Next Generation FRα-Targeting ADC Engineered to Maximize Potential Clinical Benefit for Patients with Lower FRα Expression
Potent Anti-Tumor Activity Exhibited in Ovarian Cancer and Other Tumor Types Regardless of FRα Expression Level
ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced 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. The findings were shared via poster presentation at the virtual American Association for Cancer Research (AACR) Annual Meeting II.
"Engineered to include multiple antibody and linker-payload innovations, IMGN151 targets tumors with a broad range of FRα expression," said Eric Westin, MD, Vice President of Clinical Development and Translational Sciences at ImmunoGen. "IMGN151 demonstrated enhanced anti-tumor activity in both in vitro and in vivo preclinical models, with complete regression of human tumor xenograft models induced in those with high, medium, and low levels of FRα expression. Based on these data, we look forward to exploring IMGN151 in the clinic in multiple FRα-positive epithelial malignancies, including ovarian, endometrial, triple negative breast, and non-small cell lung cancer."
IMGN151 PRECLINICAL DATA
Poster Presentation, Abstract 2890
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. 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.
Key findings include:
- The protease-cleavable linker deployed in IMGN151 improves stability and ADC exposure; as compared to IMGN853, pharmacokinetic studies in cynomolgus monkeys showed increased ADC half-life by 60 hours and conjugate exposure in vivo by 40%.
- The IMGN151 biparatopic format boosted antibody binding events and DM21 payload delivery in tumor cell lines; the increased payload delivery and greater membrane permeability of DM21 enhanced bystander killing activity.
- In vitro, IMGN151 was more active against FRα-positive cell lines, with the most pronounced effect in cells with low to medium levels of FRα.
- In vivo, IMGN151 demonstrated better activity over IMGN853 against low and medium levels of FRα, and equivalent activity to IMGN853 against FRα high tumors with lower effective dose; all tested doses were well tolerated.
Additional information can be found at www.aacr.org.
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.
ImmunoGen is developing the next generation of antibody-drug conjugates (ADCs) to improve outcomes for cancer patients. By generating targeted therapies with enhanced anti-tumor activity and favorable tolerability profiles, we aim to disrupt the progression of cancer and offer our patients more good days. We call this our commitment to "target a better now."
Learn more about who we are, what we do, and how we do it at www.immunogen.com.
FORWARD LOOKING STATEMENTS
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