Eli Lilly to develop, market ALS therapy for UNC13A function
Preclinical data showed QRL-204 raised protein's levels, aided synapse activities
Eli Lilly has acquired the global exclusive rights to develop and market QRL-204, QurAlis’ investigational therapy for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) that’s designed to restore UNC13A function in nerve cells.
UNC13A is an essential regulator of neurotransmitter release at synapses, a key process for communicating between nerve cells. But up to 63% of ALS patients and a third of FTD patients have alterations in processing UNC13A’s messenger RNA (mRNA), an intermediary molecule needed for protein production, leading to protein loss.
Under the agreement, Lilly will develop QRL-204 and other UNC13A-targeting compounds and the companies will collaborate to identify new candidates that target the UNC13A protein. The joint effort will leverage QurAlis’ proprietary FlexASO Splice Modulator Platform, which generates candidates that are optimally designed to restore certain mRNA molecules’ normal processing.
“We are determined at Lilly to uncover the next great idea, the next collaboration, the next advancement in technology that will drive us toward meaningful treatments for ALS and FTD patients. It’s all for one reason – to make life better for even more people,” Andrew Adams, senior vice president of neurodegeneration research and director of the Lilly Institute for Genetic Medicine, said in a press release.
“This partnership enables QRL-204 to rapidly move toward the clinic, while we continue to advance our other lead programs,” said Kasper Roet, PhD, QurAlis’ CEO and co-founder. “We look forward to combining our complementary strengths to uncover additional candidates that target UNC13A that have the potential to transform the treatment of neurodegenerative diseases like ALS and FTD.”
Restoring normal UNC13A mRNA processing
In nearly all ALS patients and about half of people with FTD, a misfolded version of the TDP-43 protein accumulates to toxic levels in nerve cells. Normally inside the nucleus, the cellular compartment where genetic information is stored, TDP-43 is involved in processing mRNA molecules, including UNC13A mRNA.
When TDP-43 is abnormal, it accumulates in the cytoplasm instead and fails to carry out its functions in the nucleus. This causes the abnormal processing of UNC13A mRNA and results in the loss of UNC13A protein. This is further worsened when patients carry UNC13A gene mutations.
QRL-204 belongs to a class of treatments called an antisense oligonucleotides (ASO), which can selectively bind to specific mRNA molecules to regulate their ability to produce the final protein. It’s designed to restore the normal UNC13A mRNA processing, increasing UNC13A production.
Preclinical data presented at the recent AD/PD 2024 International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders showed QRL-204 increased UNC13A levels, normalized its location at synapses, and restored synapse activities.
“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,” Adams said.
Under the agreement, Lilly will pay QurAlis $45 million up front and invest in the company. QurAlis is also eligible for future payments of up to $577 million if certain milestones are met, along with royalties on net sales.
“On behalf of the entire team at QurAlis, we are extremely pleased to partner with Lilly, an innovation-led company advancing transformative medicines to help make life better for people around the world,” Roet said.
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