Pipeline

CU105

CU105

Expanded indications of CU06 to Hereditary Angioedema(HAE)

Sortation content
CU105 Expanded indications of CU06 to Hereditary Angioedema(HAE)
Indication Hereditary Angioedema(HAE)
Unmet Needs

• Approved HAE treatments can minimize the risk of death, but they are not effective in complete healing from the disease.

• The new gene therapies seem to provide promising opportunities for the treatment of hereditary angioedema.

• However, there are still many unmet needs, including efficacy, route, and timing of administration
→ Other new therapeutic method is needed.

Mechanism of Action

• Treatment of HAE through normalization of endothelial cell barrier

Efficacy & Safety

• Prevention of vascular hyperpermeability.

• Inhibition of BK-induced HUVEC monolayer disruption.

Market 6.5 billion US$

Indication

Cause

  • Variants of the serpin family G member 1 9SERPING1) gene encoding the serine protease inhibitor (serpin) C1 inhibitor (C1INH)

Incidence, Mortality

  • Incidence: Between 1 in 10,000 and 1 in 150,000 individuals worldwide

Symptoms

  • Recurrent nonpitting edema attacks of the deep dermis, submucosa, and subcutaneous tissues.
  • Attacks often involve the extremities, the face, the gastrointestinal tract, and the larynx.
  • Attacks usually last up to 5 days.
    → Most patients with untreated HAE experience at least 1 acute exacerbation per month.

Unmet Needs

  • Approved HAE treatments can minimize the risk of death, but they are not effective in complete healing from the disease.
  • The new gene therapies seem to provide promising opportunities for the treatment of hereditary angioedema.
  • However, there are still many unmet needs, including efficacy, route, and timing of administration.
    → Other new therapeutic method is needed.

Mechanism of Action

Pathogenesis of HAE

CU105 Principle of Action

modified from N Engl J Med (2010)
Clinic Rev Allerg Immunol (2021)

Efficacy

In vivo efficacy in BK (Bradykinin) model

Prevention of vascular hyperpermeability: measuring vascular leakage reduction with Evans Blue(dye)

 

Inhibition of BK-induced HUVEC monolayer disruption

In vivo efficacy in C1-INH deficient model

Prevention of vascular hyperpermeability: measuring vascular leakage reduction with Evans Blue(dye)

Development

In vivo VE-cadherin immunofluorescence staining in BK model

  • Purpose: To test whether CU105 reduces BK-induced vascular hyperpermeability via stabilizing VE-cadherin adherens junctions in vivo
  • Expected results: CU105 stabilizes VE-cadherin adherens junctions thereby reduces endothelial gap area and vascular hyperpermeability in vivo

Future Plan

In vivo FITC-dextran permeability assay in BK model

  • Purpose: To compare the FITC-dextran leakage difference between BK mouse model and CU105 treated group
  • Expected results: CU105 inhibits FITC-dextran leakage induced by BK in vivo

In vivo FITC-dextran permeability assay in BK model

  • Purpose: Phosphorylation of signaling molecules such as Src, VE-cadherin is involved in BK-mediated angioedema
  • Expected results: CU105 dose-dependently inhibits phosphorylation of molecules above