#China #Shanghai #Drug Discovery #Viva Biotech #Integrated Screening

Navigating the Complexities of Drug Discovery

On May 20, 2026, Viva Biotech conducted a highly informative webinar titled 'Managing Complexity in Modern Drug Discovery: A Practical Approach to Integrated Screening Chemistry.' The event featured distinguished speakers, including Dr. Bing Xia, the Vice President and Head of Early Discovery Platforms, and Dr. Tim Dwight, Senior Director of Medicinal Chemistry Business Development. Moderated by Victoria Ouroutzoglou, Associate Director of Business Development at Viva Biotech, the discussion centered on enhancing scientific rigor in the early stages of drug development.

Hit Identification: Target Context is Key

Dr. Bing Xia opened the discussion by emphasizing the critical role of target context in the hit identification process. He asserted that hit identification is not a one-size-fits-all approach; rather, it must adapt based on various factors such as biological validation, tractability, assay readiness, structural data, protein availability, resource constraints, and the prevailing intellectual property landscape. He elaborated on different strategies based on the availability of quality structural data, suggesting that fragment-based drug discovery and virtual screening could offer efficient entry points in cases where such information is accessible.

For scenarios where reliable functional or cellular assays are present, high-throughput screening (HTS) remains a formidable method for evaluating biological activity across vast compound libraries. In contrast, more intricate targets could benefit from affinity-based techniques such as DNA-encoded libraries (DEL), automated surface plasmon resonance (ASMS), or surface plasmon resonance (SPR) techniques to ascertain early druggability, especially when challenges in protein availability or assay readiness arise.

A standout feature of Viva Biotech is its V-DEL-facilitated target triage method, integrating outcomes from DEL screening, protein science expertise, quality control, and conformational state assessments, powered by the AI-driven V-DEL Friendly Index. This multifaceted approach aims to rank and prioritize targets or constructs efficiently, determining whether small molecules or linear/cyclic peptides are viable candidates, especially for pioneering or under-explored targets.

A Comprehensive Validation Process for Hits

Dr. Xia pointed out that primary screening results merely represent the inception of the hit validation journey. To confidently progress with a hit, a robust validation framework must be employed, incorporating checks for purity, dose-response confirmation, orthogonal assays, selectivity assessments, cytotoxicity evaluations, and biophysical binding studies. This rigorous validation process is paramount in differentiating actionable hits from false positives and nonspecific binders.

The internal resource of 'promiscuous frequent hits' developed at Viva Biotech serves as a crucial tool. Built from accumulated screening experiences, this dataset, which anonymizes target names, aids in making informed triage decisions and minimizes the chances of advancing potentially misleading hits through various screening efforts.

Design-Make-Test-Analyze (DMTA) Cycles

Upon successful hit validation, the Design-Make-Test-Analyze (DMTA) cycle emerges as a pivotal operational framework for advancing drug candidates. Dr. Tim Dwight emphasized the necessity of synchronized collaboration across various disciplines, including medicinal chemistry, biology, and project teams. These cycles typically follow a weekly rhythm to stay in sync with primary assay workflows, facilitating the generation of new hypotheses, refining designs, and selecting prioritized compounds.

Technologies and methodologies such as structure-based design, ligand-centric structure-activity relationship (SAR) analysis, molecular descriptors, free energy perturbation (FEP), molecular dynamics (MD) simulations, and AI/ML modeling play significant roles in enhancing compound prioritization. The aim is not merely to conjure ideas in isolation, but to rigorously test defined hypotheses to ascertain the most promising directions for development.

Dr. Dwight also noted that the scale of chemical modifications shifts with the program's evolution. During the hit-to-lead transition, extensive scaffold or functional group modifications may be crucial for mitigating liabilities and exploring alternative compounds, whereas lead optimization focuses more on small SAR-driven alterations to enhance potency, selectivity, and overall safety of the drug candidates.

The Essence of Integration

Viva Biotech underscores the importance of clear criteria for go-no-go decisions, ensuring that programs do not proceed without sufficient substantiation of efficacy, tractability, or safety. Factors such as assay enablement, protein construct quality, in vivo efficacy, therapeutic index considerations, and cross-species PK profiles are pivotal in guiding program directions.

The integration of various capabilities is not simply about co-locating different functions but revolves around strategically connecting the necessary data and expertise at each stage of the drug discovery continuum. By fostering a collaborative environment among protein science, structural biology, medicinal chemistry, and screening disciplines, Viva Biotech enhances the scientific rigor and efficiency necessary to transform initial target insights into validated hits and ultimately, lead optimization.

In conclusion, Viva Biotech's integrated approach provides a roadmap for navigating the complexities of modern drug discovery, enabling pharmaceutical partners to advance with confidence from initial ideas to validated candidates ready for further development.