Our proprietary platform for a novel class of gene therapies that are effective, safe, and applicable to rare as well as prevalent diseases.

Our core technology is based on functionalizing AAV or LNP, by conjugation of rationally designed ligands onto vectors surface, improving tissue targeting and efficient payload delivery.

The misfolding and accumulation of disease-related proteins are common hallmarks of several neurodegenerative diseases. As examples, beta-amyloid and tau in Alzheimer’s disease (AD), alpha-synuclein (aSyn) in Parkinson disease (PD) and related disorders, mutated huntingtin in Huntington’s disease (HD), and TAR DNA-binding protein 43 (TDP-43) in Amyotrophic Lateral Sclerosis (ALS), are shown to contribute to neurodegeneration and disease progression.

The presence of TDP-43 proteinopathy, characterized by the accumulation of highly modified and misfolded TDP-43 molecules in the cytoplasm, is a hallmark of various neurodegenerative diseases including ALS. Proposed mechanisms underlying TDP-43 proteinopathies involve disruptions in nuclear-cytoplasmic localization homeostasis, aggregation of ubiquitinated and hyper-phosphorylated TDP-43, and increased protein truncation of cytoplasmic TDP-43.

Pathological accumulation of aSyn is the common distinguishing trait amongst the group of brain disorders known as synucleinopathies, which include PD, Dementia with Lewy bodies (DLB), and Multiple System Atrophy (MSA). These disorders progressively develop neuronal and glial inclusions enriched with misfolded, phosphorylated and insoluble aSyn.

Over the past decade, several treatment strategies directly targeting protein aggregates have been evaluated in preclinical and clinical studies. For example, in ALS, several therapeutic strategies, spanning biologics to small molecules, that directly address TDP-43 pathology are under evaluation. In PD, diverse approaches include removal of aggregated aSyn with passive or active immunization or by expression of vectorized antibodies, modulating kinetics of misfolding with small molecule anti-aggregants, lowering aSyn gene expression by antisense oligonucleotides or inhibitory RNA.

The autophagy lysosomal pathway (ALP) is a central cellular pathway enabling the degradation of toxic protein aggregates. Key factors of the ALP, such as Glucocerebrosidase (GBA1) and Transcription Factor EB (TFEB), have been shown to play important roles in protein aggregate clearance mechanisms (Figure X). 

At Coave, using our ALIGATER™ platform, we have generated a coAAV-based genetic medicine approach to deliver safe, low doses of GBA1 and TFEB precisely targeted to relevant structures (tissues and cells) of the central nervous system (CNS), aiming to activate or restore the autophagy and lysosomal functions to eliminate or prevent the accumulation of toxic protein aggregates associated with neurodegenerative disease.

The misfolding and accumulation of disease-related proteins are common hallmarks of several neurodegenerative diseases. As examples, beta-amyloid and tau in Alzheimer’s disease (AD), alpha-synuclein (aSyn) in Parkinson disease (PD) and related disorders, mutated huntingtin in Huntington’s disease (HD), and TAR DNA-binding protein 43 (TDP-43) in Amyotrophic Lateral Sclerosis (ALS), are shown to contribute to neurodegeneration and disease progression.

The presence of TDP-43 proteinopathy, characterized by the accumulation of highly modified and misfolded TDP-43 molecules in the cytoplasm, is a hallmark of various neurodegenerative diseases including ALS. Proposed mechanisms underlying TDP-43 proteinopathies involve disruptions in nuclear-cytoplasmic localization homeostasis, aggregation of ubiquitinated and hyper-phosphorylated TDP-43, and increased protein truncation of cytoplasmic TDP-43.

Pathological accumulation of aSyn is the common distinguishing trait amongst the group of brain disorders known as synucleinopathies, which include PD, Dementia with Lewy bodies (DLB), and Multiple System Atrophy (MSA). These disorders progressively develop neuronal and glial inclusions enriched with misfolded, phosphorylated and insoluble aSyn.

Over the past decade, several treatment strategies directly targeting protein aggregates have been evaluated in preclinical and clinical studies. For example, in ALS, several therapeutic strategies, spanning biologics to small molecules, that directly address TDP-43 pathology are under evaluation. In PD, diverse approaches include removal of aggregated aSyn with passive or active immunization or by expression of vectorized antibodies, modulating kinetics of misfolding with small molecule anti-aggregants, lowering aSyn gene expression by antisense oligonucleotides or inhibitory RNA.

The autophagy lysosomal pathway (ALP) is a central cellular pathway enabling the degradation of toxic protein aggregates. Key factors of the ALP, such as Glucocerebrosidase (GBA1) and Transcription Factor EB (TFEB), have been shown to play important roles in protein aggregate clearance mechanisms (Figure X). 

At Coave, using our ALIGATER™ platform, we have generated a coAAV-based genetic medicine approach to deliver safe, low doses of GBA1 and TFEB precisely targeted to relevant structures (tissues and cells) of the central nervous system (CNS), aiming to activate or restore the autophagy and lysosomal functions to eliminate or prevent the accumulation of toxic protein aggregates associated with neurodegenerative disease.

ALS is a rare neurodegenerative condition marked by the swift and relentless decline of motor neuron function and survival, resulting in paralysis and ultimately respiratory failure, culminating in death usually within five years after diagnosis. The etiology of ALS remains unknown and non-genetically defined in 90-95% of cases, with no cure .

The incidence of ALS in the US and Europe is approximately 2 in 100,000, equating to approx. 30,000 patients in the US and 50,000 in Europe.

Protein aggregation and dysregulation of the autophagy-lysosome pathway are hallmarks of ALS, with evidence of accumulation of autophagosomes, disrupted lysosomes, and TDP-43 aggregates in patients’ brains (Beckers et al., 2021). Transcription factor EB (TFEB) has emerged as a master regulator of the autophagy lysosomal pathway, and is therefore a promising therapeutic target for clearing toxic aggregates (Napolitano and Ballabio, 2016). Stage-dependent alterations in TFEB expression have been observed in ALS models, with decreased TFEB activity in patient brain samples. TFEB overexpression mediated by gene therapy is anticipated to mitigate toxic protein accumulation thus offering a strategy to halt motor neuron degeneration and impede ALS progression. TFEB represents a crucial avenue for ALS treatment, echoing its significance in other neurodegenerative diseases.

Inherited retinal dystrophies are rare ophthalmic pathologies that can be divided into two groups:

1. Pigmentary retinopathies, which include retinitis pigmentosa (RP) and Leber congenital amaurosis
2. Macular dystrophies

Retinitis pigmentosa is the most common form of inherited retinal dystrophy representing 50% of all retinal dystrophies.

While multiple genes are implicated in each of these groups, within each patient or family, only one causative gene is involved.

We are a talented, passionate group of colleagues with a desire to translate innovative science into novel gene therapies for patients with neurodegenerative and ocular diseases and beyond.

We are committed to building a vibrant team combining deep expertise in AAV vector engineering and genetic construct design, innovative and advanced therapeutic product development, and manufacturing.

We are looking for more talented individuals to join our team.