• Pipeline

Focus on genetically-driven neurodegenerative diseases

Evox is strategically focused on advancing therapies against clearly defined genetic targets to transform therapeutic outcomes for severe neurodegenerative diseases.

Our programs targeting MSH3 and ATXN2 are supported by human genetic data implicating these targets as key modulators of disease pathology along with corroborating preclinical evidence demonstrating that target knockdown is disease-modifying.

In addition to advancing proprietary neurodegenerative programs, Evox pursues strategic partnerships within and beyond the CNS, leveraging our gene editing platform to broaden therapeutic opportunities and address a wider spectrum of severe diseases.

  • Preclinical
  • IND enabling
  • Clinical

Worldwide Rights

Proprietary

Huntington’s disease (HD)

  • Preclinical
  • IND enabling
  • Clinical

Therapeutic mechanism of action

Our therapeutic candidate targets MSH3, a key gene implicated in the instability and expansion of CAG repeats that drive Huntington’s disease pathology. By intervening at this crucial step in the disease process, we aim to stabilize repeat expansions, halt disease progression and significantly improve long-term patient outcomes.

Key supporting data

  • Human GWAS data demonstrates that lowering MSH3 is disease-modifying with a large effect size.1,2,3
  • Naturally occurring mutations in MSH3 that are predicted to reduce activity are associated with slower disease progression in humans.4,5,6
  • MSH3 is pathologically upregulated in the key cells impacted by HD.7,8,
  • Lowering MSH3 in preclinical studies slows somatic CAG expansion and improves disease pathology.9,10

About Huntington’s disease

Huntington’s disease (HD) is one of the most common autosomal dominant neurodegenerative diseases with approximately 70,000 patients across the U.S. and Western Europe. Typically manifesting in patients during their 30s and 40s, HD causes neurons to die resulting in uncontrolled movements, difficulty with walking, talking and swallowing and cognitive decline. Although treatments can help manage symptoms, there is no cure for HD and patients usually die 15-20 years after diagnosis.

Amyotrophic lateral sclerosis (ALS)

  • Preclinical
  • IND enabling
  • Clinical

Therapeutic mechanism of action

Our therapeutic candidate is designed to prevent protein dysfunction common to all ALS cases, with the ultimate goal of stopping disease progression and preserving remaining motor neuron function in patients. By targeting ATXN2, a key mediator of TDP-43 pathology in 97% of ALS patients, we aim to reduce toxic protein aggregates that leads to cell death and disease progression.

Key supporting data

  • ATXN2 is a genetically validated modifier of TDP43 pathology underlying 97% of ALS cases. 1,2,3
  • Deep ATXN2 knockdown in preclinical studies is disease-modifying. 4,5,6

About Amyotrophic lateral sclerosis (ALS)

ALS, or Lou Gehrig’s disease, is a devastating neurodegenerative disorder characterised by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and, ultimately, respiratory failure. With a median survival of just 2–4 years following diagnosis, ALS affects approximately 4.1–8.4 per 100,000 people globally. The disease occurs in sporadic (90%) and familial (10%) forms, with familial cases linked to single-gene mutations. Current treatments focus on symptom management and offer limited benefits, leaving an urgent need for innovative therapies that address the root causes of this multifaceted disease.

Spinocerebellar ataxia type 2 (SCA2)

  • Preclinical
  • IND enabling
  • Clinical

Therapeutic mechanism of action

Our therapeutic candidate specifically targets the root cause of SCA2 by addressing expansions in the ATXN2 gene, with the potential to halt or even reverse disease progression.

SCA2 is a rare, autosomal dominant neurodegenerative disorder that typical manifests in mid-adulthood. It is characterised by progressive cerebellar ataxia, leading to impaired coordination, balance, and fine motor skills. Over time, individuals may experience additional symptoms such as speech difficulties, tremors, and even cognitive impairment, with severe cases significantly disrupting patients’ lives.

About Spinocerebellar ataxia type 2 (SCA2)

Affecting approximately 4,000 patients in the Western world, SCA2 is one of the most common spinocerebellar ataxias. There is currently no cure, and available treatment options solely offer symptom management.

Rett syndrome

  • Preclinical
  • IND enabling
  • Clinical

Therapeutic mechanism of action

Our therapeutic approach targets the root cause of Rett syndrome by restoring functional MECP2 expression in the central nervous system. Rett syndrome is caused in the majority of cases by pathogenic loss-of-function variants in the X-linked MECP2 gene, which encodes methyl-CpG-binding protein 2, a critical regulator of neuronal gene expression, synaptic maturation and brain function 1,2,3,4.

Because MECP2 is highly dosage-sensitive, therapeutic replacement requires precise control: insufficient MECP2 activity causes Rett syndrome, while increased MECP2 dosage is associated with MECP2 duplication syndrome and severe neurological disease5,6. Our non-viral delivery platform is designed to enable targeted delivery of MECP2 therapeutics to the brain, with the goal of achieving a carefully tuned restoration of MECP2 function across relevant central nervous system cell populations. This approach has the potential to address the underlying biology of Rett syndrome through controlled restoration of MECP2 function, while offering a differentiated non-viral strategy for CNS delivery in a field where precise MECP2 dosing remains a central therapeutic challenge.

Therapeutic mechanism of action

Our therapeutic approach targets the root cause of Rett syndrome by restoring functional MECP2 expression in the central nervous system. Rett syndrome is caused in the majority of cases by pathogenic loss-of-function variants in the X-linked MECP2 gene, which encodes methyl-CpG-binding protein 2, a critical regulator of neuronal gene expression, synaptic maturation and brain function 1,2,3,4.

Because MECP2 is highly dosage-sensitive, therapeutic replacement requires precise control: insufficient MECP2 activity causes Rett syndrome, while increased MECP2 dosage is associated with MECP2 duplication syndrome and severe neurological disease5,6. Our non-viral delivery platform is designed to enable targeted delivery of MECP2 therapeutics to the brain, with the goal of achieving a carefully tuned restoration of MECP2 function across relevant central nervous system cell populations. This approach has the potential to address the underlying biology of Rett syndrome through controlled restoration of MECP2 function, while offering a differentiated non-viral strategy for CNS delivery in a field where precise MECP2 dosing remains a central therapeutic challenge.

About Rett syndrome

Rett syndrome is a rare, severe neurodevelopmental disorder that predominantly affects girls and typically emerges after an initial period of apparently typical early development2,3. The condition is characterised by developmental regression, including loss of spoken language and purposeful hand use, followed by persistent motor impairment, hand stereotypies, seizures, abnormal breathing patterns, sleep disturbance, feeding difficulties, scoliosis and cognitive disability2,3,4.

Rett syndrome affects approximately 1 in 10,000–15,000 female live births and is most commonly associated with de novo pathogenic variants in MECP2, which are reported in more than 90% of individuals with typical Rett syndrome2,3,4. While multidisciplinary care remains central to disease management, therapeutic options are limited. Trofinetide became the first FDA-approved treatment for Rett syndrome in 2023 and has demonstrated symptomatic clinical benefit, but there remains no approved therapy that directly corrects MECP2 deficiency or has been shown to modify the underlying genetic cause of disease8,9,10. This continued unmet need supports the development of therapies designed to restore MECP2 function at its source.

Partnership opportunites​

CNS & other extrahepatic indications

  • Preclinical
  • IND enabling
  • Clinical

Data References

  1. Flower M, Lomeikaite V, Ciosi M, et al. MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1. Brain. 2019;142(7):1876-1886. doi:10.1093/brain/awz115
  2. Lee JM, Correia K, Loupe J, et al. CAG repeat not polyglutamine length determines timing of Huntington’s disease onset. Cell. 2019;178(4):887-900.e14. doi:10.1016/j.cell.2019.06.036
  3. Lee JM, Wheeler VC, Chao MJ, et al. Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease. Cell. 2015;162(3):516-526. doi:10.1016/j.cell.2015.07.003
  4. Ciosi M, Maxwell A, Cumming SA, et al. A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes. EBioMedicine. 2019;48:568-580. doi:10.1016/j.
  5. Flower M, Lomeikaite V, Ciosi M, et al. MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1. Brain. 2019;142(7):1876-1886. doi:10.1093/brain/awz115
  6. Moss DJH, Pardiñas AF, Langbehn D, et al. Identification of genetic variants associated with Huntington’s disease progression: a genome-wide association study. The Lancet Neurology. 2017;16(9):701-711. doi:10.1016/s1474-4422(17)30161-8
  7. Lee JM, Huang Y, Orth M, et al. Genetic modifiers of Huntington disease differentially influence motor and cognitive domains. The American Journal of Human Genetics. 2022;109(5):885-899. doi:10.1016/j.ajhg.2022.03.004
  8. Mätlik K, Baffuto M, Kus L, et al. Cell-type-specific CAG repeat expansions and toxicity of mutant Huntingtin in human striatum and cerebellum. Nature Genetics. 2024;56(3):383-394. doi:10.1038/s41588-024-01653-6
  9. Bunting EL, Donaldson J, Cumming SA, et al. Antisense oligonucleotide–mediated MSH3 suppression reduces somatic CAG repeat expansion in Huntington’s disease iPSC–derived striatal neurons. Science Translational Medicine. 2025;17(785):eadn4600. doi:10.1126/
  10. Wang N, Zhang S, Langfelder P, et al. Distinct mismatch-repair complex genes set neuronal CAG-repeat expansion rate to drive selective pathogenesis in HD mice. Cell. 2025;188(6):1524-1544.e22. doi:10.1016/j.cell.2025.01.031
  1. Becker LA, Huang B, Bieri G, et al. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature. 2017;544(7650):367-371. doi:10.1038/nature22038
  2. De Sá RV, Sudria-Lopez E, Luna MC, et al. ATAXIN-2 intermediate-length polyglutamine expansions elicit ALS-associated metabolic and immune phenotypes. Nature Communications. 2024;15(1):7484. doi:10.1038/s41467-024-51676-0
  3. Elden AC, Kim HJ, Hart MP, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature. 2010;466(7310):1069-1075. doi:10.1038/nature09320
  4. Amado DA, Robbins AB, Whiteman KR, et al. AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice. Nature Communications. 2025;16(1):5334. doi:10.1038/s41467-025-60497-8
  5. Becker LA, Huang B, Bieri G, et al. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature. 2017;544(7650):367-371. doi:10.1038/nature22038
  6. C MAZ, Moore HJ, Smith TJ, et al. Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins. Nature Communications. 2023;14(1):6492. doi:10.1038/s41467-023-42147-z
  7. Hawley ZCE, Li X, Bodnar D, et al. Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1C71G ALS mouse model. Acta Neuropathologica Communications. 2025;13(1):116. doi:10.1186/s40478-025-02005-z
  1. Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics. 1999;23:185–188.
  2. Webb T, Latif F. Rett syndrome and the MECP2 gene. Journal of Medical Genetics. 2001;38(4):217–223. [jmg.bmj.com]
  3. Bricker K, Vaughn BV. Rett syndrome: a review of clinical manifestations and therapeutic approaches. Frontiers in Sleep. 2024;3:1373489. [pmc.ncbi.nlm.nih.gov], [frontiersin.org]
  4. Lopes AG, Loganathan SK, Caliaperumal J. Rett syndrome and the role of MECP2: signaling to clinical trials. Brain Sciences. 2024;14(2):120. [pmc.ncbi.nlm.nih.gov]
  5. Sandweiss AJ, Brandt VL, Zoghbi HY. Advances in understanding of Rett syndrome and MECP2 duplication syndrome: prospects for future therapies. The Lancet Neurology. 2020;19(8):689–698. [thelancet.com]
  6. Huang JL, Sharifi O, Yasui DH, LaSalle JM. MeCP2 at the crossroads of hypoxia, oxidative stress, and gene regulation in Rett syndrome. Epigenomics. 2025;17(17):1281–1291. [tandfonline.com]
  7. Sharifi O, Yasui DH. The molecular functions of MeCP2 in Rett syndrome pathology. Frontiers in Genetics. 2021;12:624290. [frontiersin.org]
  8. Neul JL, Percy AK, Benke TA, et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nature Medicine. 2023. [nature.com]
  9. Selvam P, Mares Beltrán CF, Sen K, Morales Corado A, ACMG Therapeutics Committee. Trofinetide approved for children and adults with Rett syndrome: a therapeutics bulletin of the American College of Medical Genetics and Genomics. Genetics in Medicine Open. 2024;2:101856. [pmc.ncbi.nlm.nih.gov]
  10. Mohammed HE, Bady Z, Haseeb ME, et al. Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials. BMC Medicine. 2024;22:299. [pmc.ncbi.nlm.nih.gov]

Partnership opportunities

Our proprietary genome editing technology leverages the natural delivery power of exosomes to precisely and safely transport gene editing technologies into historically difficult to access organs such as the brain. The flexibility of our ExoEdit® platform enables adaptation to multiple genome editing modalities and therapeutic areas, supporting the development of transformative therapies that go beyond the reach of existing treatments.

Interested in learning more about partnership opportunities?

Get in Touch