{"id":249990,"date":"2017-12-05T18:33:37","date_gmt":"2017-12-05T20:33:37","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=249990\/"},"modified":"2017-12-13T19:20:03","modified_gmt":"2017-12-13T21:20:03","slug":"laboratory-drives-innovation","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/laboratory-drives-innovation\/","title":{"rendered":"Laboratory drives innovation"},"content":{"rendered":"
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Eduardo Cesar<\/span><\/a> Automatic chemical reactor used in researching new drugs, at the Molecular Design and Synthesis LaboratoryEduardo Cesar<\/span><\/p><\/div>\n

To advance its projects in innovation and internationalization, the Brazilian company Ach\u00e9 is launching a nanotechnology laboratory that will develop innovative production processes to enhance and control the human body\u2019s absorption of pharmaceuticals. Located at the company headquarters in Guarulhos, in the S\u00e3o Paulo Metropolitan Region, the Nanotechnology Innovation Laboratory Enterprise (Nile) is a joint initiative of Ach\u00e9 and Ferring Pharmaceuticals, a multinational biopharmaceutical company based in Switzerland. \u201cWe\u2019re going to use nanotechnology to boost the bioavailability of drugs that are hard to absorb, especially when we\u2019re talking about oral versions. This will be possible, for example, by encasing the active ingredient in nanocapsules, enhancing passage of these drugs through the intestinal cells so they can reach the bloodstream and thus have the desired therapeutic effect,\u201d explains chemical engineer Cristiano Guimar\u00e3es, director of Ach\u00e9\u2019s Center for Radical Innovation.<\/p>\n

Nanotechnology also allows an injectable drug to be converted to a pill. \u201cThis is the dream of many pharmaceutical companies, and there is research showing that it\u2019s possible. Some drugs come only in injectable form because their molecules are very large and it\u2019s difficult or impossible for them to be absorbed through the gastrointestinal tract. The solution is to inject them directly into the bloodstream. It would be wonderful for diabetics, for example, if there were an oral version of insulin,\u201d adds pharmacist Edson Bernes, director of Ach\u00e9\u2019s Center for Incremental Innovation.<\/p>\n

The company\u2019s drive to accelerate innovation is evidenced by its participation, since early 2016, in the Structural Genomics Consortium (SGC), a public-private partnership based in Toronto that brings together 400 researchers from around the world and supports the discovery of new drugs through the open science model, where ideas, projects, and resources are shared among partnering universities and businesses during a pre-competition phase.<\/p>\n\n\n\n\n\n\n\n\n\n\n
Company<\/strong><\/td>\n<\/tr>\n
Ach\u00e9<\/td>\n<\/tr>\n
Center For Innovation<\/strong><\/td>\n<\/tr>\n
Guarulhos (SP)<\/td>\n<\/tr>\n
No. Of Employees<\/strong><\/td>\n<\/tr>\n
300<\/td>\n<\/tr>\n
Principal Products<\/strong><\/td>\n<\/tr>\n
Pharmaceuticals<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Ach\u00e9 was the first and so far is the only Brazilian company to join the SGC and enter into a partnership with one of the consortium\u2019s six laboratories worldwide. The lab is located at the SGC-Unicamp Protein Kinase Chemical Biology Center (SGC-Unicamp), at the University of Campinas, and is headed by biologist Paulo Arruda. The other five laboratories are located at the University of Toronto, Oxford University, Goethe University Frankfurt, the University of North Carolina at Chapel Hill, and the Karolinska Institute, in Sweden. The SGC, whose CEO is physician Aled Edwards, from the University of Toronto, enjoys financial support from pharmaceutical companies like Bayer, Merck, and Pfizer\u2014and, in the case of SGC-Unicamp, from FAPESP, under a Research Partnership for Technological Innovation (PITE) project. \u201cSGC-Unicamp focuses on protein kinases that control various aspects of human biology, such as inflammatory processes, viral infections, and cancer. The human genome encodes a total of 520 protein kinases, but science has an in-depth understanding of only around 50. SGC-Unicamp concentrates on kinases that have been little studied. We try to discover the functions of these under-researched kinases, because they may become important target sites [place where the drug acts] in the development of new drugs,\u201d says Arruda.<\/p>\n

\u201cSince kinases are linked to processes of cell proliferation, our interest in this class of enzymes inevitably entails their application in the treatment of different types of cancer. To understand this potential, it is vital to engage in the interactive chemical design and synthesis of molecules until finding the one that inhibits only one kinase among all of them. It\u2019s like finding the perfect key [the inhibitor molecule] for a one-of-a-kind lock [the kinase of interest] that acts in a potentially relevant biological process. We call this key the molecule probe, or chemical probe,\u201d explains Guimar\u00e3es.<\/p>\n

The companies that take part in the SGC contribute in a number of ways: by providing funding, donating reagents and molecules, rendering technical consulting services, proposing targets of interest, and collaborating scientifically, as in the case of Ach\u00e9. When the SGC, through its collaborative network, successfully identifies a molecule probe for a biological target and the target shows therapeutic potential, subsequent research activities are undertaken confidentially by the companies that express interest in the therapeutic target and work to develop a drug to act on this target. This procedure is part of SGC norms, which aim to do away with redundancy and wasteful spending in drug research\u2014wastefulness that can amount to billions of dollars.<\/p>\n

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Eduardo Cesar<\/span><\/a> Researching kinases, proteins that regulate biological processesEduardo Cesar<\/span><\/p><\/div>\n

Under the partnership between SGC-Unicamp and Ach\u00e9, more than 100 molecules have already been designed and synthesized with the goal of obtaining chemical probes specific to two kinases, VRK1 and PRP4. \u201cHundreds or even thousands of molecules have to be tested for each kinase. We have to ascertain whether they are specific to the protein and see what chemical modifications have to be made to achieve this specificity,\u201d says Guimar\u00e3es. \u201cAfter developing the probe, it\u2019s the pharmaceutical company\u2019s job to see whether this initial compound can be transformed into a drug, using medicinal chemistry strategies. All the companies involved in the SGC have access to a tremendous amount of data and can choose what to go ahead with,\u201d says Arruda.<\/p>\n

Shifting direction<\/strong>
\nIn 2015, Ach\u00e9 built a Molecular Design and Synthesis Laboratory to develop and produce molecules that might be new drug candidates. In addition to conducting Ach\u00e9\u2019s radical innovation projects, this laboratory is pivotal to its partnership with SGC-Unicamp. \u201cWe do the synthesis, and they test them on kinases that they themselves produce, purify, and crystallize,\u201d says Guimar\u00e3es.<\/p>\n

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Eduardo Cesar<\/span><\/a> Chamber for handling oncological productsEduardo Cesar<\/span><\/p><\/div>\n

Ach\u00e9 has followed a course that is in tune with a process of change that began within Brazil\u2019s pharmaceutical industry over 10 years ago. \u201cFollowing the Generic Drug Act [1999], Brazil\u2019s major pharmaceutical companies had to upgrade their processes so they would be able to produce bioequivalent drugs, which means copying existing molecules while maintaining the same quality as the original. As a result, they made a reasonable technological leap and then realized that long-term survival required them to make even bigger strides toward innovation,\u201d explains civil engineer Sergio Queiroz, professor at the Department of Science and Technology Policy of Unicamp\u2019s Institute of Geosciences and deputy coordinator of Innovation for the FAPESP Office of the Scientific Director. Generic drugs also forced businesses to capitalize and increase their investment capacity. \u201cThe example of Ach\u00e9\u2019s participation in the SGC clearly signals an effort to acquire expertise,\u201d says Queiroz.<\/p>\n

In addition to producing generic and similar drugs, Ach\u00e9 also develops new drugs through its incremental and radical innovation platforms. The company recorded net earnings of R$2.7 billion in 2016\u2014up 15.1% over 2015\u2014and invested R$203 million, or 7.5% of its net profit, in the set of five directorates that make up its Center for Innovation, created in 2015. Three of the five work exclusively in research and development (R&D): Radical Innovation (the discovery of new active ingredients), Incremental Innovation (the development of new technologies or formulations for existing drugs), and Formulation and Analytical Development (scaling up an active ingredient or technology for commercial production). The other three directorates are Business Development, Alliances and Internationalization, and Medical and Scientific. Some 300 people are part of the Center for Innovation. Of this total, 9%\u201427 individuals\u2014have their master\u2019s, doctorate, or postdoctorate. Twelve of the fourteen Radical Innovation team members, coordinated by Guimar\u00e3es, have graduate degrees.<\/p>\n

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Eduardo Cesar<\/span><\/a> Analytical development laboratory for new drugsEduardo Cesar<\/span><\/p><\/div>\n

\u201cThe Brazilian pharmaceutical companies that invest in this area also do so at a rate of around 7%. The big global leaders in drug development and production invest over 10% of their earnings in R&D. Before generic drugs, the figure for Brazilian companies was 1% to 2% at most,\u201d says Reinaldo Guimar\u00e3es, vice-president of the Brazilian Association of Fine Chemistry, Biotechnology, and Specialty Industries (ABIFINA), the umbrella organization for Brazilian pharmaceutical companies.<\/p>\n

Topical plant therapy<\/strong>
\nAch\u00e9\u2019s prior experience in launching a groundbreaking new product that attained commercial success also played into the company\u2019s new push. In 2006, Ach\u00e9 introduced the topical anti-inflammatory Acheflan, a herbal medicine made from the oil of leaves of Cordia verbenacea<\/em>, a plant native to the Atlantic Forest that is readily found in fields and backyards. Acheflan became the market leader in herbal medicine prescriptions, with a 27.6% market share and sales of just over one million units in 2016, yielding annual revenue of R$30.3 million. Ranking second, at 14.78%, was Flexive, a plant remedy manufactured by Merck using comfrey (Symphytum officinale)<\/em>. Exports to Japan, Chile, Mexico, Costa Rica, Ecuador, and Peru account for 10% of earnings from Acheflan. Researchers at Unicamp and the Federal University of Santa Catarina collaborated in developing the herbal medicine (see Pesquisa FAPESP<\/em> Issue No. 110<\/a>).<\/p>\n

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Eduardo Cesar<\/span><\/a> Directors of innovation at Ach\u00e9: (left to right<\/em>) Miller Freitas, Edson Bernes, Stephani Sav\u00e9rio, Eduardo Motti, and Cristiano Guimar\u00e3esEduardo Cesar<\/span><\/p><\/div>\n

Ach\u00e9 has nearly 20 radical innovation projects underway. One of these, already farther along, is intended to treat vitiligo, an autoimmune disease with dermatological symptoms, characterized by the loss of melanocytes and subsequent loss of skin pigmentation. This herbal medicine has reached the final phase of preclinical development, when in vitro assays and animal studies are done. The medication is made from gerv\u00e3o<\/em>, a plant of the genus Stachytarpheta <\/em>that is found in Northeast Brazil. The company took up the work begun by the Federal University of Para\u00edba (UFPB) after receiving a license on the patent for treating vitiligo with the plant.<\/p>\n

\u201cWe expect this herbal medicine to constitute a new milestone in pharmaceutical innovation in Brazil,\u201d states Stephani Sav\u00e9rio, director of Ach\u00e9\u2019s Center for Innovation. To make distribution as efficient as possible in the main markets worldwide, the company is looking for a partner, another company, to come on board during the clinical trial phase, when human testing is done. \u201cWe developed it up to the preclinical phase to demonstrate its efficacy and safety. Then we went in search of a partner to share the risks and heavy investments inherent to global clinical development,\u201d explains Sav\u00e9rio. The cost of a clinical phase with human subjects ranges from about $50 million to hundreds of millions of dollars, depending on the therapeutic indication,\u201d says Sav\u00e9rio.<\/p>\n

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