Analysts weigh Bristol Myers Squibb’s $1.5bn Orbital Therapeutics deal as a bold but risky pivot

Bristol Myers Squibb (NYSE: BMY) is making one of its boldest strategic pivots in years with a $1.5 billion all-cash acquisition of Orbital Therapeutics, a Cambridge-based biotechnology company developing RNA medicines that reprogram immune cells directly inside the human body. The deal, which analysts describe as both visionary and risky, extends the American pharmaceutical major’s reach into in vivo CAR T-cell therapy—a nascent but potentially transformative approach that could one day reset the immune system to treat autoimmune diseases.

For Bristol Myers Squibb, the acquisition represents a calculated bet on scientific innovation at a time when legacy revenue streams face mounting patent and pricing pressures. For investors, it underscores the company’s determination to stay on the offensive in a rapidly evolving cell therapy landscape, even if the near-term payoff remains uncertain.

The deal significantly strengthens Bristol Myers Squibb’s already diverse cell therapy portfolio and underlines its intent to expand beyond oncology into chronic immune-related disorders. The acquisition fits neatly into the company’s long-term strategy of pairing its expertise in CAR T-cell development with cutting-edge RNA delivery platforms capable of producing engineered immune cells directly inside the patient.

When is Bristol Myers Squibb expected to close its $1.5 billion Orbital Therapeutics acquisition, and what conditions could delay it?

The acquisition is expected to close by late 2025, subject to customary closing conditions including expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Until completion, Bristol Myers Squibb and Orbital Therapeutics will continue to operate as separate and independent entities. Upon closing, Bristol Myers Squibb will pay USD 1.5 billion in cash and assume full ownership of Orbital’s RNA platform, intellectual property portfolio, and development pipeline, including OTX-201, its lead preclinical asset. The accounting treatment—whether categorized as a business combination or asset acquisition—will be determined after the transaction formally concludes.

Market response was restrained but analytical. Shares of Bristol Myers Squibb fell slightly in early trading after the announcement, with institutional investors largely interpreting the deal as a long-term R&D bet rather than a near-term profit driver. Analysts said the move reinforces management’s push to replenish innovation pipelines as blockbuster drugs approach patent expiration.

Why is Bristol Myers Squibb betting on in vivo CAR T-cell technology as the next frontier in autoimmune therapy?

Traditional ex vivo CAR T therapies, including Bristol Myers Squibb’s approved products Abecma and Breyanzi, require extracting a patient’s immune cells, genetically modifying them in a lab, and reinfusing them—a complex process limited by manufacturing capacity and cost. Orbital Therapeutics’ in vivo approach aims to bypass those bottlenecks entirely.

Its lead preclinical program, OTX-201, leverages circular RNA technology to encode a CD19-targeted chimeric antigen receptor (CAR) within the patient’s body. Delivered through targeted lipid nanoparticles, the therapy instructs the immune system to generate therapeutic CAR T cells internally. This innovation could drastically reduce treatment timelines and costs, expanding patient access far beyond the specialized centers required for ex vivo manufacturing.

Bristol Myers Squibb’s Chief Research Officer Robert Plenge noted that the acquisition adds a potentially “best-in-class” platform for depleting autoreactive B cells and resetting immune balance in diseases such as lupus and multiple sclerosis. Analysts agreed that this could represent a step change for autoimmune care—offering not just symptom relief but true immune recalibration.

How does Orbital Therapeutics’ RNA platform enhance Bristol Myers Squibb’s cell therapy capabilities?

At the core of the acquisition is Orbital’s proprietary RNA platform, which integrates circular and linear RNA engineering, AI-assisted design, and advanced lipid nanoparticle delivery. The technology provides a modular toolkit for durable, programmable RNA therapeutics capable of targeting a wide range of tissues and disease mechanisms.

This platform complements Bristol Myers Squibb’s expertise in cellular immunology, providing the tools to design therapies that can be produced directly inside the patient. By merging Orbital’s RNA know-how with its own cell therapy pipeline, Bristol Myers Squibb expects to cut development timelines, improve manufacturability, and accelerate clinical testing across oncology and immunology programs alike.

Lynelle B. Hoch, President of Bristol Myers Squibb’s Cell Therapy Organization, said the company now has the opportunity to evaluate multiple platform approaches for inducing immune reset in autoimmune diseases while refining its in vivo technology during early-phase clinical work.

Orbital’s Chief Executive Officer Ron Philip called the agreement a “transformational milestone” for RNA medicine, noting that the integration with a global pharmaceutical leader will help scale RNA therapeutics to reach more patients, across more tissues and disease areas, than ever before.

What are the financial and strategic drivers behind Bristol Myers Squibb’s $1.5 billion acquisition?

Financially, the deal represents a straightforward cash purchase at closing, consolidating ownership of Orbital’s assets and research programs. Strategically, it positions Bristol Myers Squibb to remain competitive as its key franchises—Opdivo, Revlimid, and Eliquis—face ongoing revenue headwinds.

The American pharmaceutical major has been actively seeking external innovation to rejuvenate its portfolio, as seen in its earlier purchase of 2seventy bio for approximately USD 286 million. That deal gave Bristol Myers Squibb full control of Abecma, its flagship CAR T product for multiple myeloma. The Orbital transaction builds on that same strategy but takes it a step further—shifting from ex vivo manufacturing to programmable in vivo cell generation.

Analysts view the acquisition as an R&D-heavy investment designed to secure Bristol Myers Squibb’s leadership in next-generation immunotherapy. While earnings impact will likely be negligible in the near term, the acquisition deepens the company’s innovation moat and may prove pivotal in sustaining growth into the next decade.

How are investors interpreting the deal amid broader sentiment around Bristol Myers Squibb stock?

Investor sentiment remains cautiously optimistic. The stock has declined around 14 percent over the past year, reflecting concerns over patent expirations and pricing pressures, but institutional investors see the Orbital acquisition as a positive signal that the company is willing to invest aggressively in long-horizon science.

Analysts maintain a consensus “Hold” rating with upside potential in the medium term. Some point out that the risk-reward profile of RNA-based cell therapy remains uncertain, while others emphasize that Bristol Myers Squibb’s scale, regulatory experience, and proven commercialization record could help de-risk the early stages of development.

In essence, the acquisition is viewed as an innovation hedge—an effort to diversify risk while positioning the firm for long-term breakthroughs.

What challenges could Bristol Myers Squibb face in translating in vivo CAR T into clinical success?

Despite its promise, in vivo CAR T therapy faces major scientific and regulatory challenges. Achieving precise RNA delivery to immune cells, maintaining control over CAR expression levels, and preventing off-target immune reactions are complex engineering problems. Sustaining durable responses without causing cytokine release syndrome will require meticulous design and clinical monitoring.

Regulators are also proceeding cautiously. The U.S. Food and Drug Administration and the European Medicines Agency are expected to require extensive long-term safety follow-up for the first wave of in vivo gene or cell therapies. Bristol Myers Squibb’s prior CAR T approvals give it experience navigating these frameworks, but applying those lessons to autoimmune indications introduces new variables.

Competition is intensifying as well. Pharmaceutical companies including AbbVie, AstraZeneca, and Gilead Sciences are actively investing in similar RNA-based and lipid-nanoparticle delivery systems. More than 70 preclinical in vivo CAR T programs are in development globally, suggesting a crowded race where execution speed and safety differentiation will be key.

How does the acquisition align with Bristol Myers Squibb’s long-term innovation roadmap?

The acquisition underscores Bristol Myers Squibb’s strategic evolution from a traditional pharmaceutical manufacturer into a platform-driven biopharma innovator. By embedding Orbital’s RNA engineering technology into its R&D infrastructure, the company gains end-to-end control over a new therapeutic modality that can span oncology, immunology, and rare diseases.

For patients, the implications are profound. If successful, in vivo CAR T could transform autoimmune disease treatment from chronic management to one-time immune reset. For Bristol Myers Squibb, it represents the next logical extension of its cell therapy dominance—enabling scalable production and potentially broader global access.

Institutional analysts describe the acquisition as “scientifically bold and commercially sensible,” noting that it complements the company’s historical strength in immune modulation while expanding its future therapeutic reach.

Is Bristol Myers Squibb’s $1.5 billion acquisition of Orbital Therapeutics a bold strategic leap or a risky experiment in in vivo CAR T therapy?

Viewed through an industry lens, this is a calculated leap grounded in Bristol Myers Squibb’s long-standing leadership in immunotherapy. The company is effectively betting that in vivo cell engineering will deliver the same disruption to autoimmune care that mRNA vaccines brought to infectious disease.

However, the risks are not trivial. OTX-201 is still preclinical, meaning any proof-of-concept is years away. Success will depend on cross-disciplinary execution—integrating RNA chemistry, delivery science, immunology, and manufacturing within one cohesive development model. For investors, that means patience will be essential.

Analysts characterize the deal as a “venture-style investment inside a blue-chip portfolio.” If the science holds, Bristol Myers Squibb could redefine the economics of cell therapy by eliminating ex vivo bottlenecks. If it falters, the company still retains a diversified revenue base and one of the industry’s most advanced R&D pipelines.

For now, the message to the market is clear: Bristol Myers Squibb is doubling down on innovation, determined to stay ahead of scientific and competitive cycles by taking disciplined risks that could set new standards in patient care.