Pharmaceuticals

Over the next 10 to 15 years, the worldwide pharmaceutical market is expected to grow from about $300+ billion (2003 data on world-wide pharmaceutical industry reports) to over a trillion dollars, driven primarily by the flood of new drug targets some of them having been identified through genomics and through the co-development of drugs and accompanying genomics response tests. The primary objective of DNAPrint™‘s near term research and development efforts in pharmacogenomics will be to expand our library of predictive drug response tests to include multiple therapeutic areas which include commonly used FDA approved drug therapies. Longer term, this work will provide us the expertise to apply pharmacogenomics methods to our own developing drug pipeline, to reduce the risk and expense of the clinical trial process. A primary purpose of Phase II is for the drug-developer to learn how to improve the drug’s response and better target the patient population for the pivotal Phase III; if the drug works better in a segment of the population then the company can design more effective Phase III clinical trials to focus on that specific group of patients thereby maximizing the efficacy and minimizing the side effects of the new medication. However, most pharmaceutical companies and Clinical Research Organizations (CRO’s) that run the trials; still do not employ powerful genome-based methods to characterize their patients during the trial process. We hope that by using our technology, we will be able to target our drugs to segments of the population that are genetically compatible and thereby enjoy a higher trial and post-market success rate. In many respects, we hope our medicines will be more compatible with our patients over a longer period of time.

Although much of our efforts at present are mainly focused on third-party drugs – those manufactured by other companies, we have recently licensed in our first lead drug candidate, PT-401 a dimer of Erythropoietin. The Erythropoietin monomer currently in the market is used to treat the anemia associated with chronic renal (kidney) failure, anemia observed in cancer patients on chemotherapy and in Zidovudine-treated HIV-infected patients, and in surgery patients to reduce the need for allogeneic blood transfusions. PT-401 will be developed for similar indications and also for the treatment of new conditions not related to anemia.

We currently have several pharmacogenomic tests in development:

OVANOME™ - DNAPrint™ scientists are working on a genomic-based diagnostic tool to match ovarian cancer patients with the most suitable form and dose of chemotherapy. Currently, cancer patients are treated with anti-cancer drugs whose efficacy is known in terms of population averages. In reality, individual cancer patients exhibit unpredictable and unique responses to virtually all commonly used chemotherapeutic compounds. Individual genetic differences have long been suspected to play a role in this variable drug response and this is particularly true for the current standard of care for ovarian cancer – Paclitaxel (Taxol) / Carboplatin (manufactured by Bristol-Myers Squibb). For cancer patients, decisions about treatment regimes are often fateful, and second chances at treatment are sometimes not successful. A better understanding of the relationship between genes and drug response can replace the current trial and error process of chemotherapy treatment and guide physicians and patients toward the optimal treatments at the outset of therapy. In early March 2000, DNAPrint™ announced success with this project at the Society of Gynecological Oncologists meeting in Miami, and at the BIO IT World Expo in Boston.

Our scientists have identified several Single Nucleotide Polymorphism (“SNP”) markers whose haploid alleles are predictive for non-response to the Taxol and Carboplatin drug combination.

The next step for OVANOME™ is to be tested in prospective clinical trials. These trials will give the final validation and determine the clinical usefulness of the predictive test. . Our Chief Medical Officer, Hector J. Gomez, MD, PhD will lead the clinical development process.

FDA rules regarding pharmacogenomics testing are still evolving and everyone in the industry is seeking additional guidance from the FDA on this issue. Until OVANOME™ is FDA approved or deemed to not require FDA approval, we plan on generating revenues by developing and testing OVANOME and similar tests for other drugs through physician guided Investigative New Drug studies. Recently, we announced that we have begun a formal evaluation of patient’s and patient samples in conjunction with the Moffitt Cancer Center and associated Groups of specialists.

STATINOME™ - This test is currently being developed for the cardiac drug market, and is expected to enable a classification of patients as adverse responders or normal responders to a class of drugs known as “statins”. Statins are drugs used to treat patients who are at increased risk of heart disease. Approximately 50% of the U.S. population is at risk of heart disease as a result of high cholesterol. While statins have been demonstrated to be effective at cholesterol reduction, decreasing incidence of heart disease by 10.3% from 1990 to 1994, adverse reactions can include liver damage and kidney failure as well as potentially fatal muscle degradation. Approximately 2-5% of patients must discontinue statin use due to these adverse side effects. Once perfected, we believe STATINOME™ should be able to improve the rewards associated with taking statins by reducing the risks associated with adverse response sometimes seen in minority of patients.

In addition to OVANOME™, we have initiated several studies for cancer drugs with the H. Lee Moffitt Cancer Research Center in Tampa, FL (colon cancer, post-operative nausea and vomiting in cancer patients undergoing surgery and multiple Myeloma). We hope to develop the additional expertise to help us better guide the clinical development of compounds that we will be acquiring for our own drug development pipeline.