Wells Fargo’s 2026 sector outlook for small- and mid-cap biotechnology companies highlights a concentrated group of names the firm views as having the highest probability of outperformance next year. From a coverage universe of 22 companies, analysts singled out six firms - Ionis Pharmaceuticals, Beam Therapeutics, Taysha Gene Therapies, Sarepta Therapeutics, Spyre Therapeutics and RAPT Therapeutics - citing dense calendars of clinical and regulatory catalysts, commercial momentum and financial de-risking as the primary drivers.
Big-picture framing
The analysts emphasize that these six selections are their strongest ideas among SMID-cap biotechs for 2026. Their rationale ranges across late-stage pivotal readouts, potential regulatory decisions, evolving commercial rollouts and balance-sheet considerations that could shorten the path to cash-flow breakeven for some companies.
Ionis Pharmaceuticals (IONS)
Ionis enters the 2026 outlook having posted a notable return in 2025, and Wells Fargo positions the company for another year of relative strength. Ionis’ 2025 performance rose 126%, and the firm’s 2026 profile is built around multiple late-stage catalysts. The key events called out include pelacarsen Phase 3 Lp(a) data expected in the first half of 2026, which analysts say could open access to a large cardiovascular market. Additional milestones cited are BIIB080 Phase 2 Alzheimer’s results targeted for mid-2026, pending regulatory decisions for TRYNGOLZA and bepirovirsen and WAINUA Phase 3 ATTR-CM data slated for the second half of 2026. That WAINUA readout is portrayed as offering more than 15% upside potential. Wells Fargo also notes Ionis’ guidance toward cash-flow breakeven by 2028, a factor that the bank considers to reduce financial risk while the company advances multiple programs.
Beam Therapeutics
Beam is drawn into the top list primarily on the basis of its base-editing program for alpha-1 antitrypsin deficiency (AATD). Results from that program are expected in early 2026, and analysts point to the therapy’s root-cause mechanism as a potential rationale for an accelerated-approval pathway from the FDA. The report frames a positive data outcome as creating roughly 50% upside for the stock, and notes that higher AAT levels observed with a two-dose regimen would strengthen the efficacy case. The analysts cite expert consensus indicating that Beam’s targeted efficacy thresholds appear achievable, which sets up a high-impact readout early in 2026.
Taysha Gene Therapies (TSHA)
Taysha is cited for its pivotal Rett syndrome program, where the company has reportedly secured favorable regulatory alignment on trial design. Wells Fargo expects the pivotal trial’s six-month interim analysis, due in the third or fourth quarter of 2026, to succeed and to drive approximately 50% upside if confirmed. A positive interim would, in the analysts’ view, create a pathway toward a first-in-class biologics license application (BLA) filing. The combination of regulatory footing and encouraging early-stage results places Taysha among the highest-confidence small-cap gene therapy picks in the bank’s coverage set.
Sarepta Therapeutics (SRPT)
Sarepta’s 2026 outlook is characterized as contingent on amplifying its commercial launch for ELEVIDYS alongside multiple clinical catalysts. Wells Fargo describes Sarepta’s guidance for $500 million in ambulant sales as conservative and models U.S. sales nearer $720 million for 2026. Notable upside events highlighted by the analysts include Cohort 8 data in the second half of 2026 that could support sirolimus-based mitigation of liver injury risk, the potential restoration of a non-ambulant label and readouts from the company’s DM1 and FSHD siRNA programs. Collectively, these represent multiple potential value-inflection points that could propel Sarepta above baseline expectations.
Spyre Therapeutics (SYRE)
Spyre receives attention for a broad immunology pipeline and a solid cash position that the analysts calculate provides runway into the second half of 2028. The firm’s pro-forma cash is reported at $783 million, a balance that Wells Fargo says positions Spyre to advance an extensive set of clinical programs. Catalysts flagged for 2026 include several combination-therapy readouts in ulcerative colitis and Crohn’s disease as well as expansion into rheumatology indications such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). The analysts note that Spyre’s TL1A plus α4β7 approach has demonstrated superior results to TNF blockers in cited comparisons, supporting a potential best-in-class claim.
RAPT Therapeutics (RAPT)
RAPT is included among the bank’s highest-confidence names on the basis of differentiated programs spanning immunology and oncology and an appealing valuation setup entering 2026. While the report excerpts provided do not elaborate the same program-specific detail included for other names, RAPT is explicitly named among the top selections and is noted as carrying an Overweight rating with meaningful price-target upside in the analysts’ view.
What this means for markets
Wells Fargo’s concentrated list underscores the degree to which near-term binary events - pivotal readouts, regulatory decisions and commercial execution - can drive SMID-cap biotech performance. The selections span cardiovascular, central nervous system, gene therapy, neuromuscular, and immunology franchises, signaling potential activity across multiple subsectors of the healthcare and biotech market in 2026.