OUR PIPELINE



acu-SS1
Systemic Scleroderma



We have discovered and validated that a deficit in the mitochondrial deacetylase Sirtuin 3 (SIRT3) is a pathogenic mechanism underlying fibrosis in Systemic Scleroderma in humans and that SIRT3 has cell-intrinsic potent anti-fibrotic properties. Our novel compound ACU-SS1 stimulates SIRT3 expression in a dose dependent manner displays inhibitory TGF-ß-induced fibrotic responses/signaling in fibroblasts, and effects on mitochondrial ROS generation. Attenuates fibrosis and restores SIRT3 levels in preclinical mouse models and been has validated via knock out models. ACU-SS1 potentially offers a novel new therapeutic option for the treatment of Systemic Scleroderma.



ACU-NE1
Neurodegeneration
HIV-Associated Neurocognitive Disorder
(HAND)





Mechanism of action



Demonstrated Efficacy In HIV induced mouse model as a potential first in class therapeutic for the treatment of HIV-Neurocognitive Disorder

  • Mice were tested to assess cognitive function by seeing if they could recognize a novel object in a familiar environment Cognitive abnormalities seen in HAND mice were significantly reversed by ACU-NE1
  • ACU-NE1 demonstrated efficacy in key HAND Biomarkers Significantly reduced the astrogliosis, ameliorated the neuronal abnormalities, and inhibited the activation of monocular phagocytes
  • Systemic Administration Feasible: Readily permeate the blood brain barrier and the blood-cerebrospinal fluid Novel new nano-emulsion targeting intranasal and systemic administration.

We are currently performing additional pre-clinical research and IND enabling development activities.



ACU-NE1
Alzheimer's Disease



Mechanism of Action



Our first in class SIRT3 Agonist has the potential to transform the treatment of AD resulting in a higher cognitive function, better quality of life, and reduction of the finical burden to society for the treatment of this devastating disease.


Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking.

  • Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, and recent studies have shed new light on the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. Results indicate that SIRT3 dysfunction leads to p53-mediated mitochondrial and neuronal damage in AD.
  • Sirt3 mRNA and protein expression in multiple Brain regions were significantly lower in AD compared to those in cognitively normal subjects. We also identified a strong association between Sirt3 and cognition along with a clear inverse correlation between Sirt3 and tau pathology.
  • These results that Sirt3 may be a novel player in the pathogenesis of AD. Strategies to modulate Sirt3 expression could disrupt Aβ-induced overproduction of tau and be useful in the treatment of AD.
  • ACU-NE1 has also been shown to inhibit the activity of GSK-3β, a key signaling event implicated in tau hyperphosphorylation. Our preliminary studies indicate that ACU-NE1 compound reduces the Amyloid beta levels (BACE 1 activity & Abeta42) in a dose dependent manner.
  • We plan to advance ACU-NE1 into additional pre-clinical formulation, pharmacology, and IND enabling toxicology studies


ACU-ME1
melanoma: Vemurafenib Resistant



Our compound inhibits the phosphorylation of DRP1, thus stimulating a phenotype suggestive of respiration through mitochondrial normalization. Acts selectively in vemurafenib resistant melanomas to increase both respiration and prevents from becoming glycolitic, leading to activity against aggressive resistant melanoma in vivo.

  • The majority of human melanomas express mutations in BRAF, and because of this mutation, much effort has gone into targeting BRAF and downstream pathways.
  • New targeted therapies have been developed to inhibit BRAF signaling and downstream pathways. These drugs often produce dramatic responses, but unfortunately, these responses usually last for a few months.
  • Our compounds: demonstrated significant antitumor activity in vivo against A375 malignant melanoma
  • ACU-D3 demonstrates significant antitumor activity in vivo against vemurafenib-resistant melanoma LM36R. Suggesting acquired signaling differences through resistance of BRAF inhibition.

We are currently performing additional pre-clinical research and IND enabling development activities.



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Accuitis, Inc.