Denali Therapeutics is advancing its TransportVehicle platform for delivering therapeutics across the blood-brain barrier as the company’s first commercial product, AVLAYAH, gains momentum and two TransportVehicle-enabled Alzheimer’s disease programs move through clinical development.
Denali’s TransportVehicle platform is designed to deliver large therapeutic molecules, including antibodies, enzymes and oligonucleotides, throughout the body and into the brain. In animal models, antibodies and enzymes engineered with the technology demonstrated more than 10-fold to 30-fold greater brain exposure than comparable molecules without the technology. Oligonucleotides engineered with the platform demonstrated more than 1,000-fold greater brain exposure in primates than systemically delivered oligonucleotides without the technology.
The platform has now helped produce Denali’s first commercial medicine. AVLAYAH, also known as tividenofusp alfa-eknm, is the first and only FDA-approved medicine in an emerging class of biotherapeutics that leverage the transferrin receptor to cross the blood-brain barrier. The enzyme replacement therapy received accelerated FDA approval for the treatment of neurologic manifestations of Hunter syndrome in certain pediatric patients.
AVLAYAH generated $3.6 million in net product revenue during its first full quarter of commercial availability. Denali projects that revenue will increase to between $10 million and $12 million in the third quarter, with initial interest in starting treatment tracking ahead of the company’s internal expectations.
Approximately 80% of healthcare organizations treating eligible Hunter syndrome patients have been reached through launch webinars and Denali’s field organization. Published commercial coverage policies represent more than 50% of covered lives, and 14 state Medicaid programs have published AVLAYAH coverage.
Denali is also extending the TransportVehicle approach into Alzheimer’s disease. DNL628 is an Oligonucleotide TransportVehicle-enabled antisense oligonucleotide designed to cross the blood-brain barrier and reduce tau by targeting the MAPT gene. Initial biomarker data from its Phase 1b study are expected in the first half of 2027. DNL921 is an Antibody TransportVehicle-enabled antibody designed to cross the blood-brain barrier and target amyloid plaques, with safety and proof-of-concept data expected in 2027.
The company’s financial position was strengthened by the sale of a Rare Pediatric Disease Priority Review Voucher awarded following AVLAYAH’s FDA approval. Denali received $195 million in July, bringing pro forma cash, cash equivalents and marketable securities to more than $1.1 billion.
KEY QUOTES:
“We are excited by the positive response to our AVLAYAH launch from the Hunter syndrome community and the physicians caring for these patients. It reflects years of partnership with patients, families, advocacy organizations and investigators, together with the outstanding execution of our commercial team.”
“This quarter marks an important step in Denali’s growth. AVLAYAH establishes our commercial foundation, validates our TransportVehicle platform and supports the continued expansion of our portfolio of medicines. During the quarter, we also advanced two TransportVehicle-enabled programs into clinical development, expanding our Alzheimer’s disease pipeline. We believe this combination of a commercial business, a broad clinical pipeline and a scalable platform uniquely positions Denali to deliver sustainable value.”
Ryan Watts, Ph.D., CEO of Denali Therapeutics
