In the context of cell therapy, product innovation is the introduction of a cellular product that is new or has significantly improved characteristics or intended uses. Over the past decade, a great deal of attention has been given to cell therapy product innovation, as demonstrated by the thousands of cell therapy products that have now entered clinical trials worldwide.
In contrast, process innovation refers to the implementation of a new or significantly improved production or delivery method. In the context of cell therapy, process innovation has received much less attention from the marketplace.
As described by Utterback and Abernathy in 1975, product innovation always precedes process innovation, but there must be an important inflection point in the curve where one overtakes the other.
Unfortunately, one of the major issues with moving cell therapy products from “bench to bedside” has been manufacturing bottlenecks. The heterogeneous nature of cell therapy products has introduced manufacturing complexity and regulatory concerns, as well as scale-up complexities that are not present within traditional pharmaceutical manufacturing. There is a growing need for manufacturing advances to support existing cell therapy products as they move through clinical trials and into the marketplace
As stated by Jon Rowley, Founder and CTO of RoosterBio, “To date, here has been substantial cell therapy product innovation. It is now time for the industry to focus on cell therapy manufacturing process innovation.” RoosterBio has taken on this challenge by commercializing several first-in-class products, including bioreactor media feeds and plug and play bioreactor kits, with the goal to “allow anyone to become an expert in stem cell manufacturing.”
In addition, there is another company that is having a massive impact in the realm of the cell therapy process innovation.
Could Cynata Break the Process Innovation Barrier?
Thus far, the most important company tackling cell therapy process innovation is Australian based regenerative medicine company, Cynata Therapeutics Limited (ASX: CYP). Cynata is the only company in the world with technology for the mass-production of therapeutic mesenchymal stem cells (MSCs) of consistent quality and without reliance on multiple donors. It accomplishes this through its proprietary Cymerus™ platform technology that produces induced pluripotent stem cell (iPSC) derived MSCs.
In the image below, a comparison of the Cymerus™ platform versus first generation manufacturing processes are compared. As shown, the Cymerus™ platform enables MSCs to be manufactured effectively and efficiently by eliminating the need to use multiple donors, multiple times. MSC clinical trials have traditionally struggled with clinical endpoints and demonstrated variable results, because they rely on a heterogeneous cellular product sourced from multiple individuals.
Moreover, the literature now confirms that even modest expansion of MSCs isolated from primary tissue sources such as bone marrow leads to senescence and other profound changes in the properties of the cells. As Cynata’s process relies on expansion at the level of iPSCs it does not suffer from this substantial shortcoming. The Cymerus™ technology overcomes the challenges inherent in first generation production methods by industrializing the production of MSCs.
Cynata’s process innovation represents a giant leap forward in the production of MSCs, which is currently expensive, requires multiple extractions from different donors and relies on excessive expansion (division) of the cells to manufacture sufficient product. Cynata’s unique approach is also an important value catalyst for the company, because it creates lower risk for the company. For the regenerative medicine industry at large, the Cymerus approach represents the first time ever that a consistent and robust MSC therapeutic product can be developed without recourse to the complexities of multiple donors.
In a further first, the Company recently commenced patient treatment in a world first Phase 1 clinical trial involving an iPSC-derived allogeneic product. The trial is expected to enroll a total of 16 patients and complete late in 2017. The approval to commence this trial, which is underway at sites in the UK and Australia, substantially minimizes the regulatory risk surrounding iPSC-derived cell therapy products.
Unfortunately, in pharmaceutical product commercialization, the practical aspects of how to manufacture the product is often a last minute thought. Not surprisingly, this is one of the key market drivers for the burgeoning cell therapy CDMO (contract development and manufacturing organization) industry, which is seeing strong year-over-year growth. There are now more than two dozen cell therapy CDMOs operating worldwide, led by three large market competitors, WuXi Apptec, Lonza Group, and PCT, a Caladrius company.
Today, WuXi Apptec alone possesses 206,000 ft2 of cell therapy manufacturing space spread across three different manufacturing sites in Philadelphia PA (a 16,000 ft2 facility for manufacture of cell therapies, a 45,000 ft2 facility for allogeneic and autologous cell-based products, and a 150,000 ft2 facility for viral vector-based products).
While cell therapy companies struggle with cell therapy process innovation, they will continue to seek solutions through partnerships with CDMOs. Unfortunately, this doesn’t solve the challenges facing cell therapy companies; it only passes these challenges onto third-party manufacturing partners.
Five Keys to Cynata’s Cymerus Technology Platform
There are 5 major advantages to Cynata’s Cymerus technology platform, which include:
- Versatility – Using iPSCs as the basis for producing commercially relevant quantities of MSCs.
- Manufacturing Costs and Complexity – Cymerus eliminates the need to repeatedly source, screen and qualify new donors. Comparability studies are not required for Cymerus product as the source is always the same.
- Manufacturing Scalability – Cynata manufactures MSCs using a starting material, iPSCs, which are capable of essentially limitless self-renewal and so expects to source all cells from a single donation from a single donor.
- Safety – It is expected that the level of purity of Cynata’s cell products will be very high, which may translate into a lower likelihood of stimulating an immune response in the recipient.
- Clinical Predictability – Cynata’s expected reduced batch-to-batch variability may increase predictability of clinical outcomes. With expansion at the level of the iPSC starting material the efficacy issues associated with senescence are minimized.
Additionally, Cynata is one of the earliest market competitors to introduce cell therapy process innovation. It is exactly this unusual focus on cell therapy process innovation that attracted FUJIFILM Corporation, which now holds a 9% equity stake in the company. For those unfamiliar with the Fujifilm deal, Fujifilm took a A$3.97 million strategic equity stake in Cynata in January 2017, with the potential for future upfront and milestone payments in excess of A$60 million and double-digit royalties on Cynata’s CYP-001 (GvHD) product net sales.
What is Next for Cell Therapy Process Innovation?
As we reach the inflection point on the product to process innovation continuum, the questions become: How soon can Cynata take the development this technology through clinical trials (a question which has now been partially answered with the commencement of a Phase 1 in GvHD)? Will the Cymerus technology be a true platform technology used to address indications ranging from GvHD, to cardiovascular disease, pulmonary disease, brain cancer, and more? What other companies will pursue cell therapy process innovation?
While many questions remain unanswered, what is clear is that a growing investment of time, energy, funds, and brainpower needs to be directed into process innovation to drive future growth of the cell therapy industry.
While cell therapy product innovation has historically been the focus of much attention, it is now time for process innovation to step into the spotlight.
 The title of Utterback and Abernathy’s 1975 book was “Dynamic Model of Process and Product Innovation.”