Inside AviadoBio And Astellas's Shared Mission To Bring Gene Therapy To Patients With FTD-GRN

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

Gene therapy holds tremendous promise for neurodegenerative diseases, but the road to realizing its potential is long, complex, and often uncertain. For AviadoBio and its partner Astellas, that challenge is a call to action. I caught up with Lisa Deschamps, CEO and Executive Board Member of AviadoBio, and Richard Wilson, Primary Focus Lead for Genetic Regulation at Astellas, to learn more about their work to advance AVB-101, an investigational gene therapy for frontotemporal dementia with progranulin mutations (FTD-GRN). They reflect on the drivers behind their perseverance, the strategic value of their partnership, the importance of staying patient-focused, and what it takes to navigate the scientific, regulatory, and translational hurdles in rare neurodegenerative disease. Here’s what they had to say.

Gene therapy development is known for its long timelines and complex hurdles. What drives your perseverance as you work to bring AVB-101 to patients with frontotemporal dementia with progranulin mutations (FTD-GRN)?

Lisa Deschamps, CEO and Executive Board Member, AviadoBio: We are driven by the hope that we can make a fundamental difference in the lives of people living with FTD-GRN. I’ve seen firsthand the transformative effect gene therapy can have in rare disease where entire treatment paradigms are changed. Globally we have had a very positive experience working with regulators to advance this program to the clinical stage and into trials for patients. We are motivated by the challenge of finding a path forward for people with FTD, one of the most common forms of dementia in those under the age of 65. FTD is frequently misdiagnosed and underrecognized, and there are no approved disease-modifying treatments. Ultimately, families living with this devastating disease are the reason we remain steadfast in our commitment to advance AVB-101.

Your recent collaboration with Astellas represents a major milestone for AviadoBio. How does this partnership reinforce your ability to navigate the scientific, regulatory, and commercial challenges of gene therapy?

Deschamps: For me, this partnership reflects what’s possible when biotech innovation meets global pharma scale with both sides truly invested in the outcome. At AviadoBio, we say we’re relentlessly chasing cures. It’s essential to do that alongside a partner who believes in the same mission. From our perspective, it’s more than science; what drew us together was a shared belief in delivering breakthroughs for patients with no other options. Our partnership with Astellas offers the opportunity to collaborate in clinical development, manufacturing and commercialization with an organization who is committed to our mission and genetic medicines. Astellas has the expertise, passion, and global footprint to bring these medicines into the hands of patients all around the world. For a small biotech like AviadoBio, that’s transformative.

Richard Wilson, Primary Focus Lead, Genetic Regulation, Astellas: From Astellas’ side, we know the work AviadoBio is doing is a strong fit, expanding our work in gene therapy in line with our long-term strategic view – and in an area where AviadoBio brings expertise and capabilities with their highly differentiated approach in an increasingly competitive space.

We also felt that the partnership would enable us to achieve more, together. At Astellas, we are determined to create a better future for patients living with serious and underserved diseases. With ambitious partners such as AviadoBio, our passionate teams are combining expertise and capabilities across discovery, development, manufacturing and commercial so we can help bring the next generation of gene therapies to as many patients as possible, as quickly as possible.

FTD-GRN is a particularly devastating and under-recognized condition. Why is it important for the industry to remain committed to developing therapies for rare and complex neurodegenerative diseases, even when the path isn’t straightforward?

Deschamps: As we move forward, there is a tremendous opportunity to enhance awareness and education in this disease area. FTD is one of the most common forms of dementia in people under the age of 65, and yet, it is widely under-diagnosed. People diagnosed with FTD-GRN are often in the prime of their lives and the disease has a detrimental effect on their overall quality of life – impacting relationships with family and friends, employment, and financial security. Treating dementia is enormously challenging, which is why the unmet need remains so high. At the recent FDA Cell and Gene therapy roundtable discussion, we saw clear signals that the agency is increasingly prioritizing faster and more flexible approval pathways for rare, pediatric, and gene-based therapies. Through our research efforts, we know that one discovery can unlock clues to the next discovery; this is why we remain committed to developing new treatments for rare diseases. We are continuing to contribute to a greater body of scientific knowledge every day with the goal to develop therapies for patients who need them.

Wilson: Patients need us to remain committed. A few months ago, I had the privilege of joining AviadoBio for The Association for Frontotemporal Degenerations’ Hope Rising Benefit. It was powerful to listen to so many stories of lives changed by the diagnosis of FTD, as well as the resilience and courage that followed.

Scientific and technological advances are also making it increasingly feasible to overcome challenges in neurodegenerative diseases, like the blood-brain barrier. AVB-101’s intrathalamic delivery strategy is designed to bypass this barrier and enable precise distribution to areas of the brain most affected by the disease. By partnering, we as an innovation community have the potential to truly transform care by bringing a much-needed therapy to the community.

Many companies face setbacks in early-stage gene therapy development. What lessons have you learned through AviadoBio’s journey that could help other biotech leaders remain resilient and patient-focused?

Deschamps: There are many lessons we all have learned along our journey, but the most important one to always remember is to remain true to our mission. For me, and for our team at AviadoBio, that is to develop life changing medicines for neurological diseases. When you keep that mindset at the heart of everything you do, decisions become much easier. Certainly, the last few years in biotech have been particularly challenging – the macro environment, especially as it relates to fundraising – has been difficult. But at times like this, I believe the best lessons are gained. The need to prioritize, remain disciplined, financially prudent, and laser-focused on advancing your programs becomes your core and only focus. We know that patients are waiting, and so we try to ensure we hire the best talent, focus only on what can advance our programs and constantly seek to understand and learn from others with the goal to progress forward to deliver transformative medicines.

Wilson: From the pharma perspective, I would advise any biotech leader to immerse themselves in the broad innovation ecosystem – from industry to academia and regulatory partners – to get early feedback on study design and endpoints. Our collective understanding of how to effectively translate and advance early science continues to improve, so take full advantage of that.

In terms of remaining patient-focused, it is exciting that we’ve seen a critical, industry-wide shift in this direction, and real action in practice. However, challenges around how we best put patients at the heart of trials still exist – from slow enrollment to drop-out rates, and complex protocols that don’t always meet patients’ needs. Increased and earlier patient involvement through a continuous ‘feedback-loop’ approach could help address these challenges.

The AVB-101 approach includes targeted delivery into the brain using AAV vectors. What technical or translational challenges has your team had to overcome, and how has perseverance played a role in addressing them?

Deschamps: Effectively crossing the blood brain barrier in treating neurological conditions has been a key challenge across the field. Our investigational gene therapy, AVB-101, has a very targeted and precise delivery approach. It is administered directly into the thalamus, bypassing the blood-brain barrier. The thalamus is an “information relay hub” for the brain, receiving sensory and motor information from the body, which it then distributes using billions of pathways throughout the brain. It is also one of the brain areas found to have the highest expression of progranulin. When AVB-101 is administered into the thalamus, it delivers a working copy of the GRN gene to thalamic neurons. The aim of our therapy is to increase progranulin levels to as close to normal as possible throughout the brain. By increasing levels of progranulin in brain tissue, AviadoBio hopes to restore physiological function to patients living with FTD-GRN.

I am incredibly proud of our team and the perseverance they demonstrated to develop the expertise, capabilities, and infrastructure to implement the first ever intrathalamic delivery in FTD – a global first. In addition, our team activated the ASPIRE-FTD trial in multiple countries around the world ensuring that we had a patient-centric global footprint to reach countries where FTD is prevalent. We have 9 regulatory approvals and are currently recruiting in the U.S., U.K., Poland, Spain, Netherlands, Sweden, and Canada. Our small and nimble team has worked tirelessly to ensure we are working with leading institutions, and while this footprint is ambitious for a Phase I/II trial it allows us to move quickly from the current study to the next phase of clinical development and beyond.

Wilson: While there has been significant progress in gene therapy research and regulatory approvals, one key remaining challenge is producing therapeutic genetic material and viral vector delivery systems efficiently, economically, and at scale to meet demand.

At Astellas, we take a long-term strategic view to R&D. We are clear on our goal of realizing the transformative potential of gene therapy for patients and acknowledge this won’t happen overnight. Over the course of several years, we have built end-to-end capabilities and manufacturing expertise, opening cutting-edge facilities like our gene therapy manufacturing site in Sanford, North Carolina, among others. We are continuing our trajectory of dramatic increases in both productivity and yield; this helps ensure we can support clinical and commercial demand for our gene therapy pipeline well into the future, making us more agile and dynamic.