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With the development of omics technology, information technology, gene technology and in-depth study of disease biology, the rational design, virtual screening, high-throughput synthesis, structural modification, preparation technology and other technologies of peptide drugs have been continuously improved, and a representative company of "peptide new economy" has emerged, and PeptiDream is the most influential technology-deep biopharmaceutical enterprise
in the global peptide industry.
in the global peptide industry.
PeptiDream is a Japan-based biopharmaceutical CRO company with a proprietary Peptide Discovery Platform System (PDPS) capable of efficiently producing a highly diverse library of non-standard peptides for the identification of highly potent and selective hit (hit) peptides and then the development of peptide, small molecule, or conjugated peptide-based therapies
。 Since going public in 2013, PeptiDream has grown from a lab startup to the most profitable company in the Japanese pharmaceutical industry, with its technology attracting global pharmaceutical giants
including Novartis, Genentech, Merck, AstraZeneca, and Takeda Pharmaceutical.
PeptiDream's business model is based on the core technology platform PDPS to develop three profit models: 1) R&D cooperation; 2) technology transfer; 3) Internal research and development;
PeptiDream's business model is based on the core technology platform PDPS to develop three profit models: 1) R&D cooperation; 2) technology transfer; 3) Internal research and development; 1) R&D cooperation: According to the demand goals of pharmaceutical enterprises, a small amount of prepaid fees are charged first, and then the PDPS technology platform enters the application, such as PDPS technology successfully finds or screens out suitable target peptide compounds, and PeptiDream obtains a large phased payment
.
2) Technology transfer: PeptiDream transfers PDPS technology to pharmaceutical companies for use
in its own labs.
The pharmaceutical company pays an upfront payment of a one-time licensing fee, and continues to pay annual technology transfer fees and maintenance fees
after about 1 year.
(3) Internal research and development: PeptiDream uses PDPS technology to conduct research and development of new peptide compounds in-house, which is licensed to interested pharmaceutical companies
.
Pharmaceutical companies are required to pay PeptiDream preclinical, clinical and commercialization milestone payments for product candidates, a business model that scales and costs more than the above
.
On July 27 and July 29 last year, within three days, PeptiDream officially announced that it had reached cooperation with Takeda Pharmaceutical and Alnylam, signing cooperation agreements of US$3.
5 billion and US$2.
2 billion respectively, which attracted widespread attention
in the industry.
5 billion and US$2.
2 billion respectively, which attracted widespread attention
in the industry.
Why did Takeda Pharmaceutical, Alnylam choose to bet on PeptiDream's core technology platform?
Why did Takeda Pharmaceutical, Alnylam choose to bet on PeptiDream's core technology platform?PDPS platform, the world's leading peptide molecular discovery system
PDPS platform, the world's leading peptide molecular discovery system In 1997, Professor Hiroaki Suga, one of the founders of PeptiDream, received his Ph.
D.
in chemistry from the Massachusetts Institute of Technology and taught at
the University of Buffalo in the United States.
Hiroaki Suga found that a ribozyme can arbitrarily combine more than 400 different amino acids with tRNA, while the existing peptide synthesis system can only use 20 natural amino acid molecules, Hiroaki Suga called Flexizyme, which has also become the lowest core technology
of PeptiDream.
of PeptiDream.
PeptiDream's core PDPS technology includes three parts: Flexizyme and peptide translation technology; Cyclization and modification technology; PD demonstrates technology
.
1) Flexizyme technology and PDTS (Peptide Discovery Translation System).
Traditional ribosome synthesis of peptides is mainly through the transport of tRNA and the complementary action of base pairs between tRNA and ribosomes to connect amino acids to the peptide chain in turn, this process usually occurs in the cells of the organism, this process includes two important reactions: 1.
Aminoacyl-tRNA synthases (ARSs) catalyze the attachment of amino acids to their respective tRNAs; 2.
tRNA is paired
with mRNA in ribosome recognition.
The first step can be applied to in vitro synthesis of peptides: recombinant ARSs bind special amino acids (AAs) to tRNA, but substrate hybridization is low
.
Flexizyme can efficiently catalyze the binding of natural amino acids and special amino acids with tRNA to synthesize tRNA-amino acid complexes for the next step of translation
.
PDTS is the synthesis system for the second key reaction described above: a cell-free transcription/translation system
for the synthesis of peptides via ribosomes.
When PDTS is used alone, it can only synthesize peptides consisting of 20 natural amino acids, but when combined with Flexizyme technology, various peptides
can be synthesized using more than 400 special amino acids.
2) Peptide cyclization technology and modification technology, another important construction technology
of PDPS.
Cyclizes various chain peptides and converts them into special cyclic peptides
.
Peptide cyclization technology changes the group at one end of the peptide chain so that it can be connected end-to-end through a chemical reaction to form a cyclic peptide
.
of PDPS.
Compared with common linear peptides, special cyclic peptides have many advantages, such as more rigid structure, higher affinity and selectivity for target proteins, and more stability in vivo
.
PDPS also includes a variety of other special peptide modification techniques that can significantly reduce the time
required for hit peptide searches.
3) PD display (PeptiDream Display) The above two technologies make it possible to quickly prepare a variety of peptide libraries, and then it is necessary to select hit peptides that may have therapeutic effects from a library of thousands of peptides
.
Compared to other display technologies, PD display is able to identify and screen out hit peptides in a short time, with extremely high reproducibility and repeatability
.
The company continuously optimizes the PD display to match the peptide flow technology
under investigation.
.
▲Source: PeptiDream official website
At present, PeptiDream has a total of 124 drug development pipelines, most of which are concentrated in the drug development stage, and 4 R&D projects have entered clinical phase
I.
PeptiDream's success did not happen overnight, its PDPS technology platform has a long introduction cycle and has been technically proven
in commercial applications for more than 20 years.
In general, the development of peptide platforms requires an experienced team to spend many years incubating the technology and then doing platform verification
.
The advantage of PeptiDream is that they have the core underlying technology and more than 20 full-time scientists to deeply cultivate this field, invest enough time and patience for technology precipitation, and complete the qualitative change process
from scientific research to application, from accumulation to creation, from creation to breakthrough.
in commercial applications for more than 20 years.
Beyond the liver to create more opportunities for siRNA therapies
Beyond the liver to create more opportunities for siRNA therapies mRNA, siRNA, antisense nucleic acid, RNAa and other therapies make the nucleic acid drug track full of various new possibilities
on the road to the treatment of human diseases.
Under the continuous development trend of new technologies, peptide delivery systems have become the key to the efficacy of
nucleic acid drugs.
Alnylam leveraged PeptiDream's peptide discovery platform to select a range of receptors for its oligonucleotide drug pipeline, and PeptiDream will select, optimize and synthesize peptides
for each receptor.
Subsequently, Alnylam will generate peptide-siRNA conjugates and conduct in vitro and in vivo studies to select the most appropriate peptide
.
Explore opportunities for treatment of multiple diseases by targeting disease-causing mRNA transcripts in multiple tissue types
.
for each receptor.
Following the collaboration, Dr.
Kevin Fitzgerald, Alnylam's Chief Scientific Officer, said, "We are delighted to partner with PeptiDream to see the PDPS platform identify robust ligand-receptors for extrahepatic tissues, solve the problem of delivering RNAi therapies to the liver, and facilitate the delivery of siRNA drugs to the human CNS, eyes and lungs
.
" ”
As RNAi oligonucleic acid drugs, siRNA has a wide range of clinical indications and can be used for tumors, rare diseases, viral diseases, cardiovascular diseases, inflammatory diseases, etc
.
However, siRNA drugs themselves preferentially target the kidneys and liver, are easily degraded by nucleases, and siRNA drugs do not cross the blood-brain barrier, so the target tissue of such drugs is limited
.
The emergence of peptides has become recognized as the "ideal" nucleic acid delivery vehicle in the industry because of their good biocompatibility, biodegradability, and flexibility of chemical modification to meet a variety of clinical needs
.
Compared to peptides alone, PDCs provide additional functions such as improved drug solubility, target selectivity, and circumvention of
multidrug resistance.
Takeda adds $3.
5 billion to break through the blood-brain barrier
5 billion to break through the blood-brain barrier
In July 2021, Takeda Pharmaceutical Japan and Peptidream expanded a research collaboration and licensing agreement to develop peptide-drug conjugates (PDCs) in the field of chronic neurodegenerative diseases, focusing on expanding the use of TfR1-bound peptide ligands for CNS targets associated with neurodegenerative diseases, which, when combined with various therapeutic payloads, enable the payload to cross the blood-brain barrier, which can significantly improve efficacy
.
Under the terms of the agreement, PeptiDream received approximately $3.
5 billion in partnership fees
.
In addition, Takeda will receive royalties on
the net sales of this product.
It is worth mentioning that PDC for neuromuscular diseases was first developed
by PeptiDream.
PDC covalently binds specific peptide sequences with cytotoxins through a decomposable linker to target diseased tissues in the form of increasing local cytotoxin concentrations, reducing toxic effects in non-diseased tissues, reducing adverse reactions, and achieving the purpose of
synergistic attenuation.
by PeptiDream.
PDC covalently binds specific peptide sequences with cytotoxins through a decomposable linker to target diseased tissues in the form of increasing local cytotoxin concentrations, reducing toxic effects in non-diseased tissues, reducing adverse reactions, and achieving the purpose of
synergistic attenuation.
"Tremendous progress
has been made since we began our research collaboration with PeptiDream.
PeptiDream's TfR1 binding technology provides an effective treatment for
neurodegenerative diseases.
Takeda University's director of the neuroscience treatment area said
.
PDC combines the advantages of peptides with a small molecular weight that is biodegradable without causing an immunogenic reaction
.
By modifying the amino acid sequence of the peptide chain, the conjugated hydrophobicity and ionization properties of PDC can be changed, the problems of poor water solubility and untimely metabolism can be solved, and the cell and tissue permeability can be promoted at the same time, which overcomes the problem
of high wear rate in clinical development of small molecule drugs due to poor physical and chemical properties.
Some specific peptide carriers can also overcome tumor drug resistance and enable drug delivery
across the blood-brain barrier.
In addition, compared with ADC technology, peptide coupling drug PDC has a variety of industrial advantages, such as better uniformity, lower production cost and cycle
.
Alnylam's collaboration with Takeda demonstrates recognition
of the PeptiDream peptide discovery platform and its ability to identify compounds that can optimize clinical research.
Today, PeptiDream has partnered with many of the world's leading pharmaceutical companies, including Amgen, AstraZeneca, Genentech, Eli Lilly, BMS, GlaxoSmithKline, Novartis, Merck, and Mitsubishi
Tanabe.
At the same time, the pharmaceutical companies cooperated with Arterial New Medicine Discovery PeptiDream continued to repurchase PDPS technology as high as 70% in terms of other product pipeline selection, and PeptiDream is becoming the first choice
of global large pharmaceutical companies in the field of peptide discovery platform.
