As Companies Flee Ex Vivo Cell Therapy, Even Automated Manufacturing Platforms Face Validation Hurdles

Cell therapy developers have spent the past month pulling back from ex vivo manufacturing approaches, and the pattern extends even to companies built specifically to solve that category's cost and scalability problems. Bristol Myers Squibb has ended its cell therapy manufacturing alliance with Cellares after determining that the company's automated Cell Shuttle platform could not meet the requirements necessary to produce commercial Breyanzi (lisocabtagene maraleucel), BMS's CD19-directed CAR-T cell therapy for large B-cell lymphoma.¹ "Following a comprehensive evaluation, Bristol Myers Squibb determined that the Cellares-partnered Cell Shuttle system could not meet the necessary requirements to make commercial Breyanzi," a BMS spokesperson told BioSpace. "This determination is specific to Breyanzi and its established, regulatory-approved manufacturing process."¹ Cellares disputed that characterization: "The Cell Shuttle System has already manufactured GMP drug product in an FDA-regulated clinical program, with doses meeting all release specifications, delivered on time and administered to patients," the company said in a statement, adding that it "strongly disagrees" with BMS's characterization and does not discuss confidential customer program details publicly.¹

The loss of the contract has direct workforce consequences. Cellares CEO Fabian Gerlinghaus confirmed on LinkedIn that the company is laying off staff following the loss of a partnership with a large pharmaceutical company, without naming BMS specifically.¹ A WARN Act filing sent to BioSpace by California's Employment Development Department shows Cellares will permanently eliminate approximately 100 positions effective October 20, spanning roles from an alliance manager to a janitorial specialist to the company's vice president of commercial operations; more than half of the affected employees held "senior" titles across engineering, marketing, recruitment, and software.¹ The cuts come roughly 10 months after Cellares raised $257 million specifically to fund a path toward commercial-scale production in 2027.²

How significant was this partnership?

BMS and Cellares originally struck their agreement in April 2024, a worldwide capacity reservation and supply deal valued at up to $380 million in upfront and milestone payments, giving BMS access to Cell Shuttle systems dedicated for exclusive use across Cellares' facilities in the US, EU, and Japan.³ The relationship deepened from there: BMS joined Cellares' Technology Adoption Partnership program in August 2023 to evaluate transferring CAR-T manufacturing processes onto Cell Shuttle, and the companies expanded their agreement in mid-2026 to begin a second proof-of-concept tech transfer for an additional CAR-T program.⁴ Cellares has positioned its Cell Shuttle platform — a fully closed, automated "factory in a box" system designed to support roughly 90% of cell therapy modalities across both autologous and allogeneic processes — as a way to move the field from artisanal, manual production toward industrial-scale, reproducible manufacturing.⁵

Post-approval manufacturing changes for cell therapies carry inherent risk regardless of the platform involved. Anna McMahon, Cellares' director of regulatory affairs, told BioSpace last year that switching manufacturing platforms after approval is "a significant investment," advising companies to "ensure that the new platform is sustainable and a long-term solution" before committing.¹ BMS currently produces Breyanzi through several internal sites plus external manufacturers including Oxford Biomedica.¹

Regulatory pathways built specifically for advanced manufacturing technologies add another layer to the dispute. Cellares has previously cited the FDA's Advanced Manufacturing Technologies (AMT) designation awarded to Cell Shuttle as a tool that could support manufacturing changes during development and after approval — the exact scenario at issue in the BMS dispute. Pierre-Alain Ruffieux, PhD, group executive of Bioprocess at Cytiva, addressed the broader regulatory gap facing this category of manufacturing in a Q&A with BioPharm International®: "Regulatory frameworks are a central factor in enabling both innovation and sustainability. Existing pathways, largely designed for traditional biologics, are not always well suited to platform-based or patient-specific therapies."⁶

Timing matters as much as technology in these transitions. Alan K. Smith, PhD, executive director of global scientific portfolio management for cell and gene therapy at Charles River Laboratories, told BioPharm International in a Q&A that manufacturing platform decisions are best made early in a program's lifecycle rather than retrofitted onto an existing process: "Plan early and often, with an eye toward commercial capabilities. Use tools that are available, and will be available in the near term, to automate processes, reduce labor costs, and deploy AI for certain tasks."⁷ BMS's own explanation for ending the Cellares partnership pointed to exactly this kind of mismatch — the determination was specific to Breyanzi's "established, regulatory-approved manufacturing process," a process that predated the automation effort rather than having been built around it from the start.¹

Cell therapy manufacturing and capacity has been a recurring thread in recent coverage. The same week BioPharm International rounded up developments including Resolution Therapeutics' completed enrollment in its RTX001 engineered macrophage trial for liver disease, Samsung Biologics' $262 million manufacturing agreement, and CordenPharma's €80 million sterile injectable capacity expansion, the BMS-Cellares termination had already become public — underscoring how quickly the cell therapy manufacturing and capacity conversation is moving on multiple fronts simultaneously.⁸

Why does this fit into a broader pattern this year?

This setback lands amid a string of announcements in which cell therapy developers have pulled back from established manufacturing approaches. In early September, ArsenalBio announced it would halt all development of its ex vivo CAR T-cell clinical assets, cutting roughly 99 of its 127 employees, to redirect entirely toward in vivo-engineered CAR T programs — citing the cost, manufacturing complexity, and patient-access limitations inherent to ex vivo autologous production.⁹ Days later, TScan Therapeutics made a strikingly similar move, pausing its Phase 3 ALLOHA-2 trial and cutting approximately 75% of its workforce to prioritize in vivo-engineered TCR-T therapy, for nearly identical reasons.¹⁰

The underlying rationale for that shift had already been building industry-wide well before either company acted on it. In BioPharm International coverage published in late May, Jens Vogel, president and chief operating officer at Mirai Bio, argued that persistent supply-chain constraints — including the continued need for human leukocyte antigen (HLA) matching, even with allogeneic approaches that allow some scale-up — point toward one solution: replacing complex ex vivo engineering and manufacturing of cells with targeted engineering of cells in vivo.¹¹

That view isn't universally shared, however. Speaking at the 2026 ASGCT Annual Meeting, Dr. Stone — who spent more than a decade building TTP's cell and gene therapy automation systems, including platforms now in routine commercial use — cautioned against reading the industry's growing in vivo interest as a wholesale abandonment of ex vivo or allogeneic platforms. Instead, he said, developers are increasingly using clinical and post-approval commercial data to assess which modality is best suited to a given biological and manufacturing challenge, rather than defaulting to any single approach across the board.¹²

The pattern has continued to develop even as this article was being reported. On September 14, Cellectis announced its own strategic transformation into an in vivo gene editing company, exiting its allogeneic CAR T-cell candidates lasme-cel and eti-cel entirely and redirecting resources toward .HEAL-101 and .HEAL-201, in vivo editing candidates for severe lipid disorders.¹³ Notably, Cellectis's stated rationale differs from ArsenalBio's and TScan's: rather than citing ex vivo manufacturing cost or patient-access constraints directly, the company pointed to a deteriorating commercial outlook for its allogeneic CAR T candidates, as improved frontline treatment regimens and intensifying competition from bispecific antibodies and in vivo CAR-T approaches shrank the addressable patient population for later-line therapy.¹³ Cellectis CEO André Choulika framed the shift around the appeal of the in vivo approach itself: "Gene surgery has the potential to transform the treatment of high-risk metabolic diseases by delivering long-lasting benefits through a single IV injection."¹³ Taken together, ArsenalBio, TScan, and Cellectis reflect at least two distinct pressures driving companies away from ex vivo cell therapy this year — manufacturing and access limitations in the first two cases, and eroding commercial opportunity in the third — even as automation specialists like Cellares face their own validation setbacks trying to solve the ex vivo manufacturing problem directly.

Cellares' setback is a different kind of story from any of these — a manufacturing technology dispute rather than a strategic pivot away from ex vivo production altogether — but it lands squarely in the same conversation. Where ArsenalBio, TScan, and Cellectis are walking away from ex vivo manufacturing or allogeneic cell therapy as a category, the BMS-Cellares dispute suggests that even automation-focused solutions built specifically to solve ex vivo manufacturing's cost and scalability problems face significant validation hurdles when applied to an already-approved, regulatory-locked production process. Ryan Larson, PhD, SVP, head of research at Umoja BioPharma, framed the underlying access problem driving much of this activity in a video interview with BioPharm International at the 2025 American Society of Gene and Cell Therapy annual meeting: "Access to ex vivo autologous cell therapies continues to be a challenge wherein a large fraction of patients that may be eligible for those therapies are not able to gain access to them for a variety of reasons."¹⁴

What happens next?

Cellares said it continues to support both clinical- and commercial-stage cell therapy programs beyond the terminated BMS relationship.¹ The company's layoffs take effect October 20; its next disclosed milestone is the commercial-scale production target it raised its $257 million Series round to support in 2027.²

References

1. Taylor NP. BMS Ends Cellares Pact Over Cell Therapy Production Problems, Triggering Layoffs. BioSpace. Published August 26, 2026. Accessed September 14, 2026.
2. Taylor NP. BMS-Partnered Cellares Raises $257M for Cell Therapy Manufacturing Expansion. BioSpace. Published January 28, 2026. Accessed September 14, 2026.
3. Mirasol F. Bristol Myers Squibb and Cellares Enter Into $380 Million Agreement for Technology to Manufacture CAR-T Cell Therapies. BioPharm International. Published April 23, 2024. Accessed September 14, 2026.
4. Mirasol F. Cellares Expands Agreement with Bristol Myers Squibb for Second CAR-T Program. BioPharm International. Published October 13, 2023. Accessed September 14, 2026.
5. Markarian J. Automation Aids Cell and Gene Therapy Production. BioPharm International. Published July 1. 2023. Accessed September 14, 2026.
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9. Schoenthaler E. ArsenalBio Sheds Most of Staff, Pivots Entirely to In Vivo CAR T. BioPharm International. Published September 2, 2026. Accessed September 14, 2026.
10. Schoenthaler E. TScan Therapeutics Cuts 75% of Staff, Pivots to In Vivo TCR-T for Solid Tumors. BioPharm International. Published September 2, 2026. Accessed September 14, 2026.
11. Challener C. Challenges to the Development of Emerging Therapies. BioPharm International. Published April 8, 2025. Accessed September 14, 2026.
12. Mirasol F, Stone E. Why the Need to Expand Industry Focus Beyond Gene Editing Toward Scalable Cell Therapy Manufacturing? BioPharm International. Published May 19, 2026. Published May 19, 2026. Accessed September 14, 2026.
13. Mirasol F. Cellectis Shifts to In Vivo Gene Editing With .HEAL-101, .HEAL-201. BioPharm International. Published September 14, 2026. Accessed September 14, 2026.
14. Haigney S. ASGCT 2025: Emerging Modalities for Cancer Treatments. BioPharm International. Published May 12, 2025. Accessed September 14, 2026.