QRL-201, a novel therapy targeting STMN2 expression, enters phase 1 ALS trial

Cambridge, Massachusetts-based QurAlis has dosed the first patient with  the biotherapeutic QRL-201 in a Phase 1 clinical trial (ANQUR) in Canada. QRL-201 is a novel therapy targeting the restoration of STATHMIN-2 (STMN2) expression in amyotrophic lateral sclerosis (ALS) patients. QurAlis believes ANQUR the first study to evaluate such a treatment.

Stathmin-2 (STMN2), also known as superior cervical ganglia neural specific 10 (SCG10), belongs to the stathmin protein family involved in the regulation and dynamics of microtubules. Predominantly expressed in neurons, STMN2 serves key functions in neuronal development, axonal growth and regeneration.

Recent research has revealed the significance of STMN2 in neurodegenerative diseases, especially ALS and frontotemporal dementia (FTD). Researchers have linked the pathogenesis of those conditions to the loss of STMN2 function.

“In mice, STMN2 deletion causes axonal degeneration and loss of muscle innervation, w…

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QurAlis targets UNC13A RNA mis-splicing in ALS and FTD with novel FlexASO platform

QurAlis, a privately-held company specializing in precision medicines for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, has debuted its latest program. This initiative targets UNC13A RNA mis-splicing, a critical gene alteration present in ALS and frontotemporal dementia (FTD). FTD has recently gained renewed attention following the disclosure of Bruce Willis’ diagnosis of the condition. UNC13A is a vital regulator of neurotransmitter release at synapses, and the genetic alteration resulting in mis-splicing is estimated to occur in 58% of ALS patients and up to half of FTD cases.

To tackle this gene alteration, QurAlis has developed its proprietary FlexASO splice modulator platform. This technology uses antisense oligonucleotides (ASOs) to correct mis-splicing, restore UNC13A protein production, and reduce cryptic exons that may contribute to disease progression. Kasper Roet, QurAlis CEO, explained that “FlexASOs operate on the s…

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FDA approves Amylyx ALS drug Relyvrio 

Amylyx Pharmaceuticals (Nasdaq:AML) has won FDA approval for Relyvrio (AMX0035; sodium phenylbutyrate and ursodoxicoltaurine), notching the first win for amyotrophic lateral sclerosis (ALS) in five years.

The drug received Health Canada approval in June. The drug is known as Albrioza in that country.

In a summary, FDA reviewers note that the limited clinical data available for the drug have resulted in “in a degree of residual uncertainty about the evidence of effectiveness” of the drug. The agency notes that the lack of clarity is acceptable given the significant disease burden of ALS.

“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” said Dr. Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a news release. “The FDA remains committed to facilitating the development of additional ALS treatments.”

AML shar…

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U.S. government launches CP-RND, a public-private partnership for rare neurodegenerative diseases

The FDA and NIH have debuted the Critical Path for Rare Neurodegenerative Diseases (CP-RND), a public-private partnership focused on developing new therapies for amyotrophic lateral sclerosis (ALS) and rare neurodegenerative diseases.

One of the goals of the CP-RND is to foster innovation in drug discovery and development as well as clinical testing. In addition, CP-RND will aim to develop a therapy that halts the progression of ALS.

In a similar vein, FDA launched its Action Plan for Rare Neurodegenerative Diseases in June, including amyotrophic lateral sclerosis (ALS).

FDA and NIH have chosen Tucson, Arizona-based Critical Path Institute (C-Path) to help guide the CP-RND initiative.

Founded in 2005 as a public-private partnership, C-Path is an independent, nonprofit organization.

Earlier this year, C-Path established Amsterdam as the head of its European operations.

In its work on the CP-RND project, C-Path will gather experts in r…

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FDA launches 5-year initiative for rare neurodegenerative diseases 

FDA has unveiled its Action Plan for Rare Neurodegenerative Diseases, including amyotrophic lateral sclerosis (ALS).

The plan will involve the use of public-private partnerships and incorporate feedback from patients. The initiative will encompass regulatory science initiatives, changes to existing programs and new policy initiatives.

Milestones of the initiative include the creation of an FDA rare neurodegenerative diseases task force and public-private partnerships for rare neurodegenerative diseases in the fiscal year 2022. In addition, from fiscal years 2022 to 2026, the plan aims to develop disease-specific science strategies.

The initiative is an outgrowth of a Public Law 117-79, the “Accelerating Access to Critical Therapies for ALS Act” (ACT for ALS) President Biden signed into law on December 23, 2021.

“We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” said…

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Inside Canada’s approval of Amylyx’s ALS drug Albrioza

One of the things that differentiates amyotrophic lateral sclerosis (ALS) from other rare diseases is that “it is a catastrophic diagnosis,” said Chris Aiello, Head of Canada and General Manager, Amylyx Pharmaceuticals. “Patients do not really have much to go on in terms of pharmacological treatments.” 

Last week, Amylyx Pharmaceuticals received Health Canada approval for the ALS therapy Albrioza (AMX0035) with conditions. 

The regulatory nod represents the first approval for an ALS drug in recent memory. 

A 2017 article in Frontiers in Aging Neuroscience noted that “the overwhelming majority” of human clinical trials for ALS drug candidates failed to show efficacy. Since 1980, there have been more than 80 randomized controlled trials in ALS, and only two therapies, riluzole and edaravone, have found widespread use. 

Chris Aiello

“These patients …

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Understanding the promise of Albrioza: Q&A with the CEO of ALS Society of Canada

Amyotrophic lateral sclerosis (ALS) remains a bewildering disease. Although it is rare, it is not uncommon. The lifetime risk of developing the condition is roughly 1 in 300 by age 85. 

The heterogeneity of the disease is also unique, said Tammy Pighin Moore, CEO of the ALS Society of Canada. “About 5% to 10% of the people diagnosed with ALS have a familial or hereditary connection to it that we can easily understand because of the genes implicated,” Moore said.  

Symptoms can begin in the limb (known as ‘limb onset’) or first affect speech or swallowing (known as ‘bulbar onset’). Some patients with the disease die months after diagnosis, while others may live for decades. For example, the famed physicist Stephen Hawking lived with the condition for 55 years. The average life expectancy after diagnosis is two to five years. 

Health Canada recently became the first country to approve the ALS drug Albrioza (AMX0035) from…

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Investigational ALS drug could slow disease progression

Irvine, Calif.-based Eledon Pharmaceuticals has announced promising topline results from a Phase 2a study of tegoprubart, marking the first time an investigational drug has demonstrated a reduction of inflammatory biomarkers associated with progression of amyotrophic lateral sclerosis (ALS).

“We have an investigational drug acting based on what we hypothesized it would do based on the underlying biology,” said Dr. David-Alexandre Gros, CEO of Eledon. The ALS patients in the trial are “showing some clear impacts on their inflammatory signature.”

Dr. David-Alexandre Gros

Better known as Lou Gherig’s disease, ALS affects approximately 30,000 people in the U.S., who gradually lose the ability to speak, swallow, walk or breathe independently.

Roughly 5,000 new cases are diagnosed with the disease each year.

“There’s a significant unmet need in ALS,…

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Scientists find new potential drug targets for neurodegenerative diseases

Maria Clara “Maca” Franco, center, with Kyle Nguyen, left, and Lydia Bastian. Franco’s research investigates neurodegenerative diseases. Image courtesy of Oregon State University.

Researchers at Oregon State University (OSU) have discovered a new class of potential drug targets for diseases like Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS).

The scientists are working to identify the best method to attack the targets — oxidized proteins. The most potent oxidant of the bunch is peroxynitrite, which is produced in conditions involving inflammation. Oxidized proteins and free radicals can damage DNA, lipids and proteins implicated in neurodegenerative diseases and other conditions.

Peroxynitrite is produced thanks to the diffusion-limited reaction of nitric oxide and superoxide.

Peroxynitrite appears to be especially pernicious when it oxidizes heat shock prote…

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QurAlis bolsters its executive team with three new leaders

Cambridge, Massachusetts–based biotech QurAlis Corp., has appointed Bryan Boggs as head of regulatory affairs. In addition, Christopher Gerry Lohan will join as head of clinical operations, and Guzide Adhikari will take on the role of head of global supply chain management.

The company is focused on developing novel treatments for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases with genetically validated targets.

The three new hires will “play a critical role as we advance our deep pipeline of novel therapeutics for ALS and beyond to help patients desperately in need of treatment options,” said QurAlis CEO Kasper Roet in a statement.

Boggs joins QurAlis from Eli Lilly, where he worked for more than 30 years. His most recent role at the company was director, global regulatory and pharmacovigilance.

Lohan has more than 20 years of clinical research experience. In his last role, he worked as the director of clinical operation…

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Amylyx Pharmaceuticals preps NDA filing for ALS drug AMX0035  

Cambridge, Massachusetts–based Amylyx Pharmaceuticals intends to submit a New Drug Application (NDA) to FDA for AMX0035 (sodium phenylbutyrate and taurursodiol) to treat amyotrophic lateral sclerosis (ALS), which is also known as Lou Gehrig’s disease. 

The company decided to file after a series of meetings with the FDA, including a pre-NDA meeting on July 15.  

AMX0035 was the subject of the Phase 2 CENTAUR trial, which involved 137 participants with ALS. In that trial, the drug met its primary efficacy endpoint of slowing ALS based on the ALS Functional Rating Scale-Revised (ALSFRS-R). 

A forthcoming Phase 3 trial will evaluate the safety and efficacy of the drug over 48 weeks. 

Before reversing course, FDA had asked Amylyx to submit positive Phase 3 trial results before filing a New Drug Application.

To date, there are limited treatment options available for ALS. A 2020 paper in Neuropharmacology. 

Concluded that the two drugs with…

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QurAlis selects development candidate for ALS

Privately-held biotech QurAlis plans to begin clinical development for the first-in-class molecule QRL-201 for amyotrophic lateral sclerosis (ALS) in the second half of 2022.

QRL-201 is now the subject of IND-enabling studies.

The drug candidate targets the restoration of STATHMIN-2 (STMN2) expression in ALS. STMN2 is a protein encoded by the STMN2 gene that is involved in neural repair. ALS is often associated with decreased expression of STMN2.

In ALS patient-derived motor neuron disease models with TDP43 pathology, QRL-201 restored STMN2 loss of function.

A 2008 study in Current Opinion in Neurology found that TDP43 is involved in ALS and frontotemporal dementia (FTD) pathogenesis.

TDP43 pathology is also present in some Alzheimer’s and Parkinson’s disease patients.

“QRL-201 could potentially benefit ALS patients who have a loss of STMN2 due to TDP43 pathology, which could, in turn, slow disease progression,” explained Kasper Roet…

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