biostudies-literatureUnknown15(9)Zheng SBiologics are increasingly being co-developed in combination or as novel constructs like bispecific antibodies (BsAbs) with the goal of targeting multiple, non-redundant mechanisms of action. Rational design of combinations and dual-targeting approaches that consider disease complexities have the potential to improve efficacy and safety, to increase duration of clinical benefit, and to minimize clinical resistance mechanisms. Here we summarize examples of BsAbs and biologic combinations that have been approved by health authorities and present drug development considerations when deciding between these two strategies. These include an understanding of target biology, nonclinical safety risks, dose optimization strategies, the regulatory framework, pharmacokinetic, immunogenicity, and bioanClinical and translational science2096-2104https://www.ebi.ac.uk/biostudies/studies/S-EPMC9468564biostudies-literatureChanging the drug development and therapeutic paradigm with biologic drug combinations and bispecifics: How to choose between these two approaches?PMC9468564Wang YMSheng JZheng SPrell RHamuro LfalseChanging the drug development and therapeutic paradigm with biologic drug combinations and bispecifics: How to choose between these two approaches?Biologics are increasingly being co-developed in combination or as novel constructs like bispecific antibodies (BsAbs) with the goal of targeting multiple, non-redundant mechanisms of action. Rational design of combinations and dual-targeting approaches that consider disease complexities have the potential to improve efficacy and safety, to increase duration of clinical benefit, and to minimize clinical resistance mechanisms. Here we summarize examples of BsAbs and biologic combinations that have been approved by health authorities and present drug development considerations when deciding between these two strategies. These include an understanding of target biology, nonclinical safety risks, dose optimization strategies, the regulatory framework, pharmacokinetic, immunogenicity, and bioan2022-01-01T00:00:00Z2022 Sep2025-04-05T10:45:27.961Z2025-04-05T10:45:27.961ZS-EPMC94685643561154510.1111/cts.13345