PERTH, Australia – Que Oncology Inc., a joint venture between Emory University and the University of Queensland, has kicked off its phase II trials in the U.S. and Australia for its lead therapy to treat hot flashes in breast cancer patients.

An orally available small molecule, Q-122 is a nonhormonal therapy that works through the hypothalamus where thermoregulation is controlled.

Roughly 80% of breast cancer is hormone-driven, so to reduce recurrence rates, women go onto endocrine therapy – tamoxifen or aromatase inhibitors – that reduces or blocks the action of the hormone estrogen that stimulates the growth of breast cancer, Que Oncology CEO Rob Crombie told BioWorld.

"When you reduce the level of estrogen or testosterone you get an overactive firing of neurons in the hypothalamus, resulting in hot flashes," he said. "In menopause, that feedback loop in the hypothalamus is missing, so there is an overfiring of neurons.

"Breast cancer patients get severe hot flashes and night sweats, which disrupts sleep, so they get these side effects that have a major impact on the quality of life at the very time that these patients should be getting supportive care and recovering."

Up to 75% of women undergoing long-term preventative breast cancer treatment suffer hot flashes and night sweats, with some facing more than 20 events in one day, Crombie said.

"Of course, hormone replacement therapy [HRT] would be the most obvious therapy to treat hot flashes, but you can't use HRT in this patient population."

While Q-122 provides supportive care, it could represent a major unmet need, he said.

Typically, off-label drugs for treating depression or seizures are used, and those are moderately effective in reducing hot flashes, but they come with a range of side effects, and physicians are concerned about the lack of efficacy as well as the safety issues of some of those drugs.

Endocrine therapy was previously prescribed for five years post-diagnosis but that has recently been extended to 10 years post-diagnosis because it has been shown to reduce cancer significantly.

"The bad news is that adherence rates for these drugs drops to only 50 percent within five years, because the side effects are so severe that women come off their cancer therapy.

"That is the driver for this nonhormonal therapy, and there is nothing else on the market for breast cancer patients," he said.

The differentiator will be safety for a chronic condition in treating those women for 10 years, he said.

Clinical trials well underway

Phase I trials with Q-122 showed an excellent safety profile in more than 60 patients and healthy volunteers. In a previous phase Ib trial in women undergoing estrogen reduction therapy for breast cancer, 85% of women showed a reduction in both the frequency and severity of their hot flashes.

"Through our phase II trials we hope to replicate the data that we have already seen in this patient group as we develop a treatment to substantially improve the quality of life for women on long-term endocrine therapy," Crombie said.

The placebo-controlled, double-blinded phase II multicenter trial will study the efficacy of lead compound Q-122 at the Brigham and Women's Hospital, Boston; Johns Hopkins Kimmel Cancer Center, Baltimore; and Indiana University, Indiana. Four additional sites are running trials in Australia.

"We've been operating in stealth mode until now as we focused on getting the clinical program shaped, and trials are up and running in the U.S. and Australia," he said.

The phase IIa program will involve 131 patients in two arms with patients dosed twice daily – 100 mg in the morning and 100 mg in the evening, he said. The phase IIa program will be wrapped up by the end of the year.

"We're working with the world's best clinicians, and that is driven by the fact that we are treating these unmet needs, so there's a strong driver on the part of the clinicians to participate in the study because they see their patients have very few safe and effective options."

The company has enough funds to get through the phase IIa trials. Que Oncology was founded in 2013 by The University of Queensland's main commercialization company, Uniquest Pty Ltd. and Emory University in Atlanta around intellectual property licensed from both institutions. Both parties provided seed investment and support prior to the series A financing.

The AU$21.5 million (US$15.3 million) series A round was led by Australia's Medical Research Commercialization Fund and Uniseed in June 2017.

Beyond its initial indication, the compound has the potential to expand into related conditions such as hot flashes associated with menopause and hot flashes experienced by men undergoing prostate cancer treatment.

Crombie has founded several startup companies. Most recently he was the inaugural CEO of ASX-listed cancer drug company Prescient Therapeutics Ltd. He was formerly head of Melbourne Operations for Arana Therapeutics Ltd., which was acquired by Cephalon Inc. (now Teva Pharmaceuticals).

Crombie said he has a "track record of identifying nice clinical assets and getting to an exit."

Although he is located in Melbourne, the company is headquartered in Atlanta in the U.S., and the team is split between the two continents.

"We get the best of both worlds," he said, "with access to the U.S. market but our Australian subsidiary can access the benefits of the Australian R&D tax incentive."

Lead inventor Dennis Liotta, whose lab is at Emory University, is associated with 10 FDA-approved therapies.

"We're hoping some of his medicinal chemistry magic rubs off on this," Crombie said.