‍Market Refinement and Separation in 2026

The past several years in advanced therapies have followed a consistent arc.
2024 was defined by recalibration as capital tightened and expectations reset.
2025 became a year of refinement, with companies narrowing focus, cutting pipelines, and spending more time on execution than ambition. As we head into 2026, the industry feels like it is entering a different phase.

The question is no longer whether these modalities work. Across cell therapy, gene therapy, oligonucleotides, and RNA-based approaches, the science has largely been proven. What now determines outcomes is far more practical, and in some cases less comfortable: commercial fit, operational feasibility, and capital discipline. In that context, 2026 looks like a year of divergence. Some approaches will keep pulling ahead. Others will move forward, but more slowly, constrained less by biology than by workflow, economics, and execution. And what is hot today may have a longer road ahead than we all think.

Cell Therapies: Commercial-Driven Growth

Ex vivo cell therapy will continue to grow in 2026, but probably not in the way many once expected. Most of that growth will come from existing commercial franchises rather than a wave of new programs entering the top of the funnel. Approved products will move into earlier lines of therapy, expand geographically, and benefit from incremental improvements in manufacturing reliability and turnaround time. On their own, those factors are enough to sustain growth.

What we are unlikely to see is a broad influx of new, differentiated ex vivo programs pushing through late-stage development in a material way.

The constraint is no longer scientific feasibility or even manufacturability. It is physician friction. Even with strong efficacy, ex vivo cell therapies remain difficult to prescribe, operationally heavy for referring physicians, and poorly aligned with how most specialists are used to practicing medicine outside of major centers. Until ordering, coordination, and patient management become meaningfully simpler, adoption will stay concentrated among institutions that already have the infrastructure and experience to deliver these therapies.

As a result, 2026 will place more weight on commercial execution than on pipeline breadth. Next-generation constructs such as dual CARs, logic-gated designs, and new cell types will continue to generate interest, but the bar will be higher. Not just whether they work, but whether they can be deployed at scale. Cell therapy will remain a powerful modality. In 2026, it will increasingly behave like a franchise business rather than a discovery engine.

Oligonucleotide Momentum: Manufacturing in Focus

Oligonucleotides enter 2026 with sustained momentum and growing strategic importance across biopharma. Unlike several other advanced modalities, oligos now sit at a relatively comfortable intersection of biology, regulation, and commercial precedent. That position is likely to be reinforced in 2026 through concrete asset-level outcomes, particularly in neuromuscular disease.

Late-stage programs such as delpacibart zotadirsen and delpacibart braxlosiran, now under Novartis following its acquisition of Avidity, will be closely watched across Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy. At the same time, WVE-N531 from Wave Life Sciences will further test how durable and generalizable RNA-based approaches in Duchenne can be. At least one of the aforementioned assets receiving FDA approval or a meaningful regulatory milestone would not be surprising and would further cement the modality’s relevance beyond ultra-rare disease.

Attention is also shifting away from whether oligos work to how they should be manufactured at scale. The discussion around chemical synthesis versus enzymatic manufacturing is becoming less academic and more strategic, with sponsors weighing tradeoffs across cost, scalability, sustainability, and long-term control. In practice, there is likely room for both approaches, depending on indication, dose requirements, and where an asset sits in its lifecycle. However, fully enzymatic synthesis is unlikely to see material adoption this year given idle chemical capacity across the market, the pace at which sponsors need to advance assets, and broader capital constraints.

AAV Gene Therapy: Continued Progress Post Reset

AAV gene therapy enters 2026 on firmer footing than it has had in several years. In just the last year, private AAV developers have seen an influx of invested capital on the order of 3-quarters of a billion dollars. This capital has been concentrated in a smaller number of more mature companies with defensible programs. After a period of aggressive pipeline pruning, more disciplined indication selection, and steady manufacturing improvements, the field now looks narrower, but also more defensible. That discipline is beginning to show up in tangible ways.

In 2026, we expect one or more meaningful regulatory milestones or approvals, including RGX-121 for MPS II from REGENXBIO, along with additional clinically relevant data readouts from late-stage programs. What we do not expect is a return to broad, platform-level enthusiasm.

Commercial activity in AAV is more likely to remain asset-centric, with partnerships and acquisitions structured around individual programs or specific territories rather than full-platform takeouts. These deals will be driven by late-stage assets, defined patient populations, and clear manufacturing strategies, not capsid novelty alone.

As a result, AAV continues to move away from platform narratives and toward product-by-product evaluation, where differentiation is defined by clinical design, manufacturability, and commercial execution.

mRNA and In Vivo Editing: Progress Without a Breakout

Despite continued technical progress, 2026 is unlikely to be a breakout year for mRNA therapeutics or in vivo gene editing, despite some of the bets that large pharma made through ’25.

Delivery remains the central gating factor, especially for applications beyond oncology and select rare diseases. Competitive density is still high, and the risk-benefit calculus for broader indications remains difficult to justify. Lipid-based delivery platforms, while the primary platform, remain far from straightforward to manufacture and engineer. The potential need for targeting moieties in applications such as in vivo cell therapy further complicates manufacturability in ways the market still underestimates.

We expect steady advances in targeted delivery technologies, enabling platforms, and early proof points, particularly in immunology, inflammation, and oncology. Outside of those areas, however, commercial clarity is likely to remain elusive.

In many ways, mRNA and in vivo editing in 2026 resemble where AAV stood several years ago. Promising, clearly progressing, but still searching for repeatable commercial templates.

Capital and Investors: A Disciplined Approach

From an investment perspective, 2026 is likely to be better than 2025, but still firmly grounded in a more disciplined operating environment.

Capital will continue to favor tools, services, and high-value inputs that reduce development friction and improve execution. Process technologies, consumables, reagents, and enabling platforms with clear customer pull remain attractive to both strategic and financial investors.

On the therapeutic side, capital will stay concentrated around late-stage or near-commercial assets with differentiated delivery, manufacturability, and reimbursement narratives. Platform ambition on its own is no longer enough to unlock funding. This is not a retreat from innovation. It is a repricing of risk and reward across the biopharma ecosystem.

Looking Ahead: A Year of Divergence

The defining feature of 2026 will not be disruption. It will be separation. Modalities and programs with commercial clarity and operational feasibility will continue to pull ahead. Others will progress, but at a slower pace, constrained by execution and economics rather than scientific failure.

For biopharma leaders, investors, and ecosystem partners, success in 2026 will depend less on vision and more on prioritization, focus, and a willingness to make difficult tradeoffs.

Advanced therapies are no longer emerging. They are maturing. And in that maturation, the next set of winners is becoming easier to identify.