“When you are seeing great results in your research lab, you think that everything has been done. But then when you try to humanise your drug, a new adventure starts, because the CMC process is very difficult. In my opinion, it’s as difficult as demonstrating efficacy.” – Mari Carmen Álvarez
Mari Carmen Álvarez PhD. is the Managing Director of Tetraneuron, a pioneering Spanish biotech developing novel gene therapies for neurodegenerative diseases. With nearly two decades in biotech leadership, she founded Valencia University’s first biotech spin-off and brings expertise spanning innovation management, business development, and fundraising from seed to Series A.
In the latest PharmaSource podcast episode, Mari Carmen explains why scaling gene therapy development requires more than strong science, how to navigate the complex CDMO ecosystem, and what she learned from a previous biotech failure that shaped her approach to leadership and patient impact.
Building Scientific Foundations Before Business Growth
Mari Carmen emphasises that early-stage biotechs must prioritise scientific strength over rapid business expansion. Her approach focuses on maintaining team cohesion during the transition from academic research to commercial development.
“From the very beginning, you need to know that you are not able to do everything by yourself, and you have to navigate very carefully between your budgets and the needs of the company,” she explains.
The key is managing the cultural shift from laboratory to business environment. “The movement from a lab to a company should be very smooth and easy, applying common sense. If you try to persuade these people to enter a business environment in a very fast way, the results are worse than if you move very slowly, step by step, to a more mature business.”
When it comes to capability gaps, Mari Carmen identifies CMC as a critical area requiring external expertise. “When I joined the company, we realised that we needed strong knowledge around the CMC area. CMC is something we can talk about for many hours, because it’s a specific topic in gene therapy development.”
Strategic CDMO Selection and Partnership Building
Tetraneuron’s external manufacturing strategy relies heavily on building strong relationships with experienced CDMOs. The company’s approach to partner selection demonstrates the importance of thorough due diligence and geographic considerations.
“First of all, you need to take your time to select the good CDMO for you. In our case, we chose a CDMO here in Spain with great experience in gene therapy – they have been one of the pioneers in manufacturing these advanced therapies,” Mari Carmen explains.
The partnership model extends beyond transactional relationships to trust-based collaboration. “The relationship that you have with your provider needs to be strong, and you need to trust your partner. We can’t have in-house specific experts in every area of the process, so we work with consultants, but the relationship with your provider is key.”
Tetraneuron employs a hybrid internal-external model that combines CDMO expertise with consultant networks. “We have an army of consultants to help us in different steps, but the relationship with your CDMO provider needs to be strong. You need to trust your partner because we don’t have in-house specific experts in every area.”
Managing CDMO Manufacturing Uncertainty and Risk
Mari Carmen provides candid insights into the realities of gene therapy manufacturing through CDMOs, emphasising the need to accept inherent uncertainty in the development process.
“CDMOs try to be robust, but they never guarantee the result of the next step. So you have to navigate this instability. Every scale, from two litres to ten litres, every step is a great adventure because you never know what’s going to happen with your product,” she explains.
The scaling challenges are particularly acute in gene therapy manufacturing. “The process from manufacturing a gene therapy in microlitres to millilitres or litres is a big jump. Every scale is a great adventure because you never know what’s going to happen with your product.”
These manufacturing complexities are compounded by the financial pressures unique to gene therapy development. “When you are developing gene therapy, all the manufacturing process is very expensive compared with small molecules, so you need to be well funded. The risk that investors perceive around gene therapy is higher, including the failure in the manufacturing process.”
Navigating Gene Therapy’s Unique Manufacturing Challenges
Tetraneuron’s approach to Alzheimer’s therapy presents unique manufacturing complexities. The company targets a master gene regulating neuronal homeostasis, which typically creates toxicological issues when expressed in vivo.
“Most strategies involving master gene regulation have toxicological issues because you are working with a master gene involved in many relations with other genes. In our case, we have never seen this toxicity, which is unique in the field,” Mari Carmen notes.
Learning from Failure and Managing Long-Term Vision
Mari Carmen’s previous experience with a failed myotonic dystrophy company provides valuable perspective on biotech leadership. After ten years of development, the company closed due to scale-up problems with their small molecule approach.
“I felt very bad, like a personal loser. But with time, I realised it wasn’t about me, it was about patients. All during these ten years, we kept researching and adding new data around the disease.”
This experience shaped her current approach to investor relations and team motivation. “You need to manage the expectations of investors. Every delay is a year of work. In our case, investors are not used to investing in biotech, so managing expectations is crucial.”
The long-term nature of biotech development requires a patient-focused mindset. “Every work you are doing daily has an impact or will have an impact on patients. Maybe it’s in ten years, maybe twenty years. The new information you discover around the disease can help others find the final cure.”
Future Outlook for Gene Therapy Manufacturing
Mari Carmen sees the gene therapy landscape evolving beyond rare diseases toward common conditions like Alzheimer’s. This shift requires addressing manufacturing costs and accessibility challenges through improved CDMO partnerships.
“Companies like Tetraneuron are approaching gene therapy for common diseases, working outside the rare diseases field. If we can combine knowledge around gene therapies with good manufacturing technologies, making prices lower and therapies more accessible, that could be game-changing.”
Success requires collaborative effort across the entire ecosystem. “This needs commitment not only from therapy sponsors but also from CDMOs and big pharma. We need to work altogether.”
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