Lilly Gains Exclusive Global License for QRL-204 from QurAlis to Treat ALS and FTD

QurAlis Corporation has announced a significant partnership with Eli Lilly and Company to advance the development of QRL-204, a splice-switching antisense oligonucleotide (ASO) designed to restore the function of the UNC13A gene. This collaboration seeks to address neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). QRL-204 is generated using QurAlis' proprietary FlexASO™ Platform and represents Lilly's first program targeting the UNC13A gene in ALS and FTD.

The agreement grants Lilly exclusive global rights to develop and commercialize QRL-204, alongside other compounds targeting UNC13A. In return, QurAlis receives an upfront payment of $45 million from Lilly, along with an additional equity investment. Furthermore, QurAlis stands to gain milestone payments up to $577 million and tiered royalties based on net sales. The partnership also includes a research and development (R&D) collaboration to further expand the pool of candidates targeting UNC13A by leveraging QurAlis' FlexASO™ Splice Modulator Platform. This platform aims to create splice-switching ASOs with enhanced potency and therapeutic index, correcting UNC13A mis-splicing and improving protein production.

Andrew Adams, Senior Vice President of Neurodegeneration Research at Lilly, emphasized the potential of genetic precision medicines like QRL-204 to significantly impact neurodegenerative diseases. He expressed enthusiasm for the collaboration with QurAlis, highlighting the promise of targeting specific components of disease pathology for ALS and FTD patients. Kasper Roet, CEO and co-founder of QurAlis, echoed this sentiment, stressing the importance of the partnership in rapidly advancing QRL-204 towards clinical trials while continuing to develop other lead programs.

ALS is a progressive neurodegenerative disorder marked by the degeneration of motor neurons in the spinal cord, brainstem, and brain. Both sporadic and familial forms of ALS are characterized by the mis-localization of TAR DNA Binding Protein-43 (TDP-43) in the cytoplasm, a major pathological feature observed in 90 percent of ALS cases and approximately 50 percent of FTD cases. UNC13A, a crucial regulator of neurotransmitter release at synapses, becomes mis-spliced due to the loss of nuclear TDP-43. Up to 63 percent of ALS patients and one-third of FTD patients exhibit this mis-splicing, which significantly disrupts the function of the UNC13A protein.

Preclinical studies presented at the 2024 International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD™) demonstrated the efficacy of QurAlis' UNC13A splice-switching ASOs. These studies showed that the ASOs effectively modulate UNC13A splicing, restoring normal synaptic activities in both ALS and FTD models. The ASOs also prevented cryptic exon inclusion in UNC13A transcripts, increased UNC13A protein levels, and normalized the protein’s localization at synapses.

QurAlis is committed to pioneering advancements in neurodegenerative disease research, driven by a dedicated pursuit of knowledge and a focus on precision medicine. The company was founded by a team of neurodegenerative biologists from Harvard Medical School and Harvard University. QurAlis aims to develop therapies that target specific components of ALS and FTD pathology, offering new hope for patients suffering from these debilitating conditions.