This blog contains information originally published as part of the Buisiness of Biotech podcast

Pillar, M. (Host). (2021, March 28). Cell Therapy Platform Dev With Precigen CEO Dr. Helen Sabzevari [Audio podcast episode]. The Business of Biotech. BioProcess Online

When driving new, novel, and needed therapies toward commercial success, two of the biggest challenges in gene therapy development are optimizing cost and scalability.

These are challenges Dr. Helen Sabzevari is ready to face as the CEO of Precigen, a biopharmaceutical company dedicated to pursuing solutions for a range of intractable diseases through early discovery and clinical-stage research. Dr. Sabzevari — whose previous work includes tenures in both academia and with EMD Serono, Compass Therapeutics, and Intrexon (now Precigen) — has spent years considering what it takes for rapid drug development and commercial viability in today’s market.

In a recent episode of The Business of Biotech, Dr. Sabzevari discussed how Precigen has used customized therapeutic and platform technologies to tackle scale-up in the CAR-T therapeutics space, giving both patients and investors confidence they’re getting the most effective therapy at the best price.

Off the Shelf vs. Customization

From 2018 to 2020, Precigen developed a valuable portfolio including the UltraCAR-T™ therapy, which Dr. Sabzevari calls “the most cutting-edge therapy in immuno-oncology today.” In addition to having a potentially improved safety profile compared to CAR-T treatments, UltraCAR-T therapies don’t require multiple weeks of expansion in culture, making manufacturing and delivery to patients more efficient. Studies of UltraCAR-T therapies for the treatment of ovarian cancer and acute myeloid leukemia are ongoing.

To manufacture UltraCAR-T therapies quickly and in a cost-effective manner, Precigen developed the UltraPorator™ system, its proprietary, in-house technology including both hardware and software solutions. The UltraPorator system offers an option for UltraCAR-T scale-up and commercialization, significantly reducing processing time and contamination risk. The platform was designed to enable rapid manufacturing for a range of gene and cell therapies beyond UltraCAR-T and is available as a stand-alone device for strategic partnerships.

Using the UltraPorator system, Precigen has been able to overcome one of the biggest obstacles many emerging biopharmas struggle with — technology platforms that aren’t advanced enough to achieve commercial viability or scalability. This limitation often results in time delays and cost overruns, as developers realize somewhere in Phase 1 or Phase 2 that their therapy isn’t globally viable. The UltraPorator platform is poised to revolutionize everything about the space, from delivery to cost to efficacy.

We asked Dr. Sabzevari about the value inherent to developing both a therapy and a therapeutic production technology in parallel. She says the heart of the issue they’re addressing is that transfecting T-cells with lentivirus to produce CARs that can recognize the antigens of tumors has proven costly and time-consuming for most developers. “It’s been unsuccessful in solid tumors, and even in hematological tumors, where it’s an approved therapy. It’s not being used that much, because of the time, manufacturing complexity, and price tag.”

Time Impact of Custom-Tailored Manufacturing

The issues with producing these novel therapies add up to the biggest hurdles of all, Dr. Sabzevari says: “It takes time. You can only do it in certain GMP facilities, it sometimes takes more than four weeks, and it’s associated with very high costs. It can cost between $350,000 and $500,000 for one dose.”

To circumvent this, Precigen created Sleeping Beauty, its non-viral delivery mechanism that transfects cells overnight in the clean room of a hospital or bone marrow facility. “Basically, you just take the cells of the same patient, and next day you return it back to them,” she says. Using the UltraPorator platform along with Sleeping Beauty reduces safety issues for the patient, shortens transfection time, and streamlines the process by introducing CAR-T cells that can expand within the patient. More traditional decentralized systems, in contrast, cost hundreds of thousands to create a single dose, introducing logistical and production-related challenges in the process.

Long-Term Benefits vs. Trade-Offs

Making the manufacturing of these therapies more efficient was at the top of Dr. Sabzevari’s list from the start. “Half a million dollars for one dose? Most insurances will not cover it, and then only certain people can get it.”

While many other companies using traditional lentivirus platforms are engaging in gene editing and off-the-shelf therapies, these solutions still create issues with limited doses and exorbitant costs. Regulatory hurdles can also sometimes present challenges for companies trying to innovate, but Precigen has engaged in continuous discussions with the FDA and other regulators to ensure they’re on the same page as they continue to pursue novel solutions in the gene therapy space.

“For us, it was important to have these meetings with our regulatory colleagues at the earliest stages,” she told BioProcess Online. “You have to continuously be in touch and discuss, and for me, to anticipate what’s to come.”

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