In vivo cell and gene therapy has become a central topic at Phacilitate’s Advanced Therapies Week in San Diego, reflecting recent industry developments such as Eli Lilly’s $2.4 billion acquisition of Orna Therapeutics.
Susan Nichols, CEO of Propel Bio, highlighted the growing interest during a session that reviewed the past year and looked ahead to future trends. “In vivo is the new allogeneic,” Nichols said. She explained that while ex vivo cell therapy requires removing and modifying patient cells outside the body before reinfusion, in vivo approaches deliver treatments directly into patients without this step.
Nichols pointed out both the potential and current limitations: “In vivo cell and gene therapies have ‘huge promise [and] heavy investment,’” she said, but noted that clinical data is still limited. “As one advisor put it, in vivo approaches are full of promise, but the investment momentum is outpacing the clinical data.”
Major pharmaceutical companies are moving into this space. Eli Lilly’s recent purchase of Orna Therapeutics brings technology using circular RNA with lipid nanoparticles to help patients’ bodies generate their own cell therapies. Francisco Ramírez-Valle, head of Immunology Research and Early Clinical Development at Lilly, stated: “We look forward to working with Orna colleagues to potentially unlock an entirely new class of genetic medicines and cell therapies for patients who today have limited or no treatment options.”
Lilly CEO David Ricks previously commented on accessibility challenges for these therapies: “The data is amazing,” he told Reuters in 2019, “but practically, it’s not reaching many people.” The company believes Orna’s approach could address this issue.
Orna’s lead program focuses on B cell–driven autoimmune diseases and has yet to begin clinical testing.
Patient advocate Victoria Gray shared her perspective during a panel discussion. As the first person with sickle cell disease (SCD) treated with Vertex Pharmaceuticals’ and CRISPR Therapeutics’ gene editing therapy Casgevy, she emphasized how in vivo gene therapy could expand access by eliminating the need for immunosuppressive chemotherapy. “I would love to see the science advance for patients like myself” who must undergo chemotherapy conditioning regimens, Gray said. She described chemotherapy as “the hardest part” of her treatment journey.
Kristen Hege, former senior vice president at Bristol Myers Squibb, discussed further implications: “When we think about in vivo gene therapy, I think a lot of people talk about patient access, cost of goods, but there’s more than that.” She noted that pre-infusion chemotherapy can suppress immunity for weeks and increase infection risk or even cause leukemia. Removing this requirement could be a significant benefit if in vivo methods prove effective.
Other companies are also investing in these technologies. Regeneron recently partnered with Tessera Therapeutics to develop an in vivo genome editor for alpha-1 antitrypsin deficiency (AATD). Tessera is also advancing a single-dose IV treatment aimed at correcting sickle cell mutations.
Hege added that regulatory frameworks differ between ex vivo and in vivo therapies due to differences in what can be measured or controlled during manufacturing versus inside patients themselves.
Nichols summarized industry sentiment by saying: “Belief is currently leading data, not following it.”
Ultragenyx Pharmaceutical presented long-term cognitive improvement results from its UX111 gene therapy candidate for Sanfilippo A syndrome last week. While the FDA rejected UX111 last July over manufacturing concerns rather than clinical outcomes, Nichols concluded: “Regulation is no longer the gating issue.”
BioSpace served as a media partner for Phacilitate’s Advanced Therapies Week held February 9–12 at the San Diego Convention Center.
