Geoff, you have been in senior positions in many companies in the life sciences field. What exactly led you to become the head of Generation Bio?
My journey to leading Generation Bio is deeply rooted in my medical background and passion for addressing unmet needs in rare genetic diseases. Trained as both a pediatrician and an internist, I spent significant portions of my career developing rare disease drugs at Genzyme and Swedish Orphan Biovitrum (Sobi). These experiences highlighted two major gaps: the need for early genetic intervention and the challenge of making cutting-edge treatments globally accessible. Inspired by the transformative potential of medicines and the limitations in providing them broadly, I sought technologies that could bridge these gaps.
The turning point came after my tenure at Sobi, when I took time to explore advancements in genetic medicine. I was drawn to Generation Bio's innovative, non-viral approach to genetic delivery using redosable lipid nanoparticle delivery and long-term DNA cargo. This approach promised a solution to early and scalable intervention, offering the potential to treat genetic diseases from childhood in a way that could be adjusted and sustained over a lifetime. This vision and the company's early stage of development with just 12 employees in 2017 convinced me to join and lead the efforts towards realizing this transformative potential.
There has been a recent restructuring at Generation Bio. What were the reasons for behind that move?
The restructuring at Generation Bio reflects our commitment to innovation and our response to the inherent challenges in biotechnology development. Our initial focus on developing a new modality platform, a feat rarely accomplished in the public domain, required us to address two major challenges: unlocking non-viral genetic medicines and overcoming the limitations of delivery to specific tissues such as the liver and immune cells. Our journey has been about creating a scalable and redosable delivery system that can reach beyond these limitations, opening pathways to treat a broader range of diseases.
This journey led to the invention of a targeted lipid nanoparticle system capable of efficient tissue delivery beyond the liver, and the development of 'immune quiet' DNA that evades innate immune detection. Recognizing our readiness to transition from invention to building a portfolio of medicines, we made strategic decisions to focus on core technologies and ensure financial stability through to 2027. This strategic pivot is driven by our advancements in delivery systems and DNA cargo, setting the stage for clinical program development in a challenging macroeconomic environment.
Aare you the only ones who have successfully developed immune quiet DNA?
Yes, we believe we are at the forefront of developing immune quiet DNA. This breakthrough technology has demonstrated its ability to evade innate immune detection effectively, a critical advancement verified through extensive testing in both mice and monkeys. Monkeys, in particular, offer a reliable model for human immune system responses, making our achievements in this area particularly promising. This innovation marks a significant milestone not only for Generation Bio but potentially for genetic medicine as a whole, paving the way for new treatment paradigms.
Why do you prefer DNA over RNA therapeutics?
Our preference for DNA over RNA is grounded in the inherent advantages of DNA for lasting therapeutic impact. Messenger RNA (mRNA) therapies, while transformative, have a limited duration of action, requiring frequent dosing to sustain therapeutic effects. DNA, on the other hand, offers a sustainable, long-term solution by residing in the nucleus and continuously producing therapeutic proteins over years. This durability allows for more flexible dosing schedules, potentially extending to every five years, and the ability to adjust treatment levels per individual patient needs. Furthermore, our DNA platform is designed to be non-integrating, ensuring it remains separate from the host's chromosomes, enhancing safety and reducing the risk associated with gene editing. This approach underpins our strategy to provide more effective, long-lasting, and adaptable genetic treatments.
Can you talk about your invention called RES in terms of scalability potential?
The scalability of our drugs stems from two components: the lipid nanoparticles and the DNA cargo. Our breakthrough, rapid enzymatic synthesis (RES), addresses the costly and time-consuming production of structured DNA, traditionally dependent on cell systems. This process historically required extensive purification over six to eight weeks, producing a variety of DNA formats limited by cellular capabilities. RES revolutionizes this by eliminating the need for cell culture, allowing us to create structured DNA in any format within just four hours, resulting in almost 100% pure single DNA species. This not only accelerates production but also significantly enhances purity and scalability, marking a pivotal advancement in genetic medicine by offering speed, purity, and the ability to scale efficiently.
Do you intend to develop your own therapeutics as well?
Our primary goal has always been to make medicines. The strategic shift we made last year to extend our cash runway was aimed at starting product development, especially focusing on combining our specific delivery technology with genetic cargo.
Initially, we are using messenger RNA for an in vivo approach to treat sickle cell disease and beta-thalassemia, aiming to reprogram blood cells directly within the body, bypassing the complex and costly ex vivo methods. This innovative approach significantly reduces production time and costs, providing a more accessible and effective treatment option, potentially reaching beyond the 1-2% of patients currently treated due to these limitations.
How do you assess the investment climate for a company like yours today?
The investment climate for biotech and life science innovation, while challenging, holds immense potential for transformative impacts on health and economic growth. Developing new modalities is capital-intensive and requires a long-term investment horizon. However, shifts in the macroeconomic environment can influence investor focus, often shortening their outlook to immediate returns, which poses challenges for preclinical and early-stage companies like ours. Despite these challenges, it is crucial for companies in our sector to manage resources efficiently to navigate through periods of economic contraction and expansion, ensuring progress even in a volatile investment climate.
Are you optimistic about the immediate future of the biotech industry and your company's objectives?
While I am optimistic about the continued acceleration of biotech and life science innovation, I remain cautious about the near-term financing environment for our sector. The pace of innovation is unlikely to slow, but 2024 might continue to pose challenges for life science financing, particularly in an election year. Our aim is to position Generation Bio to navigate through this period, ensuring we are well-prepared for when the market begins to recover. It is a time of adaptation and resilience, as we face conditions not seen in decades, but I believe in the eventual recovery and growth of the biotech sector.
In a few words, why should readers remember Generation Bio?
Generation Bio stands at the cusp of a new era in treating genetic diseases, striving to mark a before and after in the field of cell and gene therapy. Our vision is to transform the treatment paradigm to make therapies redosable, sustainable, and accessible on a global scale, tackling diseases in previously unreachable tissues. We envision a future where treating genetic conditions is as routine and drama-free as refueling your car, emphasizing safety, redosability, and adaptability to the needs of patients worldwide. This ambition to fundamentally change the trajectory of genetic disease treatment is what should make Generation Bio memorable to all, especially those new to the life sciences.
