PERTH, Australia – Adelaide-based Bionomics Ltd.'s lead candidate, BNC-210, failed to meet the primary endpoint of decreasing symptoms in patients with post-traumatic stress disorder (PTSD) in its phase II trial, and the company is stopping development in PTSD. Shares of Bionomics (ASX:BNO) closed Tuesday at A17 cents (US12 cents), down A33 cents, or 66 percent, on the news.

"Unfortunately, we haven't been able to deliver the results we had hoped for in patients with post-traumatic stress disorder, where there is such a large unmet need," Bionomics CEO Deborah Rathgen said during a Tuesday conference call.

The RESTORE trial of the negative allosteric modulator of alpha7 nicotinic acetylcholine receptor enrolled 193 patients across 26 sites in the U.S. and Australia. The primary endpoint was a decrease in PTSD symptoms between placebo and BNC-210 treatment groups as measured by the clinician-administered PTSD scale (CAPS-5) at 12 weeks.

Other efficacy measures included clinician and patient global assessments of depression, anxiety, sleep scales, measures of quality of life and disability and a computerized cognitive assessment.

"There was no trend for superiority of any BNC-210 treatment group," Bionomics Chief Medical Officer Paul Rolan said during the call.

Even so, Nolan pointed to a "significant reduction in CAPS-5 subscale and individual questions related to depression at weeks one, four and eight" in the highest-dose group, and said there were "trends for improvement" in scales related to hyperarousal and reactivity in BNC-210-treated groups.

Potential for anxiety

Two earlier trials of BNC-210 in panic attacks and generalized anxiety disorder (GAD) both delivered positive clinical trial results and have "shown the effects of BNC-210 as being consistent with an anti-anxiety drug that is active after a single administration," Rathgen said.

Bionomics will complete its ongoing phase II trial of BNC-210 in elderly patients with agitation, which is expected to read out in the first quarter of 2019.

"In this regard, it was pleasing to see evidence of antidepressant effects, and more relevant to the agitation trial, evidence of anti-anxiety effects through components of the CAPS-5 in the PTSD trial," she said, stressing that the compound was safe and well-tolerated "with no evidence of sedation, cognitive impairment or addictive potential."

Murray Stein, a professor of psychiatry at the University of California, San Diego, said that there has been a "pressing dire need for new treatments for PTSD," as no new treatments have been approved in more than 20 years. PTSD is a complex disorder, with symptoms differing from one patient to another, he said.

"Even though results here were negative for PTSD, I think it doesn't discount the possibility that BNC-210 may still have benefits on certain components of symptoms" such as in depression or anxiety, he said, adding that he was pleased that Bionomics would continue developing the drug for other indications "that may be easier to demonstrate the effect of the drug."

"My secret hope is that if this drug does well in other indications, that Bionomics might be able to circle back and re-invest in the PTSD program," Stein told analysts during the Q&A.

Considering the lack of an efficient, safe, targeted and approved therapy for agitation, especially within the increasing market of Alzheimer's disease (AD) in the elderly, "we believe the field is wide open for new therapeutic options to treat this indication, such as Bionomics' BNC-210," wrote H.C Wainwright & Co. analyst Joseph Pantginis in a Sept. 11 research note.

The analyst said the current standards of care, benzodiazepines and antipsychotics, have two major pitfalls: overall low efficacy and clinical inconsistency; and a high-risk profile, including a mortality risk of antipsychotics and drug interactions as well as addiction and sedative properties of benzodiazepines.

"There is still a lot to the BNC-210 story," Rathgen said, highlighting Bionomics' drug discovery platform and its ongoing programs in core CNS areas. She said the company expects to deliver "one and possibly two new therapeutic candidates in this financial year."

"One of the success areas that Bionomics has had is in the licensing of preclinical candidates coming from our platform."

She pointed to Bionomics' deal with Merck & Co. Inc. (known as MSD outside the U.S.), which was "one of the largest preclinical deals ever done by an Australian biotech company." An alpha7 nicotinic acetylcholine receptor, BNC-375 comes out of Multicore, one of four technology platforms owned by Bionomics.

Merck is assessing BNC-375 for cognitive impairment in Alzheimer's disease and Parkinson's disease in a phase I trial. The Merck deal included a $20 million up-front payment in 2014, research funding through 2017 and a $10 million clinical milestone payment when the compound entered the clinic in February. The deal is valued up to $506 million plus additional royalties on net sales. (See BioWorld Today, June 25, 2014.)

Rathgen said Bionomics would stop all other work with BNC-210 until its agitation trial reads out. The company has closed its organization in the U.S. and is now focused on cost-cutting measures and prioritizing its portfolio. She said all other development work would be reliant on potential partners.