Periodic Reporting for period 2 - CAESAR IBD Project (The CAESAR IBD Project: Developing Therapeutic Antibodies for Pets)
Berichtszeitraum: 2023-05-01 bis 2024-04-30
The CAESAR-IBD project attempts to develop therapeutic antibodies to treat IBD in dogs. Based on similar diseases known from humans, e.g. Morbus Crohn, adivo develops antibodies targeting pro-inflammatory factors well established in human medicine. Both targets selected for antibody discovery (primary and backup target) show great benefits in treating IBD related diseases in humans.
Adivo developed a phage display platform called CAESAR, the first fully synthetic canine phage display platform which allows de novo selection of therapeutic antibodies for various diseases in dogs.
This platform is used for both targets, to identify novel antibody candidates efficiently blocking the interaction of the pro-inflammatory factors and their receptors.
The objectives of the project are the identification of an in vitro validated LEAD candidate for the primary or backup target (D1.1). This includes the biophysical characterization of the substrate to ensure its successful production in a future CMC process (D1.2). This candidate is preclinically tested in an ex-vivo 3D organoid model to prove functionality in target tissue (D2.1). The lead substrate is then in vivo clinically validated determining dose and safety. This data package is used for future out-licensing activities (D3.1 D3.2 D3.3). The in vivo validated lead candidate is entering cell development phase for GMP production, aiming for a high expressing stable cell line (D4.1). Lastly, pre-commercial activities are carried out to support the business case for out-licensing activities (D5.1 D52).
At the end of the funding period, we finished the first half of the affinity maturation procedure for the backup target (D1.1 and D1.2). We successfully established a functional cell assay which supports the validation of functionality in target tissue (D2.1).
Adivo developed a phage display platform called CAESAR, the first fully synthetic canine phage display platform which allows de novo selection of therapeutic antibodies for various diseases in dogs.
This platform is used for both targets, to identify novel antibody candidates efficiently blocking the interaction of the pro-inflammatory factors and their receptors.
The objectives of the project are the identification of an in vitro validated LEAD candidate for the primary or backup target (D1.1). This includes the biophysical characterization of the substrate to ensure its successful production in a future CMC process (D1.2). This candidate is preclinically tested in an ex-vivo 3D organoid model to prove functionality in target tissue (D2.1). The lead substrate is then in vivo clinically validated determining dose and safety. This data package is used for future out-licensing activities (D3.1 D3.2 D3.3). The in vivo validated lead candidate is entering cell development phase for GMP production, aiming for a high expressing stable cell line (D4.1). Lastly, pre-commercial activities are carried out to support the business case for out-licensing activities (D5.1 D52).
At the end of the funding period, we finished the first half of the affinity maturation procedure for the backup target (D1.1 and D1.2). We successfully established a functional cell assay which supports the validation of functionality in target tissue (D2.1).
WP1 covered the identification and in vitro characterization of a set of lead candidates for the primary or the backup target. For the primary target, a broad lead candidate selection campaign was carried out, including a comprehensive affinity maturation campaign and research scale IgG production for biophysical an alysis. These activities revealed that it was not possible to achieve significant affinities in the subnanomolar KD range for this particular target. Therefore, efforts were shifted towards the backup target. This campaign was initiated with in-house antigen production. Subsequently, intial panning campaigns similar to the primary target were carried out. A very alrge number of binders could be identified and in vitro characterized. Therefore, ligand binding inhibition assays were established as well as a functional cell assay. A set of 10 candidates was affinity matured similar to the primary target selection campaign, identifying a large set of candidates showing significant improved affinities. At this stage of the project, the funding period was terminated. This set of candidates for the backup target is still serving as the basis for continued development to identify a lead candidate to efficiently treat IBD in dogs. The project is currently ongoing.
The development of a therapeutic antibody efficiently blocking pro-inflammatory pathways like the backup target will provide pets and their owners with state-of-the art treatment of IBD as known from human medicine. Ultimately, pet owner will finally have a long-lasting treatment solution for severe cases of IBD.