We'll go the other way
Russian pharmacists will put the development of innovative drugs on stream
Russian pharmacists have developed a "smart" technology platform to create drugs that can turn the standard view in the world of therapy for severe oncological and autoimmune diseases. For the first time in our country, BIOCAD scientists have combined de novo gene synthesis and high-performance screening techniques with mathematical modeling techniques. This has opened up almost limitless possibilities. Now it is possible to quickly and efficiently create highly specific drugs, the active component of which is not only monoclonal antibodies based on optimized natural molecules, but also fundamentally new molecules, even those that have never existed in nature.
Thanks to the use of a "smart" technology platform, a laboratory stage has been passed in the creation of a revolutionary drug for the treatment of one of the most aggressive types of skin cancer – melanoma. With the help of a platform of several billion antigen-binding fragments of antibodies to the PD-1 antigen, several dozen molecules were selected that could block the functions of this receptor, which contributes to the development, including this type of cancer, in the necessary way.
For the first time in 30 years, a fundamentally new type of medicines has appeared, which increases the life expectancy of patients in the last stages of melanoma. This tumor is resistant to the main groups of existing chemotherapeutic drugs. The clinical effect on the growth of metastases is achieved only in 10-20% of cases. According to experts, the use of monoclonal antibodies to the PD-1 antigen will lead to a stop in tumor development in 30-40% of patients. This will be a real breakthrough in the treatment of metastatic melanoma. And thanks to the achievements of domestic pharmaceuticals, Russian patients will be among the first to get access to it. It is expected that the drug will enter the market in 2018-2019.
Today, in Europe and the USA, the number of innovative drugs that enter the market is sharply decreasing. Only a few medicines per year receive registration. There are many reasons: very high costs for conducting clinical trials, tough bureaucratic obstacles. Big Pharma is in crisis, it is looking for ways to improve the efficiency of promoting medicines from the laboratory to the market. The Russian "New Pharma" has every chance to work ahead of the curve and release a pool of innovative drugs faster than its Western counterparts.
From a molecule with unpredictable characteristics to a precisely specified resultInitially, the "smart" technological platform was developed by BIOCAD specialists to create drugs based on monoclonal antibodies within the framework of the MabNext project, but now it can already be potentially used for any protein innovative medicines.
The platform is working at the stage of laboratory development of the substance of the drug.
When the technology was just beginning to take shape, several tens of thousands of candidates were selected from huge natural libraries containing billions of antibodies by display methods. After their thorough analysis, several of the best moved on to the next stage – preclinical animal studies. Thus, at each stage, the best molecules were selected in the hope of finding one that would become a new blockbuster. It was almost impossible to predict with a high degree of probability whether successful molecules that help people would be among the candidates who passed all the tests.
The introduction of a "smart" technology platform has fundamentally changed the approach to the search for therapeutic molecules. Now, at the very start of any project, the target profile of a molecule that will help patients is formed, and at each stage of the "pipeline" it is known what characteristics it should have. If the selected antibodies do not fully satisfy the desired result, bioinformatics comes to the rescue.
With the help of mathematical modeling in the in silico space (in a computer), a model of antibody-target interaction is created and possible changes that need to be made to the structure of candidates are determined to ensure exact compliance with the properties set at the start. Thus, it is possible to take care of the physicochemical properties of the molecules being developed and the nucleotide composition of their genes in advance, and then reproduce the desired result using de novo gene synthesis from small bricks-oligonucleotides obtained by chemical means. This will ensure the high quality of the drug that patients will receive in the future.
Testing of any mathematical models in practiceThe technique of high-performance de novo gene synthesis in comparison with classical molecular genetic methods of mutagenesis (changes in single nucleotides of the genetic code) makes it possible to test all mathematical calculations about the functionality of potential therapeutic molecules in practice in real laboratory field conditions in a few days.
The introduction of a "smart" technological platform for the development of protein substances of medicines allows you to obtain thousands of different protein molecules and carry out their characterization and optimization in the shortest possible time.
The ability to optimize the properties of already selected candidates during the development process allows us to ensure high quality and the necessary efficiency of the created molecules. Thus, bioinformatic analysis can predict "hot spots" in the amino acid sequence of antibodies or their fragments, the change of which will lead to such significant improvements in the properties of the molecule, such as, for example, an affinity craze or a decrease in possible immunogenicity.
A "smart" technology platform is able to learn by itself and teach othersA few years ago, laboratory analysis of molecules took from 7 to 14 months, and manual labor limited the selection of molecules to several hundred.
The risk of the human factor influencing the result was very significant. As a result of the introduction of a new intelligent platform, the time for the development of a monoclonal antibody was reduced by 3 times – to several months, while the sample for analysis at the start grew to more than 40,000 molecules, without taking into account their constant optimization during development.
Now modern robotic equipment in a short time puts at the disposal of scientists a huge array of data, which is transferred to the information cloud, the space in silico (mathematical laboratory). This is a kind of unified virtual database, to which the scientific staff of the BIOCAD company have online access.
The robotic equipment directly sends the results of a particular stage of research to the cloud, the system itself collects information, processes it using mathematical methods and prepares instructions for subsequent stages. The "smart" technology platform is easily trainable. Accumulating more and more statistical knowledge from project to project, she makes changes to the instructions for further stages of research and future projects.
Future checkThe "smart" technology platform has been tested in practice.
Hundreds of antigen-binding fragments of antibodies to various antigens, in particular, to the PD-1 antigen, were selected. It is he who allows the development of one of the most aggressive types of skin cancer – melanoma. The candidates of monoclonal antibodies selected in the course of laboratory studies have a high affinity for the PD-1 antigen, effectively block its activity, while demonstrating a low level of potential immunogenicity.
This is just one of the first results of the "smart" technology platform. As part of the MabNext program, BIOCAD creates original highly effective drugs based on monoclonal antibodies for the treatment of oncological and autoimmune diseases. There are 15 innovative medicines at different stages of development. One of them is a monoclonal antibody against interleukin-17. The drug has no analogues on the world market and is significantly superior to candidates developed by foreign companies.
"The task for the future is to bring the system to the level of artificial intelligence. Already now Russian pharmacists are trying to understand what will be treated in 4-5 years, what properties the drugs of the future should have. But in order to be able to create a new generation of medicines today, a fundamentally different approach is needed, this is what is embodied in the "smart" technology platform. Today it makes no sense to adopt Western technologies in the field of pharmaceuticals. On average, the life cycle of an innovation does not exceed 5 years. Therefore, while the borrowed technologies will be implemented in Russia, they will already become obsolete. The only successful way to develop the Russian pharmaceutical industry is to create fundamentally new breakthrough blockbusters," says Dmitry Morozov, CEO of BIOCAD.
Background information:
BIOCAD is an innovative full–cycle biopharmaceutical company, the leader in the number of clinical trials among domestic manufacturers. Using the best of the advanced achievements of science and management, BIOCAD creates fundamentally new opportunities for the treatment of diseases and improving the quality of life of patients. The development of original and reproduced medicines is carried out in the company's own research centers. All drugs are manufactured strictly according to international GMP standards. BIOCAD produces medicines and substances in the following areas: gynecology, urology, oncology and hematology, autoimmune and infectious diseases. The total number of employees is more than 700 people, about 150 of whom are research employees of research laboratories. In 2013, the company's revenue amounted to 3 billion rubles. BIOCAD has a wide network of subsidiaries abroad: in Belarus, Ukraine, Brazil, China, India and the USA.
Portal "Eternal youth" http://vechnayamolodost.ru26.11.2014