Photo by Reginald A. Pearman Jr. (washingtonpost.com)

John Holaday took a few minutes away from the Tech Investor Conference to sit down with WashTech for a live discussion.

John Holaday, CEO of Rockville's EntreMed Inc. took a few minutes away from the 1998 Technology Investor Conference at the International Trade Center in Washington, D.C. to sit down with WashTech for a live discussion.

EntreMed, a Rockville biotechnology company, recently found itself at the center of a media and stockholder frenzy, when word got out that it was testing a combination of drugs that, when given together in mice, appear to eradicate many kinds of tumors with few side effects.

EntreMed is also conducting tests on thalidomide, the controversial drug that caused birth defects when given to pregnant women for morning sickness in the late 1950s and early 1960s. The company is testing thalidomide to see if it would starve tumors by blocking the formation of new blood vessels.

The transcript of this discussion follows:

WashTech: Thank you, Dr. Holaday, for joining us today from the Tech Investor Conference. Having participated in this morning's panel discussion, "Beltway Bioscience: Patient Investing," in what particular sectors do you think the local biotech industry will excel?

John Holaday: I think we have a good cross-section of biotech companies with a critical mass of biotech companies in the U.S. located in the greater Washington area – with some in the Genomics area to vaccine companies and companies like EntreMed that emphasize therapeutic proteins and small molecules.

WashTech: We know you have a company presentation to prepare for this afternoon, so without further ado, let's get started with some questions from washingtonpost.com readers.

Falls Church, VA: How do you answer critics who say there's not a shred of proof that Angiostatin and Endostatin will work for humans, and, that EntreMed was therefore irresponsible in leaking word about the compound?

John Holaday: EntreMed was not responsible for "leaking" word about Angiostatin and Endostatin. Instead, the New York Times issued a report about previously published research results demonstrating the promise of Endostatin based upon mouse experiments. Our reaction was to provide a cautious but responsible reply to the enormous interest that was generated by that article. This information was in the public domain months earlier. We never made any comments about human trials other than to say that we anticipated their initiation within 18 months, and hoped that with a rapid regulatory process and successful results this compound could be made available to cancer patients within the next five to seven years.

Pensacola, FL: Are you working on any agents that show promise in the treatment of prostate cancer?

John Holaday: Although recent interest has focused upon EntreMed's development of proteins like Endostatin that stop blood vessel growth and thereby starve tumors to death in mice, we have an active series of clinical trials underway with the National Cancer Institute demonstrating thalidomide's promise in treating prostate cancer, brain tumors, breast cancer and Kaposi's sarcoma. We have shown in a limited number of prostate cancer patients with hormone-refractory, metastatic disease, that thalidomide appears to attack the disease as indicated by decreases in PSA levels, and possible increases in survival time. One of the eighteen patients studied demonstrated a decrease in bone metastases, as well. We and the NCI are now designing more complete studies to further extend the clinical trial data as we work together to accelerate the development of thalidomide.

Bethesda, MD: I was horrified to read that EntreMed is considering using thalidomide as treatment for cancer and blindness. Isn't it true that once the FDA approves something, the prescription of the drug is in the hands of a given physician? What then stands in the way of the physician prescribing this terribly dangerous drug to a woman who's unaware that she's pregnant?

John Holaday: Thalidomide is indeed notorious for the birth defects that it caused when sold in Europe as a sedative. However, we now know that the birth defects were caused by blocking blood vessel growth in the fetus, thereby causing deformities. In treating cancer, any cytotoxic chemotherapy in present use will either deform or abort the fetus, and women of childbearing years will likely be sterilized by these severe drugs. Nonetheless, the FDA has already planned severe controls on the use of thalidomide, requiring women of child-bearing age to first have a pregnancy test, and then demonstrate two methods of birth control before, during and after taking thalidomide.

Tysons Corner, VA: What drives your research – particular diseases, a new technology or potential returns? How do you balance these issues?

John Holaday: EntreMed is "The Angiogenesis Company" that recognized early-on the enormous potential of antiangiogenic therapeutics developed at Children's Hospital by Dr. Folkman. We provided them with the resources to continue their creative discoveries, while we took on the task of pre-clinical and clinical development. One key to success was balancing the risk of finding early, but promising therapies, with the enormous benefit if successful. Leveraging our growth with strategic partnerships (e.g. Bristol-Myers Squibb) helped us obtain the necessary resources to expedite the development of our product candidates. EntreMed's research is science driven, based upon solid data and the willingness to keep an open mind. Within this context, we study the role of blood and blood vessels in health and disease.

San Francisco, CA: Will the public fully benefit from the human genome project research if it's conducted in the private sector?

John Holaday: EntreMed focuses on antiangiogenic drug development as a promising new strategy for the treatment of cancer, blindness, and arthritis. The human genome project is more of a technological quest to define our genetic makeup, with the hope that new drugs or disease understanding will evolve. We believe that there is an excellent future for companies that help to define our genetic makeup, whether privately or publicly funded. If new drugs evolve, they will certainly benefit the public. Likewise, we have every expectation that new antiangiogenic therapies such as those under development at EntreMed will also revolutionize medical treatment for cancer and other diseases where new blood vessel growth plays a significant role.

Reston, VA: From the viewpoint of an investor, small biotech companies often end up purchased by larger manufacturing companies. What makes this necessary and is it in EntreMed's future?

John Holaday: EntreMed's strategy is to discover and develop revolutionary new ways of treating diseases, and continue to build shareholder value based upon the ultimate success of our products in the clinic. Now, EntreMed is largely a research and development-based company. In the future, we plan to grow into a more fully integrated organization in order to bring the greatest return to our shareholders and ensure the expeditious development of our products from the bench to the bedside. We think we can do this better by ourselves, with larger pharmaceutical companies as partners, not owners.

Alexandria, VA: Your company's stock price has tripled since word got out about Angiostatin and Endostatin. EntreMed is not yet a moneymaking company, however. Is this stock run-up justified, based on pure hype?

John Holaday: EntreMed is a research and development biopharmaceutical company that currently has four antiangiogenic drug candidates in both clinical and pre-clinical development. In addition, we have a second core technology that increases the ability of blood to deliver oxygen to tissues. Until we sell our first product, we will be valued based upon solid science and its opportunity to bring a return to shareholders. Our best shareholder recognizes the enormous clinical potential of our products, and stays with the company for the long run until products are sold. We do not hype our stock, we build our products with anticipation that the ultimate reward to patients and shareholders will be reflected as our products are sold. In over 100 media interviews stimulated by the article in the New York Times, we consistently stated that:
1. The real news was published as the cover of Nature in November when Endostatin was revealed by Dr. Folkman as a drug that reversed severe tumors in mice without developing drug resistance.
2. EntreMed is presently testing Endostatin in mice, and with the National Cancer Institute, we hope to be in clinical trials with humans within the next 18 months.
3. People should be cautious in expectations, since it may be a long road from mice to humans.

Washington, D.C.: What is your personal motivation for chasing the cancer cure?

John Holaday: Rather than using the word "cure," we try to project cautious optimism that our novel strategies for shrinking mouse tumors by blocking the blood vessels that feed them may ultimately make cancer a chronic disease instead of a fatal one. I have personally experienced the enormous sense of helplessness and loss with family members who have had cancer, and understand well the urgency in finding a cure. We at EntreMed are focusing our resources to meet that challenge.

WashTech: And that's all we have time for today. We wish you the best of luck, Dr. Holaday, in your future research and we'll be watching for EntreMed in the news. Thanks again for taking time to join us today.

John Holaday: Thanks for the opportunity to share some thoughts with this important audience. Any further questions could be directed to our Web site: www.entremed.com. We also encourage cancer patients and their families and friends to contact the National Institute of Health for information about relevant clinical trials at 1 800 4CANCER.