December 6, 2021

QurAlis Presents New Data Confirming Role of STATHMIN-2 in Neuronal Disease Biology at 32nd International Symposium on ALS/MND

New research connecting function of STATHMIN-2, TDP-43, and ALS cell biology further validates QRL-201, Company’s lead development candidate in ALS

Additional data presented include first-time confirmation of TDP-43 biomarker in living ALS patients, as well as discovery of new methods to enable neuronal drug R&D

CAMBRIDGE, Mass., December 7, 2021—QurAlis Corporation, a biotech company developing breakthrough precision medicines for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases with genetically validated targets, today announced the presentation of preclinical findings from its STATHMIN-2 (STMN2) program, including novel biology linking TDP-43 loss to impaired Golgi trafficking through STMN2 function and rescue by QurAlis’ antisense oligonucleotides (ASOs), as well as research to enable central nervous system (CNS) drug discovery in poster sessions at the 32nd International Symposium on ALS/MND being held virtually, December 7-10, 2021.

Details of the presentations are as follows:

Title: The Time Course and Impacts of TDP-43 Loss on STATHMIN-2 Gene Expression, Protein Abundance, Golgi Apparatus Morphology, Neurite Outgrowth, and Response to Proteotoxic Stress in Human Induced Pluripotent Derived Motor Neurons
Authors: Taylor Gray, Marisa Kamelgarn, PhD, Jason Bussgang, Sandy Hinckley, PhD, Daniel Elbaum, PhD
Presenting Author: Taylor Gray
Poster Session A: December 7, 2021 at 11:50AM-1:20PM EST
Poster/Abstract Number: HCB-04

“STATHMIN-2 is a well-known protein important for neural repair and axonal stability, the expression of which is significantly decreased in nearly all ALS patients. TDP-43 is an RNA binding protein involved in regulation of RNA splicing. In addition to nearly all ALS patients, TDP-43 pathology is also associated with other neurodegenerative diseases including frontotemporal dementia which is the second most common form of dementia, Alzheimer’s Disease, and Parkinson’s disease. Our research shows for the first time the connection between STMN2, TDP-43, and important cell biology of ALS. These findings, which include potent rescue of relevant neurodegenerative phenotypes by QurAlis’ ASOs, further validate our approach and our therapeutic product development candidate QRL-201, for the recovery of STMN2 expression in ALS patients,” said Daniel Elbaum, PhD, QurAlis’ Chief Scientific Officer, and study co-author.

Title: Biomarkers for Patient Stratification and Target Engagement in ALS Patients with TDP-43 Pathology
Authors: Sandy Hinckley, PhD, Hafiz Mohmmadabdul, PhD, Daniel Elbaum, PhD
Presenting Author: Sandy Hinckley, PhD
Poster Session A: December 7, 2021 11:50-13:20 EST
Poster/Abstract Number: BIO-06

“Results from this study show for the first time the detection of TDP-43 pathology in a living person and these findings could have a profound impact in the discovery of new disease pathways,” said Sandy Hinckley, PhD, Director, Head of Biology at QurAlis, and study co-author.
“We look forward to applying this knowledge to the research and discovery of treatments for ALS and other neurodegenerative diseases like frontotemporal dementia and Alzheimer’s Disease.”

Title: Rapid Generation of Motor Neurons Using Modified Ngn2 Induced iPSC’s to Study ALS Disease
Authors: Erika Norabuena, James Chow, Sandy Hinckley, PhD
Presenting Author: Erika Norabuena
Poster Session C: December 9, 2021 at 11:50AM-1:20PM EST
Poster/Abstract Number: IVT-18

Dr. Hinckley stated, “One of the challenges in the research of neurodegenerative diseases, such as ALS, is the availability of neuronal cells. QurAlis has developed a protocol to rapidly achieve a highly pure population of motor neurons identified by common motor neuron markers, cutting the time of neuronal generation by two-thirds. Our approach is incredibly enabling from a drug discovery perspective to help neuronal research move more rapidly.”

Title: Shipment of Transduced Live iPSC-derived Motor Neurons
Authors: Yasmin Hamwi, Jason Bussgang, Taylor Gray, Sandy Hinckley, PhD
Presenting Author: Yasmin Hamwi
Poster Session C: December 9, 2021 at 11:50AM-1:20PM EST
Poster/Abstract Number: IVT-06

“There are currently well-established procedures for shipping genetic and biological material but very little published about the shipment of live human iPSC-derived motor neurons. The fragility of these cells makes them susceptible to temperature shifts thus increasing the chance of cell death during manipulation. We have found an efficient method for transferring live transduced iPSC-derived motor neurons over 48 hours while maintaining a high level of survival with normal morphology after thaw. We believe this method will enable collaborative research to help discover much-needed treatments for these devastating neurodegenerative diseases,” said Dr. Elbaum.

All posters will be available on the QurAlis website at the conclusion of the Symposium.

The Link Between STATHMIN-2 and TDP-43

Using human neuronal stem cell models from amyotrophic lateral sclerosis (ALS) patients, QurAlis co-founder and Harvard professor Kevin Eggan, PhD, discovered in 2019 that the expression of STATHMIN-2 (STMN2) is regulated by TDP-43. Also known as SCG-10, STMN2 is a protein important for stabilization of microtubules which form an important component of the cytoskeleton of cells and axons. STATHMIN-2 is highly expressed in human motor neurons, the cells that primarily degenerate in patients suffering from ALS. In animal models, STMN2 deletion was found to cause axonal degeneration, which is the primary functional deficit that leads to paralysis in ALS patients. The Eggan Lab showed that loss of normal TDP-43 function leads to a highly significant decrease in expression of STMN2 and an impairment in neuronal repair which could be rescued by restoring STMN2 levels. These results were published in Nature Neuroscience.

About QurAlis Corporation

QurAlis is trailblazing the path to conquering amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases with genetically validated targets with next-generation precision medicines. QurAlis’ proprietary platforms and unique biomarkers enable the design and development of drugs that act directly on disease-causing genetic alterations. Founded by an internationally recognized team of neurodegenerative biologists from Harvard Medical School and Harvard University, QurAlis is advancing a deep pipeline of antisense oligonucleotides and small molecule programs including addressing sub-forms of ALS that account for the majority of ALS patients. For more information, please visit www.quralis.com or follow us on Twitter @QurAlisCo.

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