Denali Therapeutics (DNLI) investor relations material

Commercial launch and product positioning

• AVLAYAH, approved in March, is indicated for Hunter syndrome and marks a significant advance in blood-brain barrier transport therapies.

• Early commercial uptake is strong across all patient segments, with the first commercial patients on drug and high engagement from both physicians and patients.

• The market is well-defined, as nearly all Hunter syndrome patients are already identified and treated, making the focus on switching from the existing standard of care.

• AVLAYAH is priced at a premium to ELAPRASE, with expectations that AVLAYAH and DNL126 together represent a $1 billion market opportunity.

• Initial reimbursement and payer engagement have been positive, with most prior authorizations proceeding smoothly.

Label, clinical development, and future expansion

• The current label covers pediatric patients with neurologic manifestations, about 70% of the population, and may expand to adults after the COMPASS study reads out by the end of next year.

• The COMPASS study includes adults up to 26 years old, aiming to lift the pediatric-only restriction.

• Dose escalation protocols are being well-received, with early hospital-based dosing not seen as a barrier.

• Global distribution agreements are in place, but the primary focus remains on the U.S. launch.

Pipeline and platform strategy

• DNL126 for Sanfilippo (MPS IIIA) showed an 80% mean reduction in heparan sulfate in phase I-II, with BLA filing targeted for 2027.

• The infrastructure for AVLAYAH will be leveraged for DNL126 and other enzyme replacement therapies, minimizing the need for additional resources.

• Pompe disease program will test transferrin receptor targeting for improved muscle and bone distribution, aiming for significant differentiation from current therapies.