ROCKVILLE, MD—On a brisk, sun-splashed midweek morning in the suburbs of Washington DC, the staff at MaxCyte have double reason to celebrate. Every Wednesday, they are treated to free lunch in the canteen, today’s feast a handsome and fragrant spread of curries from a local Indian restaurant.
But on this particular morning, the staff have gathered early to hear from a VIP guest who has flown in all the way from Mississippi: Victoria Gray, the trailblazing sickle cell disease (SCD) patient who became the first volunteer in the exa-cel CRISPR-based cell therapy trial, sponsored by Vertex Pharmaceuticals and CRISPR Therapeutics. That therapy, now branded as Casgevy, was approved by the U.S. Food and Drug Administration in December 2023.
The new CEO of MaxCyte, Maher Masoud, invited Gray to visit the company headquarters, accompanied by her husband Earl. Following a tour of the facilities, during which she got to inspect one of the instruments that featured in the preparation of her gene-edited stem cells, she sat down for an interview with hematologist Vivien Sheehan, MD, PhD (Emory University School of Medicine).
Gray shared her inspiring journey in front of the MaxCyte staff. The CRISPR intervention in July 2019 boosted production of fetal hemoglobin in her blood, compensating for the inherited SCD mutation. (Last month, Gray gave an in-depth interview for GEN’s “The State of Cell and Gene Therapy” virtual summit. She was recently featured on the ABC program Good Morning America, which had arranged a surprise meeting with fellow exa-cel trial participant, Jimi Olaghere.)
MaxCyte, too, has reason to celebrate. The company’s electroporation prowess, honed since the company was founded in 1999, played a critical part in the successful gene editing of Victoria’s cells and indeed those of the dozens of other SCD patients who participated in the trial. That feat could be replayed many times over the next few years as the company signs agreements with more pharma companies pushing autologous and allogeneic cell therapies into the clinic.
After Victoria poses for photographs in the company lobby with staff, she is driven back to her hotel clutching a box filled with company swag, including a model of the electroporation device that created her “supercells”. In 2019, MaxCyte introduced a new ExPERT range of four electroporation instruments: the research-grade ATx; the GTx, which is the GMP system used by customers in the clinic; the STx, for protein production and drug discovery; and the VLx that has 10 times the scale of the GTx. (The ‘x’ in the brand name is, unsurprisingly, shaped like a double helix.)
Company DNA
Masoud is settling into his role as CEO of MaxCyte, having spent seven years at the company as General Counsel and head of business development. He also has a molecular biology background, having worked at Human Genome Sciences earlier in his career. Masoud was appointed president and CEO on January 1, 2024, taking over from co-founder and CEO Doug Doerfler.
“It’s humbling to work with people like Jim Brady and some of the scientists here,” Masoud told me. “Hopefully I can live up to the big shoes of everyone here!”
MaxCyte was originally spun out from EntreMed, the angiogenesis company co-founded by Judah Folkman, MD, in 1999. Originally named TheraMed, it was led by the late John Holaday and then Doerfler. Those leaders “always thought that cells could be a therapy. That was the vision for this company,” said Masoud. Even when cell therapy was more science fiction than reality, “the vision was always that you can engineer cells and hopefully those cells become a treatment for patients.”
Another key member of the leadership team is distinguished scientist Sergey Dzekunov, PhD, credited as one of the founders of the electroporation systems themselves. The Ukrainian ex-pat has been with MaxCyte since 2000. “He’s our biophysics expert—the brains behind what’s inside the instruments,” said Masoud.
The DNA of the company is built around electroporation, Masoud told me. Helping to steer the evolution of MaxCyte’s electroporation technology over the past two decades has been James Brady, PhD, senior vice president of technical applications and customer support.
“At the time, cell therapy was kind of a backwater,” Brady recalled. “People that were working in cell therapy weren’t making modifications to cells. They used it for regenerative medicine applications. Fortunately, electroporation—and our electroporation in particular—has applications in many different areas. We found that there was also a market for this technology for drug screening, for companies that wanted to generate cells for cell-based assays, and then we got into the recombinant protein production market.”
“The ability to engineer or transfect billions of cells at one time allowed people to make antibodies in relevant cell types very quickly,” Brady continued. “Thanks to the cell-based assay market, drug discovery, and bioproduction, we managed to build a business. Then with CRISPR and CAR-T coming into vogue about 10–15 years ago, it was something we were poised to take advantage of. I think we were probably the first ones to approach it from a clinical perspective.”
Licensing knowledge
MaxCyte doesn’t merely sell electroporation instruments but strategic licenses that give customers the greatest chance of success. It also stands to benefit MaxCyte financially of course.
Masoud explains that what the company has built over the past two decades is “understanding all the scientific applications around electroporation… We can engineer a cell—that’s been our expertise. We work with various companies to understand their engineering needs. And then it’s the scientific support that Jim, his team of Field Application Scientists, and the other players in this organization who ensure that we can do this better than anybody else,” Masoud said.
Indeed, that level of scientific support and attention to detail to maximize the customers’ chance of success are a key ingredient in the MaxCyte business model.
“In essence, we have proprietary IP around the technology itself. But what we do is something truly better than any other organization,” Masoud said. “We build method and process IP around all the application know-how, pre- and post-electroporation. We work jointly sometimes with our customers and partners and we do it in-house. We share that knowledge on a licensed basis with any customer that wants to go into the clinic or commercialize a product.”
“So, it’s a foundational IP,” Masoud continues. “We have the ‘hardware IP’ but it’s more than that. It’s the method and the application IP as well. It’s not as simple as just running cells through a system and then you’re done with it. There’s a lot of know-how… If there are any issues in the manufacturing process, we’ll do everything we can to make sure that we can help that customer in the clinical space and upon commercialization,” Masoud said.
“We don’t want to just drop a system off and say we’re done,” he added. “The conditions needed around [electroporation] need to be almost perfect to have a therapeutic that’s going to be approved by the FDA. That requires something more than just buying a box. It requires working with a company where, if there are any issues in that process, we’re there to help figure out those issues.”
Masoud says MaxCyte believes in “building that relationship with a customer,” from preclinical research to entering the clinic and commercialization. “We give [them] the same level of scientific support whether you’re a one-person organization or Vertex… That’s the differentiation we provide, above and beyond other competitors.”
Fifteen months before the FDA approval of Casgevy, MaxCyte signed a strategic platform license (SPL) with Vertex, granting the Boston-based biotech non-exclusive clinical and commercial rights to use MaxCyte’s Flow Electroporation technology and the ExPERT platform in the development of its CRISPR-based exa-cel therapy. The deal entitled MaxCyte to receive platform licensing fees and program-related revenue.
Vertex has announced partnerships with at least two contract development and manufacturing organizations (CDMOs) for Casgevy production, RoslinCT and Charles River Labs.
The SPL agreement extended a relationship that Brady and colleagues nurtured with CRISPR Therapeutics in the very early days of that company, when it was originally known as Inception Genomics, long before there was an exa-cel program. Brady’s team invested time in optimizing methods to introduce CRISPR gene editing into cells, including the best format, molar ratio and cellular concentrations for CRISPR molecules. That expertise is now paying dividends with a total of 26 SPLs so far with various gene-editing and cell-therapy biotechs, including Beam Therapeutics, Prime Medicine, Caribou Biosciences, and Editas Medicine.
Inside the box
Electroporation sounds relatively straightforward, but the devil is in the details. Brady explains that the technique doesn’t create pores in the cell membrane as much as “temporary perturbations,”bvia the brief application of electrical pulses that allows water to temporarily flow in and out of the cell.
Brady was not about to disclose any trade secrets. “The exact details around our electroporation parameters are proprietary, but realistically, you push a button and within less than two seconds, it’s done. We optimize things like the number of pulses, the shape of the pulses, and pulse patterns,” he said. That level of control offers a major advantage of electroporation compared to other methods for delivering reagents into cells. Typically, cells are prepared at a density of 50–100 million cells per ml, with volumes ranging from as low as 15 µl to 100 ml.
The electroporation process itself is quite gentle to the cells. “Any change you make is temporary,” he said. Any issues regarding cell viability are usually due to what is being introduced into the cell, not the means of introducing them. “There’s a limit to how many molecules you could pack into a cell or it starts to suffer. We try to find that sweet spot where we maximize the number of edits that take place, but we don’t want to overload the cells to the point where it’s detrimental to the cell.”
Much of what Brady’s team does centers on optimizing conditions around the electroporation procedure as well as before and after. That means establishing “the right cell culture conditions, the right loading agent concentrations, the right electroporation conditions. It’s garbage in, garbage out—making sure that what goes in, the cells are healthy, the loading agents are prepared to the right specifications and then afterwards the cells have the right conditions, cytokines and nutrients.”
Nothing is left to trial and error. The CDMOs that worked with Vertex to handle the gene editing of the SCD hematopoietic stem cells (HSCs) use an instrument in which the specific conditions and parameters of the reagent transfer have been pre-programmed by MaxCyte scientists. The system has obviously proven effective in introducing CRISPR reagents into cells, Brady says, but it is versatile to handle many other reagents, including base and prime editors.
As for the choice of cells, it is a bit more challenging to work with HSCs, Brady notes. “They’re hard to acquire in large numbers and they’re smaller, so sometimes more challenging to load. The big challenge with all primary cells is that they can be very sensitive to nucleic acids.” Fortunately, for a relatively simple CRISPR edit as in the exa-cel trial, “you’re not introducing DNA.” And as Brady notes, his team has learned a lot working with HSCs for the past 15 years.
The GTx instrument offers pharma clients and their CDMO partners clinical compliance. And from studies on a single patient, the process is eminently scalable to the point of transfecting billions of cells using flow electroporation without the need for any type of re-optimization.
When working with a new client or CDMO, Brady dispatches members of his team to ensure that the instrument is working accurately and reproducibly. “I used to go years ago, but I’ve hired people that are smarter and have better social skills than I do. So, they make me stay back at home!” Brady joked.
Brady and his colleagues took a reporter on a brief tour of the MaxCyte facilities, including a peek inside the 1,400-square-foot clean room where the all-important flow chambers are being prepared and sealed under sterile conditions. The room is unusually quiet. But then again, it is Wednesday, and the butter chicken is well worth a second helping.
