A Year Of Separation: Which Advanced Modalities Are Built For Commercial Scale In 2026?
By Carl Schoellhammer, Ph.D., partner, DeciBio
Advanced therapeutics are entering a new phase. Over the past decade, the central question across cell therapy, gene therapy, oligonucleotides, and RNA-based modalities was whether the biology could work. In many cases, that question has now been answered. Clinical validation exists. Regulatory precedent exists. Products are on the market.
As 2026 begins, the determining factors are shifting. Outcomes are increasingly governed by commercial fit, operational feasibility, and capital efficiency, rather than scientific plausibility. The result is not uniform acceleration but divergence. Some modalities are positioned to expand on an established foundation. Others will continue progressing, but at a pace defined by delivery complexity, workflow constraints, or economics.
This is not a slowdown in innovation but a transition into a phase where advanced therapies begin to behave like product categories rather than scientific experiments.
Cell Therapy: Growth Through Execution, Not Proliferation
Ex vivo cell therapy continues to grow, but the growth profile is becoming clearer. Expansion is driven largely by existing commercial franchises — label extensions, earlier-line use, geographic rollout, and incremental manufacturing improvements. Those levers alone are sufficient to support near-term growth.
What is not materializing is a broad wave of new late-stage programs reshaping the landscape. The constraint is no longer feasibility or even production capability. It is clinical workflow. These therapies remain operationally intensive, requiring coordination across institutions, specialized handling, and infrastructure that most care settings do not naturally possess.
This places increasing emphasis on deployment rather than discovery. Next-generation constructs — dual CARs, logic-gated designs, alternative cell types — still generate scientific interest. But the commercial bar has shifted toward a different question: not just whether the construct improves biology but whether it can be integrated into care pathways at scale.
Cell therapy is not losing relevance. It is maturing into a modality where execution, reliability, and system integration determine trajectory.
Oligonucleotides: Momentum Meets Manufacturing Reality
Oligonucleotides enter 2026 with sustained credibility. Clinical validation, regulatory familiarity, and expanding application in neuromuscular disease have reinforced their position within the therapeutic toolkit. As a result, the point of differentiation is moving downstream, toward manufacturing strategy and supply architecture.
The conversation around chemical versus enzymatic synthesis reflects this shift. The debate is no longer primarily technical; it is economic and strategic. Sponsors are weighing scalability, cost structure, environmental considerations, and control over long-term production. In practice, multiple manufacturing paradigms are likely to coexist, tailored to indication, dose, and life cycle stage.
For RNA stakeholders, this represents a familiar evolution: once biology stabilizes, process becomes the competitive frontier. The question is less how to design a sequence and more how to reliably produce it at the scale commercial medicine requires.
AAV Gene Therapy: In Vivo Expression Platforms Grow More Disciplined
AAV gene therapy is also stabilizing, though in a narrower and more selective form than earlier platform narratives suggested. Capital has concentrated in mature programs with defined indications and clearer manufacturing strategies. Pipeline breadth has contracted, but overall defensibility has increased.
From an RNA perspective, AAV is best viewed as an in vivo expression system. Clinical performance ultimately depends on how effectively vector design governs transcription, tissue specificity, and the durability of RNA expression. Capsid biology remains important, but differentiation is increasingly tied to expression control and manufacturability, not novelty alone.
This mirrors trends across RNA therapeutics, where delivery performance and scalable production are overtaking platform innovation as value drivers. Commercial activity in AAV is becoming more asset-centric, structured around individual programs rather than broad platform acquisitions. Clinical design, production strategy, and defined patient populations now anchor transactions.
In this sense, AAV illustrates how expression-based technologies mature: enthusiasm transitions from platform potential to product-level execution. Expectations for 2026 center on regulatory milestones and late-stage data, not a return to expansive early-stage narratives.
mRNA And In Vivo Editing: Technical Progress, Commercial Uncertainty
mRNA therapeutics and in vivo gene editing continue to advance, but 2026 is unlikely to represent a breakout commercial year. Delivery remains the primary gating factor, particularly outside oncology and rare disease. Lipid-based systems, while enabling, are complex to engineer and manufacture, and targeted delivery strategies introduce additional production challenges.
These platforms occupy a stage analogous to where AAV stood several years ago: clearly progressing, scientifically credible, but still working toward repeatable commercial models. Proof points in immunology, inflammation, and oncology are expected to grow. Broader indications remain limited by delivery precision and manufacturability.
The implication is structural. Biology is not the principal obstacle; deployment is.
Capital Allocation: Discipline As A Feature, Not A Constraint
Investment behavior reflects this broader transition. Capital is concentrating around late-stage or near-commercial assets, enabling technologies, and process innovations that reduce execution risk. Tools, reagents, and manufacturing platforms that improve reliability or lower cost remain attractive.
Platform ambition alone is no longer sufficient to attract sustained funding. This is less a retrenchment than a repricing of risk, with increased emphasis on differentiated delivery, production scalability, and reimbursement alignment.
A Phase Defined By Separation
The defining characteristic of 2026 is not disruption. It is separation. Modalities and programs that combine validated biology with operational and commercial clarity will continue to advance. Others will progress more gradually, constrained by infrastructure, workflow, or economics rather than scientific feasibility.
Advanced therapies have moved beyond emergence. They are entering a stage where success depends on prioritization, focus, and the ability to translate platform capability into deployable products. For the RNA ecosystem in particular, the competitive advantage is shifting toward those who can integrate delivery performance, manufacturing strategy, and clinical practicality into a coherent system.
The science remains strong. The differentiator now is execution.
About The Expert
Carl Schoellhammer, Ph.D., is an associate partner and leads DeciBio’s advanced therapies practice. He has experience across biopharma, manufacturing/bioprocessing, and supply chain considerations. He has executed on projects related to pipeline prioritization and life cycle management, indication road mapping, growth strategy, and M&A, across healthcare, life science tools, and pharma (cell and gene therapies). Previously, he co-founded and led Suono Bio, a therapeutics startup. Schoellhammer holds a B.S. from the University of California, Berkeley, and a Ph.D. from MIT, where he trained with Prof. Robert Langer.