Novel HTS-Compatible Peptide Discovery Platform for the Direct Identification of Functionally Active GPCR Ligands from Cell-based Screens
Sally Wang Liang
Senior Vice President Business Development, PepLib
G protein-coupled receptors (GPCRs) modulate numerous and diverse human physiological processes and remain important targets for drug discovery. Nearly 34% of all FDA approved drugs act on unique GPCRs of which 80% are small molecules, mostly due to the convenient discovery of small molecule ligands in cell based GPCR functional screens (agonism/antagonism). More than half of the known non-olfactory GPCRs that have not yet been explored in clinical trials, and so therapeutic potential, particularly in genetic and immune system disorders remains to be detemined. Peptides have proven to be excellent modality for drug discovery due to their high potency, selectivity, and safety. However, peptides are only a small portion of the GPCR targeting drugs and function mainly as agonists. Predominant strategy for the discovery of peptide clinical candidates relies on the modification of endogenous peptide GPCR ligands, as traditional affinity-based peptide discovery platforms are not compatible with cell-based functional assays.
To maximize the potential of peptides as GPCR drugs, PepLib has developed a peptide discovery platform capable of the direct discovery of functionally active peptide hits from a screen. The PepLib’s proprietary Peptide Information Compression Technology (PICT) enabled the design and synthesis of a library of 80mer cyclic peptides containing half a billion unique sequences in a one-well one-compound genetic tag-free library format. The capabilities of the PepLib discovery platform extend beyond just binding assays to cell-based functional assays, which breaks through the traditional limitations of display-based peptide screening technologies. This HTS-compatible platform has successfully discovered peptide leads as agonists and antagonists against a range of GPCRs. In the initial discovery campaign, a primary cell-based screen (agonist or antagonist mode) is used to identify functionally active 80-mer peptide hits. Peptide hits with the highest activity were then taken through a ‘decompression process’ to convert 80-mer hits into 20-mer or smaller (cyclic and/or linear) peptide leads with potency in the sub-micro/nanomolar range suitable for peptide medicinal chemistry lead optimistation.
Sally Wang Liang JD MPH is Senior VP of Business Development, Head of the Global Business Unit at PepLib, a peptide discovery and therapeutics company with a proprietary screening platform with functional assay and membrane protein screening capabilities. She leads a global BD team in all aspects of deal-making and led the recently closed major pharma collaboration.
She comes to PepLib as a life sciences business executive and a multidisciplinary IP & Regulatory lawyer with 15+ years of healthcare industry experience. She is actively involved in the biotech ecosystem: consults as a Venture Partner at Viva Bioinnovator (VBI), sitting on the boards of three biotechs, Scientific Advisory Board member of New Equilibrium Biosciences, Expert-in-Residence at the Harvard iLab, and mentor with MassBIO and Activate-Nucleate. Previously, she was Entrepreneur-in-Residence (Acting VP of Investments and General Counsel) at the biotech involved in in-licensing promising university technology into NewCo. She was CEO and Co-founder of an international telemedicine company, and as Chief Strategy Officer and EVP of IP and Regulatory of a leading digital therapeutics company. As a lawyer, she practiced pharmaceutical patent litigation and IP licensing at the premier intellectual property firm and clerked for a federal judge. She was also involved in life sciences policy making on the national level at the Food and Drug Administration Office of Policy and the US Senate Health Education Labor Pension Committee Health Office. She began her career as a management consultant at Clarion Healthcare, advising many of the world’s largest pharmaceutical companies and top biotech firms on business strategy. Sally received a A.B. in Biology from Harvard College, a J.D. from Harvard Law School, and a M.P.H from Harvard T.H. Chan School of Public Health.