In 2019, the therapeutic modalities available to drug developers were well-established: small molecules (~90% of approved drugs), monoclonal antibodies (~8%), and a handful of recombinant proteins, vaccines, and cell therapies (~2%).

Five years later, the landscape has transformed. There are now at least a dozen distinct therapeutic modalities with approved drugs or late-stage clinical data. The number of modalities with commercial products has doubled. The addressable market for "new modality" drugs — everything beyond small molecules and antibodies — is projected to exceed $150 billion annually by 2030.

The Modality Landscape

RNA Therapeutics: The $100B Market Taking Shape

The biggest story in therapeutic modalities is the quiet rise of RNA-targeting medicines. Alnylam Pharmaceuticals, the pioneer of RNA interference (RNAi) therapeutics, reported over $1 billion in quarterly revenue for Q1 2026 — the first RNAi company to cross that threshold. Its market cap has grown 8x since 2020.

RNAi works by silencing disease-causing genes at the mRNA level — preventing the production of harmful proteins. Alnylam has five approved drugs (Onpattro, Givlaari, Oxlumo, Amvuttra, and one more approved in 2025), with a pipeline covering cardiovascular, metabolic, and neurologic diseases. Arrowhead Pharmaceuticals has seen its stock rise 532% in the past year on positive Phase 3 data for plozasiran, an RNAi therapeutic for hypertriglyceridemia.

Antisense oligonucleotides (ASOs) are a related approach, pioneered by Ionis Pharmaceuticals. Nusinersen (Spinraza) for spinal muscular atrophy remains the landmark ASO success, but Ionis has expanded into cardiovascular disease with olezarsen and multiple neurology programs.

mRNA therapeutics are the X-factor. After the COVID-19 vaccine success (which made Moderna and BioNTech household names), both companies are pivoting to therapeutic mRNA — encoding therapeutic proteins (antibodies, enzymes, cytokines) in mRNA molecules that are delivered via lipid nanoparticles. Moderna has 25+ active clinical programs, including mRNA therapies for cancer (individualized neoantigen therapy), rare diseases (methylmalonic acidemia), and cardiovascular disease.

The key advantage of mRNA is programmability: the same LNP delivery platform works for any protein-encoding sequence. The key challenge is durability: mRNA is transient, requiring repeated dosing. For some indications (vaccines, acute conditions), transience is a feature. For chronic diseases, it's a limitation.

CAR-T and Cell Therapy: Curing Cancer, One Patient at a Time

Chimeric antigen receptor T-cell therapy has evolved from a last-resort treatment for relapsed/refractory B-cell malignancies to a multi-line therapy with six approved products and expanding indications. The key development in 2024-2026 is the move toward off-the-shelf (allogeneic) CAR-T — using donor-derived T cells rather than the patient's own cells.

Allogeneic CAR-T would solve the manufacturing bottleneck (current CAR-T takes 2-4 weeks to manufacture per patient) and reduce costs from $400,000+ to a target of $50,000-100,000. Caribou Biosciences, CRISPR Therapeutics, and Allogene Therapeutics are in Phase 2/3 with off-the-shelf CAR-T products targeting CD19 and BCMA.

ADCs and Bispecifics: Engineering Antibodies Can Do More

Antibody-drug conjugates (ADCs) — antibodies chemically linked to potent chemotherapy drugs — have become a $12 billion market with 13 approved drugs. The innovation in 2024-2026 has been in linker technology (more stable, more tumor-selective drug release) and novel payloads (topoisomerase I inhibitors, PBD dimers). Enhertu (Daiichi Sankyo/AstraZeneca) alone is on track for $5 billion in annual sales for HER2-positive cancers.

Bispecific antibodies — antibodies that bind two different targets simultaneously — have five approved drugs as of Q1 2026. The application is primarily in oncology (T-cell engagers that bring T cells to cancer cells), but bispecifics for neurodegenerative, autoimmune, and infectious diseases are in development. The platform nature of bispecifics — once you solve the protein engineering, you can generate new candidates rapidly — makes this one of the highest-productivity modalities in the industry.

The Convergence

The most important development in modalities is not any single technology. It's the convergence. The same company can now deploy mRNA, RNAi, cell therapy, and gene editing against the same disease target, selecting the modality based on the biology rather than the company's platform.

This modality-agnostic approach is what distinguishes the leading biotech companies of 2026 from the previous generation. Alnylam is developing RNAi and gene editing. Moderna has mRNA and cell therapy programs. CRISPR Therapeutics is developing gene editing, cell therapy, and regenerative medicine applications. The platform wars of 2017-2023 are giving way to integrated modality strategies.

The winners will be the companies that can match modality to biology — not the ones with the best single technology.

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Data Sources: Company quarterly filings (Alnylam, Ionis, Arrowhead, Moderna, BioNTech — Q1 2026), FDA drug approval database (new molecular entities by modality), PharmaProjects modality classification data, EvaluatePharma consensus forecasts, company pipeline disclosures (Q1 2026).

About the Author: Martin DAVILA is a bioeconomy analyst and the founder of Bioinfometrics.