Climbing into the ring with one of the harder – albeit rare – cancers to beat, Atterocor Inc. started a Phase I trial with ATR-101, designed to selectively cause apoptosis in adrenal cell carcinoma (ACC).

Along with safety, the company will be looking at tumor responses and biomarkers that might suggest efficacy, said Julia Owens, co-founder, president and CEO of the Ann Arbor, Mich.-based firm.

“If we see intriguing results there, of course we would want to have a dialogue with the [FDA],” which – like European regulators – already has granted ATR-101 orphan status and, if all goes well, could designate it a breakthrough therapy.

Afflicting about 1,000 people in the U.S., ACC “is unique to many solid tumors, in that it’s an endocrine tumor, where you have so many steroid, synthetic intermediates, metabolites and enzymes that are up-regulated and cause all sorts of additional morbidity and mortality above and beyond cancer,” Owens said.

The only approved therapy for ACC is Lysodren (mitotane, Bristol-Myers Squibb Co.), an oral, cytotoxic derivative of pesticide DDT used in first-line settings despite its problematic side effects and pharmacokinetics.

OSI Pharmaceuticals Inc., of Melville, N.Y., had been developing OSI-906, an insulin-like growth factor-1 (IGF-1) inhibitor in Phase III trials when the company was taken over in 2010 for $4 billion by Tokyo-based Astellas Pharma Inc. Three years later, when Astellas downsized, it shut down the OSI unit, but the ACC therapy hadn’t shown much promise anyway, Owens said. (See BioWorld Today, May 18, 2010, and May 15, 2013.)

“I haven’t heard any official announcements or seen any published results, but as I understand it, most groups have abandoned the IGF approach for ACC,” she told BioWorld Today. “While I’ve heard there were on-off responses here and there, [OSI-906] didn’t show a big change.”

ATR-101 is adrenal-specific, “whereas OSI and others who were pursuing the IGF compounds were going after niche indications to get on the market fast, as a way of [later] getting into other indications,” Owens said. “Our strategy is really not the same.”

Although ATR-101 is being developed as a single agent, the reality of cancer drugs is such that it would likely end up being used in combination with one or more others, she said.

A semivirtual company with six employees, Atterocor was founded last year, when the firm raised $16 million in Series A funds. “’Attero’ is Latin for ‘destroy, target or interfere,’ and ‘cor’ stands for ‘adrenal cortex,’” Owens said. “So, basically, we’re looking to interfere with the aberrant activities of the cells of the adrenal cortex that give rise to adrenal cancer.”

The complicated nature of ACC and its scarcity has made enrolling trials a challenge, but last year data were published from a study by the European Network for the Study of Adrenal Tumors (ENSAT) that enrolled 304 patients, proving that large studies are possible, she said.

ENSAT sites in Europe and the U.S. tested mitotane plus etoposide, doxorubicin and cisplatin (EDC) against mitotane plus streptozotocin.

“The bottom line was, neither did very well, but the EDC regimen was slightly better, and has become the best there is the field,” with a response rate of about 23 percent, Owens said. “This is a disease that’s just so aggressive. It tends to be chemo-refractory and, based on the IGF inhibitors’ [lack of success], it doesn’t appear that a single, molecularly directed therapy is going to be sufficient.”

University of Michigan head football coach Glenn “Bo” Schembechler established the Millie Schembechler Adrenal Cancer fund at the University of Michigan (UM) after his wife’s death from ACC in 1992. It’s the nation’s only multidisciplinary ACC group. Also, 10 years ago, the first-ever conference dealing exclusively with ACC was held, and “that conference has now been happening roughly every other year,” Owens said. “It was in Paris in February. Only when you can bring together a broader consortium of people can this sort of progress happen.”

The other founder of Atterocor is Gary Hammer, who is also the Millie Schembechler Professor of Adrenal Cancer at UM, as well as the director of the endocrine oncology program there and director of the Center for Organogenesis.

Atterocor’s Series A money came from venture capital (VC) firms Frazier Healthcare, Osage University Partners and 5AM Ventures, along with the Regents of the University of Michigan under the Michigan Investment in New Technology Startups program and the Michigan Pre-Seed Capital Fund.

“Part of what was compelling [in] the VC pitch, when we raised our financing last year, was the premise was that we could get into the clinic within a year, and have data within a year after that, and could be set up at that point to raise additional financing to take this to the market ourselves,” Owens said. “You don’t need even 100 [sales] reps for this,” since sales of the drug, if it’s commercialized, would be largely driven by key opinion leaders in the ACC field, she said.