Program	Indication	Discovery	IND enabling	Phase 1
Anti-Nitrated Alpha Synuclein Antibody	Parkinson's Disease	NDC-0524
Anti-Nitrated Alpha Synuclein Ab	Multiple System Atrophy	NDC-0524
Anti-Nitrated Alpha Synuclein Ab	Dementia with Lewy Bodies	NDC-0524
Brain Shuttle-NDC-0524	Parkinson's Disease
Synuclein Nitrase Inhibitor	Parkinson's Disease
Platform	Oncology

Anti-Nitrated Alpha Synuclein Antibody
Parkinson's Disease
Discovery	IND enabling	Phase 1
NDC-0524
Anti-Nitrated Alpha Synuclein Ab
Multiple System Atrophy
Discovery	IND enabling	Phase 1
NDC-0524
Anti-Nitrated Alpha Synuclein Ab
Dementia with Lewy Bodies
Discovery	IND enabling	Phase 1
NDC-0524
Brain Shuttle-NDC-0524
Parkinson's Disease
Discovery	IND enabling	Phase 1
Synuclein Nitrase Inhibitor
Parkinson's Disease
Discovery	IND enabling	Phase 1
Platform
Oncology
Discovery	IND enabling	Phase 1

Parkinson’s Disease

A key example of the power of our NITROME platform is our discovery of Synuclein Nitrase (the specific synuclein nitration enzyme canonically named GLOD4). This represents a significant scientific breakthrough that provides an ideal therapeutic target to halt Parkinson’s disease (PD). Currently, there is no effective intervention to slow, halt or reverse the progression of Parkinson’s disease.

The buildup of aggregated alpha-synuclein is a hallmark of PD. Our data suggest that the nitration of alpha synuclein plays a key role in PD pathology and neuronal dysfunction.

These synuclein aggregates are heavily nitrated, and this nitration strongly induces neurodegenerative disease in preclinical models, promoting neuronal death. Additionally, we have found that nitrated synuclein is elevated in the cerebral spinal fluid of PD patients suggesting it could be the pathogenic species driving spread between brain regions.

Together, these findings identify nitrated alpha-synuclein as a compelling therapeutic target for PD.

Our lead program is NDC-0524, an antibody that was specifically designed to selectively bind to nitrated alpha-synuclein while leaving the normal protein intact, with the goal of addressing the underlying cause of PD rather than simply treating its symptoms. In multiple in vitro and in vivo models of Parkinson’s disease, this first-in-class antibody slowed disease progression and significantly reduced the spread of alpha-synuclein pathology between brain regions. With IND-enabling studies completed and a biomarker-driven clinical development strategy in place, NDC-0524 is positioned for first-in-human Phase 1/2a clinical evaluation.

Our second program focuses on the development of potent, brain-penetrant small-molecule inhibitors of Synuclein Nitrase, the enzyme responsible for generating pathogenic nitrated alpha-synuclein. By blocking nitrated alpha-synuclein production, this approach offers the potential for an oral, disease-modifying therapy that complements antibody-based approaches by directly inhibiting an upstream driver of Parkinson’s disease pathology.

Cancer

The NITROME platform has also identified several nitrases and nitro-substrates that play an important role in cancer as well as in immuno-oncology.

These nitrases and their nitro-substrates have been shown to play a key role as tumor survival factors, mediators of apoptosis and promoters of resistance to PD-1 checkpoint inhibitors.

Several studies have shown that the overexpression of some nitrases was associated with poorer overall survival in multiple cancer types and that elimination of the nitrase in cellular models slowed tumor growth, reduced viability, and increased the rate of apoptosis.

We are identifying inhibitors of nitrases to target cancer-promoting nitrases and their nitro-substrates in underserved solid and hematological tumors.

Future Opportunities

Given the broad and diverse biology of nitrases and their nitro-substrates, Nitrase Therapeutics is also evaluating programs in other therapeutic areas where nitrases and nitro-substrates play a role in disease establishment or progression, including acute lung injury, lung fibrosis, and autoimmune diseases.

Based on the breadth of nitrases and nitro-substrates that Nitrase Therapeutics has discovered to-date, the pipeline and potential collaboration opportunities across therapeutic areas is vast.