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Iconix Study Drives Methods For Discovering And Validating Predictive Toxicology Biomarkers

June 13, 2017

Iconix Pharmaceuticals, Inc. today announced that a study by Iconix scientists on the use of genomic data to find biomarkers to predict adverse effects of drug candidates has received the "Best Paper of 2005" award from the well known industry journal Toxicologic Pathology. The paper describes the discovery of a key biomarker that predicts kidney toxicity weeks in advance of its occurrence, something that is not possible with current toxicological methods. By providing all the information required to enable other laboratories to further validate the biomarker, the paper also addresses issues about the use of genomic biomarkers that were raised in the FDA's "Guidance for Industry: Pharmacogenomic Data Submissions," issued last year.

"By applying genomic biomarkers to identify toxicity issues we will see substantial improvements in the costs, elapsed time and prioritization process for moving the most promising drug candidates forward for further development," said Dr. Donald Halbert, head of R&D for Iconix.

The paper is titled "A Gene Expression Signature that Predicts the Future Onset of Drug-Induced Renal Tubular Toxicity." The full reference can be obtained from Iconix's website at iconixpharm.

The study addresses key issues that many believe have been hampering the widespread adoption of toxicity biomarkers, such as the use of a sufficiently large dataset for biomarker derivation, and evaluation on an independent data set to confirm the putative value of genomic biomarkers. Specifically, the signature (biomarker) was derived from short-term repeat dose studies in rats representing 64 nephrotoxic or non-nephrotoxic compounds. The signature, consisting of only 35 genes, was then tested on independent samples from rats treated with 21 structurally and mechanistically distinct compounds with known positive or negative nephrotoxicity outcomes. The signature correctly predicted the ability of test compounds to induce tubular degeneration 76% of the time (in 16 of 21 test compounds) before the pathology was detectable by standard clinical and histological methods. This proof of concept study demonstrates that genomic data can be more sensitive than existing methods for the early detection of compound-induced pathology in the kidney and is also significant as it sets the foundation for the development of other predictive, and more sensitive, genomic biomarkers.

"The study was designed to evaluate whether genomics could indeed predict drug-induced pathology weeks in advance of traditional methods such as clinical chemistry and histological evaluation," said Mark Fielden, PhD, lead author on the study at Iconix Pharmaceuticals. "What we've been able to demonstrate lends further support for the use of genomic data to address the need for more predictive tools in preclinical and clinical drug testing."

The paper published in Toxicologic Pathology comprehensively describes the signature including all values necessary to allow additional prospective validation by the research community. It is part of an ongoing effort by Iconix to promote and confirm the broad value of genomic biomarkers and their scientific accuracy via external validation.

The paper was selected for the Toxicologic Pathology Best Paper award based on its general quality and on subject matter that represents a significant advance by presenting a new concept or method with important applications, one that is deemed likely to be cited often in the literature for many years. The award signals the growing acceptance of genomics by the pathology community and the pharmaceutical industry overall.

About Iconix

Iconix Pharmaceuticals, Inc., the leader in toxicogenomics products and services, has pioneered the integration of chemistry and genomics to enable the pharmaceutical and other industries to develop safer drug candidates and compounds. The company's technologies increase the odds of advancing the right candidates to the clinic, reduce attrition rates in late stage trials and help keep the costs of drug discovery in check. Iconix provides reference systems and universally recognized expertise to predict toxic liabilities, side effects and mechanisms of toxicity for drug candidates and environmental chemicals. Iconix's DrugMatrix system has been installed at the U.S. Food and Drug Administration for use by CDER (Center for Drug Evaluation and Research) scientists and reviewers in a range of toxicogenomics applications and is used by the US FDA to evaluate voluntarily genomic data submissions. The company has major research collaborations and technology alliances with Bristol Myers Squibb, Abbott Laboratories, and Eli Lilly and has strategic partnerships with leading life sciences companies including Affymetrix, MDS Pharma Services (TSE:MDS; NYSE: MDZ) and GE Healthcare.

Headquartered in Mountain View, California, Iconix was founded in 1998 and is privately held. For more information, visit iconixpharm.

Iconix Pharmaceuticals, Inc.
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