One of the major challenges in modern pharmacology is delivering treatments inside cells. This process, known in the industry as drug delivery, must ensure that medications reach the specific organs, cells, and tissues that need them. However, this remains an unmet need. At the Center for Research in Biological Chemistry and Molecular Materials (CiQUS) of the University of Santiago de Compostela (USC), researchers are tackling this challenge through the TraffikGene-Tx project. The core of this study is a promising technology that enables gene-based drugs to safely cross cellular barriers and reach the interior of cells. The project is now in its final stages and in the process of launching a spin-off.
"This is a highly versatile technology that could be applied to various advanced therapy concepts," says Alberto Fuertes, a CiQUS researcher and one of the promoters of TraffikGene. Unlike existing mechanisms such as lipid nanoparticles or viral vectors, this technology is peptide-based, making it more biomimetic and easier to optimize. "Our value proposition is to design custom transport peptides to address the limitations that other drug delivery technologies still face," he adds.
The project is currently in the technology transfer phase. As Fuertes explains, many research initiatives attempt to reach the market but fail because they cannot demonstrate the ability to manufacture molecules in a relevant regulatory environment. In pharmacology, this framework consists of two quality standards: GMP (Good Manufacturing Practices), which govern how the product is manufactured, and GLP (Good Laboratory Practices), which regulate how research and analysis are conducted.
Demonstrating production capacity and scalability
TraffikGene has already demonstrated the ability to manufacture its most advanced transport molecule candidate under GMP conditions and has proven its effectiveness in preclinical mouse models. "Our transport molecules achieve over 90% selectivity to the spleen or lungs of mice, and our technology allows us to perform successive chemical optimizations to modify these transport properties," Fuertes explains. While they initially lacked in vivo data, they now have results supporting a portfolio of potential transport products that can reach organs and tissues where competitors face limitations due to restrictions in optimizing the chemical properties of their carriers.
The TraffikGene team must advance toward commercialization while meeting industry requirements. "We are working with a CDMO (Contract Development and Manufacturing Organization) to develop a standardized and scalable process for mixing our transport molecule with therapeutic nucleic acids," Fuertes explains. A CDMO is an external company responsible for developing a compound—in this case, a peptide—scaling it from the lab to production, and manufacturing it under regulated standards.
In the lab, researchers worked with small-scale formulations, typically under one milliliter, but in the future, they will need to achieve industrial-scale production. As a pharmacological process, every step must align with regulatory requirements. Before bringing therapeutic formulations into a clinical setting, they must also conduct a GLP toxicology study to assess the compound's safety by inoculating different TraffikGene formulations at scaled doses in rats, demonstrating non-toxicity. "Our EIC Transition project has funding to carry out this GLP study this year, which would be a significant milestone for the spin-off and would reinforce the excellent safety profile we have demonstrated in mice so far," Fuertes notes.
Spin-off roadmap
The idea of creating a company began in 2018 during Dr. Marisa Juanes' thesis, where she developed this technology as a tool to modify cells in culture under the supervision of Professor Javier Montenegro. Juanes and Montenegro, along with Dr. Irene Lostalé-Seijo, make up the TraffikGene founding team. The research group had already conducted competitive studies with commercial kits and reagents for nucleic acid transport, finding that some TraffikGene candidates were more effective and less toxic than existing commercial solutions.
They initially considered commercializing the technology as a lab kit, but the pandemic prompted a shift toward a more ambitious focus on in vivo applications and mRNA therapies. "This change in direction is one of the reasons it has taken us several more years to reach this point," explains the CiQUS researcher. Now, TraffikGene-Tx's value proposition is clear: "We are effective, more affordable, less toxic, and can optimize the technology to reach organs that others cannot easily access."
Collaborations and biotech funding
At this stage of seeking collaborations and investment, it is important to understand what the TraffikGene team needs: "We need strategic partnerships with companies," says Fuertes. The starting point is market interest in USC's technology and the opportunity to test the developed transport molecules in laboratories. They have already established a collaboration with a Norwegian biotech company to test the combined delivery technology with their molecule of interest, verifying its potential and advantages.
The next step is to partner with a major pharmaceutical company. "This is a challenge in itself because they have very defined objectives," notes Marisa Juanes, though she believes it is an achievable goal. Even though such industries already have candidates for defined therapeutic targets, selectively reaching the site of action—such as a specific cell subtype within the lung—remains a problem that limits therapy development. Sometimes, only 0.5% of the active ingredient reaches its target, so low efficiency can lead to side effects. This is where TraffikGene's advantage lies: selectivity without compromising efficacy and safety.
Simultaneously, they are seeking private investment to cover the future expenses of the soon-to-be-established company. "The ideal scenario would be to secure investors from Spanish biotechnology-focused funds," says Juanes. The perfect outcome would be investors who not only provide capital but also a network of contacts to grow the business—a mechanism known as smart money.
How to commercialize successfully?
In biotechnology and pharmacology, the concept of commercialization is complex, as Alberto Fuertes explains. Obtaining approval from the European Medicines Agency (EMA) for product commercialization can take up to 10 years due to the need for highly regulated preclinical and clinical trials, which require significant investment. Reaching the clinical stage may take shorter timelines, such as four or five years. In this case, the spin-off's revenue model would involve co-development agreements with other companies, leading to licenses and royalties.
"It is very difficult for a small start-up developing preclinical technology to complete this entire process alone," Fuertes notes. Therefore, it is common for high-risk, high-potential projects like TraffikGene to partner with larger pharmaceutical companies to maximize impact: "There are not many cases of spin-offs that commercialize their own product. If things go well, acquisition opportunities may arise within five to ten years, allowing initial investors to recover their investment," he explains.
In the medium term, the researcher's goal is clear: "To see TraffikGene technology as part of a product in clinical development, as this would be the best way for our efforts to impact patients." In a market where drug delivery has been booming since 2020, TraffikGene could become a key enabler of advanced therapies. Ultimately, the motivation behind launching a spin-off is the potential to help patients: "In my opinion, there is nothing more rewarding for a researcher than seeing a lab-born project make a real difference in people's lives," Fuertes concludes.
By Andrea Veiga, GCiencia
The CiQUS holds the CIGUS recognition by the Xunta de Galicia, that accredits the quality and impact of its research, and receives financial support from the European Union through the Galicia FEDER Program 2021-2027.
de izq. a dcha: Alberto Fuertes, Marisa Juanes y Javier Montenegro en el CiQUS