RARE Daily

QurAlis Grants Lilly Exclusive Global License for Preclinical ASO for Neurodegenerative Diseases

June 3, 2024

Rare Daily Staff

QurAlis entered into an exclusive license agreement with Eli Lilly in which it granted Lilly global rights to develop and commercialize QRL-204, a potentially best-in-class splice-switching antisense oligonucleotide designed to restore function of the UNC13A gene in amyotrophic lateral sclerosis, frontotemporal dementia, and other neurodegenerative diseases.

“This partnership enables QRL-204 to rapidly move toward the clinic, while we continue to advance our other lead programs,” said Kasper Roet, CEO and co-founder of QurAlis.

Under the terms of their agreement, QurAlis will receive an upfront payment of $45 million, plus an additional equity investment. QurAlis is also eligible for future milestone payments of up to $577 million and tiered royalties on net sales.

The collaborative agreement includes research and development to identify and develop additional candidates targeting UNC13A, leveraging QurAlis’ proprietary FlexASO Splice Modulator Platform, which was developed to generate splice-switching ASOs with improved potency and increased therapeutic index. QurAlis’ ASOs correct UNC13A mis-splicing, restore UNC13A protein production and reduce cryptic exons that may contribute to disease progression.

“Genetic precision medicines like QRL-204 that target specific causal components of disease pathology hold great promise for delivering meaningful advances against a range of neurodegenerative diseases like ALS and FTD,” said Andrew Adams, senior vice president, neurodegeneration research, and director, Lilly Institute for Genetic Medicine.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by the loss of neurons in the spinal cord, brainstem, and brain. A defining feature of both sporadic and familial disease is the cytoplasmic mis-localization of TAR DNA Binding Protein-43 (TDP-43). TDP-43 pathology is implicated in 90 percent of ALS cases and approximately 50 percent of FTD cases.

UNC13A is an essential regulator of neurotransmitter release at synapses and is one of several pre-mRNAs that becomes mis-spliced due to loss of nuclear TDP-43 in disease. Up to 63 percent of ALS patients and up to one-third of FTD patients carry a single nucleotide polymorphism in the UNC13A gene or show TDP-43 pathology, which greatly exacerbates UNC13A mis-splicing leading to loss of function of the UNC13A protein.

Preclinical data recently presented at the AD/PD 2024 International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders showed QurAlis’ UNC13A splice-switching ASOs modulate UNC13A splicing and restore normal synaptic activities in ALS and FTD. QurAlis’ ASOs prevented cryptic exon inclusion in UNC13A transcripts, increased UNC13A protein levels, and normalized localization of UNC13A protein at the synapse.

Photo: Kasper Roet, CEO and co-founder of QurAlis

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