Building internal manufacturing as a preclinical company

By: Ryan Crisman, Ph.D., co-founder and Chief Technical Officer

In the fast-paced landscape of biotechnology, the demand for advanced tools and techniques is on a relentless rise. Lentiviral vectors (LVVs), which are a cornerstone in immunology and cell and gene therapy, have garnered significant attention due to their versatility and potential applications in cancer, genetic diseases, vaccine development, and academic research. Umoja seeks to harness the full potential of LVVs to overcome the challenges in the current CAR-T space by using LVVs to directly modify a patient’s immune system in vivo to fight cancer – and potentially treat certain forms of auto-immune diseases as well. To unlock this vast potential, establishing a dedicated LVV manufacturing facility was not a choice, but a necessity. In this blog, we’ll delve into the reasons why Umoja built our own LVV manufacturing facility and how it is paramount in advancing access to life-changing therapies.

Accelerating benchtop to commercial
There are less than 50 contract development and manufacturing organizations (CDMOs) that can manufacture cGMP LVVs, most of them focusing on autologous cell therapy. About half of them are supplying active pharmaceutical ingredients (APIs) for commercial product. As a start-up with a long time to wait before a commercial launch, we were not a priority within these facilities.

Of the remaining, many did not have a customer yet, and we were not comfortable being the first, especially with our enhanced surface engineering of our viral particles and analytical needs as a novel direct injection drug product.

We were left with a handful of CDMOs that had 16+ month lead times for one cGMP run.  They offered minimal flexibility during that window if we wanted to make changes or needed another batch. Additionally, we would be required to transfer to a commercial facility if we showed clinical success.

By building our own facility, we have the flexibility and adaptability that is critical during early-stage drug development and a clear line of sight to commercial scale production.  

Novel recipe vs high throughput production
CDMOs are critical to the success of the biotechnology industry. Most are great at taking a known recipe and repeating as needed. However, the production and release of our surface-engineered LVVs is a novel process that requires a deep understanding of the interplay of the biology, analytics, and how the process impacts the product. This requires strong collaboration from our early discovery Vector Biology team through our Manufacturing and Quality organizations to make sure we maintain consistency in vector production and ensure reproducibility in experiments and clinical trials. A dedicated facility with deep scientific knowledge of our drug product, a robust analytical platform, and trained personnel could only be met by building out our own internal capabilities.

Scalability and Cost Efficiency
The demand for LVVs is projected to increase significantly as cell and gene therapies progress from research to clinical applications. Competition for capacity at CDMOs continues to rise, resulting in less flexibility and adaptability for start-up companies. Additionally, trained personnel who know how to produce these complex biologics are becoming more and more scarce. Building our internal manufacturing facility allows us to hire and retain a team with the flexibility needed for early clinical trials while providing us the adaptability for scalability, enabling production to meet growing demands efficiently. Additionally, economies of scale can be realized, reducing production costs in the long run and making these therapies more accessible to patients.

Attracting Talent and Collaboration
Establishing an internal cutting-edge LVV manufacturing facility has been a significant factor that has allowed us to attract the top talent in the cell and gene therapy sector. Those of us who have lived the comparability challenges in the autologous cell therapy space know that having trained personnel that control our manufacturing destiny allows us to move our products forward while still providing the flexibility needed in the early stages of clinical trials. Skilled researchers and technicians are drawn to facilities that own their own products and are equipped with state-of-the-art tools and resources. Moreover, such facilities encourage collaboration with academic institutions, big-pharma companies, and other research organizations, fostering innovation and knowledge exchange.

Ensuring Supply Chain Reliability
The COVID-19 pandemic highlighted the fragility of global supply chains for critical medical resources. By having a dedicated manufacturing facility, we reduce reliance on external suppliers and ensure a stable and uninterrupted supply of LVVs, especially during times of crisis.

As we pave the way in a new class of immunotherapies, being a leader at the intersection of scientific innovation and commercially viable drug products is crucial. The establishment of our own LVV manufacturing facility is both a strategic move and an imperative step towards realizing the full potential of LVVs in cell and gene therapy. With our facility, we will accelerate a new class of cancer therapies, enabling our team to work together to provide the best product and process to have the biggest impact on patients. The next question for us was where to build our facility. In my next blog post I will discuss why we chose Colorado as our location to change the way we think about cancer immunotherapy.