huMNC2-CAR44 CAR T cells / Minerva Biotech - LARVOL DELTA

First-in-human autologous CAR-T for metastatic breast cancers to target growth factor receptor MUC1*. (ASCO 2024) - P1 | "All patients receive 300 mg/m 2 cyclophosphamide and 30 mg/m 2 fludarabine for 3 days prior to CAR-T treatment...Based on responses of initial huMNC2-CAR44 patients, inclusion criteria were amended to an Enrichment Trial Design...Based on IHC analysis of human breast cancer TMAs, the H-score restriction would include roughly 40% of breast cancers. The increased ability of huMNC2-CAR22 to kill low antigen expressing cancer cells may support future studies of patients expressing low levels of MUC1*."

IO biomarker • Metastases • P1 data • Breast Cancer • Novel Coronavirus Disease • Oncology • Solid Tumor • MUC1

Phase I first-in-human MUC1* targeted autologous CAR T cells for the treatment of metastatic breast cancers (AACR 2024) - "Purpose: First-in-human Phase I study for advanced MUC1* positive breast cancer with autologous T cells engineered to express either a chimeric antigen receptor, huMNC2-CAR44 or huMNC2-CAR22, which specifically bind to a cleaved form of MUC1 (MUC1*); evaluate the safety and preliminary anti-tumor activity. MUC1* (muk 1 star) is the growth factor receptor form of MUC1, created by cleavage and release of the N-terminal portion of MUC1. These data support a conclusion that the MUC1* antibody, huMNC2, is safe and could have high therapeutic value as a CAR T treatment for solid tumors with moderate to high antigen density. As the huMNC2-CAR22 (1XX) trial proceeds, we will assess if patient responses mirror our animal results that show that the 1XX mutations confer increased persistence, reduced exhaustion and the ability to kill tumors with low antigen density."

CAR T-Cell Therapy • IO biomarker • Metastases • P1 data • Breast Cancer • Oncology • Solid Tumor • CD8 • MUC1

1st-in-human CAR T targets MUC1 transmembrane cleavage product (SABCS 2023) - P1 | "Background: huMNC2-CAR44 and huMNC2-CAR22 are autologous CAR T cell therapies under study in an ongoing 1st-in-human trial for metastatic breast cancers (NCT04020575), being performed at City of Hope...Patients receive cyclophosphamide (300 mg/m2/day) and fludarabine (30 mg/m2/day) for 3 days prior to CAR T cell infusion...Determine MTD/RP2D. Contact: City of Hope Comprehensive Cancer Center Joanne Mortimer, MD 1-800-826-4673 Minerva18625@coh.org"

Breast Cancer • HER2 Breast Cancer • HER-2 • MUC1 • PGR

Autologous huMNC2-CAR44 or huMNC2-CAR22 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*) (clinicaltrials.gov) - P1 | N=69 | Recruiting | Sponsor: Minerva Biotechnologies Corporation | Trial primary completion date: Jan 2023 ➔ Jan 2025

Metastases • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MUC1 • PGR

Phase I/II Trial of MUC1*-CAR-1XX T Cells (ASGCT 2023) - "Results to date of huMNC2-CAR44 Phase I/II trial validate this new target, MUC1*, for cellular therapies for the treatment of solid tumor cancers. We expect huMNC2-CAR22 to be a significant improvement over its predecessor, huMNC2-CAR44, based on its greatly increased persistence, reduced CRS in human as well as its ability to kill low antigen expressing cancer cells."

P1/2 data • Breast Cancer • Oncology • Solid Tumor • CD19 • MUC1

[VIRTUAL] First-in-human CAR T targets MUC1 transmembrane cleavage product (AACR 2021) - P1 | "We incorporated one of these cancer-specific antibodies into a CAR T. huMNC2-CAR44 is in a 1st-in-human clinical trial [NCT04020575] for metastatic breast cancers, currently being performed at the Fred Hutchinson Cancer Research Center... MUC1* is the predominant form of MUC1 on cancerous tissues. Antibodies that bind to a specific conformation within the ectopic growth factor binding site in the MUC1* extra cellular domain are tumor selective. CAR T cells incorporating these antibodies are highly effective against solid tumors in animals."

P1 data • Breast Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • CD8 • MUC1

Phase I/II first-in-human CAR T–targeting MUC1 transmembrane cleavage product (MUC1*) in patients with metastatic breast cancer. (ASCO 2022) - P1 | "huMNC2-CAR44 T cells completely obliterated a variety of MUC1* positive solid tumors in NSG mice in vivo...Dose escalation is standard 3+3 design with dosing levels ranging from 3.3x10^5 to 1.0x10^7 CAR+ cells/kg, and fludarabine/cyclophosphamide lymphodepletion pre-treatment...Six (6) patients have been enrolled and five (5) patients have been treated to date. Phase II will be comprised of 3 cohorts of 15 patients in each arm of luminal, HER2+ and triple negative breast cancers for a total of 45 patients in Phase II."

Clinical • IO biomarker • P1/2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MUC1

CAR T That Targets MUC1 Transmembrane Cleavage Product Has Increased Persistence and Kills Low Antigen Cells (ASGCT 2022) - "Update: Our 1st-in-human clinical trial of anti-MUC1* CAR T, huMNC2-CAR44, for the treatment of metastatic breast cancers has validated the target, MUC1*, with early evidence of efficacy and safety, but has also highlighted the problem of CAR T cell persistence for the treatment of solid tumor cancers...Recognition of breast cancer specimens appears not to be limited by cancer sub-type. Screen-fail rate in patients, at this point, mirrors the percent positivity for MUC1* expression seen in the in vitro IHC studies."

Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MUC1

Minerva Biotechnologies Announces Opening 1st-In-Human Phase I/II Trial of a MUC1* Targeting CAR T for Metastatic Breast Cancers at City of Hope (Businesswire) - "Minerva Biotechnologies Corporation announced today that its trial of huMNC2-CAR44 T cells (NCT04020575) has now opened at City of Hope, Duarte, California. This is a first-in-human trial targeting the tumor-associated form of MUC1, called MUC1* (muk 1 star). MUC1* is the transmembrane cleavage product that is a growth factor receptor that drives growth of an estimated 93% of breast cancers. The antibody that targets Minerva’s CAR T to the tumor binds to an ectopic site that is only exposed after cleavage and release of the tandem repeat domain."

Trial status • Breast Cancer • Oncology • Solid Tumor

Autologous huMNC2-CAR44 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*) (clinicaltrials.gov) - P1; N=69; Recruiting; Sponsor: Minerva Biotechnologies Corporation; Active, not recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MRI • MUC1 • PGR

[VIRTUAL] Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor, huMNC2-CAR44 specific for a cleaved form of MUC1 (MUC1*). (ASCO 2021) - P1 | "Lymphodepletion with cyclophosphamide and fludarabine is followed by infusion of huMNC2-CAR44 CAR-T cells in escalating doses (3.3 x 105 CAR+ T cells/kg – 1 x 107 CAR+ T cells/kg) . Study is open to screening and enrollment in dose escalation . Up to 69 patients may be enrolled in dose escalation and expansion phases."

IO biomarker • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Infectious Disease • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD19 • CD4 • CD8 • HER-2 • MUC1

Autologous huMNC2-CAR44 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*) (clinicaltrials.gov) - P1; N=69; Active, not recruiting; Sponsor: Minerva Biotechnologies Corporation; Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MRI • MUC1 • PGR

[VIRTUAL] Minerva Biotechnologies (BIO 2021) - P1 | "huMNC2-CAR44 T cells are in a 1st-in-human Phase I/II trial for metastatic breast cancers (NCT04020575) at the Fred Hutchinson/Bezos Immunotherapy Clinic; trial is now expanding to City of Hope and the Barbara Ann Karmanos Cancer Institute...Pipeline includes antibody against the onco-embryonic growth factor and a small molecule. Both show robust inhibition/prevention of metastasis in animals."

Breast Cancer • Oncology • Solid Tumor

Autologous huMNC2-CAR44 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*) (clinicaltrials.gov) - P1; N=69; Recruiting; Sponsor: Minerva Biotechnologies Corporation; Trial completion date: Sep 2023 ➔ Jan 2035; Initiation date: Sep 2019 ➔ Jan 2020; Trial primary completion date: Sep 2022 ➔ Jan 2023

Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MUC1

Autologous huMNC2-CAR44 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*) (clinicaltrials.gov) - P1; N=69; Not yet recruiting; Sponsor: Minerva Biotechnologies Corporation

New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MUC1

Autologous huMNC2-CAR44 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*) (clinicaltrials.gov) - P1; N=69; Recruiting; Sponsor: Minerva Biotechnologies Corporation; Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MUC1

Minerva Biotechnologies Announces License Agreement with Memorial Sloan Kettering Cancer Center for 1XX Technology (Businesswire) - "Minerva Biotechnologies (Minerva) today announced that it has licensed from Memorial Sloan Kettering Cancer Center (MSK) '1XX' technology for use with Minerva’s proprietary anti-MUC1* antibodies to increase CAR T cell persistence in patients...Minerva is currently in a first-in-human clinical trial for metastatic breast cancers with a CAR T (huMNC2-CAR44) targeting a cleaved form of MUC1 called MUC1* (NCT04020575)....Minerva will gain non-exclusive access to two of MSK's innovative CAR T technologies, including the 1XX CAR T cell signaling construct, whose activation potential more closely resembles that of naturally occurring T cells."

Licensing / partnership • Breast Cancer • Oncology