Photo: KRABS
Published on 04/15/2024
By Roseli Andion | Agência FAPESP – A technique studied by researchers at the Federal University of the ABC (UFABC) in São Paulo state, Brazil, may soon result in a novel alternative for the treatment of patients with atopic dermatitis. The proposed technique using a serine protease inhibitor antibody performed well in laboratory tests, encouraging molecular biologist Marcelo Bergamin Zani to found a company to develop a solution based on the technique.
According to Zani, the biological alternative for treatment of atopic dermatitis formulated with a topical drug is unique. Its only competitor is an injectable medication administered monthly and costing thousands of Brazilian Reais (BRL) per dose.
“That’s unaffordable for most people,” Zani said. “Our proposal will be much cheaper because it’s topical and so a smaller dose can be used.”
Injected doses have to be based on body weight because the drug circulates throughout the organism, whereas the startup’s formula is applied to the skin locally and in far smaller doses.
The competing treatment also has a different formulation and target. “Their drug doesn’t combat the characteristics of the disease. It attacks the immune system’s signaling molecules. It has several side effects since it blocks molecules relating to immune system signaling in general. Our product acts on the enzyme that causes epidermal flaking,” Zani explained.
Shortly before the pandemic, the startup won approval for a research project from FAPESP’s Innovative Research in Small Business Program (PIPE), but funding began only in October 2021 owing to the lockdown.
Patent application
KRABS is now negotiating with a Brazilian pharmaceutical company to produce the medication once it has passed clinical trials in human patients and has won approval from ANVISA, the regulatory agency responsible for supervising pharmaceuticals and medical devices. Approval is expected early in 2026. Meanwhile, UFABC has applied for a patent in Brazil, and KRABS has filed patent applications in the United States and Europe. The solution is unique worldwide, and the startup holds sole licensing rights.
According to Zani, atopic dermatitis is caused by enzyme or immune dysregulation and is often lifelong with no known cure. Treatment with a biological drug is advisable, as non-biologicals can have adverse effects on overall health in the event of long-lasting exposure.
“It’s best to use a product that has no adverse effects on health. Biologicals are suitable in this situation. The alternative we offer is unique,” Zani said.
KRABS also develops novel antibodies using phage display, a technique that can be deployed to produce molecules capable of functioning as drugs or diagnostic tools based on monoclonal antibodies. The quick tests used to detect various diseases are typical examples.
For molecular biologist Jair Chagas, a retired professor at the Federal University of São Paulo (UNIFESP) and a co-owner of KRABS, anyone interested in developing monoclonal antibodies can commission the startup to do so on its platform. “We have a library of 10 billion different molecules that can recognize a wide array of targets. It’s important to note that we don’t do animal testing,” he said.
Antibodies can be selected relatively easily via the platform, and placed using molecular biology techniques in cells that will express them. Indeed, this is how the researchers identified the antibody against kallikrein 7 for use in the atopic dermatitis drug. They selected a molecule from the library that inhibits the enzyme and developed a hydrogel formulation.
Common in dogs
Atopic dermatitis is common in dogs, and the startup plans to test the product on canine subjects. “It’s the main complaint of dog owners. We have an animal model that doesn’t require inducing the disease because it already exists and can be treated with this product,” Chagas said.
While development of the drug continues, the startup is preparing for the stages that will follow clinical trials in humans. “For whoever manufactures the product, there will also be an advantage of it already existing in the pet market if the dog model proves successful,” Chagas said.
“We’ve conducted different trial phases at the same time so as to have the structure ready when the trials are completed,” Zani said.
Plans are being laid for the creation of protocols for human clinical trials. “We want to prepare the documentation so that it’s ready as soon as we begin these trials,” Chagas said.
There is also a possibility that the formula can be indicated for Netherton syndrome, a rare recessive autosomal disease. If so, the medication will be treated as an orphan drug and will be eligible for fast-track approval by ANVISA and the Food and Drug Administration (FDA) in the US.
According to Zani, an economic assessment by the team shows the product can be marketed for between BRL 150 and BRL 300 per tube (now about USD 30-USD 60), depending on certain variables. The price to consumers will evidently be far less than the competitor’s. “For the veterinary market, the product is certainly worth making,” Chagas said.
KRABS is currently being incubated at UFABC. It is also participating in the Center for Translational Science and Development of Biopharmaceuticals, one of FAPESP’s Science for Development Centers (CCDs). This one is hosted by São Paulo State University at its Botucatu Center for Research on Venoms and Venomous Animals (CEVAP-UNESP), where a biological input factory is being set up. “That includes products like the one we’re developing,” Chagas said.
The startup plans to use the factory, when ready, to make the first few product batches. Researchers at FAPESP’s CCDs work on projects aimed at solving specific economic, technological and/or social problems. “Our firm is tied into the research and development system as part of this program,” Chagas said.
Source: https://agencia.fapesp.br/51398
