Development of new drugs: open innovations
Horizontal transfer of molecules
Galina Kostina, special correspondent of the Expert magazine.
The official launch of the project, which can become symbolic for the Russian pharmaceutical industry, took place. The Viriom company, specially created by the HimRar High Technology Center last fall, received permission to start clinical trials of drugs for HIV therapy. The project itself is the result of a contract between HimRara and Roche, one of the largest pharmaceutical companies in the world. This transaction, which is not trivial for the Russian pharmaceutical industry, fits perfectly into the framework of the so–called open innovation concept - a new paradigm for the development of global pharmaceuticals. The concept has replaced the traditional model of drug development that is in crisis. Bigpharma, concerned about the growth of investments in new drugs against the background of declining revenues, is changing its inherent closeness in development to interaction with a large circle of partners. Until recently, bigfarma had no full-fledged development partners in Russia. And now a precedent has been set.
The model is tiredResearchers of the global pharmaceutical market come to a paradoxical and disappointing conclusion: the industry annually registers new drugs no more than half a century ago.
On average, about 20 new medicines are registered per year, and only 5-6 of them can be considered truly innovative. This stagnation seems to be poorly explained, since investments in development (R&D) have been growing by about 13% per year since the 50s (in 2009 they amounted to more than $ 50 billion), the fundamental knowledge base on the mechanisms of various diseases has been constantly expanding and the competence of specialists working in pharmaceutical companies has been strengthened. The industry did not bring the expected breakthroughs in innovative developments and numerous mergers and acquisitions, for which huge funds have been spent in the last twenty years. The pace of development of biotechnology also did not meet expectations: it was assumed that the creation of new biological products, unlike chemically synthesized ones, would be more intensive.
The current increase in research costs is taking place against the background of declining revenues due to the termination of patents of many blockbusters in 2010-2014. This, according to the calculations of some analysts, jeopardizes sales worth more than $ 200 billion. There are fewer and fewer potential blockbusters among the registered drugs, profits will not be able to be a sufficient source for innovation. Experts predict that if this trend continues, the global pharmaceutical industry will face very sad times. They see one of the main causes of the crisis in the "fatigue" and conservatism of the traditional R&D model. After all, almost the entire chain of development of a new drug – target selection, screening of chemical compounds and selection or creation of biotechnological candidates, preclinics, clinical trials, preparation for registration – everything was carried out in the closed space of the company.
The way out was suggested by small pharmaceutical companies – they turned out to be more productive in development with less investment. If investments in one product for large companies can range from one to five billion dollars, then for small companies – several hundred million, or even less. Previously, big pharma simply absorbed these effective "babies", subordinating them to its R&D tactics. Now Krupnyak has a multi-level partnership with small firms, universities, contracting scientific organizations that collectively possess knowledge and courage in development. According to experts, with this approach, the company actually becomes much larger than it is, since it has greater access to intellectual property and extracts more benefits from it. Cooperation allows you to reduce financial risks – after all, some of them are borne by the partner company, and often reduce time, which is important for such long projects as drug development, which takes 10-12 years on average.
Such cooperation has been called the open innovation model or innovation networks. Recently, large pharmaceutical companies have begun to acquire dozens and hundreds of connections, while actively communicating, including with competitors. There is an opinion that this model will help to bring out of the paradigmatic crisis not only large Western companies, but also small ones that lost investors as a result of the financial crisis. There was a hope that Russian companies could also fit into this model – following the example of HIMRAR.
Exchange of powers and rightsThe founders of HIMRAR started in the late nineties as service contractors for large and not very Western pharmaceutical companies, performing synthesis and screening of chemical compounds, possible drug candidates.
Later they began to conduct preclinical tests. Since 2004, HimRar has diversified its activities and started to engage in its own developments and clinical trials. Dozens of molecules are currently in the works, of which five candidates have passed preclinical tests, four are at the clinic stage (in the field of diseases of the central nervous system, hepatitis C, oncology). Despite its relatively small experience in the development of innovative products, the HimRar center was able to become a partner of one of the largest pharmaceutical companies with a turnover of 47.6 billion dollars.
"Since we do a lot of contract work for global pharmaceutical companies, we communicate with them a lot and monitor their situation. That's how we found out that Roche is winding down its research in the field of virology in order to concentrate on oncology," says Andrey Ivashchenko, head of the HimRar company. – Roche could give its projects to competitors or scientists who participated in the project to create a small company. But they chose us. Probably because we have shown unprecedented activity. It was like we were under their feet all the time. But we weren't exactly a dark horse. Our virologists were familiar with Roche virologists, and they knew the high level of our specialists." The authoritative review of the head of the Russian representative office of Roche, Milos Petrovich, who has been at the head of the company in Russia for many years and closely follows the development of the Russian pharmaceutical industry and specialized science, also helped. "If earlier," Petrovich states, "it was not worth talking about innovative developments in Russia at all, now we see the activity of some companies and we believe that it is already quite possible to establish mutual cooperation."
The matchmaking of the two companies lasted about a year. Lawyers, patent specialists, managers worked, scientists consulted. As a result, an agreement was reached: Roche transfers two molecules to ChemRar – candidates for HIV drugs that have passed preclinical trials. HimRar is creating a Viriom company for this project, whose scientific council also includes Roche specialists. Viriom invests and conducts clinical trials, and if successful, prepares drugs for registration and commercialization on the Russian and CIS markets, Roche – on the world market. Both companies receive royalties from the partner's sales.
Now, according to Milos Petrovich, Viriom is working very energetically. The Russian company duplicated several stages of preclinical tests (not out of distrust, but to get some additional data), making sure in the process that Roche conducted all preclinical tests flawlessly.
Both companies benefit from such a partnership. As part of its structural adjustment, Roche concentrates its efforts, both scientific and financial, mainly on oncology. More and more external partners are involved in development in other areas, although they are also working in the strategic oncological direction. In development, it is sometimes important to get away not only from the blinded scientific view of the object of research, but also from the pressure of a large corporation demanding a finished product from its division. Small companies or university groups are more relaxed in this sense, and therefore more successful. It is also important that some of the partners undertake the financing of the relevant stages of development, sharing the risks, but also counting on significant profits.
HimRar can also get good experience and good money in addition to good experience. The company's turnover, while it was engaged in service research, did not exceed $ 30 million. "The development of innovative drugs can significantly increase the company's revenues," Andrey Ivashchenko believes. – A successful candidate for a drug, reaching the second stage of clinical trials, is already becoming interesting for big pharma and can be sold to it for several hundred million dollars. If it is successful in the third stage, its price will increase even more. In projects that involve the division of rights, as in the example with Roche, if successful, royalties can also amount to hundreds of millions of dollars. Of course, this can significantly expand our capabilities in the development of new original drugs."
Milos Petrovich develops the idea of Roche's partnership prospects with Russian companies: "Roche is starting to expand into the field of Russian scientific potential. We have not only entrusted an important stage in the R&D cycle of this project to a Russian company, but we are also negotiating Russian developments that may be of interest to our company. Our partners get the opportunity to improve in the development of innovative drugs, and in case of success – access to the world market. So far, Russia could not boast on the world market of its pharmaceutical innovations, which could become a very good source of income. But the experience of other countries is indicative. At one time, Pfizer gave one of the molecules at an early stage of development to the Croatian company Pliva. Pliva brought it to mind and gave it to Pfizer for commercialization. Now few people have not heard of such a drug as sumamed, it has brought multibillion-dollar revenues, and royalties are “Pliv” from these sales, Croatia's revenues from tourism and the food industry were higher."
We begin to hoe the valley of deathHimRara and Roche plan to discuss other joint projects this spring.
"When we met in February with Mr. Humer, Chairman of the Board of Directors of Roche, we talked about the possibility that Roche would give us a few more molecules," says Andrey Ivashchenko. – It was about antiviral drugs, about candidates in the field of the central nervous system. In turn, we have a development that Roche is interested in." HimRar uses the so-called tactics of rapid pursuit: if someone from big pharma finds a new "hot" target and develops a drug, then competitors want to get something similar, and HimRar prepares such analogues. One of them is in the field of oncology – an analogue of one of Roche's drugs. And Roche is interested in the fact that the second-in-class drug also appears in its portfolio, and not in the portfolio of competitors.
According to Milos Petrovich, an example of such cooperation is worthy of replication: "We see the activity of the Russian government, which wants to increase public access to innovative drugs, not all those in need received them before. This means a serious expansion of the market, which will move the entire industry forward: not only Western companies, which are still the main suppliers of original drugs, but also Russian pharma. And partnership can stimulate its faster development."
HimRar, which participated in the development of the strategy for the development of the Russian pharmaceutical industry until 2020, offered an active transfer of Western technologies at the first stage. According to Ivashchenko, both the financial and technological crisis in the global pharmaceutical industry can contribute to the fact that some of the Western developments were transferred to Russia. This, in turn, will stimulate the development of the Russian industry. "Remember the classic picture – a huge pit between science and business, it is also called the valley of death. Science generates something, but business does not want to pick up at an early stage," Ivashchenko figuratively develops the idea. – In my opinion, now it is possible to fill up the pit not only from the side of science, but also to pull up industrial applied science so that it can pick up academic developments. And our example, I hope, will be an incentive to this. Yes, while our pharmaceutical companies are mainly focused on generics and get good profits from this, but this growth will be exhausted. They will not be able to compete systematically with China and India. The only chance to survive is to have innovative drugs in your portfolio. And our business will become interested in innovation after a while."
Now, according to Ivashchenko, while our business has not yet woken up, it is possible to fill a niche with external innovations. Many small but effective companies in the West are falling apart not for scientific reasons, they are suspended at various stages due to lack of funding. "We have held dozens of negotiations with such companies,– says Ivashchenko. – And we are ready to take several projects. We recently signed an agreement with the American company aFraxis to co-invest in the development of a drug for the treatment of one of the forms of autism, and a good result for us may be not only satisfaction in the creation of a new drug, but also a significant royalty." Andrey Ivashchenko regrets that the company does not have enough funds to invest not in three or five projects, but in a dozen. "We have been offering RVC and Rusnano for a long time to create a special fund for such projects in order to pick up similar Western developments together with us and other Russian firms, for example, at the preclinical stages," Ivashchenko continues. – This is beneficial because they have already done part of the work, and if they are lucky, they are ready to share almost half of their rights to global sales. The more such projects there are, the faster the hole between science and business will be filled, the infrastructure will be formed faster, because many players will begin to appear there – small biotechs, contract organizations, patent offices, venture capitalists. Several successful examples will contribute to the formation of alliances of venture funds, both public and private, with companies whose portfolio will constantly feature original developments."
Portal "Eternal youth" http://vechnayamolodost.ru20.04.2010