotherapy with fludarabine (30 mg/m2/d) and cyclophosphamide (300 mg/m2/d) for 3 d followed by a single infusion of KITE-585...Key exclusion criteria include plasma cell leukemia, nonsecretory MM, active infection, a history of central nervous system involvement, active autoimmune disease, or prior allogeneic stem cell transplant. The study opened to accrual in October 2017."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Leukemia • Multiple Myeloma

A phase I study of intraperitoneal MCY-M11 Anti-mesothelin CAR for women with platinum resistant high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube, or subjects with peritoneal mesothelioma with recurrence after prior chemotherapy (ESMO 2019) - P1; "Legal entity responsible for the study: MaxCyte Inc. Funding: MaxCyte Inc."

Clinical • P1 data

[VIRTUAL] Feasibility and preliminary safety and efficacy of first-in-human intraperitoneal delivery of MCY-M11, anti-human-mesothelin CAR mRNA transfected into peripheral blood mononuclear cells, for ovarian cancer and malignant peritoneal mesothelioma. (ASCO 2020) - P1 | "Feasibility of 1-day manufacturing of MCY-M11 for ip delivery is demonstrated. Treatment has been safe. Initial SD observed in DL2 and DL3 with one-cycle infusions is encouraging and supports exploration of additional strategies such as the addition of preconditioning chemotherapy and multiple cycles to increase efficacy."

Clinical • P1 data • Cardiovascular • Gynecologic Cancers • Hematological Disorders • Immunology • Lung Cancer • Mesothelioma • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer • MSLN

Intraperitoneal MCY-M11 (Mesothelin-targeting CAR) for Treatment of Advanced Ovarian Cancer and Peritoneal Mesothelioma (clinicaltrials.gov) - P1; N=14; Terminated; Sponsor: MaxCyte, Inc.; Trial completion date: May 2022 ➔ Aug 2021; Active, not recruiting ➔ Terminated; Sponsor shift in focus

Clinical • Trial completion date • Trial termination • Fallopian Tube Cancer • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

Intraperitoneal MCY-M11 (Mesothelin-targeting CAR) for Treatment of Advanced Ovarian Cancer and Peritoneal Mesothelioma (clinicaltrials.gov) - P1; N=14; Active, not recruiting; Sponsor: MaxCyte, Inc.; Recruiting ➔ Active, not recruiting; N=27 ➔ 14

Clinical • Enrollment change • Enrollment closed • Fallopian Tube Cancer • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

"ICYMI: CARMA Cell Therapies presented at #SITC2020 about our lead anti-mesothelin CAR-PBMC #celltherapy candidate, MCY-M11." (@MaxCyte_info)

Oncology • MSLN

CARMA Cell Therapies to Share Results of In-vitro Characterization of MCY-M11 at SITC 2020 Annual Meeting (PRNewswire) - "MaxCyte, Inc...announces that its subsidiary CARMA Cell Therapies will share results of a detailed phenotypic and functional characterization of MCY-M11...at the Society for Immunotherapy of Cancer's (SITC) 35th anniversary meeting...We are encouraged by these in vitro findings, which demonstrate MCY-M11's potential to enable a long-term antitumor response."

Preclinical • Oncology

"#CARMACellTherapies™ Expands Phase I Trial of #AntiMesothelin #mRNA #CARPBMCCellTherapy #MCYM11 https://t.co/qEHJggY2zc" (@1stOncology)

Intraperitoneal MCY-M11 (Mesothelin-targeting CAR) for Treatment of Advanced Ovarian Cancer and Peritoneal Mesothelioma (clinicaltrials.gov) - P1; N=27; Recruiting; Sponsor: MaxCyte, Inc.; N=15 ➔ 27; Trial completion date: Dec 2020 ➔ May 2022

Enrollment change • Trial completion date • Fallopian Tube Cancer • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

CARMA Cell Therapies Expands Phase I Trial of Anti-Mesothelin mRNA CAR-PBMC Cell Therapy MCY-M11 (PRNewswire) - "MaxCyte, Inc…announces the expansion of subsidiary CARMA Cell Therapies' ongoing Phase I intraperitoneal delivery and dose-escalation trial of MCY-M11, its lead anti-mesothelin CAR-PBMC cell therapy candidate. The expansion will involve a new parallel cohort of patients and the initiation of two additional clinical sites. The new parallel Phase I cohort will evaluate intraperitoneal delivery of MCY-M11 at escalating doses in additional patients with relapsed/refractory ovarian cancer and malignant peritoneal mesothelioma, with the addition of a preconditioning regimen of cyclophosphamide prior to MCY-M11 infusion."

Trial status • Gynecologic Cancers • Mesothelioma • Oncology • Ovarian Cancer

High Rates of Minimal Residual Disease-Negative (MRD−) Complete Responses (CR) in Adult and Pediatric and Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL) Treated With KTE-C19 (Anti-CD19 Chimeric Antigen Receptor [CAR] T Cells): Preliminary Results of the ZUMA-3 and ZUMA-4 Trials (ASH 2016) - P1/2; "CRS and NT were successfully managed to resolution with either tocilizumab, corticosteroids, and/or siltuximab in addition to other supportive care for all 5 patients. KTE-C19 is administered at a target dose of either 1 or 2 × 106 anti-CD19 CAR T cells/kg after low-dose conditioning with fludarabine (25 mg/m2/day for 3 days) and cyclophosphamide (900 mg/m2/day [CyFlu]; Wayne ASCO 2016; Shah ESMO 2016). The administered dose of KTE-C19 after low-dose CyFlu conditioning has been tolerable and to date appears safe for further analysis in adult and pediatric patients with high leukemic burden R/R ALL. Initial results demonstrate promising efficacy, and the central manufacturing process is deemed feasible. The phase 1 portions of ZUMA-3 and ZUMA-4 are ongoing with planned expansion to phase 2."

Biomarker • Clinical • Residual disease • Acute Lymphocytic Leukemia • Biosimilar • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

"#ASCO20 SAY WHAT !!! MCY-M11, anti-human-mesothelin CAR mRNA transfected MRNA is transfected by nonviral eleectroporation-process completed <1 day ! Multiple doses and cycles !! GIVEN INTRAPERITONEALLY !! https://t.co/4MsnukEXqk @BJRimelMD #ovariancancer #mesothelioma" (@OmidHamidMD)

Gynecologic Cancers • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer

MaxCyte to share preliminary phase I data on MCY-M11 at ASCO 2020 Annual Meeting (PRNewswire) - "MaxCyte…announces that clinical data from the first three cohorts of the ongoing Phase I dose-escalation trial demonstrating safety of MCY-M11 and feasibility of one-day manufacturing will be shared at the American Society of Clinical Oncology's (ASCO) upcoming annual meeting. The ASCO20 Virtual Scientific Program will be held May 29-31, 2020…Preliminary clinical results for the trial are expected to be announced in H2 2020."

P1 data • Gynecologic Cancers • Mesothelioma • Oncology • Ovarian Cancer

MaxCyte advances phase 1 clinical trial of lead CARMA mRNA-based cell therapy to third cohort of patients (PRNewswire) - “MaxCyte…announces today that, having completed dosing of the second cohort of patients, clinical investigators have initiated dosing in the third cohort of patients of MaxCyte's Phase I clinical trial with the next higher cell dose of MCY-M11. This lead, wholly-owned, non-viral mRNA-based cell therapy candidate from MaxCyte's CARMA platform is a mesothelin-targeting chimeric antigen receptor (CAR) therapy being tested in individuals with relapsed/refractory ovarian cancer and peritoneal mesothelioma.”

Enrollment status

MaxCyte progresses phase I clinical trial of lead mRNA-based cell therapy from its Carma platform (PRNewswire) - “MaxCyte…announced today that it has initiated dosing for the second cohort of patients in its US Phase I clinical trial with MCY-M11…MCY-M11 is a mesothelin-targeting chimeric antigen receptor (CAR) therapy being tested in individuals with relapsed/refractory ovarian cancer and peritoneal mesothelioma.”

Enrollment status

Single Day CAR Manufacturing Platform Using mRNA and Flow Electroporation Technology (ASGCT 2019) - P1; "...We report here the implementation of CARMA platform to produce an anti-mesothelin scfv, modified PBMC cell therapy product, MCY-M11...The product is currently being tested in a first in human clinical trial for advanced epithelial ovarian cancer and peritoneal mesothelioma (ClinicalTrials.gov Identifier: NCT03608618). The CARMA one-day manufacturing process using cGMP mRNA has the potential to significantly transform CAR therapy strategies by providing a meaningful reduction in wait time for patients receiving treatment."