Our Drug Discovery Strategy

At PeptiDream, we use our proprietary drug discovery and development platform, PDPS (Peptide Discovery Platform System), to identify macrocyclic peptides with high binding and specificity to target proteins, which we define as hit compounds. Using the data and insight derived from the hit compounds, we have 3 strategies to discover and develop novel therapeutic agents: (1) Peptide and small molecule therapeutics, (2) peptide-drug conjugates (PDCs), and (3) multi-functional peptide conjugates (MPCs).

(1) Peptide and small molecule therapeutics

Our basic approach using the hit compounds from PDPS as a starting point is to modify the structure of the peptide and optimize its pharmacological properties (e.g., biological activity, selectivity, pharmacokinetics) to develop into candidates for peptide therapeutics. In the optimization process, we analyze the 3D structure of how the peptide binds to target proteins using X-ray crystallography and cryo-electron microscopy and incorporate non-natural amino acids to obtain peptides with similar of biological activity and selectivity as antibodies, and enhance pharmacokinetic properties. Recent studies have shown that it is possible to generate orally available macrocyclic peptides, which was previously thought to be near impossible. In projects where development of orally available macrocyclic peptides is difficult, it is also possible to convert the peptides into small molecule therapeutics by using in silico modeling and computational chemistry techniques to analyze the structural data obtained from the peptide-protein complexes.

(2) Peptide-Drug Conjugates (PDCs)

The concept of the PDC strategy is to use peptides to selectively deliver bioactive payloads (e.g., radionuclides, oligonucleotides, small molecules, and toxic agents) to target tissue and/or cells.
Unlike peptide and small molecule therapeutics (described above in (1)), the peptides in PDCs are not required to have biological activity. The carrier peptide in PDCs are required to have high binding and specificity to the target protein so that it can selectively deliver the payload to the target, and also have the right pharmacokinetic properties, which are all known to be easily adjustable in peptides. The payloads require a carrier for various reasons such as 1) the payload is easily metabolized and excreted before it can reach the target tissue and/or cell, and 2) off-target toxicity may occur if the payload reaches tissues and/or cells other than the target.
Antibody-drug conjugates (ADCs), which use antibodies to selectively deliver toxic compounds, are based on the same concept, and several ADCs have been developed and approved. PDCs represent a next-generation strategy and are receiving considerable attention due to the unique features of peptides as carriers, such as easier control of pharmacokinetics, low immunogenicity, relatively easy complexation to the target and manufacturing regardless of payload type. At PeptiDream, we are developing various types of PDCs with different payloads, including RI-PDCs, oligonucleotide-PDCs, and cytotoxic-PDCs.

(3) Multi-Functional Peptide Conjugates (MPCs)

MPCs are therapeutic agents designed to have multiple mechanisms by tethering peptides with specificity to different target proteins (and different mechanisms of action) together. We have developed methods to chemically synthesize conjugates which incorporating multiple different peptides, which enables us to expand the variety of MPCs. MPCs have the potential to address therapeutic areas with high drug discovery hurdles which require cocktail therapies and involve development efforts for multiple drugs to be administered together. Similar concepts include bispecific and multispecific antibodies, an area in oncology and immuno-oncology where research and development has intensified in recent years.