Rare Daily Staff

Ipsen and Exicure signed an exclusive collaboration agreement to research, develop, and commercialize novel spherical nucleic acids as potential investigational treatments for the rare neurodegenerative conditions Huntington’s disease and Angelman syndrome.

Huntington’s disease (HD) is a progressive, fatal neurodegenerative disorder caused by an expanded CAG trinucleotide repetition in the huntingtin (HTT) gene in chromosome 4. HD is characterized by involuntary movements, psychiatric disorders, cognitive deterioration, and early mortality, with death often occurring within 10 to 20 years after motor symptoms appear. Mean age of onset of motor symptoms is around 40 years of age, with longer CAG repeats causing earlier disease onset. There is currently no approved therapy to address the underlying molecular cause of HD to slow or stop disease progression.

Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by severe intellectual deficit, speech impairment, epilepsy, ataxic movements and behavioral abnormalities. AS results from loss of function of the maternally inherited copy of the ubiquitin-protein ligase E3A (UBE3A) gene on chromosome 15. Disruption of UBE3A function in neurons prevents synapse formation and remodeling, leading to significant neurodevelopmental disability. There is currently no approved disease-modifying therapy for AS and standard-of-care treatment is supportive, such as medications for seizures and behavioral abnormalities.

Under the terms of their agreement, Ipsen will receive exclusive options to license spherical nucleic acids (SNA)-based therapeutics arising from two collaboration programs for Huntington’s disease and Angelman syndrome. Ipsen will pay Exicure an upfront payment of $20 million upon closing and Exicure will be responsible for discovery and certain preclinical development activities. In the event Ipsen exercises its option, Ipsen will be responsible for further development and commercialization of the licensed products. Exicure will be eligible to receive up to $1 billion in option exercise fees and milestone payments should Ipsen opt into both programs, as well as tiered royalties.

Exicure’s SNAs provide distinct chemical and biochemical properties to oligonucleotides. Oligonucleotides are synthetic structures of nucleic acids that can be used to modulate gene expression via a range of processes, including gene activation, inhibition, and splice-modulation. These molecules have demonstrated potential in many different therapeutic areas. Achieving efficient oligonucleotide delivery to target organs and tissues, including the brain, remains a major limitation to their use. In preclinical models, SNAs have been shown to enhance the cell penetration, biodistribution and organ persistence properties of oligonucleotides, which may potentially enhance drug delivery to previously inaccessible target tissues, including deep brain regions.

“In collaboration with Ipsen, we have the opportunity to apply our technology to Huntington’s disease and Angelman syndrome, both indications requiring deep brain penetration and technological advances to reach previously hard-to-drug targets,” said David Giljohann, CEO of Exicure. “We believe our platform technology with its deep penetration and persistence of medicinal effect will allow Exicure and Ipsen to overcome challenges from first-generation oligonucleotides and bring new medicines to patients in need.”

Photo: David Gilijohann, CEO of Exicure

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