The inaugural edition of Bioconjugation Insights features a wide variety of stakeholders from across the bioconjugation space, sharing their perspectives on recent progress, current challenges, and future directions in the field.

Confirmed contributors to this special edition include:

• Rakesh Dixit - (Cofounder, President and CSO of Regio Biosciences, CEO of Bionavigen, and CSO of Tmab Therapeutics)
• Moein Moghimi - (Professor of Pharmaceutics and Nanomedicine, School of Pharmacy, and Research Professor, Institute of Cellular Medicine, Newcastle University; and Adjoint Professor, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Denver Medical Center)
• Michelle Morrow - (CSO, Avacta Therapetics)
• Helen Bright - (CSO, Centauri Therapeutics)
• Yu-Tzu Tai - (Associate Director, ADC & Translational Research, Oxford Biotherapeutics)

• Diversifying the therapeutic uses of ADCs—what will follow the example of drugs such as Kadcyla and Adcetris?
  • Addressing the limitations of ADCs in non-cancer disease areas and identifying viable targets
    • Minimizing systemic toxicity in ADCs for chronic and autoimmune diseases
• Enhancing site-specific conjugation to minimize heterogeneity in ADCs
• Navigating IP challenges to open up opportunities in the ADC landscape
• Adoption of bi/multifunctional payloads and innovative linker chemistries for precise drug release and stability
  • Integration of bispecific approaches to target multiple pathways or diseases simultaneously
• Designing rapidly clearable ADCs and leveraging structure-activity relationships (SAR) to minimize off-target effects
• Managing geopolitical risk and harnessing dual-sourcing strategies for ADC supply chains

• Enhancing sensitivity and specificity in bioconjugates for imaging applications
• Overcoming challenges in scaling production of PET and SPECT imaging agents
• Developing more robust conjugation methods for fluorescent and luminescent probes
• Addressing biocompatibility and immune response risks in diagnostic bioconjugates 
• Solving issues of cross-reactivity and false positives in biomarker detection assays
• Troubleshooting the integration of bioconjugates into theranostics applications
• Success factors in scaling up production of radioconjugates and ensuring stability during manufacturing
• Addressing gaps in the analytical toolkit for the characterization of radioconjugates and imaging agents
• Enhancing linker chemistries in nanoparticle conjugates to allow for controlled release of imaging agents

• Identifying and addressing key gaps in regulatory/CMC guidance for oligonucleotide and peptide conjugates
• Enabling accurate characterization of non-ADC bioconjugates through standardized analytical tools (HPLC, mass spectrometry) 
• Will advancing these tools improve real-time monitoring of conjugate efficiency and degradation kinetics?
• Realizing the therapeutic potential of oligonucleotide-based conjugates in targeted medicine
• Advances in peptide-based drug delivery to overcome endosomal escape barriers 
• How and where is PEGylation being incorporated, and to what effect? (e.g., to decrease immunogenicity)
• Quantifying the clinical potential of bioconjugates for regenerative medicines and vaccine development
• Exploring the application of conjugated peptides in vaccines and chronic disease treatments to enhance immune response
• Solving regulatory hurdles for next-generation vaccine conjugates

• Enhancing stability and delivery of oligonucleotide conjugates in vivo
  • Maintaining the structural and functional integrity of the bioconjugate components during the manufacturing process
• Ensuring biocompatibility and controlled release in polymer-drug conjugates
• Addressing stability challenges in nanoparticle-based conjugates
• Tackling immunogenicity in polymer- and enzyme-conjugated therapeutics through sustained drug release
• Developing robust analytical tools for assessing stability and characterizing increasingly complex bioconjugates 
• Improving cell targeting and endosomal escape mechanisms for nanoparticle-drug conjugates

• Addressing in vivo challenges related to ADC stability to maintain therapeutic activity until reaching the target
  • Stabilizing ADCs in physiological environments while ensuring efficient payload release
• Overcoming endosomal escape inefficiencies for improved cytosolic access
• Innovating linker design to address stability, biocompatibility, and release kinetics
  • Assessing the pros and cons of traditional versus emerging ADC manufacturing processes and technologies 
• How to successfully apply click chemistry and enzymatic approaches in bioconjugate manufacturing?
• Leveraging next-generation analytical tools for enhanced ADC characterization
• Breaking new ground in antigen targeting and validation
• Optimizing drug-antibody ratio (DAR) to maximize efficacy while minimizing toxicity
• Improving dosing regimens—assessing the available tools and strategies (e.g., ADME profiling)