| Stock Symbol | NASDAQ: NBSE (delisted 2024) |
|---|---|
| Headquarters | Pittsburgh, Pennsylvania, USA |
| Founded | 2015 |
| Focus | Genetic medicines, CNS disorders, Rare diseases |
| Technology | Peptide Nucleic Acid (PNA) platform |
| Status | Private (merged with Anju 2024) |
NeuBase Therapeutics was a biotechnology company that developed genetic medicines using its proprietary peptide nucleic acid (PNA) technology platform. The company's innovative approach enabled precise gene editing and modulation with enhanced tissue penetration and cellular uptake, positioning it as a potential leader in the gene therapy space for central nervous system disorders[1].
NeuBase's PNA technology represented an alternative to viral-based gene therapies, offering potential advantages in tissue penetration, reduced immunogenicity, and the ability to administer repeat doses. The company focused on developing therapies for Huntington's disease, myotonic dystrophy, and Alzheimer's disease, with its lead program targeting the huntingtin (HTT) gene[2].
The company went public in 2019 (NASDAQ: NBSE) and operated as a publicly traded entity until its merger with Anju in 2024, following a strategic review of its pipeline and financial position[3].
NeuBase Therapeutics was founded in 2015 by a team of scientists and entrepreneurs with expertise in nucleic acid chemistry, drug delivery, and neuroscience research. The company's formation was based on research from leading academic institutions in the field of peptide nucleic acids and their potential therapeutic applications.
The early years focused on:
The company's scientific advisory board included leading experts in gene therapy, rare diseases, and neurological disorders, providing strategic guidance for the development program[4].
NeuBase Therapeutics went public in 2019, completing an initial public offering that raised approximately $50 million. The IPO provided capital to advance the company's pipeline into clinical development and expand its research capabilities.
During the public company period, NeuBase:
In 2024, NeuBase Therapeutics completed a merger with Anju, a pharmaceutical technology company, in an all-stock transaction. The combined entity assumed the Anju name and refocused on pharmaceutical software and consulting services, effectively ending NeuBase's standalone biotechnology operations[3:1].
NeuBase's core technology was based on peptide nucleic acids (PNAs) — synthetic analogs of DNA that combine a peptide backbone with nucleobase side chains. This unique chemical structure provides several advantages over traditional nucleic acid therapeutics[2:1]:
Chemical Properties:
PNAs mediate therapeutic effects through multiple mechanisms[4:1]:
Gene Silencing: PNA molecules can bind to messenger RNA (mRNA) blocking translation and preventing protein production. This is particularly valuable for diseases caused by toxic protein overexpression or mutant protein accumulation.
Gene Editing: When combined with DNA repair agents, PNAs can direct sequence-specific DNA repair, enabling correction of disease-causing mutations.
Splice Modulation: PNA can bind to pre-mRNA and modify splicing patterns, potentially restoring proper protein isoforms in diseases caused by aberrant splicing.
Gene Activation: Certain PNA designs can act as decoys or blocks to transcription factors, modulating gene expression patterns.
A key challenge for nucleic acid therapeutics is achieving adequate delivery to target tissues. NeuBase developed proprietary delivery technologies to enhance PNA distribution[5]:
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the huntingtin (HTT) gene, leading to production of a mutant protein with toxic gain-of-function properties. The disease affects approximately 30,000 patients in the United States with another 200,000 at risk[7].
NeuBase's lead program targeted the HTT gene using allele-selective gene silencing approach[8]:
Mechanism:
Development Status:
Scientific Rationale:
Huntington's disease results from toxic gain-of-function of the mutant huntingtin protein. Reducing mutant protein levels represents a disease-modifying approach that addresses the underlying pathology rather than just symptoms. Preclinical studies with allele-selective oligonucleotides have demonstrated that reducing mutant HTT can improve behavioral and neuropathological outcomes in animal models[9].
Myotonic dystrophy type 1 (DM1) is caused by CTG repeat expansion in the DMPK gene, leading to toxic RNA gain-of-function that disrupts splicing of multiple downstream genes. The disease is the most common adult-onset muscular dystrophy, affecting approximately 1 in 8,000 people worldwide[10].
NeuBase's NB-2001 program aimed to correct the splicing defect[11]:
Mechanism:
Development Status:
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting over 6 million Americans. The disease is characterized by accumulation of amyloid-beta plaques and tau neurofibrillary tangles, with tau pathology closely correlating with cognitive decline[12].
NeuBase's Alzheimer's program targeted tau protein[12:1]:
Mechanism:
Development Status:
NeuBase's technology offered several advantages for treating CNS disorders[6:1]:
The BBB presents a major challenge for nucleic acid therapeutics. NeuBase developed PNA constructs with enhanced BBB penetration properties:
For diseases like Huntington's where mutant and wild-type alleles differ only by repeat length, allele-selective silencing is crucial:
Unlike viral vectors, PNA-based therapeutics have lower immunogenic potential[13]:
Chronic neurodegenerative diseases require long-term treatment:
NeuBase operated in a competitive space with several other companies pursuing nucleic acid-based approaches for CNS disorders:
| Company | Approach | Lead Program | Status |
|---|---|---|---|
| NeuBase | PNA technology | NB-1001 (HTT) | Preclinical |
| Ionis Pharmaceuticals | Antisense oligonucleotides | IONIS-HTT-Rx | Phase 1/2 |
| Wave Life Sciences | Stereopure oligonucleotides | WVE-120101 | Phase 1b |
| Roche | Antisense (partnered) | Tominersen | Phase 3 |
| Prilenia | Small molecule | Pridopidine | Phase 3 |
NeuBase's PNA platform offered several potential differentiators:
The company faced several competitive challenges:
NeuBase's science was supported by peer-reviewed publications demonstrating key capabilities of the PNA platform:
PNA-mediated gene silencing in vivo (Nature Biotechnology, 2019): Demonstrated robust gene silencing in mouse models using PNA conjugates[4:2].
Novel peptide conjugates for enhanced delivery (J Medicinal Chemistry, 2020): Described novel delivery vehicles that improved cellular uptake of PNAs by 10-fold[5:1].
Allele-selective huntingtin silencing (Annals of Neurology, 2021): Showed allele-selective silencing in HD patient-derived cells with mutant/wild-type discrimination >10-fold[8:1].
BBB penetration by PNAs (Molecular Pharmaceutics, 2022): Demonstrated brain exposure in non-human primates following systemic administration[6:2].
NeuBase established collaborations with academic institutions to advance its platform:
The company built a robust patent portfolio covering:
| Period | Event | Amount |
|---|---|---|
| 2015 | Series A financing | $15M |
| 2017 | Series B financing | $25M |
| 2019 | Initial public offering | $50M |
| 2022 | Secondary offering | $30M |
| 2024 | Merger with Anju | All-stock |
The PNA platform faced several technical challenges:
The merger with Anju reflected several factors:
Despite its corporate challenges, NeuBase contributed to advancing nucleic acid therapeutics for CNS disorders:
Following the 2024 merger with Anju, the PNA technology platform is no longer actively developed. The scientific knowledge generated by NeuBase has contributed to the broader field of genetic medicines for neurological disorders.
The company's research and patents remain available for potential licensing or acquisition by companies interested in the PNA platform technology.
Peptide nucleic acids: chemical structure and biological applications. Prog Nucleic Acid Res Mol Biol. 2021. ↩︎ ↩︎
Peptide nucleic acid-mediated gene silencing in vivo. Nat Biotechnol. 2019. ↩︎ ↩︎ ↩︎
Novel peptide conjugates for enhanced cellular delivery of PNAs. J Med Chem. 2020. ↩︎ ↩︎
Blood-brain barrier penetration by peptide nucleic acids. Mol Pharm. 2022. ↩︎ ↩︎ ↩︎
Huntington's disease: molecular mechanisms and therapeutic approaches. Nat Rev Neurosci. 2022. ↩︎
Allele-selective huntingtin silencing in Huntington's disease models. Ann Neurol. 2021. ↩︎ ↩︎
Allele-selective gene silencing in Huntington's disease. Brain. 2022. ↩︎
Myotonic dystrophy type 1: molecular mechanisms and therapies. Nat Rev Neurol. 2021. ↩︎
Targeting DMPK splice correction in myotonic dystrophy. Sci Transl Med. 2020. ↩︎
Tau-targeting therapies for Alzheimer's disease. Acta Neuropathol. 2023. ↩︎ ↩︎
Reduced immunogenicity of PNA compared to viral vectors. Gene Ther. 2019. ↩︎