Advancing the Future of ADCs through Machine Learning: Lonza’s Synaffix and BigHat Biosciences Collaboration

Antibody-drug conjugates (ADCs) are at the forefront of oncology treatment, offering a targeted therapeutic approach that delivers potent drugs directly to cancer cells, thereby minimizing systemic toxicity. This partnership combines BigHat’s ML (machine learning)-based antibody design platform, Milliner™, with Synaffix’s proprietary ADC technology to develop a highly differentiated, effective, and safe ADC pipeline.

Synaffix and BigHat Biosciences: Pioneers in ADC Innovation

ADCs are designed to selectively deliver cytotoxic agents to cancer cells by harnessing the specificity of antibodies. However, achieving both selectivity and efficacy remains a challenge due to the inherent complexity of the antibody-drug conjugate structure. This is where Synaffix’s ADC technology platform becomes instrumental. Comprised of GlycoConnect™, HydraSpace®, and toxSYN® technologies, the Synaffix platform provides a comprehensive toolkit that optimizes ADC drug-like properties and enhances efficacy and tolerability. Lonza's acquisition of Synaffix in June 2023 further strengthens this offering, creating an integrated, end-to-end service that accelerates the path from DNA to Investigational New Drug (IND) application.

Synaffix's GlycoConnect™ technology provides site-specific payload attachment, utilizing antibody glycan structures to increase stability. This approach, alongside HydraSpace®, which includes a polar spacer to enhance therapeutic index, and toxSYN®, which features a suite of potent cytotoxic agents, positions Synaffix as a leading player in ADC development. These technologies collectively aim to maximize therapeutic index—a crucial parameter in ADC efficacy, denoting the balance between therapeutic effect and side effect profile.\

The Role of Machine Learning in ADC Development

BigHat Biosciences brings a powerful AI/ML-driven platform, Milliner™, to this collaboration, with the potential to redefine ADC design and production speed. Traditional antibody engineering processes can be time-consuming and resource-intensive, requiring extensive laboratory work to develop antibodies with optimal biophysical properties. Milliner™ accelerates this process by integrating synthetic biology with advanced ML models, allowing rapid iteration and optimization of antibody candidates. This platform streamlines antibody design, enabling the development of antibodies with complex functions tailored to withstand the demands of drug conjugation without compromising therapeutic efficacy.

Through this collaboration, Synaffix’s GlycoConnect™ technology benefits from BigHat’s precisely engineered antibodies, optimized for stable payload attachment and high binding affinity to target antigens. This union of ML and ADC technology not only facilitates the rapid progression of BigHat’s ADCs but also enhances their therapeutic potential by creating more robust, stable, and effective antibody-drug conjugates.

Toward a Fully Integrated ADC Development Pathway

The collaboration enables BigHat to leverage Lonza's full suite of ADC services, from antibody production to clinical trial supply. This integration allows BigHat to develop ADC candidates efficiently, reducing the timelines traditionally required for IND-enabling studies. The pathway, facilitated by Lonza’s state-of-the-art facilities, includes bioconjugation, drug product filling, and clinical batch production, all under a single quality system. This seamless, vertically integrated approach underscores Lonza’s commitment to accelerating ADC pipelines and helping biotech partners bring transformative therapies to market more swiftly.

The demand for ADCs in the oncology sector continues to rise, spurred by the pressing need for safer, targeted treatments. However, manufacturing and development bottlenecks remain, as the complexity of ADCs requires specialized knowledge and infrastructure at every step of production. The integration offered by Lonza through Synaffix’s platform is a significant advantage, providing companies like BigHat with a streamlined path from initial design to clinical readiness. With Lonza’s recent facility expansion to handle high-potency vial filling, the infrastructure is in place to meet increasing market demands while maintaining the highest quality standards.

Potential Impact of the Collaboration on ADC Therapeutics

This partnership between Synaffix and BigHat Biosciences has implications far beyond individual drug candidates, potentially influencing the future of ADCs across the oncology landscape. By combining Synaffix’s established technology with BigHat’s AI-driven antibody discovery, the collaboration can produce ADCs that deliver drugs more precisely to tumor cells, thus enhancing both safety and efficacy. This approach directly addresses the unmet medical needs in difficult-to-treat cancers, where traditional therapies often fail due to limited selectivity and high toxicity.

With Milliner™, BigHat can continuously refine and optimize antibodies, leveraging ML to minimize the attrition rate of ADC candidates during preclinical and clinical stages. As ADCs are notoriously challenging to develop, with only a limited number of approved ADCs on the market, such advances in antibody design can lead to higher success rates, faster development timelines, and more accessible treatments for patients.

Conclusion

The collaboration between Lonza’s Synaffix and BigHat Biosciences is a notable advancement in the ADC field, showcasing how the synergy of machine learning and cutting-edge bioconjugation technology can propel next-generation oncology therapies. Synaffix’s platform offers a streamlined solution for developing ADCs with high stability, selectivity, and safety, while BigHat’s ML-powered Milliner™ platform provides a faster, more effective pathway to antibody design and optimization. This partnership not only strengthens each company’s competitive edge but also highlights the transformative potential of integrating biotechnology with artificial intelligence in cancer treatment innovation. As ADC technology continues to evolve, collaborations such as this set the stage for a future where AI-enhanced biologics bring safer, more effective therapies to patients worldwide.