Emerging Drug Developer: Hollis-Eden

When Richard Hollis got up on March 7, he was the CEO of a company that was primarily known for its work advancing Neumune, a therapy for acute radiation syndrome and a prime candidate for stockpiling under the government’s Project BioShield. Only months before, Hollis-Eden Pharmaceuticals had been assured that a contract for Neumune was coming soon.

But by the end of the day, the prospect of a government contract for Neumune--a therapy that had consumed much of the company’s focus for six years--had vanished, along with Health and Human Service’s entire RFP for 100,000 doses of ARS therapy. There was no explanation, just a terse statement that its therapy was “technically unacceptable.”

For a public company, the unexpected news was particularly wrenching. The stock price cratered, wiping out a third of the company’s value. Soon after, a quarter of the company’s workforce was laid off. And Hollis’ executive team was forced to turn on a dime.

Today, Hollis is looking to change the San Diego-based company’s reputation. Forget ARS. Years before the government KO’d its hopes for Neumune, the same science was helping Hollis-Eden advance two preclinical drug candidates. And it has some ambitious plans to swiftly march them through clinical trials.

The same month that Hollis-Eden was handed the Neumune shock from HHS, it was filing an IND with the FDA for HE3286. Three months after the Neumune shock, HE3286 was in Phase I as a potential new therapy for insulin resistance. A month later, researchers were reporting signs of bioavailability at low doses and no safety issues. In preclinical studies, HE3286 had demonstrated an ability to lower glucose levels and increase sensitivity to insulin in Type 2 diabetes. And it was doing that without the same side effects bedeviling currently marketed blockbusters like Avandia.

By the fourth quarter, Hollis-Eden expects to have HE3286 in Phase I/II, with the second stage of the trial underway in early ’08 as researchers look for proof-of-concept data that the therapy works as an insulin sensitizer.

“We are moving 3286 rapidly,” says Hollis. But the speed is based on solid science, he adds. “This molecule has been in the works since 2000,” says Hollis. “We have six to seven years of work on this particular structure and molecule.”

Hollis-Eden’s drug platform is built around developing new drugs derived from DHEA, adrenal steroid hormones that restore signaling pathways in cells that are disrupted by disease. By changing the structure of the natural steroid, scientists can devise new therapeutic uses – an approach that theoretically could produce an array of new small molecule drugs. DHEA plays a role in immune and stress response and is often cited as a key focus in combating diseases associated with aging.

“The company was founded in ‘94 on the same principal we’re operating under today: To discover what the metabolic conversions are of this main hormone of the adrenal glands,” says Hollis. “We’ve never deviated from that premise. For 3286, we had to alter the structure of the native molecule to enable it to be stabilized so that the body can take advantage of biochemical signaling properties.”

Hollis-Eden is planning to file a second IND soon for rheumatoid arthritis. That Phase I/II trial should get underway later this year with further exploratory studies for acute indications launched around the same time. Meanwhile, an IND for HE3235, a potential new cancer therapy is scheduled for early ’08.

This is a good time for a program like 3286, says Hollis, pointing to recent safety issues that have been raised around Avandia.

“Those products have their issues,” he says. “We believe that having a drug that can control glucose levels without the side effects of current drugs positions the product, adds value.”

And that kind of value can be partially realized in a potential partnering deal.

“Clinical results and the value we can generate will dictate how quickly we can move into a collaboration with a third party or pharma partner,” adds Hollis. “Our goal is that we are going to develop the drug all the way through. But during that time of development, if it becomes strategically advantageous to do a deal that benefits both parties that would certainly be taken a look at closely.”

“Diabetes is one of the largest markets in healthcare,” says Hollis. “There’s no lack of potential interest with a pharma entity, if that is a place we choose to go. The field of obesity and diabetes is the epidemic of the 21st century. It’s a disease that’s also plaguing the aging. So I think that any drug that can play a meaningful role in controlling glycemic level and preventing complications is going to attract attention.”

Hollis has turned his back on Project BioShield, vowing to move on from the disaster. HHS was responsible for that mess, he says, by failing to implement Project BioShield the way lawmakers mandated in 2004. From now on, Hollis-Eden will stay focused on the commercial market for new drugs.

It is, he says, a field that is much easier to navigate.