By Debbie Strickland
Within the next few years, Pentose Pharmaceuticals Inc. is aiming to stamp out key viruses found in blood and other biological products with its anti-nucleic acid technology, and to prove clinically its antiviral drugs against human papillomavirus (HPV), herpes simplex and other viruses.
The three-year-old Cambridge, Mass., firm has three advanced product candidates: PEN103 and PEN113, both based on the patent-pending Inactine antiviral technology for blood and other biological products; and PEN203, a therapeutic anti-HPV/herpes compound generated by the firm's just-patented Papirine platform.
"Ensuring the safety of the blood supply is a major medical and public health concern, and our Inactine technology has the potential to make the blood supply safer," said Samuel Ackerman, Pentose's president and CEO. "With Papirine, Pentose is seeking to treat the No. 1 cause of human sexually transmitted diseases — the human papillomavirus . . . These [products] represent very large, near-term opportunities."
Ackerman is a former director of the Investigational New Drug Division at the FDA's Center for Biologics Evaluation and Research, and over the last 12 years has held executive positions with a number of biopharmaceutical companies, most recently serving as a vice president at OraVax Inc.
Inactine, the blood-supply virus-killer, consists of compounds that selectively bind and irreversibly modify nucleic acid, rendering it nonfunctional, while sparing other biological molecules such as proteins and carbohydrates. Because it targets nucleic acid, Inactine attacks both major classes of viruses — non-enveloped and enveloped.
FDA Submission Expected This Year
The product also potentially offers advantages over current methods, such as pasteurization and solvent-detergent technologies, because it kills viruses without damaging the product being treated.
Among viruses Inactine has been shown to inactivate are HIV, parvovirus, foot-and-mouth-disease virus, poliovirus, influenza, bovine diarrhea virus (a model virus for hepatitis C), equine encephalitis virus and ebola.
The company plans to submit a 510(k) regulatory application for the use of Inactine technology in laboratory blood collection tubes in 1998, with first commercialization possible in 1999. Pentose also plans to initiate preclinical development of Inactine for use in blood-derived products and plasma derivatives this year, to be followed by clinical testing in 1999.
Under the Papirine umbrella, now covered by U.S. patent No. 8,615,246 and European patent No. 93,920,816, the lead product candidate is PEN203, a topical agent for HPV and herpes simplex virus. In 1998, Pentose expects to file an investigational new drug application with the FDA and launch Phase I/II clinical trials of the product, which has already been tested via a collaboration between Russian and U.S. scientists.
The company's commercialization target is 2001.
In a blinded, randomized test described as equivalent to a Phase II trial, 36 percent of Papirine-treated papillomatous patients showed a complete response, vs. 6 percent of placebo-treated patients. An additional 21 percent of the Papirine group exhibited partial response, compared to 6 percent of the placebo patients. Results were statistically significant.
Papirine compounds mimic the effects of interferon, but work topically and are cheaper to make. They are structural analogues of 2-5 oligoadenylate (2-5A), the intracellular molecule that mediates many of the antiviral effects of interferon, which is known to work against HPV.
2-5A inhibits viral replication primarily by activating ribonuclease L, an enzyme that degrades viral RNA. According to the company, the Papirine products should be able to fight viral infection without significant toxicity.
Both technologies evolved from work initiated by Edward Budowsky, Pentose's scientific founder and former laboratory head of the Russian Academy of Sciences, in Moscow. Budowsky, now a permanent U.S. resident, is currently an adjunct professor and senior researcher in the departments of biology and chemical engineering at Northeastern University, in Boston.
"I have known about Dr. Budowsky's work for many years, since my time in the FDA," said Ackerman. "His work in viral nucleic acid has opened up innovative approaches to preventing and treating viral infection."
As for Pentose's business model, it is oriented toward in-licensing and middle stage drug development rather than basic drug discovery.
"We in-license promising technologies with near-term commercial opportunities, plus long-term market growth potential," said Ackerman. "Then we optimize them scientifically, demonstrate regulatory approvability, and then establish pharmaceutical partnerships for marketing . . . We call ourselves a technology-based development company."
Pentose plans to seek a partner for Inactine early this year, but will await clinical trial results on Papirine, betting that positive data will drive up value.
A second financing is likely at some point this year, Ackerman said. Pentose, which has raised $4.5 million in its Series A financing, has enough cash to carry operations into the second half of 1998.
The firm currently has nine employees, but will be doubling its work force to about 18 over the next 12 months, Ackerman said. *