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There are relatively few pharmaceutical companies in the field of peptide polypeptides, mainly due to the high barriers to research and development in this field. Companies that can master the technology for developing new peptide drugs require multidimensional biological information perspectives and the ability to develop technologies for combining multiple aspects.
In terms of target selection, the development of new peptide drugs requires tracing the biological origins of the disease. As most peptide drugs target diseases involving complex systems such as cardiovascular, metabolic/endocrine, and neurological disorders, which are mainly multi-gene diseases involving multiple abnormal signal pathways, it is difficult to treat a disease efficiently and safely with a single target. Therefore, multifunctional peptide polypeptides that have synergistic mechanisms or target multiple signal pathways will undoubtedly have better therapeutic effects. After nearly a decade of development, multifunctional peptide polypeptides have finally become well-known among the public with the approval of Pegcetacoplan and Tirzepatide in 2021-2022, becoming typical representatives of the new economy of peptide polypeptides. For example, palmitoyl pentapeptide 4 in skin care has beneficial effects beyond expectation.
As one of the best peptide synthesis companies, we would like to introduce the current development in peptide drug design.
Peptide drug design has always been one of the bottlenecks restricting the development of peptide drugs. The initial peptide drugs were extracted from natural peptide polypeptides and their development was seriously limited. With the development and maturity of chemical synthesis and genetic engineering technology, rational design of peptide polypeptides has become possible. However, its difficulty is also very high: First, obtaining the crystal of the peptide polypeptide determines its secondary and tertiary structures, identifies essential amino acids and possible substitution sites, and unstable amino acids to avoid isomerization, glycosylation, or oxidation. Secondly, natural peptide polypeptides often tend to aggregate and have low water solubility, so it is necessary to improve their physical and chemical properties, such as charge distribution, isoelectric point, pH of the formulation, and to avoid hydrophobic groups that are easy to degrade. Computer-aided drug design of peptide polypeptides is one of the important means to improve research and development efficiency and reduce research and development costs. However, since peptide polypeptide computer design is far from enough with only traditional indicators such as affinity, there are not many companies that can master systematic methodology in this field.
The common defect of peptide drugs is their short half-life and high plasma clearance rate, so most peptide drug designs require increasing their resistance to enzymatic degradation to improve their in vivo stability, and increasing their hydrodynamic radius to reduce the glomerular filtration of the kidneys. In the process of modification and structural modification, the stability of peptide polypeptides against enzyme degradation can be improved by modifying their amino acid sequence or through various acylation modifications, introducing non-natural amino acids, etc. Increasing the hydrodynamic radius of peptide drugs requires genetically engineered or chemical methods to modify their sequence or spatial structure, which has a high technical and experiential barriers, such as peptide-linked antibody technology (including Peptibody), peptide-albumin fusion technology, PEG modification technology, etc. If you want, we can provide a detailed peptide drugs list.
The most challenging stage of peptide polypeptidedevelopment is the "pre-clinical research stage", which includes CMC and pharmacology, toxicology, and PK. In terms of CMC, due to the lack of comprehensive process development capability, small biotechnology companies cannot provide platform-based process development support for their peptide drugs throughout the entire process from early clinical to commercialization. Compared with small molecules, peptide drugs are more complex. They face a variety of demands, such as non-natural amino acid synthesis, peptide polypeptide library screening, lead compound synthesis (especially involving chemical coupling), process development, analytical method development and verification, peptide formulation development, etc. Peptide polypeptide pharmacology, toxicology, and metabolism are highly challenging as peptides cannot target cells like small molecules, nor can they directly bind to intracellular receptors after passing through the cell membrane. Therefore, it is highly challenging to determine their pharmacology and pharmacokinetics through in vitro and in vivo experiments. In addition, the safety evaluation of peptide drugs also has its unique pathways, including developmental and reproductive toxicology (DART), genetic toxicity evaluation, immunogenicity evaluation (ADA), phototoxicity evaluation, carcinogenicity evaluation, impurity identification, metabolite and safety pharmacology evaluation, safety evaluation strategies for peptides containing non-protein amino acids (NPAA), etc.
In summary, the complex research and development processes and technical barriers have led to relatively mild competition in the industry of peptide drugs, which is a highly differentiated potential field.
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