Drug Candidate

TLY012

Summary

First-in-Class, myofibroblast-targeted DR5 agonist for fibrosis

Mechanism of Action

Engineered, trimeric rhTRAIL
targeting myofibroblast

Indication

NASH-Liver fibrosis
Chronic Pancreatitis
Systemic Sclerosis

Development Stage

Phase I

Background

• · Fibrosis Represents an Unmet Medical Need
  • - Can occur in any organ, leads to excessive scar tissue accumulation and organ damage
  • - Poor medical outcomes, lack of effective treatments
  • - Potential in orphan diseases and larger indication

TLY012 selectively blocks normal fibroblasts activation and induces apoptosis in myofibroblasts in fibrotic tissues.

Description

• · MFBs (a.k.a. activated fibroblasts/stellate cells) cause activation of multiple pathways that lead to scar tissue formation
• · Current investigational drugs target only single downstream pathways not the MFBs, the originator of fibrosis
• · TLY012, a PEGylated recombinant human TRAIL protein, binds upregulated Death Receptor 5 (DR5) on MFBs and effectively shuts down fibrotic pathways and inactivates MFBs.
• · TLY012 is a potential first in class treatment for various fibrotic diseases
  • - TLY012 selectively blocks and/or eradicates myofibroblasts (activated fibroblasts/stellate cells) in fibrotic regions
  • - TLY012 reverses existing fibrosis - validated in various animal models with liver, skin, and pancreatic fibrosis

Related Articles

• · Nature Communications, volume 10, Article number: 1128 (2019)
• · Hepatology, Volume64, Issue 1, 209-223