✽  Our Development Programs

VL166 ​ 

Targeting Upstream in Kidney Disease 

Kidney disease is a large umbrella term featuring many types of kidney injury. It's a major global burden with some Rare Kidney Diseases and Diabetic Kidney Disease (DKD) showing a common converging mechanism of damage in the glomerulus, the kidney's delicate filtering unit. This damage is driven by persistent inflammation and fibrosis, which ultimately leads to the loss of kidney function.

Recent research has identified heparanase (HPSE) as a critical factor in the progression of Kidney Disease including DKD. In the kidney, heparanase activity destroys the glomerular basement membrane, a vital component of the filtration barrier. This disruption not only impairs the kidney's ability to filter waste but also triggers pro-inflammatory and pro-fibrotic signaling pathways that accelerate tissue scarring.

By specifically targeting and permanently inhibiting heparanase, VL166 offers a novel therapeutic strategy upstream from existing interventions. Instead of only managing symptoms, VL166 is designed to halt one of the core molecular drivers of kidney damage. We believe this mechanism has the potential to protect kidney structure, reduce inflammation, and ultimately slow or prevent the progression to end-stage renal disease for millions of patients.

Heparanase: A Key Target in Cancer

Heparanase (HPSE) overexpression is a well-established Hallmark of Cancer and has been proven to be a key driver of tumor progression. By degrading heparan sulfate chains in the extracellular matrix, heparanase remodels the tissue surrounding the tumor. This action releases a cascade of growth factors that fuel tumor growth, promotes the formation of new blood vessels (angiogenesis) to supply the tumor, and enables cancer cells to break away and spread to distant sites (metastasis). High levels of heparanase are directly linked to increased tumor size, metastasis, and poor patient prognosis across numerous cancer types, making it a critical target for therapeutic intervention. By permanently and selectively inhibiting heparanase, VL166 aims to neutralize a central mechanism of cancer progression, potentially preventing drug resistance and restoring sensitivity to other treatments.

VL166 is being evaluated in a public-private setting for its potential in the field of oncology. A primary challenge in cancer treatment is that many advanced solid tumors develop evasion and resistance mechanisms, undermining the effectiveness of therapies. Tumors that initially respond to treatment can evolve, becoming aggressive and untreatable over time. This evolution is often driven by changes in the tumor microenvironment that promote cancer cell survival, metastasis, and drug resistance.

Partnering for Broader Impact

While our primary focus is on kidney disease, the fundamental role of heparanase as a master regulator of the cellular microenvironment presents therapeutic opportunities in a wide spectrum of other diseases. The pathological overexpression of heparanase is a key driver in conditions characterized by chronic inflammation, tissue remodeling, and fibrosis. Its ability to release potent pro-inflammatory mediators and growth factors from the extracellular matrix implicates it as a crucial target in these complex processes.

AVIGI is committed to exploring the full potential of VL166 and is actively seeking strategic partnerships to investigate its application in new therapeutic areas. We believe our highly selective and potent heparanase inhibitor could offer significant advantages in treating chronic inflammatory disorders, fibrotic diseases (such as IPF or NASH), certain viral infections, and various rare diseases with high unmet medical needs. We invite potential collaborators from academia and industry to connect with us to pioneer the next wave of heparanase-targeted therapies.