TECHNOLOGIES

LEAD PROGRAM IN BRAIN CANCER (GLYCOLYSIS INHIBITOR)

Currently, Treatment choices available to brain cancer patients are limited.  Surgery is common, but not always viable.  Chemotherapy and radiotherapy have shown some clinical benefit but neither is successful in achieving long term remission.

Although many drugs, both approved and in clinical trials, show efficacy against brain tumor cell lines, they are not viable since they do not cross the blood brain barrier (body’s natural filter for brain blood supply) and therefore cannot reach the target tumor.  Therefore, drugs that penetrate this blood brain barrier with novel mechanisms are of great interest for this tumor population.

Background

It has long been known that tumors depend on energy production pathways that are different from those of tumor cells.  This is especially true for the progression of brain tumors which become regionally hypoxic (oxygen starved) and stimulate signaling pathways to up-regulate angiogenesis and shift metabolism to preferentially utilize glycolysis as its source of energy and survival.  This metabolism shift along with a large (100 fold) up regulation of glucose receptors on brain tumor cells make inhibitors of this pathway a key target.

Drug Candidate
Simple analogs that block the progression of the glycolytic pathway and are known to cross the blood brain barrier are the lead drugs for Oncolin’s first clinical candidate.

Glycolysis: The Initial Three Key Steps

Lack of OH at C-2 Blocks Glycolysis by Inability to Undergo Isomerization to D-Fructose

Oncolin’s lead candidates have shown activity against brain tumor cell lines in in vitro testing but more importantly have shown activity in an orthotropic mouse model (human tumor implanted in mouse brain).  One candidate has shown equivalent activity with Temodar (current approved drug used to treat brain tumors) and showed superior activity when used in combination.

High Activity of Animal Survival in an Orthotopic Brain Tumor (GBM) Model

Antimetabolite, as a single agent, has the same activity as the best clinically used drug Temodar and is superior when used in combination

Oncolin is focused on the development of this drug to clinical development with an IND scheduled to be filed in approximately 18 months.

Milestones			1			2			3			4			5			6			7			8			9			10			11			12			13			14			15			16			17			18			19			20
Clincally Directed in Vivo Evaluation to Select the Best Candidate to Treat Human Brain Tumors
GMP Synthesis
Development and Validation Analytical Methods
PO Formulation/Biodistribution Studies
Preclinical Toxicology Studies
IND Preperation
IND Filing
Design of Clinical Studies
Initiation of Clinical Studies

Clinical development would begin with a Phase I/IIa trial in brain tumors as a single agent and continue development in combination with temodar, avastin and radiation.