#BIOSPAIN2023Interview | "A global effort must be made to make advanced therapies increasingly cost-effective so that they can reach all patients"

Advanced therapies are a new generation of innovative medicines with significant therapeutic potential, as they allow for the treatment of degenerative and genetic diseases, and even some types of cancer that cannot be addressed through other types of therapies. These therapies are based on genes (gene therapy), cells (cell therapy), or tissues (tissue therapy).

Specifically, gene therapy is based on the genetic modification of cells using viral vectors (such as retroviruses, adenoviruses, or lentiviruses, among others) or non-viral methods (like liposomes or naked DNA). The transportation of genes using viral vectors can be achieved through two methods: ex-vivo and in-vivo. Lentiviral vectors have been more commonly used for ex-vivo administration and are ideal in cases where pathologies affect tissues with high cellular turnover, such as blood. In these cases, disease-causing cells are extracted to be corrected through genetic manipulation in a laboratory setting and then reintroduced into the patient.

However, in recent times, we are witnessing a growing trend of using in-vivo lentiviral vectors. These are therapies in which the vectors themselves constitute the drug.

A photograph that will be analyzed in detail at BIOSPAIN 2023 by VIVEbiotech, Bronze Sponsor. Their CEO, Gurutz Linazasoro, answers some of the main questions posed by the use of lentiviral vectors in cellular therapies and genetically modified cell therapies in this interview.

AseBio. VIVEbiotech develops and manufactures lentiviral vectors used for the treatment of a wide variety of diseases. What are your main lines of work?

Gurutz Linazasoro. Currently, our vectors are being employed in over 40 projects with companies based in Europe, the United States, Australia, and Asia, and our main goal is to adapt to the specific technical and timeline requirements of each client.

VIVEbiotech operates in accordance with FDA and EMA regulations and is accredited to manufacture lentiviral vectors that can be administered both ex-vivo and in-vivo. 40% of the vectors are currently being used ex-vivo in CART therapies for immunoncology, and 20% in rare diseases. We are increasingly producing more vectors for in-vivo therapies, which currently account for 20% of our production.

AseBio. As we have seen, advanced therapies are grouped into gene therapies (GT), cell therapies (CT), and tissue therapies (TT). What are the main differences between each of these three types?

Gurutz Linazasoro. Gene therapy (GT) involves the combination of a gene and a carrier that transports it, containing a healthy variant of a mutated gene causing the disease or a gene that produces a desired effect in a target organ (e.g., releasing a deficient protein or chemical substance). In cell therapies (CT), healthy cells are administered to replace cells destroyed by a degenerative cellular process or to have therapeutic potential by facilitating the release of beneficial molecules.

Cell therapy used as cancer immunotherapy is a combination of cell therapy (CT) and gene therapy (GT) since genetically modified cells are used. Tissue therapy (TT) is a form of cellular engineering using biomolecules that exert different actions to simulate the tissue environment in which cells live.

AseBio. In the case of gene therapy, we have seen that there are two main methods of utilization. What do they consist of?

Gurutz Linazasoro. The transportation of genes using viral vectors can be achieved through two methods: ex-vivo and in-vivo. Lentiviral vectors have traditionally been used for ex-vivo administration and are ideal for cases where pathologies affect tissues with high cellular turnover, such as blood. In these cases, disease-causing cells are extracted from the patient's bone marrow or bloodstream to be corrected through genetic manipulation in a laboratory setting and then reintroduced into the patient.

In in-vivo gene therapies, the therapy (a combination of a healthy gene and a viral vector) is directly administered into the patient's bloodstream. These are therapies in which the vectors themselves constitute the drug. Lately, we are witnessing a growing trend of using in-vivo lentiviral vectors.

AseBio. Recently, from AseBio, we presented the "Map of capabilities of advanced therapies in the biotechnological industry" in Spain. What picture do we observe at the national level regarding the development of these innovative medicines?

Gurutz Linazasoro. I would like to highlight three pieces of information about the Spanish biotechnological companies' ecosystem:

• The vast majority of us are SMEs (Small and Medium-sized Enterprises).
• Market transfer is insufficient.
• There is a lack of large leading companies.

From this data, some of the challenges we face become apparent:

• The need to grow to be competitive, which implies a need for investment.
• Early, real, and loyal public-private collaboration to accelerate the market transfer processes.
• Creating value chains to compensate for the absence of large leading companies as the only way to industrialize Spanish biotechnology.

AseBio. Investment or the need for public-private collaboration is essential for the development of advanced therapies. What are the main challenges and/or barriers they face?

Gurutz Linazasoro. I would add that genuine and loyal public-private collaboration could contribute to achieving one of the major challenges faced by ATMPs (Advanced Therapy Medicinal Products) worldwide, which is their cost. A global effort must be made to make ATMPs increasingly cost-effective so that they can reach all patients without threatening the sustainability of public healthcare systems, while recognizing the tremendous added value that ATMPs provide by curing incurable diseases. The significant economic effort made by biotechnological companies in investing in innovation should be compensated.

AseBio. What does VIVEbiotech expect from BIOSPAIN 2023?

Gurutz Linazasoro. BIOSPAIN is an excellent showcase for biotechnological companies. This year's program is very appealing due to its comprehensive content, and VIVEbiotech will participate by leading a panel with top international partners. As in previous editions, networking will open up work and collaboration opportunities for many companies.

Additionally, the fact that this edition is taking place in Barcelona is also worth highlighting due to the city's pharmaceutical tradition. The modern pharmaceutical industry cannot ignore biotechnology, as the future of medicine is biotechnological.