Thirteen companies developing new ALS treatments in 2025

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to the loss of muscle control. As motor neurons deteriorate, patients experience muscle weakness, paralysis, and eventually respiratory failure. The exact cause of ALS remains unknown, and currently, there is no cure.

The treatment options for ALS are limited, focusing primarily on slowing disease progression and managing symptoms. The treatment landscape for ALS has only seen modest advancements over the past few decades.

Approved in 1995, Riluzole modestly prolongs survival in ALS patients by reducing the release of glutamate, a neurotransmitter that can be toxic to motor neurons at high levels. An important advancement in the field has to be tofersen’s approval by the U.S. Food and Drug Administration (FDA) in 2023 which was a significant step forward in personalized treatment for ALS.

The lack of treatment options finds its explanation in a particularly challenging disease area. ALS presents with diverse clinical manifestations and genetic backgrounds, complicating the development of universal treatments. Additionally, early symptoms of ALS often resemble those of other neurological disorders, leading to delays in diagnosis.

But all is not lost, far from it. The broader neurodegenerative treatment space has seen a notable resurgence in the last few years and companies are continuously looking for new treatment solutions for ALS. In this article, we take a look at 13 companies developing new ALS candidates.

Alchemab Therapeutics (in collaboration with Eli Lilly)

• Technology: B-cells sequencing
• Candidates: Multiple antibodies
• Recent news: Collaboration with Eli Lilly to develop ALS candidates

Alchemab Therapeutics is a U.K.-based biopharmaceutical company specializing in the discovery and development of naturally occurring therapeutic antibodies. Its approach focuses on identifying antibodies from individuals who exhibit resilience to certain diseases, aiming to harness these natural defenses for therapeutic purposes.

This process involves sequencing immune B-cells to discover antibodies common among resilient individuals but absent in typical disease progressors. The goal is to develop therapies that mimic the body’s natural immune responses to combat diseases like ALS.

In January 2025, Alchemab entered into a collaboration with Eli Lilly to discover, develop, and commercialize up to five novel antibody-based therapeutics for ALS. This partnership leverages Alchemab’s discovery platform to identify potential therapeutic antibodies from patients exhibiting slow ALS progression. While specific development stages of these candidates have not been publicly detailed, the collaboration might bring several candidates into trials in the years to come.

Alchemab will receive an undisclosed upfront payment and is eligible for milestone payments and royalties upon successful commercialization of the therapies. 

Annexon Biosciences

• Technology: Monoclonal antibody
• Candidates: ANX005
• Recent news: Positive phase 3 results for ANX005 in Guillain-Barré syndrome 

Annexon Biosciences’ primary focus is inhibiting C1q, the initiating molecule of the classical complement pathway, to prevent complement-mediated damage.

The complement system is a part of the immune system that helps clear pathogens and damaged cells from the body, playing a role in inflammation and immunity. It consists of a series of proteins that activate in a cascade to enhance immune responses. In ALS and other neurodegenerative diseases, however, the complement system can become overactive, leading to unintended damage to healthy neurons.

Annexon’s lead candidate, ANX005, is a monoclonal antibody that targets and inhibits C1q. By preventing the activation of the complement pathway, ANX005 aims to protect neurons from complement-mediated damage.

ANX005 has undergone a phase 2a clinical trial in ALS patients, demonstrating a slowing of disease progression. The company is preparing to advance ANX005 into late-stage phase 2b/3 development for ALS.

Additionally, in June 2024, Annexon announced positive topline results from a pivotal phase 3 trial of ANX005 in Guillain-Barré syndrome (GBS), another neurodegenerative condition. The success in GBS hints at the potential of ANX005’s mechanism of action and supports its further development in ALS. The company also plans to initiate a pivotal phase 2/3 trial for ANX005 in Huntington’s disease. 

Asha Therapeutics

• Technology: Intra-molecular glue inhibitor targeting SARM1
• Candidate: ASHA-624
• Recent News: Awarded the Barnett Drug Development Grant by the ALS Association to advance ASHA-624 into clinical trials

The company’s lead ALS program, ASHA-624 is a first-in-class, intra-molecular glue compound designed to inhibit SARM1 protein, a central regulator of nerve cell degeneration.

SARM1 activation leads to axonal degeneration and neurodegeneration in ALS. ASHA-624 works by “gluing” activated SARM1 into an inactive conformation, thereby preventing axon and neuron loss. In preclinical models, ASHA-624 demonstrated a robust safety profile and effectively reversed motor impairment to levels similar to healthy controls, while placebo-treated groups continued to decline.

ASHA-624 is currently in the preclinical stage, with plans to enter clinical trials in early 2025. The recent award of the Barnett Drug Development Grant by the ALS Association will support the advancement of ASHA-624 into clinical trials. 

Auttx

• Technology: Small molecules and antisense oligonucleotides targeting RNA processing
• Candidate: Undisclosed
• Recent News: Received a $125,000 grant from the ALS Network

Auttx is still an early-stage biotechnology company focused on developing novel therapeutics for neurological diseases resulting from abnormal gene splicing, with a particular emphasis on ALS. 

Auttx is exploring both small molecules and antisense oligonucleotides (ASOs) to correct abnormal RNA processing in ALS patients. ASOs are short, synthetic strands of nucleic acids designed to bind to specific messenger RNA (mRNA) molecules, thereby inhibiting the production of disease-causing proteins. 

In ALS, the mislocalization and aggregation of the TDP-43 protein disrupt the normal processing of RNA molecules, leading to the production of dysfunctional proteins. Auttx aims to identify compounds that can restore proper RNA splicing and function, thereby mitigating neuronal damage.

Currently, Auttx is in the early stages of therapeutic development. The company has identified ASOs capable of reversing abnormal RNA processing and is now screening a library of small molecules to expedite the development of drug candidates targeting this pathway. The recent $125,000 grant from the ALS Network will support these efforts, facilitating the progression toward preclinical studies.

Celosia Therapeutics

• Technology: Gene therapy
• Candidate: CTx2000
• Recent News: $16.75 million series A

This Australian biotech company develops gene therapies for neurodegenerative diseases, including ALS. 

Celosia uses genetic proteolysis targeting chimeras (genProTACs), a technology designed to selectively identify and remove harmful proteins that accumulate in neurodegenerative diseases like ALS. This approach acts like a molecular “clean-up crew,” tagging toxic proteins for destruction by the cell’s natural waste-disposal system – the proteasome – while leaving healthy proteins untouched.

CTx2000, its ALS candidate, uses this technology to selectively bind to the toxic form of TDP-43, tagging it for degradation by the cell’s ubiquitin-proteasome system. This targeted approach aims to halt disease progression by reducing the accumulation of pathological TDP-43 in neurons. The candidate is still in preclinical development. 

In November 2024, Celosia Therapeutics secured $16.75 million in series A funding to advance the development of CTx1000. This financing round was led by Uniseed, with significant contributions from hedge fund manager and ALS patient Iomar Barrett.

Dewpoint Therapeutics

• Technology: Small molecule condensate modulators (c-mods) targeting TDP-43
• Candidate: TDP-43 small molecule condensate modulator
• Recent News: Entered a research collaboration with Mitsubishi Tanabe Pharma Corporation 

Dewpoint Therapeutics is targeting biomolecular condensates – membrane-less organelles within cells that organize and regulate biochemical processes. 

Dewpoint’s approach involves designing small molecule condensate modulators (c-mods) that can influence the behavior of proteins within biomolecular condensates. In the context of ALS, they are targeting the mislocalization and aggregation of TDP-43. By modulating the condensates containing TDP-43, Dewpoint aims to restore its normal localization and function, potentially halting or reversing neuronal damage associated with ALS.

Last month, Dewpoint entered into a research collaboration with Mitsubishi Tanabe Pharma Corporation (MTPC) to advance their ALS treatment. Under this agreement, Dewpoint will receive an upfront payment and is eligible for milestone payments totaling up to $480 million. MTPC has an exclusive option to license the program upon reaching specified milestones, after which they would oversee global clinical development and commercialization. 

Ionis Pharmaceuticals

• Technology: Antisense oligonucleotides
• Lead asset: Tofersen 
• Recent News: ION 263 in phase 3

Ionis Pharmaceuticals, headquartered in Carlsbad, California, specializes in RNA-targeted therapies. Utilizing its proprietary antisense technology platform, Ionis focuses on discovering and developing novel treatments for a range of diseases, including neurodegenerative disorders.

Ionis employs ASOs to modulate gene expression. Ionis developed tofersen in collaboration with Biogen, an ASO targeting the superoxide dismutase 1 (SOD1) mRNA. Mutations in the SOD1 gene lead to the production of misfolded SOD1 protein, contributing to motor neuron degeneration in ALS patients. By binding to SOD1 mRNA, tofersen reduces the synthesis of the toxic SOD1 protein, aiming to slow disease progression. The drug was approved by the FDA in 2023.

Beyond tofersen, Ionis’ lead ALS asset, the biotech is developing ION363 (Ulefnersen) for fused-in sarcoma ALS (FUS-ALS) – a rare and aggressive form of ALS, often leading to early-onset and rapid disease progression. ION 363 is also an ASO binding to the FUS mRNA to prevent the synthesis of the toxic mutant FUS protein. The ALS treatment is currently in phase 3 clinical trials.

NeuroSense Therapeutics

• Technology: Combination therapy utilizing ciprofloxacin and celecoxib
• Candidate: PrimeC
• Recent News: Finalizing the protocol for a phase 3 study of PrimeC in ALS

NeuroSense Therapeutics is a clinical-stage biotechnology company developing treatments for neurodegenerative diseases, with a primary focus on ALS. Its lead candidate, PrimeC, is an extended-release oral formulation combining two FDA-approved drugs: ciprofloxacin and celecoxib. This combination is designed to synergistically target multiple mechanisms implicated in ALS progression, including motor neuron degeneration, inflammation, iron accumulation, and impaired RNA regulation.

PrimeC integrates ciprofloxacin, a fluoroquinolone antibiotic, and celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, into a single formulation. Ciprofloxacin has been observed to modulate RNA processing, while celecoxib possesses anti-inflammatory properties.

Prime C met its safety and efficacy endpoints in phase 2a and phase 2b, trials demonstrating reductions in functional and respiratory deterioration, along with statistically significant changes in ALS-related biomarkers.

Following these promising results, NeuroSense finalized the protocol for a pivotal phase 3 study and received positive feedback from the FDA in December 2024. 

Origami Therapeutics

• Technology: Small molecule protein degraders
• Candidate: ORI-113
• Recent News: Plans to expand its platform to other neurodegenerative diseases, including ALS

Origami Therapeutics, based in San Diego, California, is a biotechnology company focused on developing small molecule therapeutics to treat neurodegenerative diseases caused by toxic protein misfolding. Their proprietary platform, Oricision, enables the discovery of precision protein degraders and conformation correctors aimed at eliminating or correcting misfolded proteins while preserving normal protein function.

Origami’s approach involves designing small molecule monovalent therapeutics capable of crossing the blood-brain barrier to target and degrade disease-causing proteins. Unlike traditional protein degradation methods that may affect both normal and mutant proteins, Origami’s degraders aim to selectively eliminate only the toxic misfolded forms, thereby reducing potential side effects. 

While Origami’s lead program, ORI-113, is currently focused on targeting mutant huntingtin protein (mHTT) in Huntington’s disease, the company has expressed intentions to expand its therapeutic strategies to other neurodegenerative diseases, including ALS. Specifically, they are interested in developing compounds for genetically identified targets that tend to misfold, such as C9orf72 in ALS and frontotemporal dementia. 

As of now, its ALS treatment is in the discovery phase, along with two other programs focused on Parkinson’s and Alzheimer’s. As its original and main focus is on Huntington’s, it may be some time before an Origami ALS candidate reaches the clinic – it remains an honorable mention.

Prilenia Therapeutics

• Technology: Sigma-1 receptor agonist
• Candidate: Pridopidine
• Recent News: Phase 3 preparation for pridopidine in ALS

Prilenia Therapeutics is a clinical-stage biotechnology company focused on neurodegenerative diseases. Its lead investigational drug, pridopidine, is an oral and selective Sigma-1 receptor (S1R) agonist. Activation of S1R by pridopidine stimulates multiple cellular protective pathways essential to neuronal function and survival, potentially leading to neuroprotective effects.

In ALS, motor neurons are subjected to significant stress due to protein misfolding, mitochondrial dysfunction, and oxidative damage, all of which contribute to their degeneration. Activation of S1R by pridopidine enhances the cell’s natural defense mechanisms, including improving mitochondrial function, reducing oxidative stress, and stabilizing calcium signaling. These effects collectively help to protect motor neurons, slow their degeneration, and potentially improve functional outcomes in ALS patients. 

Pripodine is slightly more advanced in Huntington’s disease but it’s followed closely by the ALS indication. In phase 2, pridopidine showed encouraging results for the potential treatment of ALS with a good safety profile. Based on these findings, Prilenia is planning a single, global, pivotal phase 3 clinical trial to further evaluate pridopidine in ALS.

Trace Neuroscience

• Technology: Antisense oligonucleotides
• Candidate: UNC13A-targeting ASO
• Recent News: Launched in November 2024 with a $101 million series A financing

Trace Neuroscience only launched 3 months ago, in November 2024, with a significant $101 million series A round. It aims to expand genomic medicine for neurodegenerative diseases, with an initial focus on ALS. The company aims to develop therapies that restore the function of the UNC13A protein, which is crucial for synaptic communication between neurons and muscle cells – a process disrupted in ALS.

Trace’s lead program utilizes ASOs to target the mRNA of the UNC13A gene. Mutations or dysregulation of UNC13A, often due to TDP-43 protein dysfunction, are implicated in ALS pathology. By binding to UNC13A mRNA, the ASO therapy aims to correct its processing, thereby restoring normal UNC13A protein levels and improving synaptic function between nerves and muscles.

Trace Neuroscience is advancing its UNC13A-targeting ASO therapy through preclinical development. Beyond ALS, the company also envisions applications for its UNC13A-targeting therapy in other neurodegenerative diseases characterized by TDP-43 pathology, such as frontotemporal dementia and certain forms of Alzheimer’s disease.

VectorY Therapeutics

• Technology: Vectorized antibody therapy
• Candidate: VTx-002
• Recent News: Initiated a biomarker study in collaboration with UMC Utrecht to identify biomarkers for ALS

The company, established in 2020 and headquartered in Amsterdam, is developing vectorized antibody therapies for neurodegenerative diseases, including ALS. 

VectorY’s approach combines the specificity of antibodies with the durability of gene therapy. Its platform utilizes adeno-associated virus (AAV) vectors to deliver genetic instructions for the production of therapeutic antibodies directly into target cells within the central nervous system. This method enables sustained expression of antibodies, potentially reducing the need for repeated administrations.

VectorY is developing VTx-002, a vectorized antibody designed to target TDP-43 protein misfolding and aggregation. By delivering the genetic code for antibodies that can bind to and clear toxic TDP-43 aggregates from the cytoplasm, VTx-002 aims to restore normal TDP-43 function in the nucleus, thereby preserving neuronal health and function.

VTx-002 is currently in the preclinical development phase. To support its progression, VectorY has partnered with the University Medical Center (UMC) Utrecht to conduct a biomarker study aimed at identifying blood and cerebrospinal fluid biomarkers in ALS patients. These biomarkers are expected to aid in diagnosing ALS, monitoring disease progression, and enhancing the design of future clinical trials for VTx-002. In June 2024, VectorY and UMC Utrecht enrolled the first patient in their collaborative biomarker study. 

Verge Genomics

• Technology: Artificial intelligence drug discovery
• Candidate: VRG50635
• Recent News: Two ALS candidates identified in Eli Lilly collaboration

Verge Genomics uses artificial intelligence (AI) and human genomic data applied to drug discovery to develop treatments for neurodegenerative diseases including ALS. Their lead investigational drug, VRG50635, is a small molecule inhibitor of PIKfyve – a novel therapeutic target for ALS discovered using Verge’s AI-powered platform, CONVERGE.

In October 2022, Verge initiated a phase 1 clinical trial for VRG50635, marking one of the first instances of a drug entirely discovered and developed from an AI-enabled platform entering clinical trials. The trial demonstrated a favorable safety, tolerability, and pharmacokinetic profile, supporting advancement into a proof-of-concept study in ALS patients.

In November 2023, Verge Genomics announced a collaboration with Modality.AI to incorporate advanced speech biomarkers into the phase 1b proof-of-concept study for VRG50635 in ALS.

Additionally, Verge was in collaboration with Eli Lilly to discover ALS targets. It reported milestones in this collaboration in November 2024, and after 3 years, Eli Lilly selected two drug candidates to further develop. In addition to Verge’s proprietary candidate, it’s worth keeping an eye on Eli Lilly’s Als pipeline.

A new wave in ALS and neurodegenerative diseases

The landscape of ALS and the broader neurodegenerative disease research is picking up a new pace after quite a long period of stagnation.

Estimates indicate that the neurodegenerative market, valued at approximately $52 billion in 2024, is projected to reach $102.4 billion by 2034, reflecting a compound annual growth rate (CAGR) of 7%. Specifically, the ALS treatment market is anticipated to grow from $743.90 million in 2023 to $1.3 billion by 2033.

AI is a strong ally in discovering new targets to treat ALS as Verge Genomics exemplifies. It’s already showing promising results in Alzheimer’s disease, so there is no reason why it shouldn’t emulate this potential in ALS.

Another interesting thing to note is the diversity of approaches pursued by biotechs: ASOs, antibodies, gene therapies… This diversified landscape seems to indicate that ALS research is no longer stagnating.

Bigger players are also very much involved in the market. For instance, in June 2024, Roche and Ascidian Therapeutics entered a collaboration to develop RNA exon editing therapeutics targeting neurological diseases. While there’s no explicit confirmation that ALS is a direct target, Ascidian’s platform is broadly applicable to conditions caused by genetic mutations. Since ALS often involves such mutations, its approach could logically extend to ALS, but this is speculative. 

Roche isn’t the only big player getting into ALS research. Eli Lilly has been collaborating with several companies in this list to find ALS targets. Biogen has also been, and still is an important contributor in the field. It was involved in the development of tofersen in its collaboration with Ionis and is also advancing BIIB078, which targets the C9orf72 gene mutation – a common cause of genetic ALS. 

Collaborations between biotech firms and pharmaceutical giants, coupled with advancements in personalized medicine, are fostering a new era of hope for patients.

Partnering 2030: Biopharma Report

Download Inpart’s latest report revealing the priorities of out-licensers worldwide.