Lilly's First ALS Venture with QurAlis Antisense Oligonucleotide

Eli Lilly is set to deepen its involvement in the neurodegenerative disease field, nearing the potential approval of its first neurodegenerative candidate and subsequently acquiring an early-stage program from QurAlis. Announced on Monday, this partnership grants Eli Lilly international rights to QRL-204, a ‘splice-switching’ antisense oligonucleotide (ASO) designed to restore UNC13A function in patients diagnosed with amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).

Under the terms of the agreement, QurAlis will receive an initial payment of $45 million, alongside a commitment to developing additional next-generation compounds targeting UNC13A. Furthermore, Eli Lilly will make an undisclosed equity investment in QurAlis, which is based in Massachusetts. QurAlis stands to gain up to $577 million in milestone payments, in addition to tiered royalties based on sales.

QurAlis CEO Kasper Roet emphasized the urgency of pushing QRL-204 into clinical trials as soon as possible, citing that managing multiple high-potential programs necessitated a strategic partnership. Roet mentioned that Eli Lilly was ultimately selected due to its strong background and continued investment in neurodegenerative research, despite other companies also expressing interest.

Eli Lilly’s Vice President of neurodegeneration research, Mike Hutton, who also sits on the board of QurAlis, played a pivotal role in securing the partnership. Additionally, the leadership of Andrew Adams at Eli Lilly’s Genetic Medicine Institute underscored the company’s commitment to targeting genetic aspects of neurodegenerative diseases, reinforcing the sense of synergy between the two companies.

This collaboration comes at a time when Eli Lilly is preparing for an advisory committee meeting with the FDA to discuss its Alzheimer’s disease candidate, donanemab, a beta amyloid-targeting antibody. Eli Lilly’s pipeline also includes several other neurodegenerative programs in mid to late-stage development, though none currently target ALS.

A significant factor behind the partnership is QurAlis’ FlexASO technology platform, which facilitates the design of ASOs with enhanced flexibility and improved cellular access. This innovation arose from concerns regarding the clinical efficacy of tominersen, an ASO developed by Roche and Ionis Pharmaceuticals for Huntington’s disease, which faced setbacks during a Phase III trial in 2021.

Roet elaborated on how these concerns led to the creation of the FlexASO platform aimed at improving tissue penetration and access to deeper tissue layers. Unexpectedly, the platform also enhanced the potency of the ASOs while reducing off-target effects.

QRL-204’s development leverages two key components: the FlexASO platform and the target, UNC13A. UNC13A plays a crucial role in regulating synaptic vesicle release necessary for neuronal signaling. In ALS patients, this protein is often mis-spliced, leading to dysfunctional signaling. Additionally, patients with more single nucleotide polymorphisms (SNPs) exhibit more severe symptoms.

This partnership between Eli Lilly and QurAlis represents a significant step forward in the ongoing effort to address neurodegenerative diseases. With the backing of Eli Lilly’s extensive resources and QurAlis’ innovative technology, the development and potential approval of QRL-204 could bring new hope to patients suffering from ALS and FTD.