Eli Lilly Beefs Up Neuro Pipeline With Addition Of Preclinical ALS, Dementia Prospect

On Monday, privately held QurAlis Corporation entered into an exclusive license agreement with Eli Lilly and Co. LLY.

QurAlis has granted Lilly global rights to develop and commercialize QRL-204, a splice-switching antisense oligonucleotide (ASO) designed to restore UNC13A function in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases.

Under the terms of the agreement, QurAlis granted Lilly an exclusive, worldwide license to develop and commercialize QRL-204 and other UNC13A-targeting compounds in exchange for an upfront payment of $45 million to QurAlis, 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 agreement includes a research and development collaboration to identify and develop additional candidates targeting UNC13A, leveraging QurAlis’ proprietary FlexASO Splice Modulator Platform.

The QurAlis FlexASO Splice Modulator Platform 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.

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% of ALS cases and approximately 50% of FTD cases.

UNC13A is a 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% 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 exacerbates UNC13A mis-splicing, leading to loss of function of the UNC13A protein.

In July 2020, QurAlis announced an agreement to in-license pre-clinical compounds with disease-modifying potential in ALS by preventing disease-induced neuronal excitotoxicity from Eli Lilly. Financial terms were not disclosed.

Price Action: LLY shares are up 1.12% at $829.49 at the last check on Monday.

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