Metabolism of new drug modalities research advances - 2025 year in review.

New drug modalities (NDMs) continue to redefine the pharmaceutical landscape by addressing "undruggable" targets and providing innovative therapeutics for various diseases. This third annual review summarizes 15 selected publications from 2025 that advance our understanding of NDM metabolism. We focus on four major categories: (1) PROTACs and molecular glues, with an emphasis on biotransformation and chiral stability; (2) Oligonucleotide therapeutics, including in vitro and in vivo metabolism of oligonucleotides as well as a workflow for metabolite identification; (3) Macrocyclic peptides, highlighting throughput enhancements and leader-independent cyclization; and (4) Conjugated drugs, encompassing antibody-drug conjugates (ADCs) and novel Fc-fusion proteins. This collection provides critical insights into metabolism, tissue distribution, and analytical innovations intended to accelerate the transition of these complex modalities from discovery to clinical application.