Preview For Angelman Pivotal Data In 2H -- Simulation Suggests High POS

Research evidence excerpt

Preview For Angelman Pivotal Data In 2H -- Simulation Suggests High POS

RARE investment thesis hinges on Angelman program success

❑If successful, the Angelman opportunity would anchor the RARE investment thesis, given the

large addressable mkt and 1st-mover positioning (we est ~1.5-yrs competitive lead vs IONS can

establish SOC positioning). Also, RARE’s multiple regulatory designations (Breakthrough, Orphan, Rare

Pediatric, Fast Track) reflect FDA's recognition of serious unmet need and strength of preliminary clinical

evidence from phase 1/2 data that showed substantial improvement across multiple domains.

❑Consensus and Jefferies’ peak sales estimates are conservative based on the TAM. Given the multi-

$B peak sales opportunity [we estimate $1.8B WW (U.S. $1.2B; EU5 $0.6B) peak sales in 2036], success

should lead to a major inflection catalyst for RARE’s current ~$2.2B market cap and establish a multi-yr

revenue growth driver beginning 2H27. Conversely, failure would eliminate the company’s largest near-

term pipeline opportunity and force greater reliance on the base business and gene therapy programs.

We est stock +>100%/–40% (scenarios in slide 8).

❑Two gene therapy programs remain underappreciated despite near-term value – GSD1a PDUFA

8/23/26 and MPS-IIIA PDUFA 9/19/26. Perception of small commercial opportunities and more

negative gene therapy sentiment have lowered interest. However, we note RARE’s DTX401 and UX111

target diseases with zero approved disease-modifying therapies and profound unmet need (GSD1a

requires extreme dietary restriction; MPS-IIIA causes progressive neurodegeneration and early death) to

overcome challenging reimbursement and uptake dynamics. Management expects both launches to

"contribute meaningfully" despite small populations.