OUR RESEARCH MAKES A DIFFERENCE

CLINICAL POTENTIAL

Metastatic renal cancer is rarely cured. ONC175 addresses a major unmet medical need:

Powerful anti-cancer effect

Orellanine has been shown in several experimental preclinical studies on advanced (metastatic) human kidney cancer to exert powerful anti-tumor effects, suggesting that ONC175 (orellanine) may provide markedly improved clinical benefits for patients with metastatic renal cancer compared with current treatment options.

Selectivity and specificity to kidney cancer cells

ONC175, given intravenously into the bloodstream, is actively and selectively pumped into the kidney cancer cells. Preclinical studies have shown the drug to be targeted to kidneys and cancer derived from the kidney through highly specific uptake. The molecular mechanism behind the uptake has been identified as solute carriers almost exclusively expressed on renal cancer cells and proximal tubular cells of the kidney. One of the identified transporters is expressed on enterocytes as well. In non-tumor-bearing, nephrectomized, animals, orellanine has similar effects as saline.

Clinical precedence established

Humans already have been exposed to orellanine through accidental ingestion of mushrooms from the Cortinarius family. The clinical effects are well known, and no other clinical toxicity has been detected apart from the consequences of kidney failure, (i.e., uremic symptoms and signs). Epidemiological studies have shown that the long-term prognosis for patients poisoned by orellanine is comparable to other patients on active uremic care. Source: Hedman et al. BMC Nephrology volume 18, Article number: 121 (2017). This clinical experience provides a major advantage and reduces development risk.

Unique mechanism of action

Orellanine kills kidney cancer cells through a completely different mode of action than the available treatment options. It is killing kidney cancer cells by inducing oxidative stress and down-regulating the intracellular defense mechanism, leading to perturbation of mitochondrial function and induction of apoptosis and cell death.