PERTH, Australia – Adelaide, Australia-based Bionomics Inc. reported another trial failure with its lead compound, BNC-210, in elderly patients with agitation, but it is still clinging on to hopes that the compound will show a clinical benefit for post-traumatic stress disorder (PTSD).

The phase II agitation trial in elderly patients in a hospital setting failed to meet primary or secondary efficacy endpoints, and the company will cease development for that indication, said Bionomics Chief Medical Officer Paul Rolan.

The randomized, double-blinded placebo-controlled trial was designed to assess the feasibility of conducting a study in acute agitation in hospitalized elderly patients and to assess BNC-210 for safety and efficacy. The negative allosteric modulator of alpha7 nicotinic acetylcholine receptor was administered twice daily with food. The study was conducted at five sites in Australia and recruited 38 patients.

The primary endpoint was a change in agitation as measured by the Pittsburgh Agitation Scale, but there was no evidence of a treatment effect, the company said. Secondary endpoints included change in global function as measured by the Clinical Global Impressions Scale, which also showed no treatment effect compared to placebo.

There were no adverse events associated with BNC-210, and the safety profile for the drug remains strong.

After reporting a trial failure in October 2018 for BNC-210 in a phase II PTSD trial, Bionomics conducted a drug exposure-response analysis that saw a positive effect once adequate blood levels were reached, and the company decided to revive the compound for PTSD.

Variable absorption of the liquid formulation and the requirement to be taken with food was likely the culprit for earlier results that showed the trial failed to meet primary endpoints, the company said. Due to the food effect with the liquid suspension formulation, patients likely did not comply with instructions, and the drug did not reach required therapeutic levels in many patients.

The agitation trial used the same liquid formulation as the earlier failed trial, but it was hoped that since the trial was conducted in a hospital setting that compliance would not be an issue.

"Whilst the results of the trial do not support further development of BNC-210 for treatment of agitation, given BNC-210's consistent safety profile and the demonstration by pharmacometric exposure-response modeling of its potential to treat post-traumatic stress disorder, we remain confident in pursuing PTSD, provided that we can achieve the blood exposure levels predicted by the modeling analysis" said Rolan said.

The company will invest in a single dose-ascending study with a new solid-dose formulation in healthy volunteers to demonstrate that blood levels of BNC-210 can reach the level necessary to meet primary efficacy endpoints. Results are expected in the fourth quarter of 2019.

Exposure-response modeling has shown the potential for BNC-210 to have significant benefit in PTSD provided that adequate blood levels are achieved. The trial results showed that the liquid formulation did not give sufficient exposure in the outpatient setting.

Absorption is improved threefold with food, Rolan said, and Bionomics has reformulated the liquid formulation into a new oral formulation that has been evaluated in healthy human volunteers and appears to have much less variability with potential to overcome the food effect seen in the liquid formulation.

"If the proposed study with the solid-dose formulation confirms that the required blood levels are achievable, and the FDA guidance supports a second phase II trial of BNC-210 in PTSD, then Bionomics intends to proceed with the further formulation development and preparation for a second phase II trial," the CEO said.

He noted that further funding would be necessary to continue another phase II study, and the company would launch a formal process to engage shareholders and partners.

There has been a pressing need for new treatments for PTSD, as no new treatments have been approved in more than 20 years.

Bionomics will now seek FDA guidance on next steps for BNC-210 for PTSD, including the design of a further trial and determining whether BNC-210 is eligible for fast track designation.

The company reported that the next inflection point for its collaboration with Merck & Co. Inc. "is no longer anticipated," but it was unable to provide additional details.

Bionomics shares on Australia's Securities Exchange (ASX:BNO) closed at AU4 cents (US3 cents) on Friday.