Bridging the Gap Between Hits and Leads
After the excitement of identifying potential hits, biotech companies face the critical task of transforming these hits into viable lead compounds—a phase known as hit-to-lead (H2L) transition. This stage is fraught with complexities, requiring deep characterisation and validation to ensure that only the most promising compounds move forward.
Challenges in Hit-to-Lead Transition
- Complex Mechanisms of Action: Understanding how a compound interacts with its target and other biological systems is critical.
- Selectivity and Specificity: Ensuring the compound affects only the desired target without off-target interactions.
- Limited Resources: Biotechs may lack the in-house capabilities to conduct comprehensive studies across multiple assays.
The Stakes Are High
Advancing poor candidates can result in wasted resources, draining time and money and delaying the entire development program. Moreover, insufficient data can lead to regulatory setbacks, as agencies require robust validation for approvals. Additionally, undetected off-target effects or toxicities can pose significant safety risks in later stages, potentially leading to costly failures.
The Power of Biotech-CRO Partnerships
Engaging a CRO with a partnership mentality can make a significant difference in the hit-to-lead (H2L) phase. This collaboration offers orthogonal validation by utilizing multiple independent assays, such as biochemical and biophysical methods, to confirm target engagement and reduce false positives. Additionally, it provides access to advanced characterization techniques, including Surface Plasmon Resonance (SPR), nano Differential Scanning Fluorimetry (nanoDSF), Isothermal Titration Calorimetry (ITC), and Grating-Coupled Interferometry (GCI). The strategic guidance available through this partnership ensures that studies are designed to yield meaningful data for decision-making, encompassing aspects like kinetic and thermodynamic profiling, while also allowing for flexible collaboration that can adjust study designs as new data emerges, ensuring resources are focused where they are most needed.
As unexpected results can emerge during H2L studies, a strong partnership fosters joint problem-solving, with CRO scientists collaborating alongside the biotech team to interpret data anomalies and adjust strategies, such as identifying and mitigating assay artifacts. This relationship also allows for resource sharing, leveraging the CRO’s infrastructure to address challenges without significant delays, including rapid access to alternative assay platforms. Continuous communication further enhances this collaboration, as regular updates ensure that both parties remain aligned and can respond quickly to new information, facilitating agile project management.
Case Study
Enhancing Hit Validation Through Collaboration
A biotech company had several promising hits but lacked the resources for in-depth validation. By partnering with Arctoris our client was able to gain gain access to advanced biophysical methods to characterise binding kinetics and affinity, providing a deeper understanding of compound interactions.
They have also benefited from our customised assay development capabilities that addressed specific challenges of their target, including dealing with aggregation-prone proteins.
Last but not least we were able to provide high-quality data that allowed our biotech client to confidently select the best candidates for lead optimisation, reducing the risk of late-stage failures.
Conclusion
Collaborative Pathways to Lead Compounds
Navigating the H2L phase requires more than technical capabilities—it requires strategic partnerships. By working closely with a CRO, biotechs can overcome the complexities of this critical stage, ensuring that only the most promising compounds advance, and ultimately increasing the likelihood of successful outcomes. By embracing a partnership mentality, biotechs can:
- Accelerate Timelines: Efficient collaboration reduces delays, allowing for quicker progression to lead optimisation.
- Enhance Data Quality: Shared expertise leads to more reliable results, increasing confidence in decision-making.
- Mitigate Risks: Proactive identification of potential issues before they become critical problems, such as off-target effects or poor pharmacokinetics.
