September 28, 2023
Sarah Meeks (SM): MaxCyte’s flow electroporation technology was developed over 20 years ago, and we have been optimizing and refining the technology as the industry develops more complex cell therapies. I think it is critically important to a lot of the R&D work underway today. The field of engineering cell therapy is fairly young, and there’s lots of innovation currently happening that will assuredly continue to happen.
MaxCyte approaches that dynamic from a unique position, with technology that is applicable across a wide spectrum: we’re cell-type agnostic, engineering modality agnostic, and therapeutic agnostic. Beyond the technology itself, we have a very strong, experienced scientific team with over 40 global technical experts on demand — we call them our field application team — that can leverage their unique experience and expertise to take innovation as it occurs and translate it for our partners and customers.
Our key cell-engineering platform differentiators are both our premier technology and our premier team of scientists, who can rapidly assess and optimize processes and accelerate process development and translation for our partners and customers. The team and the technology converge to support the creation of new therapeutic designs based on novel modalities: CRISPR/Cas9, base editing, prime editing, transposons, and novel cell types from B cells to T cells to myeloid-based cells and human stem cells. The number of relevant cell types keeps growing, and our technology and our team are well positioned to support whatever direction those fields take in the future.
SM: Most of the first-generation work in engineered autologous oncology cell therapy began using viral systems, most notably lentivirus. However, viral-based engineering presents a number of issues in terms of supply, cost, construct limitations, and other factors. It’s one way to engineer a novel vehicle for a therapeutic, but MaxCyte electroporation enables multiple edits, whether they are delivered sequential or simultaneous or both. Multiple engineering features can be introduced into the cells with the purse broadly to improve safety and efficacy. The MaxCyte system has an inherent flexibility to accommodate novel approaches.
MaxCyte currently has 23 partners developing cell therapy products for a variety of applications. That level of business is evidence of the expanding interest in nonviral approaches. It is difficult to compare electroporation to traditional methods because it truly is an enabling technology targeting new indications and new product designs within the engineered cell therapy space and thus is inherently enabling novel classes of therapies.
SM: Our platform can be implemented from early proof-of-concept stage to process development to early clinical and even migrating programs currently in the clinical, which highlights our flexibility, technical expertise and scale to accommodate our customer and partner needs. Cell therapy developers enter into a formal partnership with us so that we can seamlessly and robustly support product development into clinical and through commercial phases. Leading therapeutic developers partner with us, which provides an accountable support role to enable a clinical cell engineering process supported by our technical, regulatory, and quality teams.
With respect to the specifics of our offering, I view them as falling into several discrete buckets. First, there’s the instrumentation, the consumables, which we call processing assemblies and buffers, and all the permutations that are required to go into a very flexible platform.
Next is technical support, with customers having access to our team of field application scientists for on-demand support, which is really all-inclusive within each partnership.
Regulatory expertise is third. MaxCyte has an FDA Master File (MF) for our platform that’s been in place since 2002, and we have enabled over 45 clinical trials to date. We’ve also really beefed up our regulatory affairs group, adding a vice president of regulatory to lead a strong team of experts. Their focus is on our partners, assuring that they have what they need when they need it as they move through early development, filing an Investigational New Drug (IND) application, supporting and filing the Biologics License Application (BLA), and finally attaining market authorization.
Our fourth bucket is quality management, including the quality systems MaxCyte has put in place. Fifth is the comprehensive pipeline support we offer, including supporting products at multiple sites across different activities from process development and/or translation to clinical manufacturing in-house or at a contract development and manufacturing organization (CDMO).
In fact, MaxCyte has implemented what we call strategic global partnership support, which goes well beyond alliance management because it includes a single, hands-on point of contact for customers with scientific and business teams within MaxCyte that work with the customer as each therapeutic is developed, whether that is all in one location or includes tech transfer to another site.
We oversee that tech transfer process, such as for an autologous cell therapy being rolled out worldwide. We help determine how many sites will be needed and what will take place at each of those sites, with our scientific and business teams working to ensure not only uniformity across all sites but the realization of all possible efficiencies. We are not a CDMO with a single location. As a result, we can implement this type of partnership support and be positioned to rapidly help our partners with the activities involved in bringing a product through the clinic and into the marketplace.
Finally, the last bucket relates to manufacturing. MaxCyte has brought manufacturing in-house, ensuring that our partners will have clinical and commercial supply of instruments and consumables when they need them.
What really differentiates us is the fact that we provide this comprehensive offering and not solely an electroporation platform. We offer the instrument plus all of the other value that will help accelerate and ultimately mitigate risk in innovative product development.
SM: Oncology is a very important space for MaxCyte, but we are pursuing a number of other applications that are rapidly advancing in terms of product development, translation, and moving toward market authorization.
Some of the programs our partners are working on will compete with other products on the market or perhaps with one another. Others involve truly novel applications including autoimmune, neurodegenerative, and genetic diseases. For instance, engineered cells are being investigated not only for oncology applications but as in vivo protein factories targeting genetic diseases that wouldn’t have otherwise been targeted with an engineered cell. One example of the expanding applications enabled by MaxCyte engineered cells is Fabry disease, which would traditionally be approached using in vivo gene therapy with delivery via an adeno-associated viral (AAV) vector. Another interesting approach involves using engineered cell therapies as carrier vehicles to deliver material to a targeted tissue, such as a particular muscle. For example, this strategy is being used to develop treatments for diseases such as amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). I think this approach has the potential to expand the number of indications that can be enabled with nonviral engineered methods.
SM: Emerging and small biotech companies with limited expertise and resources can realize significant advantages by working with MaxCyte because we bring so much experience to the table that they can access without having to find multiple partners and make separate expenditures. With comprehensive support and relationship accountability, our partners realize this value in working with MaxCyte. In fact, we have a number of examples of very young companies coming right out of academic centers that have leaned on us heavily in terms of tech transfer support to a CDMO to ensure that these processes are optimized. I believe these types of organizations receive tremendous value from a relationship with MaxCyte. I don’t want to suggest that we are not a strong fit with other types of companies, but the greater the support needs, the more one stands to benefit.
SM: There are three words that describe MaxCyte in a nutshell: collaboration, innovation, and experience. We are not new to electroporation. Our platform is being used in novel applications and for novel cell types, but our team of scientists is enabling that by design. We are constantly building our skill sets with the needs of the future in mind. In fact, a critical element of our approach at MaxCyte is continuous improvement — not only of our technology but also the brain power within the company and the breadth and depth of support we provide. MaxCyte brings a great deal of experience to our customer collaborations, and we strive to operate as extensions of our customers’ businesses. Specific activities are matched to the specific needs of each customer, depending on the product, funding stage, and development phase, a capability that is particularly critical to these customers that are themselves unique and on the cutting edge of novel therapeutic classes.
SM: There are a number of gene-editing tools, with CRISPR being just one of them, that are being used to advance construct design to the point where is it is much more eloquent and innovative. Developers are looking beyond the cargo to what might be done to regulate delivery using novel promoters and regulatory elements. With base and prime editing, gene editing is getting more accurate, which is potentially enabling differential approaches.
That will be really important for expanding the eligible patient pool for some of these diseases. Editing might make it possible to build properties into these therapies that make them more patient-centric: kinder, softer, and gentler. One example would be preconditioning for sickle cell patients. Might there be features that could be engineered into the therapy to provide that preconditioning rather than having the patients go through a separate, taxing treatment regimen? Consequently, I think construct design is going to be a very interesting space moving forward.
SM: MaxCyte has a research instrument, the ATx, that is often used in early development. It precedes our flow electroporation instrument and is often placed in academic labs and translational centers. We place significant emphasis on seeding innovative academic labs because our early alignment and support tracks with the innovation and fosters long standing relationships.
Our clinical workhorse is our GTx instrument, which is used for clinical and commercial manufacturing of engineered cell therapies. Our STx addresses high-yield, transient expression of proteins and rapid stable cell line development. An even larger-scale instrument, the VLx, is just coming online. It has not yet been used in cell therapy but is being pursued in other bioprocessing applications.
SM: As I mentioned before, we don’t just drop off instruments with customers. We assure that each instrument is optimized for each customer and each specific project. We train anyone who will be using our technology, from early-stage researchers to process development folks to the operators at customer CDMOs. We reach across the full spectrum to ensure more efficient transitions throughout the life cycle, and those interactions often take place in parallel, which further enhances efficiency.
In addition, the suite of consumables that we offer enables very efficient translation from early research to the clinic. The portfolio has been designed to really meet customer needs because it can be tailored to be very accurate in terms of each individual cell therapy. Scaling up on the instrument and between instruments takes minimal to no optimization, which can save months of development time, which is impactful to limit the cash burn for these pre-revenue therapeutic developers. The rapidity at which it is possible to move from one product to another also contributes to greater efficiencies. Furthermore, the ability to have reproducibility and consistency across patients and sites is critically important and another way that MaxCyte works to improve efficiencies. Creating these efficiencies helps to drive down costs.
SM: I believe there will be a spectrum of needs. For allogeneic therapies, centralized manufacturing will be likely, with larger sites located in perhaps three different geographies to supply regional needs, depending on where the disease pockets are. I also think there will be some decentralized manufacturing for certain autologous products. In each case it will absolutely depend on the disease. Moving to point of care is clearly another area that is forthcoming. MaxCyte’s technology can be used in all of these manufacturing scenarios to able to both scale out and scale up the therapy, and we are actively working to optimize its application in any of these contexts, as well as to prepare for any new developments.
SM: I would point to Exa-cel, an investigational therapy for people with transfusion-dependent beta-thalassemia (TDT) or severe sickle cell disease (SCD) that is being jointly developed by Vertex Pharmaceuticals and CRISPR Therapeutics. Exa-cel has been manufactured on MaxCyte’s platform from the beginning. Our regulatory group has been meeting regularly with these customers to ensure that they have all of the data needed to support their filings. This project is particularly exciting because these companies are truly blazing a new trail in cell therapy. Exa-cel will be the first CRISPR-edited cell therapy, so you can imagine that there is some extra work needed to carve out a novel path with the regulatory agencies, and MaxCyte is positioned to provide extra support.
We’re just a few months from that PDUFA (Prescription Drug User Fee Act) date for Exa-cel, which will truly be a pivotal moment in this field. We’re very excited about that. We have been working with the CRISPR Therapeutics team and now the Vertex team for over 8 years since close to the inception of the product at the proof-of-concept stage.
SM: From what I see from my seat in business development and what we’re bringing on, I’m super excited about moving into rare diseases. As you know, we support a number of oncology indications and hematological malignancies. But there are increasing numbers of projects focused on rare diseases. To me, that is critically important, because all patients should be able to benefit from MaxCyte’s technology, not just those with more common diseases. Getting our technology more widely adopted for the production of treatments across both prevalent and rare disease indications is really important for MaxCyte going forward.
Sarah Meeks, Ph.D., is the Senior Vice President, Global Business Development at MaxCyte, Inc. Previously, she served as Chief Scientific Officer at Adjuvant Partners and Vice President of Business Development at Synpromics (now AskBio) where she established a leading market position for the company that included partnerships with gene therapy companies. Dr. Meeks completed her postdoctoral work in the University of Pennsylvania Gene Therapy Program and Center for Technology Transfer after receiving a PhD in biochemistry, molecular biology and biophysics, with a minor in bioethics, from the University of Minnesota.