British CRO EpiStem this week announced that it will use its screening technology in a deal with Humanetics to test agents that may protect crypt cells in the intestinal epithelium from bioterror-related radiation damage.
As part of the agreement, Humanetics, based in Eden Prairie, Minn., will use a grant for an undisclosed amount from the US Department of Defense to pay EpiStem to screen 10 potential drug candidates that the military could use prophylactically in events such as a nuclear or dirty-bomb attack or other cases of radiation exposure, to reduce the incidence of intestinal radiation-related illnesses and improve overall morbidity and mortality.
According to John Zenk, Humanetics’ chief medical and scientific officer, the agreement with EpiStem builds on an in silico collaboration it had previously signed with Minnetonka, Minn.-based Medisyn Technologies, a company that uses software to screen drugs for solubility and for certain ADME-Tox characteristics.
Humanetics usually looks for compounds that are water-soluble because of their greater bioavailability versus fat-soluble molecules.
“We get an idea of the degree of effectiveness using the software,” Zenk said. The compounds tend to be ranked according to their presumed efficacy, so the Humanetics researchers pick the compounds that are scored the highest, and then go down the list and pick the chemicals that tend to be soluble in water and have good ADME characteristics and a good toxicology profile. “Those are the ones that end up going for further screening at EpiStem.”
EpiStem supplies assays that measure qualitatively and quantitatively the effects of radiation damage in the gut, according to Catherine Booth, founder and medical director of EpiStem’s contract research division. The assays provide quantitative mechanism-of-action data to assess the efficacy of novel drug candidates.
The initial screen at EpiStem looks at, for example, the compounds’ ability to suppress radiation-induced apoptosis in the small intestine, said Booth.
“Depending on the compounds that give us a positive readout, we may take them to a more complicated level to look at the effects of high doses of radiation on the whole organism, for example, diarrhea severity readouts and things like that,” she added.
Zenk told CBA News this week that this is the second such agreement between the company and EpiStem, and that he expects three or four additional deals will follow.
Financial details of the agreement were not released.
“They are really the only group we know of that does this kind of research and does it as well as they do, particularly in the field of radiation protection,” said Zenk.
“They are really the only group we know of that does this kind of research, and does it as well as they do.”
Today, researchers have two ways to study how radiation exposure affects tissue: They can radiate the entire organism so that the interacting effects of radiation can be studied, or they can irradiate only certain tissues. EpiStem does both, said Booth.
For its part, Humanetics has been studying compounds to treat whole-body radiation, which could come from a dirty bomb, a nuclear detonation, a nuclear power-plant accident, the accidental ingestion of radioactive material, or from therapeutic radiation to treat cancer.
The drug maker had been collaborating with Medisyn Technologies, which has software that allows scientists to scan databases of molecules to see if they can identify pharmacological similarities when they normally would not suspect them.
Over the past several years, Medisyn has been screening databases of compounds that might be effective against whole-body radiation poisoning. “That is how we got involved with the second step, which was screening these compounds to see if they are effective or not,” said Zenk.
Medisyn provides Humanetics with a list of compounds that might deliver the kind of pharmacologic response that it wants, and EpiStem tests the compounds usually in groups of 10 or 12 at a time. EpiStem’s model has been very well standardized and “trusted in the industry for stem cell preservation and stem cell survival experiments,” said Zenk.
Humanetics is a privately held company that has been in business approximately 18 years. “We started out looking for drugs that would be potential immune modulators, then for a long time we were working with [dehydroepiandrosterone] derivatives,” Zenk said.
In the early 2000s, Humanetics returned to its roots as a biopharmaceutical company. Its lead compound, BIO300, is in clinical trials and looks like it may be “a potential radioprotectant,” or an agent taken before radiation exposure, Zenk said. By comparison, radiotherapeutics are taken after radiation exposure, which can cause bone marrow damage, skin ulcerations, anorexia, and diarrhea, among other symptoms.
Zenk said the company is also looking for compounds that “act as radiotherapeutics, since most of the other compounds we look at seem to be radioprotectants.
Humanetics is also working on a candidate for Alzheimer’s disease, NIC5-15, which is currently in clinical trials at the Mt. Sinai School of Medicine in New York City.
The company employs six people — it currently outsources all of its manufacturing and research — and “if all goes well with our drug candidates, then we can expand the business to include more people, but as for now, we get things done a lot quicker the way we are,” Zenk said.
According to Zenk, the company is not looking to leave a footprint in any new markets any time soon. “We are pretty busy with what we’ve got,” he said.
Meanwhile, at Mancester, UK-based EpiStem, US biodefense has been among the firm’s main projects over the past several years, Booth said. The company does a lot of work with the National Institute of Allergy and Infectious Diseases’ Medical Countermeasures Against Radiological and Nuclear Threats program.
For example, in April EpiStem announced that it has been contracted by Exponential Biotherapies to test its radioprotectant compounds against bone marrow and crypt cell damage resulting from medical or accidental radiation exposure, or radiation exposure during a terrorist attack (see CBA News, 4/4/08).
Zsolt Harsanyi, EBI’s chief executive officer and chairman of its board of directors, told CBA News at the time that EBI had been looking at other investigators who do these kinds of assays, and that the MCART scientists had recommended EpiStem’s assays for this application.