Startup designs molecules for treatment of mental disorders, cancer and other diseases

The computational platform developed by the firm, with FAPESP’s support, is capable of screening billions of molecules.

By Fábio De Castro | FAPESP Innovative R&D – A startup based in São Paulo state (Brazil) has developed an innovative computational platform for drug discovery, which is being used successfully to screen molecules for the treatment of several diseases, including mental disorders, autism, anxiety, chemical dependence, and even certain types of cancer.

Naiad Drug Development was set up at ITUFABC, an incubator run by the Federal University of the ABC (UFABC) in Santo André, to use bioinformatics to develop bioactive molecules targeting G protein-coupled receptors (GPCRs), a large family of cell-surface receptors that regulate many cell functions and are associated with a wide array of diseases.

FAPESP’s Innovative Research in Small Business Program (PIPE) supported the firm’s screening of molecules that act specifically on oxytocin receptors for therapeutic applications.

Oxytocin, whose receptors are GPCRs, is a hormone produced in the brain and released into the bloodstream by the pituitary gland. It plays an important role in childbirth, mother-child bonding and breastfeeding. Because it is also linked to warm feelings and has been shown to lower stress and anxiety, it is often referred to as the “love hormone”.

Combining artificial intelligence with an increasingly important approach known as “structured-based drug design”, the computational platform developed by Naiad is able to screen billions of molecules in search of those with therapeutic potential, precisely selecting several hundred for cellular testing in the laboratory. 

Structure-based drug design involves developing and optimizing chemical structures with the aim of identifying compounds suitable for clinical testing as potential drug candidates.

According to Pedro Henrique Camargo Penna, one of Naiad’s founders, in Phase 1 of its PIPE project the firm focused initially on the search for molecules that act agonistically on oxytocin receptors, exciting them and potentially being useful to treat mental or neurological disorders.

“We were successful in this initial phase, and were able to find several molecules that bind to oxytocin receptors but aren’t yet used as drugs,” Penna said. “The most promising molecules were selected after a round of in vitro testing and displayed significant potential to serve as a basis for the development of drugs to resolve various problems and neurological conditions, especially chemical dependence and certain symptoms of autism.”

This stage of the project also detected several molecules with potential for use in combating some relatively frequent types of cancer. “Oxytocin receptor antagonists have already been studied for use in treating premature ejaculation and improving in vitro fertilization success rates, for example, and recent research shows that blocking oxytocin receptors can substantially reduce certain tumors,” Penna said. “We, therefore, decided to expand the project and began screening for molecules that act on oxytocin receptors via different mechanisms, focusing on value creation under a range of scenarios.”

Following these successful in vitro tests, Phase 2 of the PIPE project, which has recently been approved, will focus on discovering molecules that not only act on oxytocin receptors but also display optimal characteristics in the way they are metabolized by the human body.

“In Phase 2, we’ll focus on identifying molecules with optimal pharmacodynamic and pharmacokinetic activity,” Penna said.

In structure-based drug design, he explained, proteins are designed three-dimensionally, atom by atom, using computer models of the molecules and then deploying different screening techniques to target the receptor of interest.

“There have been significant technological advances in the field,” he said. “For some time, it has been possible to screen millions of molecules in a computer. Powerful graphics cards and sophisticated software have boosted the screening process to encompass billions of molecules for each target, including oxytocin receptors. Artificial intelligence has produced even more significant advances.”

Computational capacity

In practical terms, the firm’s entire computational capacity is leveraged to find out whether the molecule matches the receptors. The next step involves functions that calculate a score for the degree to which the match is favorable. “This approach has enabled us to achieve a huge increase in the success rate in selecting molecules with potential for in vitro testing,” Penna said. “We work with high-performance computers that process a very large volume of data. The software is also a key factor, in which we’ve invested heavily. Although a large part of our platform was developed in house, we also brought in fully validated programs developed by third parties.”

Naiad has identified molecules that act on other GPCRs besides oxytocin receptors, he added. These receptors located on cell surface membranes are involved in biological processes so fundamental that some 30% of commercially available drugs act on this group of proteins.

“GPCRs play a key role in such processes as hormone response and communication between neurons. They modulate all kinds of biological processes, from the most basal to the highest level, from cellular metabolic modulation to regulation of mood and attention. For this reason, one or another GPCR is involved in practically every disease,” he said.

Naiad’s business model focuses on value creation via licensing of selected molecules to large pharmaceutical companies. “Taking the development of molecules as far as clinical trials isn’t our current focus. This stage of development is best conducted by the big companies,” Penna explained. “On the other hand, we have a great deal of experience in the computational part and screening for drug discovery. We, therefore, want to take development to the end of the preclinical part and then seek to license our innovations.”

Specialized team

To this end, Naiad has a team of highly qualified consultants. Penna is the CEO, has a degree in science and technology from UFABC, and is finishing his direct doctorate in biosystems. The technical director, Valderes de Conto, has a degree in veterinary medicine from the Federal University of Viçosa (Minas Gerais state), and a PhD in genetics from the Federal University of Rio de Janeiro (UFRJ), with postdoctoral studies at UFABC.

The other co-founders besides Penna and Conto are Antônio Kimuz Braz, a professor of molecular genetics and genomics at UFABC, and Maurício Coutinho Neto, a professor of computational chemistry at UFABC. Both are equity partners in the firm. Biologist Cláudio Miguel da Costa Neto, who acts as a consultant to the startup, is a professor at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP). Chemist Gerhard Gross, a specialist in drug development with ample international experience, also acts as a consultant.

Penna recalled that the startup was founded in 2018 after receiving a capital injection from a group of angel investors. “Some of them were entrepreneurs in the financial services industry. They were all tech enthusiasts and interested in artificial intelligence,” he said. One member of the group, Ricardo di Lazzaro Filho, now sits on the board.

“Ricardo was one of our mentors throughout the process of formation and is with us now as a board member. The angel investors decided to inject more capital at a later date, and they also helped us with implementing the protocols that are operating now. In September 2021, we received an institutional investment from Green Rock, a São Paulo-based venture capital firm,” he said.

Negotiations

Naiad is currently structuring its next round of fundraising from private investors, scheduled to close by early 2023. The firm will take part in the Brazilian delegation to the BIO International Convention, which will be held in June at San Diego, California. It has been invited to attend by the Brazilian Association of Active Pharmaceutical Ingredients Industry (ABIQUIFI) and the Brazilian Trade and Investment Promotion Agency (ApexBrasil). It plans to take this opportunity to discuss its project development pipeline and will be open to negotiations with investors and prospective business partners.

“Our methodology is proving very efficient in the detection of molecules with high pharmacological potential. Our numbers show this, and the market is watching our results. We’re confident and excited at the chance to make a significant contribution to the development of new medications,” Penna said.