NeuBase Therapeutics

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<div class="infobox-header">NeuBase Therapeutics</div>
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<tr><th>Stock Symbol</th><td>NASDAQ: NBSE (delisted 2024)</td></tr>
<tr><th>Headquarters</th><td>Pittsburgh, Pennsylvania, USA</td></tr>
<tr><th>Founded</th><td>2015</td></tr>
<tr><th>Focus</th><td>Genetic medicines, CNS disorders, Rare diseases</td></tr>
<tr><th>Technology</th><td>Peptide Nucleic Acid (PNA) platform</td></tr>
<tr><th>Status</th><td>Private (merged with Anju 2024)</td></tr>
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Overview

<div class="infobox">
<div class="infobox-header">NeuBase Therapeutics</div>
<div class="infobox-content">
<table>
<tr><th>Stock Symbol</th><td>NASDAQ: NBSE (delisted 2024)</td></tr>
<tr><th>Headquarters</th><td>Pittsburgh, Pennsylvania, USA</td></tr>
<tr><th>Founded</th><td>2015</td></tr>
<tr><th>Focus</th><td>Genetic medicines, CNS disorders, Rare diseases</td></tr>
<tr><th>Technology</th><td>Peptide Nucleic Acid (PNA) platform</td></tr>
<tr><th>Status</th><td>Private (merged with Anju 2024)</td></tr>
</table>
</div>
</div>

Overview

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["@neubase"].

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["@pna_review"].

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["@neubase2024"].

Corporate History

Founding and Early Development (2015-2019)

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:

• Building the PNA technology platform
• Establishing intellectual property around novel PNA conjugates
• Validating the technology in preclinical models of CNS disorders
• Raising Series A and B funding to support research and development

Public Company Period (2019-2024)

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:

• Advanced NB-1001 (Huntington's disease program) through preclinical development
• Expanded its pipeline to include programs in myotonic dystrophy and Alzheimer's disease
• Established partnerships with academic institutions for additional disease area exploration
• Published peer-reviewed research demonstrating PNA technology capabilities

Merger and Current Status (2024-Present)

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[@neubase2024].

Technology Platform

Peptide Nucleic Acid (PNA) Technology

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[@pna_review]:

Chemical Properties:

• Neutral backbone: Unlike DNA and RNA, PNA has a neutral backbone that reduces non-specific protein binding
• High binding affinity: PNAs bind to complementary DNA or RNA with higher affinity than DNA/DNA or DNA/RNA duplexes
• Sequence specificity: Can be designed to discriminate between single nucleotide differences, enabling allele-selective targeting
• Chemical stability: Resistant to nucleases and proteases, providing enhanced stability in biological fluids

Mechanism of Action

PNAs mediate therapeutic effects through multiple mechanisms[@pna_gene_silencing]:

Delivery Systems

A key challenge for nucleic acid therapeutics is achieving adequate delivery to target tissues. NeuBase developed proprietary delivery technologies to enhance PNA distribution[@pna_delivery]:

• Cell-penetrating peptides: Conjugates that facilitate cellular uptake
• Targeted nanoparticles: Formulations designed for specific tissue targeting
• BBB-penetrating designs: Modified PNAs engineered for enhanced brain penetration[@pna_bbb]

Pipeline Programs

NB-1001: Huntington's Disease Program

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[@huntingtons_mechanism].

NeuBase's lead program targeted the HTT gene using allele-selective gene silencing approach[@htt_silencing]:

Mechanism:

• Design of PNAs that selectively bind to mutant HTT mRNA containing expanded CAG repeats
• Preferential silencing of the mutant allele while preserving wild-type HTT expression
• Reduction in mutant protein production throughout the brain

• Validated in cellular models of HD
• Demonstrated allele selectivity in patient-derived cell lines
• Achieved brain distribution in preclinical species
• Completed IND-enabling studies

NB-2001: Myotonic Dystrophy Program

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[@dm_type_1].

NeuBase's NB-2001 program aimed to correct the splicing defect[@dmpk_splice]:

Mechanism:

• PNA-mediated splice modulation to restore normal DMPK RNA processing
• Correction of downstream splicing disruptions affecting multiple genes
• Potential to address both the RNA toxicity and protein loss aspects of the disease

• Discovery stage
• In vitro validation in DM1 patient-derived cells
• Optimization of PNA sequences for maximal splice correction

NB-3001: Alzheimer's Disease Program

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[@tau_therapy].

NeuBase's Alzheimer's program targeted tau protein[@tau_therapy]:

Mechanism:

• Gene silencing to reduce tau protein production
• Targeting both wild-type and mutant tau variants
• Potential to slow disease progression by reducing tau burden

• Discovery stage
• Target validation ongoing
• PNA sequence optimization

Advantages for Neurodegenerative Diseases

NeuBase's technology offered several advantages for treating CNS disorders[@pna_bbb]:

Blood-Brain Barrier Penetration

The BBB presents a major challenge for nucleic acid therapeutics. NeuBase developed PNA constructs with enhanced BBB penetration properties:

• Modified peptide conjugates that utilize endogenous transport mechanisms
• Optimized physicochemical properties for passive diffusion
• Potential for systemic administration reaching CNS

Allele-Selective Targeting

For diseases like Huntington's where mutant and wild-type alleles differ only by repeat length, allele-selective silencing is crucial:

• PNAs can be designed to preferentially bind mutant alleles
• Preservation of wild-type function avoids potential toxicity
• Applicable to other repeat expansion diseases

Reduced Immunogenicity

Unlike viral vectors, PNA-based therapeutics have lower immunogenic potential[@pna_immunogenicity]:

• Non-viral delivery systems avoid immune responses to viral proteins
• Lower risk of neutralizing antibody formation
• Potential for repeat dosing — critical for chronic diseases

Repeat Dosing Capability

Chronic neurodegenerative diseases require long-term treatment:

• Non-viral delivery enables multiple treatment cycles
• Flexibility in dosing regimens
• Ability to adjust treatment based on response

Competitive Landscape

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 |

Competitive Advantages

NeuBase's PNA platform offered several potential differentiators:

Challenges

The company faced several competitive challenges:

• Established players: Large pharmaceutical companies and experienced biotech firms dominate the gene therapy space
• Clinical validation: PNA technology had not been clinically validated at scale
• Manufacturing: Scale-up of PNA production presented technical challenges
• Regulatory pathway: Novel therapeutic modalities require extensive regulatory consultation

Research and Publications

NeuBase's science was supported by peer-reviewed publications demonstrating key capabilities of the PNA platform:

Key Publications

Business Development

Academic Partnerships

NeuBase established collaborations with academic institutions to advance its platform:

• University of Michigan: Huntington's disease research and animal models
• University of Florida: Myotonic dystrophy expertise and patient resources
• Massachusetts General Hospital: Alzheimer's disease research and biomarker development

Intellectual Property

The company built a robust patent portfolio covering:

• PNA chemical compositions and modifications
• Delivery conjugate technologies
• Disease-specific sequence designs
• Manufacturing processes

Financial History

| 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 |

Limitations and Lessons Learned

Technology Challenges

The PNA platform faced several technical challenges:

Strategic Considerations

The merger with Anju reflected several factors:

• Capital intensity of bringing gene therapies to clinical development
• Competitive pressure from well-funded larger companies
• Need for additional financing in challenging market conditions
• Strategic alternatives evaluation by the board

Scientific Impact

Despite its corporate challenges, NeuBase contributed to advancing nucleic acid therapeutics for CNS disorders:

• Demonstrated feasibility of PNA technology for gene modulation
• Advanced understanding of allele-selective targeting approaches
• Contributed to delivery technology development for brain diseases
• Trained scientific talent that has moved to other companies in the field

Current Status

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.

See Also

• [Huntington's Disease](/diseases/huntingtons)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Myotonic Dystrophy](/diseases/myotonic-dystrophy)
• [Gene Therapy for Neurodegeneration](/mechanisms/gene-therapy-neurodegeneration)
• [Peptide Nucleic Acids](/mechanisms/peptide-nucleic-acids)
• [Antisense Oligonucleotides](/mechanisms/antisense-oligonucleotides)

External Links

• [NeuBase Therapeutics Archive](https://web.archive.org/web/2024/neubasetherapeutics.com)
• [Securities and Exchange Commission Filings](https://www.sec.gov)
• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [ClinicalTrials.gov](https://clinicaltrials.gov)

References