• Ipsen obtains exclusive options to Spherical Nucleic Acids (SNAs™) currently under discovery evaluation for Huntington’s disease and Angelman syndrome;
• Exicure will be responsible for discovery and certain pre-clinical development activities. In the event Ipsen exercises its option to the two programs, Ipsen will be responsible for further development and worldwide commercialization;
• Exicure will receive a $20m upfront payment and is eligible to receive up to $1B in option exercise fees and milestone payments should Ipsen opt into both programs, as well as tiered royalties.
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.1 Achieving efficient oligonucleotide delivery to target organs and tissues, including the brain, remains a major limitation to their use.1,2 Exicure’s SNAs provide distinct chemical and biochemical properties to oligonucleotides. In preclinical models, SNAs have been shown to enhance the cell penetration, biodistribution and organ persistence properties of oligonucleotides, 3,4 which may potentially enhance drug delivery to previously inaccessible target tissues, including deep brain regions.5,6
Philippe Lopes-Fernandes, Chief Business Officer at Ipsen, said “Neuroscience is deeply rooted within Ipsen as a key strategic driver for our business. We are pleased to partner with Exicure to progress development of investigational treatment options for Huntington’s disease and Angelman syndrome, two areas of significant unmet need. This collaboration marks an important step in maximizing the potential of this novel technology, bringing together the expertise of Exicure and the robust heritage of Ipsen in neuroscience. With this new collaboration we will deepen our commitment to people living with neurological conditions around the world.”
“We are thrilled to partner with Ipsen, a leading global company with significant expertise and commitment to developing treatments for patients with rare neurological diseases,” said David Giljohann, Ph.D., Chief Executive Officer, Exicure, Inc. “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. 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.”
Under the agreement, Ipsen will receive exclusive options to license SNA-based therapeutics arising from two collaboration programs for Huntington’s disease and Angelman syndrome. Ipsen will pay Exicure a cash upfront payment of $20m upon closing and Exicure will be responsible for discovery and certain pre-clinical development activities. In the event Ipsen exercises its option, Ipsen will be responsible for further development and commercialization of the licensed products. Exicure will receive a $20m upfront payment and is eligible to receive up to $1B in option exercise fees and milestone payments should Ipsen opt into both programs, as well as tiered royalties.
Huntington’s disease (HD) is a progressive, fatal neurodegenerative disorder and the most common monogenic neurological disorder in the developed world, affecting about 40,000 individuals in the US.7 HD is 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. 8 There is currently no approved therapy to address the underlying molecular cause of HD to slow or stop disease progression.9
Angelman syndrome (AS) is a severe neurodevelopmental disorder. The prevalence of Angelman syndrome is estimated to be 1 in 12,000-20,000 people in the general population.10 The disorder is 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 15.11 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.12
Ipsen (ipsen.com) is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience; it also has a well-established Consumer Healthcare business. With Total Sales of over €2.5bn in FY 2020, Ipsen sells more than 20 medicines in over 115 countries, with a direct commercial presence in more than 30 countries. The Company’s research and development efforts are focused on its innovative and differentiated technological platforms located in the heart of leading biotechnological and life-science hubs: Paris-Saclay, France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China.
About Exicure, Inc.
Exicure, Inc. (exicuretx.com) is a clinical-stage biotechnology company developing therapeutics for neurology, immuno-oncology, inflammatory diseases, and other genetic disorders based on its proprietary Spherical Nucleic Acid, or SNA technology. Exicure believes that its proprietary SNA architecture has distinct chemical and biological properties that may provide advantages over other nucleic acid therapeutics and may have therapeutic potential to target diseases not typically addressed with other nucleic acid therapeutics. Exicure is in preclinical development of XCUR-FXN a lipid-nanoparticle SNA based therapeutic candidate, for the intrathecal treatment of Friedreich’s ataxia (FA). Exicure’s therapeutic candidate cavrotolimod (AST-008) is in a Phase 1b/2 clinical trial in patients with advanced solid tumors. Exicure is based in Chicago, IL and in Cambridge, MA
1. Roberts TC, Langer R, Wood MJA. Advances in oligonucleotide drug delivery. Nature Reviews Drug Discovery 2020;19:673 694. Available here: nature.com/articles/s41573-020-0075-7
2. Crawford L, Rosch J, Putnam D. Concepts, technologies, and practices for drug delivery past the blood brain barrier to the central nervous system. Journal of Controlled Release. 2016;240: 251-266. Available here: sciencedirect.com/science/article/pii/S0168365915302923?via%3Dihub#bb0020
5. Rosi NL, Giljohann DA, Thaxton S, et al. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 2006;312(5776):1027 1030. Available here: science.sciencemag.org/content/312/5776/1027?ijkey=8fbfd37b2763498a2658cc0dfaa5dc15df0e81a0&keytype2=tf_ipsecsha
7. Yohrling et al., Huntington Study Group 2019 Annual Meeting
8. Bates et al., Nature Reviews Disease Primers, 2015
9. Tabrizi et al., Nature Reviews Neurology, 2020 Available here: nature.com/articles/s41582-020-0389-4?proof=t
10. NORD. rarediseases.org/rare-diseases/angelman-syndrome/
11. Buiting et al., Nature Reviews Neurology, 2016; US Census Data.
12. NIH, National Institute of Neurological Disorders and Stroke, accessed on July 27, 2021 Available here: ninds.nih.gov/Disorders/All-Disorders/Angelman-Syndrome-Information-Page
Craig Marks - Vice President, Investor Relations
P: +44(0)75 8434 9193
Adrien Dupin de Saint-Cyr - Investor Relations Manager
P: +33(0)6 64 26 17 49
Exicure contact: Karen Sharma
P: +1 781-235-3060 - E: ksharma[.]macbiocom.com.