As published in WuXi AppTec's Innovation That Matters
Cell therapy offers a treasure chest of new medicines, but there is still much to learn about cell activities and how to deliver these potential benefits before science and the industry can fully fulfill on their promise. One of cell therapy’s earliest pioneering companies is MaxCyte, based in Gaithersburg, MD and in the United Kingdom. Leading MaxCyte is president and CEO Doug Doerfler, a biotech pioneer who has more than 35 years of experience in the discovery, development, commercialization and international financing of biotechnology products and companies. He was also a founder of MaxCyte in July 1998.
MaxCyte pioneered the development of a non-viral cell-engineering platform for the delivery of biomolecules that fulfills the stringent demands of clinical use – namely the ability to safely and reproducibly modify primary human cells with high efficiency, low cytotoxicity, and at the scale required to treat patients. This delivery platform is helping to make cell and gene therapy a reality. The MaxCyte platform provides high-performance cell-engineering platform to biopharmaceutical partners engaged in drug discovery and development, biomanufacturing and cell therapy, including gene editing and immuno-oncology.
Before MaxCyte, Doerfler was president, CEO and a director of Immunicon Corporation, a cell-based therapy and diagnostics company. He also held various executive positions with Life Technologies, Inc. that included leading its global businesses, mergers and acquisitions and its IPO. Doerfler plays an active role as a life sciences industry advocate, serving as Chair Emeritus of the Maryland Tech Council and on the executive committee of the Biotechnology Innovation Organization. He also formerly served on the executive committee of the Alliance for Regenerative Medicine.
As part of the WuXi AppTec Communications’ series on cell and gene therapy, we asked Doerfler to share his views on the challenges and benefits of making cell therapy a key part in future health care delivery.
WuXi: What kinds of diseases can be treated with cell therapies?
Doug Doerfler: Cell therapies may have application across a very wide range of diseases. There have been exciting recent clinical developments in regenerative medicine, inherited genetic diseases, infectious diseases, immune deficiency disease and hematological malignancies in cancer. Academic and Industry teams are also now making promising advances with safer and more efficacious approaches to the aforementioned developments. The field is also describing advances in the treatment of solid malignancies in cancer, and we have seen early signs of promise in neurological, auto-immune and immune diseases.
WuXi: What are the limitations of cell therapies?
Doug Doerfler: We have to keep in mind that cells are complex: They produce other cells, they activate physiological responses, and they naturally traffic to sites of disease, neoplasia, trauma and inflammation. Researchers must rely on the power of new technologies to better understand cellular mechanisms to allow clinicians to develop approaches to engineering cell function to leverage the natural power of cells to treat a broad range of diseases. Cell therapies have the potential to provide a set of tools for preventing, treating and – in some cases, curing – the broadest set of diseases. Significant research is being conducted to determine the safest and most effective way to accomplish this.
WuXi: What kinds of technologies are required to make cell therapy-based medicines?
Doug Doerfler: In general, cell therapy development requires a variety of processes, each often requiring its own technology such as cell collection (and perhaps mobilization), separation of targeted cell populations, cell expansion and stimulation, engineering, preservation, transport, administration and quality control. Advances in most all of these areas and the means by which they are integrated will be needed to truly expand the reach of cell therapy medicines.
WuXi: So, what you are saying is there is enormous therapeutics potential in cell therapy, but there is still a lot research to be done before we can deliver that potential?
Doug Doerfler: Absolutely, there is much research to be conducted in both disease pathology and cell biology as well as in technique development.
WuXi: How will cell therapies evolve over the next 10 years?
Doug Doerfler: The complexity of approaches will increase (multiple pathway engineering, for instance), and at the same time, the need will grow to deliver more rapid patient treatment and less complex and lower cost processing of these therapies.
WuXi: What are some of the major challenges in bringing cell therapies to patients? Is manufacturing the most difficult hurdle?
Doug Doerfler: Manufacturing using the approved methods is absolutely a huge hurdle for development of both clinical and commercial material. Working with a respected, experienced contract development and manufacturing organization (CDMO) can be pivotal, and fortunately there are some who have risen to the challenge.
First, and most importantly, however, is the need to ensure an appropriate efficacy and safety profile. Cell therapies require rigorous clinical evaluation just as would any new therapeutic category. Providing those treatments with broad patient access is the other major challenge.
WuXi: Is gene editing the key technology in cell therapies?
Doug Doerfler: Absolutely. We are seeing gene editing in non-viral approaches to cell engineering for immune-oncology (both allogeneic and autologous) in immune cells, and stem cells (including iPSCs) for inherited genetic diseases and immune-oncology. Gene editing is also moving into a broader array of cells depending on the diseases that are being targeted for treatment.
WuXi: What cell therapies is your company developing and what diseases do they target?
Doug Doerfler: MaxCyte is applying its patented cell engineering technology to help patients with high unmet medical needs in a broad range of conditions. MaxCyte is developing novel CARMA™ therapies for its own pipeline. CARMA is MaxCyte’s messenger RNA (mRNA) -based proprietary platform for autologous cell therapy. In addition, through its core business, the company leverages its Flow Electroporation® Technology platform to enable its biopharmaceutical industry partners to advance the development of innovative, cutting-edge medicines, particularly in cell therapy, including the use of gene editing tools in the treatment of inherited genetic diseases and immuno-oncology approaches to treating cancer. Our goal with this platform has been to help our partners unlock the full potential of their products. We have seen good response from the industry with all of the top 10 global biopharmaceutical companies utilizing our electroporation instruments. We have more than 55 partnered program licenses in cell therapy with more than half licensed for clinical use.
WuXi: How does your approach differ from other cell therapy companies?
Doug Doerfler: MaxCyte’s CARMA platform differs in several ways from cell therapies being developed by other companies. First, we use non-viral delivery of mRNA via Flow Electroporation Technology as our means of highly efficient and safe engineering of patient cells. These properties are critical to achieving the therapeutic index with low toxicity profiles. Second, we can directly engineer patient cells at the necessary scale without extensive cell manipulation prior to or after engineering. Essentially, we can isolate patient cells, engineer the cells via Flow Electroporation and process those cells for reinfuse into the patient within hours rather than days or even weeks. This eliminates large portions of the manufacturing process. We believe CARMA has the potential to not only improve therapeutic efficacy and decrease toxicity, but also drastically reduce the cost of cell therapy and reduce the time to treat patients.
WuXi: In the compendium all new medical technologies where do you see the value of cell therapy? Is it going to be the key that delivers a new generation of medicine?
Doug Doerfler: Cell therapies will complement other therapeutic interventions such as surgery, radiation, small molecule and biologic drugs and vaccines.
WuXi: What regulatory challenges do you face?
Doug Doerfler: The field requires careful and deliberate development of technologies, approaches and delivery of these vitally important medicines. Having scientifically sound regulatory agencies around the world is essential to ensuring that these therapies are properly developed for patients. We as a sector need to challenge the ways that regulators, clinicians, caregivers, payers and patients think about these approaches as they may be very different than more “traditional” therapeutic approaches.