Lilly invests $45M in QurAlis for preclinical ALS and dementia prospect

Eli Lilly is enhancing its neurodegenerative disease portfolio by securing a deal with QurAlis for a preclinical treatment targeting amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The pharmaceutical giant is investing $45 million upfront for the global rights to QRL-204, an innovative splice-switching antisense oligonucleotide (ASO) designed to restore the function of the UNC13A gene.

Originally linked to ALS and FTD years ago, the UNC13A gene's connection to these diseases was further elucidated in a 2022 study. The research indicated that variants in the UNC13A gene worsen the reduced function of TDP-43, an RNA-binding protein implicated in many ALS and FTD cases. These findings paved the way for the development of QRL-204, which aims to modulate UNC13A splicing and restore normal synaptic activities in affected patients.

QRL-204 has shown promising preclinical results, prompting Lilly to not only invest $45 million upfront but also commit to up to $577 million in future milestone payments. Andrew Adams, Ph.D., who serves as the senior vice president of neurodegeneration research at Lilly, emphasized the potential of genetic precision medicines like QRL-204. According to Adams, targeting specific causal components of disease pathology offers significant promise for advancing treatments for neurodegenerative diseases such as ALS and FTD.

In addition to advancing QRL-204 toward clinical trials, Lilly and QurAlis will collaborate to identify and develop additional therapies targeting UNC13A. The collaboration will utilize a QurAlis platform designed to create splice-switching ASOs with enhanced potency and an increased therapeutic index. Such a platform aims to maximize the efficacy and safety of these potential treatments.

UNC13A is implicated in approximately two-thirds of ALS cases and one-third of FTD cases, attracting interest from several biotechs. For instance, AcuraStem is developing an ASO targeting UNC13A for ALS and FTD, while Maze Therapeutics has also discovered a similar ASO, although it has transferred the rights to a new, undisclosed biotech.

While Lilly is a new entrant in the UNC13A-targeting field, it is no stranger to the broader ALS and FTD treatment spaces. The company expanded its ALS portfolio through a $135 million acquisition of Disarm Therapeutics in 2020 and a smaller partnership with Verge Genomics in the following year. In the realm of FTD, Lilly added a prospective treatment to its pipeline by acquiring Prevail Therapeutics for $880 million. The company also holds a stake in Arkuda Therapeutics, further strengthening its position in neurodegenerative disease research.

The collaboration between Lilly and QurAlis marks a significant step forward in the quest to develop effective treatments for ALS and FTD. By focusing on the genetic underpinnings of these diseases, the partnership aims to deliver breakthrough therapies that could offer substantial benefits to patients suffering from these debilitating conditions.