BPS 2022
The streaMLine platform for accelerated clinical candidate identification
Morten Lundh
Project Leader, Gubra
ABSTRACT
We have developed streaMLine, an innovative platform for peptide drug discovery that greatly shortens the time from hit to clinical candidate. The platform allows for synthesis and systematic screening of thousands of peptides in high through-put and down-scaled functional and stability assays. We employ a data centric approach where detailed information on all aspects of a sample lifetime is tracked. This enables accurate distinction of key chemical peptide modification from artefact background effects, using a machine learning approach. This unique strategy for peptide screening integrates with state-of-the-art in vivo pharmacology facilities, including advanced animal models and rapid determination of CMC and PK/PD relationships. Using the streaMLine platform, we have developed novel amylin mimetics with attractive therapeutic applications. Amylin receptor agonists have shown promise as anti-obesity drugs with impressive weight lowering effects. However, the use of the native amylin peptide is hampered by a high propensity for amyloid fibril formation, which can however be mitigated by formulation at low pH. We have developed amylin receptor selective analogs using the non-fibrillating peptide adrenomedullin as template, which can be formulated at neutral pH. We systematically screened peptide libraries and identified key amino acid substitutions that accurately control amylin receptor selectivity. The lead candidate shows 10 % weight loss in DIO rats, and its PK makes it suitable for once weekly dosing in humans. This unique amylin demonstrates how the streaMLine platform can facilitate drug discovery from hit to development.
BIO
PhD in molecular biology, 5 years of postdoctoral training followed by 4 years in Biotech. Experienced project leader and responsible for drug discovery innovation at Gubra.