Traditional antibody therapies primarily focus on inhibiting cellular functions, while many diseases require the activation of specific biological pathways to restore normal function. Identifying agonist antibodies that can selectively activate these pathways is challenging due to the vast number of potential binding combinations and the difficulty in predicting which combinations will result in the desired agonistic activity.

Diagonal Therapeutics utilizes a platform combining computational and experimental techniques to rapidly discover and develop agonist antibodies. The platform generates deep immune repertoires of antibody sequences, predicts antibody shapes using computational methods, and groups sequences by their binding spots on receptors. This enables the generation of multi-specific antibodies that are produced for experimental testing. Once an agonistic combination is identified, the platform optimizes molecular sequence characteristics and characterizes the antibodies in in vitro and in vivo models, leading to clinical candidate selection.

Generation of immune repertoires containing approximately 200,000 distinct antibody sequences to cover all possible binding sites on each receptor.

Computational prediction and clustering of antibody shapes to eliminate redundancies.

Grouping of distinctly shaped sequences by their unique binding spots on the receptors.

Combination of representative binders from each group into a multi-specific antibody for experimental testing.

Optimization of molecular sequence characteristics to identify molecules with the best characteristics.

Characterization of antibodies in in vitro and in vivo models to derive optimal agonists.

Diagonal Therapeutics' primary target audience includes pharmaceutical companies and research institutions focused on developing novel antibody therapies for diseases requiring pathway activation, particularly in areas with unmet medical needs such as hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH).