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>Alex Lugovskoy

About The Speaker

Alex Lugovskoy

Co-founder and CEO of Diagonal Therapeutics

Alexey Lugovskoy

Alex is a co-founder and CEO of Diagonal Therapeutics and an entrepreneur-in-residence at Atlas Venture. During his 20+ year career in biotechnology, he served as COO of Dragonfly Therapeutics, CDO of Morphic Therapeutic, VP of Therapeutics at Merrimack Pharmaceuticals, and Associate Director of Drug Discovery at Biogen. Alex is the author of over 100 patents and manuscripts.

He is an Associated Editor of the mAbs and serves on the Board of Directors of the Antibody Society. He has received an Advanced Certificate for Executives in Management, Innovation and Technology from MIT Sloan School of Management, a Ph.D. in Biophysics from Harvard University, an M.Sc. in Molecular Biophysics, and a B.Sc. in Mathematics and Physics from the Moscow Institute of Physics and Technology.

Computational epitope filtering of antibody repertoires enables reliable design of agonist antibodies to multimeric receptor complexes

Agonistic antibodies present a compelling approach to treating human diseases, but their discovery has been severely limited by the difficulty of identifying epitopes that support the productive engagement of the signaling receptor complex. Using a combination of experimental and computational approaches, we generated agonist antibodies that activate four structurally different receptor complexes.

We first mined immune repertoires to identify binding modules that bind to diverse sets of epitopes on both receptor subunits. We used a combination of machine learning and physics-based methods to identify the minimal number of modules that provide comprehensive epitope coverage. By assembling these modules into bispecific antibodies, we successfully identified clades that acted as agonists, triggering the desired cellular responses.

Our innovative techniques can be applied to generate agonist antibodies targeting any heteromeric receptor complex, thereby opening exciting possibilities for precision biologic drugs in treating various human diseases. 

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