Famous GLP-1RA Outside of the Circle, and Rapid Development of Peptide CDMO

Peptide, a unique pharmaceutical compound, with a molecular weight between small molecules and protein, plays an important role in many physiological processes (including hormones and neurotransmitters) or inflammatory reactions.

Among them, peptide generally refers to a class of compounds formed by dehydration and condensation of 3-50 α-amino acids. Peptide drug, with the advantages of good druggability, high activity, relatively weak toxic reaction, less accumulation, less cross-reaction of drugs, etc, has a total global sales of US$22 billion in 2015, being one of the fastest growing drug fields. 

Speaking of peptide drug, we have to mention GLP-1. In recent years, along with the approval of GLP-1 drug from Novo Nordisk and Eli Lilly in China, the promotion of domestic pipeline under research and the development of subsequent commercialization process, the famous GLP-1 kind is expected to promote the expansion of domestic peptide industrial chain. According to the calculation of CITIC Securities, the market size of GLP-1RA weight-loss drug is expected to be CNY 38.3 billion in China in 2030. In the first quarter of 2023, the sales volume of Novo Nordisk's semaglutide had reached US$4.223 billion, and the annual market sales volume is expected to exceed US$20 billion; Eli Lilly's Tirzepatide, which came from behind, has beaten semaglutide head-to-head, which has completed a sales volume of US$568.5 million in less than a year from the last May to the first quarter of 2023.

With the famous weight-loss drugs are famous outside of the circle, such as GLP-1RA, it has also stimulated the market's demand and concern for peptide CDMO (customized R&D and production in pharmaceutical contracts). 

Why does peptide CDMO benefit?

At present, peptide drugs are mainly synthesized by two mainstream chemical synthesis methods: liquid phase and solid phase. Liquid phase synthesis, a classical peptide synthesis method, adopts step-by-step synthesis method or fragment condensation method generally. In the step-by-step synthesis method, a single α-amino-protected amino acid is repeatedly added to the increasing amino acid composition usually starting from the C' terminal amino acid of the chain. In the fragment condensation method, target sequence is divided into fragments reasonably in general, then each fragment is synthesized step by step, and finally each fragment is condensed according to the sequence requirements. Liquid phase synthesis is more suitable for the synthesis of short peptides. 

In the solid phase synthesis, the carboxyl group of the first amino acid of the target peptide is connected to the solid-phase carrier in the form of covalent bonds, and then the amino group of this amino acid is taken as the synthesis starting point to make it undergo acylation reaction with the carboxyl group of the adjacent amino acid to form a peptide bond. Then the amino group of the resin peptide containing these two amino acids reacts with the carboxyl group of the next amino acid after deprotection, and this process is repeated until the target peptide is formed. Solid phase synthesis is more suitable for the synthesis of middle and long peptides.

However, it faces higher technical barriers in both liquid and solid phase synthesis. For example, for long-chain peptide drugs, the synthesis process often needs dozens of steps, with a big difficulty in synthesis and a low yield, and the impurities in the synthesized crude product are complex, with a large yield loss. Thus, in order to save costs and reduce R&D risks, peptide pharmaceutical company often chooses to cooperate with CDMO company in the early stage of R&D. Therefore, the continuous expansion of peptide drugs has promoted the rapid increase of demand for peptide CDMO. 

According the Polypeptide's data, the global market size of peptide API reached US$1.8 billion in 2020, of which 65% use outsourcing services, and the compound growth rate of peptide outsourcing services from 2020 to 2025 is 10%. 

China has promulgated some innovative drug policies since 2010. Under the general trend of encouraging medical innovation, China's peptide CDMO industry comes into being. In addition, China fully implemented the MAH in 2019, which also promoted the development of the industry. 

Representative peptide CDMO in China

Asymchem

As the leading CDMO solution supplier in the industry, besides consolidating the business of small molecular drugs, Asymchem actively expands the business of large molecules such as peptides, creates advanced peptide drug creative platform, builds a professional research team with rich experience, and provides customers with one-stop services such as process optimization, pilot scale-up, DMF declaration and on-site verification of peptide and peptide-containing drugs synthesis. 

Sinopep Allsino Bio

Sinopep Allsino Bio, based on its own technology platform, makes a technology combination of solid-phase synthesis and liquid-phase synthesis, creatively develops the optimal synthesis strategy of peptide drugs, and establishes a peptide scale production technology platform based on solid-liquid integration, which makes the company have a large production capacity of several kilograms of side-chain chemically modified peptides and long-chain modified peptides, making it establish a strong competitive advantage in the field of large-scale production of peptide API. 

Ambio Pharmaceuticals

Ambio Pharmaceuticals has developed various new peptide drugs successfully at present, which has been focusing on peptide development and production since its establishment. It provides integrated peptide products and services from API to preparations for more than 100 biopharmaceutical and biotechnology companies including global TOP20 pharmaceutical enterprises. Its special process for chemical synthesis of long peptides and complex peptides by liquid-solid combination can reduce the production cost of peptide and improve the peptide yield compared with the traditional recombination processes. At present, Ambio Pharmaceuticals has operated 16 peptide production lines in China and America, equiped with 1000L solid phase reactor and 5000L liquid phase reactor, with an annual output of peptide API exceeding 300kg, which has obvious advantages in technology platform, business model and innovation ability.

Shengnuo Biotec

Shengnuo Biotec is a high-tech enterprise with the core technology of polypeptide synthesis and modification, which has an advanced and efficient process R&D and large-scale production capacity of peptide drugs. It can provide research services from process route design to lab-scale test, pilot-scale test and process verification for peptide innovative drugs and generic drugs, and full-chain customized production services for API and preparations needed for drug R&D and commercial production, covering the complete drug development cycle from drug discovery, preclinical research, clinical trials and marketing.

Wuxi AppTec

Wuxi AppTec's peptide CDMO business belongs to TIDES business (which can provide solutions for the R&D of oligonucleotides, polypeptides and related chemically coupled drugs), which has the ability of process development and service in linear peptide, cyclic peptide, modified peptide, solid phase and liquid phase chemistry. In 2022, Wuxi AppTec's TIDES business income was CNY 2.037 billion, among which the business income of peptides and oligonucleotides was CNY 1.578 billion, with a year-on-year growth of 337%. In this April, Wuxi AppTec's subsidiary, Syntheall Pharmaceutical, put into production two 2000L peptide solid-phase synthesis kettles and large-scale continuous flow purification equipment in Changzhou base. Since then, the total volume of Wuxi AppTec's peptide solid-phase synthesis kettles of TIDES has exceeded 10000L.

Actually, peptide drug has always been a popular track for global biotechnology and biopharmaceutical companies to enter. However, it is very different from small molecular drugs and biological drugs, with a high professional threshold. Thus, cooperating with peptide CDMO can reduce the risk of new peptide drug R&D and accelerate the market. In addition, with a special compliance requirement, peptide drugs need to focus vertically on the talent reserve in this subdivision field and the corresponding R&D and production management processes to reduce the risks in the R&D and production processes. Thus, new drug R&D enterprises laying out the peptide drugs are difficult to exist independently and often choose to cooperate with peptide CDMO. Considering that the patents of many famous peptide drugs in the world have expired in recent years, it releases a large number of clinical needs and stimulates the rapid growth of peptide CDMO. With more and more biotechnology and biopharmaceutical companies laying out the peptide drug pipelines, innovation ability will become the key competitiveness of peptide CDMO. 

Main references: 

1. Ge Chang, Jiang Ling. "Application Analysis of Peptide Drugs" [J]. Electronic Journal of Clinical Medical Literature, 2020, 7(32): 188. 

2. "Exclusive Release | Report for 'Competition Analysis of Peptide Drug Enterprises'", Peptide Institute, 2022-07-27. 

3. "Pharmaceutical Biology: API Series Report 2: Looking for a New Growth Curve: Peptide API", Zheshang Securities, 2022-11-16.