Zonagen Initiates Mechanistic Study Intended to Satisfy FDA's Brown Fat Concerns Regarding VASOMAX.

Business Editors/Health & Medical Writers

THE WOODLANDS, Texas--(BW HealthWire)--Oct. 2, 2000

Zonagen, Inc. (Nasdaq:ZONA)(PCX:ZNG) announced today that the Company has elected to start a mechanistic study of phentolamine mesylate induced brown fat proliferation in rats. The Company had been notified by the U.S. Food and Drug Administration (FDA) that a shorter mechanistic study of brown fat proliferation may be submitted in lieu of the additional 2-year rodent study formerly requested by the FDA. Phentolamine is the active ingredient in VASOMAX(R), Zonagen's oral therapy for erectile dysfunction. Successful completion of the mechanistic study, showing effects predictive of brown fat proliferation in rats that are not expected in humans, will be required before the FDA will lift the partial clinical hold on both VASOMAX(R) and Vasofem(TM) or consider the drugs' approvability.

Michael Iatropoulos M.D. Ph.D., Research Professor of Pathology at New York Medical College, Valhalla, New York, who is the study director for, and has been instrumental in the design of the protocol for the mechanistic study noted, "Our work with phentolamine as it applies to the proliferation of brown fat in rats suggests that the mechanistic study that has been initiated stands a good chance to resolve the issue concerning the potential of a long-term risk to humans during the use of VASOMAX(R). Leading up to the design of the current study, we conducted two pilot experiments. These experiments have demonstrated that brown fat in the rat involutes with the onset of maturity. Thus, by exposing side-by-side very young (6-week old) and older (36-week old) rats to VASOMAX(R), we will be able to distinguish whether the brown fat proliferations associated with VASOMAX(R) in the 2-year rat study are induced by the compound. In this previous 2-year rat study, exposure to VASOMAX(R) started at 6 weeks of age."

Joseph Podolski, President and CEO commented, "We believe this current study has the potential to address the FDA's concerns regarding the long-term risk of brown fat proliferation in humans. It is also noteworthy that the drug is intended to be used in an older population of men. Man, like the rat, loses much of his brown fat as the species ages. We expect that the study will be completed within the next twelve months, and we will work to submit the results to the FDA as soon as we are able. However, as with any experiment, there can be no guarantee that the outcome of the study will be favorable."

Zonagen, Inc. is engaged in the development of pharmaceutical products for the reproductive system, including sexual dysfunction, vaccine adjuvants, products for fertility and female health as well as urological applications, specifically prostate cancer.

Any statements that are not historical facts contained in this release are forward-looking statements that involve risks and uncertainties, including but not limited to those relating to the uncertainties involving the Company's early stage of development, clinical trial results and FDA approval in the U.S. and approval of regulatory authorities in other jurisdictions, substantial dependence on one product, history of operating losses, future capital needs and uncertainty of additional funding, uncertainty of protection for patents and propriety technology, litigation, governmental regulation, limited sales and marketing experience and dependence on collaborators, manufacturing uncertainties and reliance on third parties, competition and technology change, product liability and availability of insurance, and other risks identified in the Company's Annual Report on Form 10-K for the year ended December 31, 1999, as filed with the Securities and Exchange Commission.