Technology

홈TechnologyPipeline

Pipeline

Pipeline
Project
Code
Indication Discovery Hit/Lead Candidate
nomination
Pre-clinical Phase I Phase 2
VTA-04 Pulmonary arterial
hypertension
(PAH)
IND - 2023 2025
Break-through
Designation
PAH

Pulmonary Arterial Hypertension (PAH)

PAH is a rare but lethal disorder caused by several pathological changes in the pulmonary vasculature. It is characterized by excessive pulmonary vascular remodeling resulting from intimal changes caused by pulmonary artery endothelial cell (PAEC) dysfunction and medial hypertrophy via increased proliferation of pulmonary artery smooth muscle cells (PASMC). This elevates pulmonary vascular resistance (PVR) and pulmonary artery pressure, which lead to a marked increase in right ventricle (RV) afterload. Eventually, heart failure develops due to RV hypertrophy.

The current approved PAH medications are predominately pulmonary vasodilators : 1) endothelin receptor antagonists, 2) phosphodiesterase type 5 (PDE5) inhibitors, 3) prostacyclin agonists, and 4) soluble guanylyl cyclase (sGC) stimulators. These therapies mostly inhibit excessive vasoconstriction and accelerate the vasodilation of pulmonary arteries, but are not based on complete therapeutic concepts, such as vascular normalization.

VTA-04 is the first compound that is useful for normalizing injured pulmonary arteries, which is one of the main features in PAH progression. Also, our therapeutic strategies with VTA-04 are novel, effective therapies that target key molecular pathways that drive the vascular pathogenesis of PAH . VTA-04 can reduce PASMC hyperplasia through the inhibition of PDGF-induced PDGFRb signaling and simultaneously induce the recovery of injured PAECs through the restoration of VEGF-induced VEGFR2 signaling.

  • PAH
  • PAH
  • Choi, M.H., et al. (2005). "Regulation of PDGF signalling and vascular remodeling by peroxiredoxin II." Nature 19:347-35 (total 427).
  • Kang, D.H., et al. (2011). "Peroxiredoxin II Is an Essential Antioxidant Enzyme that Prevents the Oxidative Inactivation of VEGF Receptor-2 in Vascular Endothelial Cells." Molecular Cell 44:545-558 (total 116).
  • Kang, D.H., et al. (2013). "Vascular injury involves the overoxidation of peroxiredoxin type II and is recovered by the peroxiredoxin-activity mimetic that induces reendothelialization." Circulation 128(8):834-844 (total 21).
PAH

Pulmonary Arterial Hypertension (PAH)

PAH is a rare but lethal disorder caused by several pathological changes in the pulmonary vasculature. It is characterized by excessive pulmonary vascular remodeling resulting from intimal changes caused by pulmonary artery endothelial cell (PAEC) dysfunction and medial hypertrophy via increased proliferation of pulmonary artery smooth muscle cells (PASMC). This elevates pulmonary vascular resistance (PVR) and pulmonary artery pressure, which lead to a marked increase in right ventricle (RV) afterload. Eventually, heart failure develops due to RV hypertrophy.

The current approved PAH medications are predominately pulmonary vasodilators : 1) endothelin receptor antagonists, 2) phosphodiesterase type 5 (PDE5) inhibitors, 3) prostacyclin agonists, and 4) soluble guanylyl cyclase (sGC) stimulators. These therapies mostly inhibit excessive vasoconstriction and accelerate the vasodilation of pulmonary arteries, but are not based on complete therapeutic concepts, such as vascular normalization.

VTA-04 is the first compound that is useful for normalizing injured pulmonary arteries, which is one of the main features in PAH progression. Also, our therapeutic strategies with VTA-04 are novel, effective therapies that target key molecular pathways that drive the vascular pathogenesis of PAH . VTA-04 can reduce PASMC hyperplasia through the inhibition of PDGF-induced PDGFRb signaling and simultaneously induce the recovery of injured PAECs through the restoration of VEGF-induced VEGFR2 signaling.

  • PAH
  • PAH
  • Choi, M.H., et al. (2005). "Regulation of PDGF signalling and vascular remodeling by peroxiredoxin II." Nature 19:347-35 (total 427).
  • Kang, D.H., et al. (2011). "Peroxiredoxin II Is an Essential Antioxidant Enzyme that Prevents the Oxidative Inactivation of VEGF Receptor-2 in Vascular Endothelial Cells." Molecular Cell 44:545-558 (total 116).
  • Kang, D.H., et al. (2013). "Vascular injury involves the overoxidation of peroxiredoxin type II and is recovered by the peroxiredoxin-activity mimetic that induces reendothelialization." Circulation 128(8):834-844 (total 21).
VTC-05 Triple-negative
breast cancer
(TNBC)
CANCER

CANCER

VTC-05 is the anticancer candidate developed using the ENTER platform. It exhibits H2O2-eliminating peroxidase activity that mimics both 2-Cys Prx and Gpx and was thus designed for the treatment of patients with TNBC (triple-negative breast cancer). In TNBC, VTC-05 specifically regulates energy metabolism under the EGFR signaling pathway and consequently arrests cell growth.

Triple Negative Breast Cancer (TNBC)

Breast Cancer (BC) was the leading cause of cancer deaths among women worldwide in 2018. It is classified into four major molecular subtypes: luminal A, luminal B, basal-like/triple-negative/basal breast cancer (TNBC)-negative, and HER2. Triple with little or no estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) have very high metastatic and recurrent behaviors. Therefore, the targeted eradication of TNBC is important to increase the relapse-free survival of BC patients. EGFR, a membrane-penetrating tyrosine kinase receptor member of the HER family, is one of the major regulators of cell proliferation and metabolism, and EGF is known to accelerate glucose consumption and lactate production in cancer cells. Particularly, EGFR overexpression is frequently observed in patients with TNBC. Thus, EGFR is the newest therapeutic target for the treatment of TNBC cells.

  • Lee, E., et al. (2020). "Glutathione peroxidase-1 regulates adhesion and metastasis of triplenegative breast cancer cells via FAK signaling." Redox Biology 29.
  • McLaughlin, R. P., et al. (2019). "A kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-targeted therapy." Breast Cancer Res 21(1): 77.
  • Shen, M., et al. (2019). "Tinagl1 Suppresses TripleNegative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling." Cancer Cell 35(1): 64-80 e67.
  • Wendt, M. K., et al. (2017). "The paradoxical functions of EGFR during breast cancer progression." Signal Transduction and Targeted Therapy 2:16042.
CANCER

CANCER

VTC-05 is the anticancer candidate developed using the ENTER platform. It exhibits H2O2-eliminating peroxidase activity that mimics both 2-Cys Prx and Gpx and was thus designed for the treatment of patients with TNBC (triple-negative breast cancer). In TNBC, VTC-05 specifically regulates energy metabolism under the EGFR signaling pathway and consequently arrests cell growth.

Triple Negative Breast Cancer (TNBC)

Breast Cancer (BC) was the leading cause of cancer deaths among women worldwide in 2018. It is classified into four major molecular subtypes: luminal A, luminal B, basal-like/triple-negative/basal breast cancer (TNBC)-negative, and HER2. Triple with little or no estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) have very high metastatic and recurrent behaviors. Therefore, the targeted eradication of TNBC is important to increase the relapse-free survival of BC patients. EGFR, a membrane-penetrating tyrosine kinase receptor member of the HER family, is one of the major regulators of cell proliferation and metabolism, and EGF is known to accelerate glucose consumption and lactate production in cancer cells. Particularly, EGFR overexpression is frequently observed in patients with TNBC. Thus, EGFR is the newest therapeutic target for the treatment of TNBC cells.

  • Lee, E., et al. (2020). "Glutathione peroxidase-1 regulates adhesion and metastasis of triplenegative breast cancer cells via FAK signaling." Redox Biology 29.
  • McLaughlin, R. P., et al. (2019). "A kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-targeted therapy." Breast Cancer Res 21(1): 77.
  • Shen, M., et al. (2019). "Tinagl1 Suppresses TripleNegative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling." Cancer Cell 35(1): 64-80 e67.
  • Wendt, M. K., et al. (2017). "The paradoxical functions of EGFR during breast cancer progression." Signal Transduction and Targeted Therapy 2:16042.
VTN-04 Neurodegenerative disease
Neurodegenerative disease

Neurodegenerative disease

Alzheimer's disease (AD)

Alzheimer's disease (AD) is the most common form of dementia, causing symptoms of dementia such as memory loss, difficulty performing daily activities, and changes in judgement, reasoning, behavior, and emotions. Today, more than 40 million people worldwide are living with AD and related dementias, and this number is growing rapidly. The major hallmarks of AD include senile plaques and neurofibrillary tangles. To date, in addition to the accumulation of Aβ and tau, the proposed mechanisms include neuronal death induced by β-amyloid(Aβ) oligomer toxicity, oxidative stress, neuroinflammation, and synaptic dysfuction. With the aging populations of many countries, the world is facing an AD crisis. There is currently no cure for AD, nor is there a treatment that will stop its progression. VasThera thus aims to evaluate the efficacy and safety of investigational candidates in our pipeline and address the unmet needs in AD research and treatment.

Alzheimer's disease and oxidative stress

Oxidative stress leads to a range of cellular disorders caused by an excess of reactive oxygen species (ROS)3. ROS might also induce aberrant protein aggregation in a variety of neurodegenerative disorders, including AD, Parkinson's disease, and amyotrophic lateral sclerosis. There is overwhelming evidence that brain tissue in AD patients is exposed to oxidative stress during the course of the disease. Since oxidative stress is characterized by an imbalance in radical production of ROS and antioxidative defense, both are considered to have a major role in the process of age-related neurodegeneration and cognitive decline. The therapeutic inhibition of oxidative stress thus might result in a decrease in pathological characteristics such as reactive astrogliosis, neuroinflammation, and neuronal death4,5.

  • Alzheimer's Association. (2012). "Alzheimer's disease facts and figures." Alzheimers Dement 8, 131-168.
  • Querfurth, H.W. (2010). "Alzheimer's disease." The New Eng J of Med 362, 329-344.
  • Cheignin, C et al. (2018). "Oxidative stress and the amyloid beta peptide in Alzheimer's disease." Redox Biol 14, 450-464.
  • Hardy J, Selkoe DJ. (2002). "The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics." Science 297, 353-356.
  • Chun H et al. (2020). "Severe reactive astrocytes precipitate pathological hallmarks of AD via H2O2- production." Nat. neurosci 23, 1555-1566.
Neurodegenerative disease

Neurodegenerative disease

Alzheimer's disease (AD)

Alzheimer's disease (AD) is the most common form of dementia, causing symptoms of dementia such as memory loss, difficulty performing daily activities, and changes in judgement, reasoning, behavior, and emotions. Today, more than 40 million people worldwide are living with AD and related dementias, and this number is growing rapidly. The major hallmarks of AD include senile plaques and neurofibrillary tangles. To date, in addition to the accumulation of Aβ and tau, the proposed mechanisms include neuronal death induced by β-amyloid(Aβ) oligomer toxicity, oxidative stress, neuroinflammation, and synaptic dysfuction. With the aging populations of many countries, the world is facing an AD crisis. There is currently no cure for AD, nor is there a treatment that will stop its progression. VasThera thus aims to evaluate the efficacy and safety of investigational candidates in our pipeline and address the unmet needs in AD research and treatment.

Alzheimer's disease and oxidative stress

Oxidative stress leads to a range of cellular disorders caused by an excess of reactive oxygen species (ROS)3. ROS might also induce aberrant protein aggregation in a variety of neurodegenerative disorders, including AD, Parkinson's disease, and amyotrophic lateral sclerosis. There is overwhelming evidence that brain tissue in AD patients is exposed to oxidative stress during the course of the disease. Since oxidative stress is characterized by an imbalance in radical production of ROS and antioxidative defense, both are considered to have a major role in the process of age-related neurodegeneration and cognitive decline. The therapeutic inhibition of oxidative stress thus might result in a decrease in pathological characteristics such as reactive astrogliosis, neuroinflammation, and neuronal death4,5.

  • Alzheimer's Association. (2012). "Alzheimer's disease facts and figures." Alzheimers Dement 8, 131-168.
  • Querfurth, H.W. (2010). "Alzheimer's disease." The New Eng J of Med 362, 329-344.
  • Cheignin, C et al. (2018). "Oxidative stress and the amyloid beta peptide in Alzheimer's disease." Redox Biol 14, 450-464.
  • Hardy J, Selkoe DJ. (2002). "The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics." Science 297, 353-356.
  • Chun H et al. (2020). "Severe reactive astrocytes precipitate pathological hallmarks of AD via H2O2- production." Nat. neurosci 23, 1555-1566.
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