JNJ-95437446: Discovery and preclinical characterization of an amivantamab-based EGFR/MET-ADC for solid tumor indications
Presenter: Benjamin Henley, MS Session: Late-Breaking Research: Experimental and Molecular Therapeutics 4 Time: 4/22/2026 9:00:00 AM → 4/22/2026 12:00:00 PM
Authors
Benjamin Henley 1 , Linxiao Chen 1 , Megan Siani 1 , Swetha Rao 1 , Yi Fan 1 , Kristen Wiley 1 , Steve Pomerantz 1 , Shalom Goldberg 1 , Onyi Irrechukwu 1 , Simone Buraschi 1 , Suresh Kumar Swaminathan 1 , Krista Burke 1 , Tammy Bush 1 , Bethany Mattson 1 , Heather Deutsch 1 , Gerald Chu 1 , Jacalyn Clawson 1 , Wan Cheung Cheung 2 , Joshua M. Bauml 1 , Ulrike Philippar 3 , Smruthi Vijayaraghavan 1 1 Johnson & Johnson Innovative Medicine, Spring House, PA, 2 Johnson & Johnson Innovative Medicine, Cambridge, MA, 3 Johnson & Johnson Innovative Medicine, Beerse, Belgium
Abstract
JNJ-95437446 is a potential best-in-class EGFR/MET bispecific antibody drug conjugate designed to deliver a cytotoxic payload to tumor cells while leveraging the unique characteristics of amivantamab. EGFR and MET are frequently expressed in solid tumors and amivantamab has demonstrated clinical efficacy in multiple non-small cell lung cancer (NSCLC) indications and is being studied in colorectal and head & neck carcinomas. Therefore, to assess the unique characteristics of JNJ-95437446, the ADC was evaluated in preclinical models of these tumor types. JNJ-95437446 uses a dual-maleimide linker-payload CPT-113 (Hangzhou DAC Biotechnology Co., Ltd.) to retain antibody stability upon conjugation. Preclinical experiments demonstrated JNJ-95437446 retained amivantamab-like binding to EGFR and MET, induced rapid internalization, and produced potent, target-dependent cytotoxicity in vitro. Additionally, the released payload from the ADC was capable of bystander cytotoxicity. JNJ-95437446 resulted in potent efficacy, including complete tumor regressions, in preclinical cell line-derived NSCLC xenograft models of adenocarcinoma and squamous cell carcinoma, and in models resistant to amivantamab. In multi-dose GLP NHP safety assessment studies, JNJ-95437446 was well tolerated at all doses tested and pharmacokinetic analysis demonstrated favorable linker/payload stability. JNJ-95437446 is an EGFR/MET-ADC exhibiting potent in vitro cytotoxicity and in vivo anti-tumor activity while being well-tolerated in a GLP NHP toxicity study. In summary, these data support development of JNJ-95437446 in a first-in-human clinical study (NCT07107230).
Disclosure
B. Henley, Johnson & Johnson Innovative Medicine Employment. L. Chen, Johnson & Johnson Innovative Medicine Employment. M. Siani, Johnson & Johnson Innovative Medicine Employment. S. Rao, Johnson & Johnson Innovative Medicine Employment. Y. Fan, Johnson & Johnson Innovative Medicine Employment. K. Wiley, Johnson & Johnson Innovative Medicine Employment. S. Pomerantz, Johnson & Johnson Innovative Medicine Employment. S. Goldberg, Johnson & Johnson Innovative Medicine Employment. O. Irrechukwu, Johnson & Johnson Innovative Medicine Employment. S. Buraschi, Johnson & Johnson Innovative Medicine Employment. S. Swaminathan, Johnson & Johnson Innovative Medicine Employment. K. Burke, Johnson & Johnson Innovative Medicine Employment. T. Bush, Johnson & Johnson Innovative Medicine Employment. B. Mattson, Johnson & Johnson Innovative Medicine Employment. H. Deutsch, Johnson & Johnson Innovative Medicine Employment. G. Chu, Johnson & Johnson Innovative Medicine Employment. J. Clawson, Johnson & Johnson Innovative Medicine Employment. W. Cheung, Johnson & Johnson Innovative Medicine Employment. J. M. Bauml, Johnson & Johnson Innovative Medicine Employment. U. Philippar, Johnson & Johnson Innovative Medicine Employment. S. Vijayaraghavan, Johnson & Johnson Innovative Medicine Employment.
Cited in
Control: 11220 · Presentation Id: 11494 · Meeting 21436