On May 15, 2020 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported preclinical data for its next generation anti-folate receptor alpha (FRα) ADC, IMGN151, which is being investigated in tumors with a broad range of FRα expression (Press release, ImmunoGen, MAY 15, 2020, View Source [SID1234558159]). The data will be shared via poster presentation at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting II being held June 22-24, 2020.
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"To address the unmet needs of additional patient populations, we sought to develop a FRα-targeting ADC active against ovarian cancer and other tumor types with a broad range of FRα expression. IMGN151 demonstrates our continued innovation in the field of ADCs, incorporating several key design elements including a novel biparatopic antibody that enhances binding with FRα and payload delivery as well as DM21, our most advanced maytansinoid derivative that, together with a peptide linker, provides improved stability and increased bystander anti-tumor activity," said Eric Westin, MD, Vice President, Clinical Development and Translational Sciences for ImmunoGen. "In preclinical models, IMGN151 showed activity not only in high FRα-expressing tumors, but also improved activity in medium and low FRα-expressing tumors, suggesting promising potential in a broad set of patients with an array of tumor types. As we continue to analyze these data, we look forward to advancing IMGN151 into preclinical development."
PRECLINICAL DATA ON IMGN151
IMGN151 comprises an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FRα, linked to a highly potent maytansinoid derivative, DM21, via a cleavable peptide linker with enhanced stability, longer half-life, and increased bystander activity. The average drug per antibody ratio is 3.5.
Key findings include:
IMGN151 activity was characterized against cell lines and xenograft models with a wide range of FRα expression and compared to mirvetuximab soravtansine (IMGN853). Cell lines and xenograft models originated from ovarian, endometrial, breast, and cervical cancer.
In tumor cells with medium and high FRα expression, IMGN151 boosted antibody binding events and payload delivery by 100% and 170%, respectively.
IMGN151 increased ADC half-life by 60 hours and conjugate exposure in vivo by 40%, as compared to IMGN853.
In vitro, IMGN151 was up to 200 times more active against four FRα-medium cell lines. IMGN151 also had better bystander killing activity in a mixed culture of target-positive and negative cells.
In vivo, IMGN151 induced complete tumor regressions of human tumor xenograft models with high, medium, and low FRα expression. All tested doses were well tolerated.
POSTER PRESENTATION
Title: "IMGN151: A Next Generation Folate Receptor Alpha Targeting Antibody Drug Conjugate Active Against Tumors with Low, Medium, and High Receptor Expression"
Day/Time: Monday, June 22, 2020 at 9:00 AM ET
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
Abstract: 2890
Additional information can be found at www.aacr.org.
ABOUT IMGN151
IMGN151 is a next-generation ADC, designed to address the unmet needs of cancer patients with tumor types expressing lower levels of folate receptor alpha (FRα). IMGN151 comprises an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FRα, linked to a highly potent maytansinoid derivative, DM21, via a cleavable peptide linker with enhanced stability, longer half-life, and increased bystander activity.