Section Summary

The antibody occupies a central role in both performance and valuation of an ADC. This section explores the properties of an antibody that become important in success of an ADC drug in CEACAM, and how these properties are used to decide the success of a clinical trial using the 187-trial dataset.

Further, analysis of the patent landscape of antibodies reinforces the conclusion that the estate is broad, but permeable. A knowledgeable aspirant should be able to find scope of differentiation in the white spaces available.

Epitope selection, an important influencer for internalization, interaction with soluble CEA (sCEA), payload compatibility, companion diagnostic strategy, patient selection, clinical trial design, patent protection, and ultimately long-term commercial positioning is examined to understand factors it can control as well as properties it cannot. The Section discusses other variables that have influence and approaches deployed for their management.

This section argues that antibody engineering may not remain an isolated discovery activity, as it seems to be the first element for shaping the clinical and commercial lifecycle the drug. Desired properties in the clinic and even in the payer – prescriber axis need to be built in.

Analysis of the current competitive landscape reveals following major findings.

1. Antibody differentiation goes beyond the epitope and affinity. Epitope is an important but small fraction of the value. Affinity requires optimization – too low, too high both are disadvantageous; Not just binding, the on rate and off rate independently play roles and require understanding to fully elaborate an ADC’s success as a drug. Multiple properties have ramifications to success or failure of safety and efficacy. These are discussed in the Section.
2. Modern CEACAM5 patent estates on several aspects stop short of explaining the clinical performance of the drug. For example, epitope or even the affinity alone cannot predict the antibody will reach the core of the tumor, deliver the payload inside the cell and have safety about not delivering the payload extracellularly. These aspects are critical for the success of an ADC as a drug. The valuation exercises will increasingly take the differentiating features, which are the functional aspects, to complement the patent analysis.
3. Multiple engineering strategies are emerging to address longstanding challenges such as soluble CEA sink, slow internalization, and tumor heterogeneity.
4. Although important IP territories are occupied, several biologically attractive and commercially meaningful whitespace opportunities remain available. The patents are offering limited coverage – the protein sequences, domains, epitopes are not granted - therefore, in many instances covered areas are also essentially available.
5. The properties of the antibody that determine the success of an ADC need elaboration and integration into the due diligence, as determinants of value. The Section derives such inferences, and a due diligence checklist is included in the Section for use to both guide a more rational valuation for the licensor, and serve as an aid to value optimization for the licensee.

Results of this study which is aimed at identifying which criteria will likely influence a molecule’s leadership over next ten years after launch argues the set of parameters are broader and need to be integrated into the drug design, testing and due diligence.

This section supplies the antibody half of the architecture framework introduced in Section 5. Payload and linker counterparts appear in Section 7 and Section 8.