A startup from São Paulo has developed an innovative computing platform for discovery of new drugswhich is being successfully applied to the screening of molecules for the treatment of several diseases, including mental disorders, autism, anxiety, chemical dependency, and even certain cancers.
Naiad Drug Development – a company incubated at ITUFABC, incubator at the Federal University of ABC (UFABC), in Santo André – is a bioinformatics startup specialized in the creation of new bioactive molecules that target the so-called “G-protein-coupled receptors” ( GPCRs), a family of receptors associated with a wide range of diseases.
The company received support from the Fapesp Research Innovative Small Business Program (PIPE) to perform the screening of molecules acting specifically on the oxytocin receptor, with a focus on therapeutic applications.
Oxytocin, whose receptor is a GPCR, is a hormone produced in the brain that plays an important role in inducing labor and breastfeeding. Due to its role in modulating mood, social interaction and anxiety, oxytocin became popularly known as “the love hormone”.
joining the artificial intelligence to the so-called “structure-based drug design”, the computational platform developed by Naiad is capable of performing the screening of billions of molecules, identifying those that have a high potential for success for therapeutic use and precisely selecting a few hundred to proceed with the tests. laboratory cell phones.
“Structure-based drug design” consists of designing and optimizing chemical structures in order to identify a compound suitable for clinical trials – that is, for select new drug candidates.
According to Pedro Henrique Camargo Penna, one of the founders of Naiad, in Phase 1 of the PIPE Project, the company initially focused on the search for molecules that act agonistically on the oxytocin receptor – that is, those that excite these receptors and may be useful for mental or neurological diseases.
“We were successful in this initial phase and managed to find several molecules that bind to the oxytocin receptor and that are not yet used as drugs. The most promising molecules were selected after a round of in vitro tests and showed great potential to serve as a basis for the development of drugs with application in various neurological problems and conditions, especially chemical dependency and some symptoms of autism”, says Penna.
In addition, the project also resulted in several molecules with potentially relevant action in the fight against some types of cancer with a high incidence in the population. “Oxytocin receptor antagonists are already being studied for the treatment of premature ejaculation and for increasing the success rate of in vitro fertilization, for example”, says the researcher. “But new studies have shown that blocking the oxytocin receptor can also significantly reduce some specific tumors. Therefore, we expanded the project and started screening molecules acting on the oxytocin receptor with different mechanisms of action, focusing on generating value in different scenarios,” he explains.
After the success of the in vitro tests carried out in the first stage, Phase 2 of the PIPE Project, recently approved, will focus on the discovery of molecules that not only have activity on the oxytocin receptor, but also present optimal characteristics in relation to the form how they are metabolized by the human body.
“In Phase 2, our focus is on the search for molecules with optimal pharmacodynamic and pharmacokinetic activity”, explains Penna.
According to him, the design of drugs based on the structure will be used. Through this technique, the protein is modeled three-dimensionally, atom by atom, from a computer model of the molecule. From there, there are different techniques to perform the screening within the receiver’s region of interest.
“There has been a huge technological advance in this area. If before it was possible to screen millions of molecules on computers, now this has been enhanced by very powerful video cards and very advanced software. With this technological leap, today we are able to screen billions of molecules for each target – among them, the oxytocin receptor. Artificial intelligence has produced an even greater leap”, he evaluates.
In practical terms, all the computational power is used to assess whether or not the molecule fits into the receptors. Functions that calculate a score are then applied, defining how favorable the fit is. “With that, we greatly increased the success rate in the selection of molecules with potential for in vitro tests”, says Penna.
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“We work with high performance workstations. They are super powerful computers, capable of processing a huge volume of data. Software is also a relevant point, in which we invest heavily. Although a good part of our platform was developed internally, we also integrate software that is already fully validated”, says the researcher.
According to Penna, in addition to molecules that act on oxytocin receptors, Naiad has also developed new molecules that act on other GPCRs. These receptors located on cell membranes are involved in such fundamental aspects of biology that approximately 30% of the drugs available on the market act on this group of proteins.
“GPCRs play a key role in processes such as hormonal response, communication between neurons and modulate biological processes of all kinds, from the most basal to the high level, from metabolic modulations at the cellular level to the regulation of mood and attention. Because of this, for practically every disease there is some GPCR involved”, explains Penna.
Naiad’s business model is focused on generating value so that selected molecules are licensed to large pharmaceutical companies.
“We are not focused, at the moment, on taking the development of molecules to clinical trials. Large companies have more room for this stage of development. On the other hand, we have great experience in the computational part and in the screening of new drugs. Therefore, our purpose is to take the development to the end of the pre-clinical part and, from there, seek licensing”, says Penna.
For this, Naiad has a team of high-level consultants who work with the company. Penna, who is the general director, has a degree in science and technology at UFABC and is finishing his direct doctorate in the area of biosystems. The technical director, Valderes de Conto, is a veterinary doctor graduated from the Federal University of Viçosa, with a doctorate in biology, in the area of genetics, at the Federal University of Rio de Janeiro (UFRJ) and a postdoctoral degree at UFABC.
In addition to Penna and Valderes, the other two founders of the startup are Antônio Kimuz Braz, professor of molecular genetics and genomics at UFABC, and Maurício Coutinho Neto, also a professor at UFABC in the area of computational chemistry. Both are shareholders of the company. Biologist Cláudio Miguel da Costa Neto, who works as a consultant for the startup, is a professor at the Faculty of Medicine of Ribeirão Preto at the University of São Paulo (FMRP-USP). Chemist Gerhard Gross, a specialist in drug development with extensive international experience, also acts as a consultant.
Penna explains that the company opened in 2018, after receiving funds from an angel investment. “It was a group of investors, individuals, some linked to the financial market and all technology enthusiasts and interested in artificial intelligence”, he says. One of the angel investors, Ricardo di Lazzaro Filho, also became a member of the company’s board.
“Ricardo was one of our mentors throughout the training process and is with us in the company. The angel investors decided to make more contributions to the company later on and also helped us to implement the protocols that we have in place today. In September 2021, we received an institutional investment from the venture capital firm Green Rock,” says Penna.
Currently, Naiad is structuring its next round of private investment, which should be closed by the beginning of 2023. The company will be part of the Brazilian delegation that will participate in June at the BIO International Convention, in San Diego, United States, at the invitation of the Brazilian Association of Pharmaceutical Inputs (Abiquifi) and the Brazilian Trade and Investment Promotion Agency (ApexBrasil), where it will discuss its pipeline of projects under development and will be open for discussions with investors and business partners.
“Our methodology is proving to be very efficient in relation to the detection of molecules with high pharmacological potential. Our numbers indicate this and the market has been paying attention to these results. We are confident and excited about the possibility of contributing significantly to the development of new drugs”, says Penna.
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