NYX-2925

Aptinyx is yet to publicly disclose layoffs but said it will “undertake cost-cutting measures.” Serial clinical trial train wreck Aptinyx is at it again. After seeing a pain prospect flunk three clinical trials, the biotech has added Parkinson's disease and dementia to its list of failed indications—prompting it to stop work on its two clinical candidates, cut costs and seek strategic alternatives. Last year, the third midphase failure of NYX-2925 prompted Aptinyx to drop the pain program and switch its attention to a pair of other NMDA receptor positive allosteric modulators, NYX-458 and NYX-783. The delivery of data from a phase 2 clinical trial of NYX-458 has prompted the company to rethink its plans once again and sent its stock down 54% to 27 cents in premarket trading. The midphase study randomized 99 patients with mild cognitive impairment or mild dementia caused by Parkinson’s or Lewy body dementia to receive NYX-458 or placebo for 12 weeks. Aptinyx began the trial on the basis of evidence that the molecule boosts cognition by addressing glutamatergic dysregulation.  Across a slate of efficacy endpoints, NYX-458 failed to deliver on the preclinical promise. Aptinyx is yet to share data from the trial but revealed the absence of clinically meaningful improvements. The efficacy endpoints included two evaluations of the patients’ everyday functions and a battery of computerized neurocognitive tests designed to assess cognition. The comprehensive failure led Aptinyx to drop plans for further development of NYX-458. The fallout has hit the rest of the business, with the biotech terminating an ongoing study of NYX-783 in post-traumatic stress disorder (PTSD) early. Aptinyx had expected to report phase 2b data in PTSD in the second half of the year. Now, the biotech will review the data generated on NYX-783 to date to inform the next steps while trying to conserve its cash and identify a way out of its current predicament. Aptinyx is yet to publicly disclose layoffs but said it will “undertake cost-cutting measures.” The biotech ended September with $67 million to its name. 

Aptinyx’s NYX-458 fell short of the primary endpoint in a Phase II trial of patients with cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies. Courtesy of Shutterstock Aptinyx ’s NYX-458 fell short of the primary endpoint in a Phase II trial of patients with cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies, the Illinois biotech announced Tuesday. The company will no longer develop NYX-458. Aptinyx will also initiate cost-cutting measures to preserve its capital while it looks for other strategic business alternatives, according to Tuesday’s press release. These measures include the termination of a Phase IIb trial of NYX-783 in post-traumatic stress disorder. The company will conduct “early analysis of the data” generated to date for NYX-783 to identify the appropriate next steps for the candidate and explore alternative options “to support the advancement of our NMDA receptor modulation platform,” Andy Kidd, M.D., president and CEO, said in a prepared statement. In what has become a common industry refrain, an Aptinyx spokesperson told BioSpace this program is being terminated due to capital constraints. “In light of challenges to raising capital, the timeline for completion and readout of the full PTSD study extends beyond the point where our debt and other obligations are expected to exceed our available cash,” the spokesperson said. Discovered through Aptinyx’s proprietary platform, NYX-458 is an oral small-molecule drug that modulates – rather than blocks or hyper-activates – the N-methyl-D-aspartate receptor, abnormal activation of which could underpin several different conditions of the central nervous system. In the failed Phase II trial, 99 patients were randomly assigned to receive a 30-mg dose of NYX-458 or placebo. After 12 weeks, the treatment arms were compared in terms of everyday function and cognitive performance. Across all measures, NYX-458 failed to show clinically meaningful improvements relative to placebo. NYX-783 is also an oral NMDA modulator. Aside from PTSD, the candidate is being trialed in opioid use disorder. Aptinyx’s Losing Streak NYX-458 isn’t Aptinyx’s first failure in the CNS space. In April 2022, the company announced that NYX-2925, also an oral modulator of the NMDA receptor, failed to demonstrate significant benefit in a Phase IIb trial in patients with painful diabetic peripheral neuropathy (DPN). While patients treated with Aptinyx’s candidate saw improvements in their average daily pain scores, the overall effect was not strong enough to statistically distinguish NYX-2925 from placebo. No safety issues were observed. After its DPN flop, Aptinyx remained hopeful that NYX-2925 could deliver promising results in an upcoming Phase IIb study of fibromyalgia, a chronic pain disorder. In August 2022, however, the candidate fell short of its primary endpoint in this indication as well. While there was an early trend toward clinically meaningful pain improvement in patients treated with NYX-2925, this effect was not sustained throughout the study and the overall benefit of the candidate was not significantly better than placebo. In its Q3 2022 results , Aptinyx revealed it was discontinuing NYX-2925 in chronic pain.