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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors

Emily Capone1,2, Rossano Lattanzio1,2, Fabio Gasparri3

  • 1Department of Innovative Technologies in Medicine & Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy.

Pharmaceutics
|April 30, 2021
PubMed

Insights

A novel antibody-drug conjugate (ADC), EV20/NMS-P945, targets HER-3 expressing cancers. This therapy demonstrated significant efficacy in preclinical models and favorable safety in toxicology studies, supporting clinical development.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • HER-3 receptor is overexpressed in various malignancies.
  • HER-3 signaling impacts tumor sensitivity to therapeutics.
  • Targeting HER-3 offers a promising therapeutic strategy.

Purpose of the Study:

  • To develop and evaluate a novel antibody-drug conjugate (ADC) targeting HER-3.
  • To assess the efficacy and safety of EV20/NMS-P945 in preclinical models.

Main Methods:

  • Generation of EV20/NMS-P945 by conjugating anti-HER-3 antibody EV20 with NMS-P528 (a duocarmycin-like derivative).
  • In vitro cytotoxicity assays on tumor cell lines.
  • In vivo efficacy studies using xenograft tumor models.
  • Pharmacokinetic and toxicological assessments in non-human primates.

Main Results:

  • EV20/NMS-P945 exhibited target-dependent cytotoxicity in vitro.
  • The ADC demonstrated therapeutic activity in xenograft models of pancreatic, prostate, head and neck, gastric, ovarian cancers, and melanoma.
  • Pharmacokinetic and toxicological studies showed favorable half-life, stability, and tolerability in monkeys.

Conclusions:

  • EV20/NMS-P945 is a potent ADC targeting HER-3.
  • The compound shows promising preclinical efficacy and safety.
  • EV20/NMS-P945 warrants further clinical investigation for HER-3-expressing cancers.
Keywords:
HER-3antibody–drug conjugatesduocarmycintargeted therapy

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