Left for dead after a failure in neuropathic pain, Aptinyx latches onto positive PhII data in PTSD
Almost two years after a Phase II fail sent investors running for the hills, Aptinyx $APTX may have found a new lifeline.
The Evanston, IL-based biotech, which focuses on brain and central nervous system disorders, announced positive Phase II data in post-traumatic stress disorder Monday afternoon with one of its NMDA receptor modulators. Armed with the topline efficacy and safety results, Aptinyx now plans to begin a pivotal study sometime in 2021.
“We are very pleased with these impressive results, which surpassed our expectations for this initial exploratory study,” CEO Norbert Riedel said in a statement.
Aptinyx’s shares nearly doubled after the bell Monday, soaring as high as 96% less than two hours after the company reported the data.
The driving force behind this rebound is a program called NYX-783, an oral NMDA receptor modulator. Designed to enhance what’s known as extinction learning, Aptinyx says NYX-783 can alleviate symptoms of the condition such as irritability, aggression, reckless or self-destructive behavior and lack of concentration.
NYX-783 was studied in a placebo-controlled, double-blinded and randomized trial with 153 patients. The Phase II took place over two four-week stages and measured two different doses, 10 mg and 50 mg, both of which showed statistically significant improvements (p=0.049 and p=0.040, respectively) on the CAPS-5 Arousal and Reactivity Score, a clinician-administered interview designed to evaluate PTSD patients.
Aptinyx also reported CAPS-5 Total Score data from the first stage of the Phase II, which it said showed clinically meaningful improvements that trended toward significance. In the drug arm, 78% of patients taking the 50 mg dose achieved a 30% improvement from baseline after four weeks, compared to 44% taking placebo (p=0.008). Within the same arm, 50% of patients saw a 50% improvement from baseline against 26% on placebo (p=0.044).
The primary endpoint of the study was the change in CAPS-5 Total Score and subscores for Stage 1 and Stage 2, combined as weighted effects.
In a conference call with investors Tuesday morning, Aptinyx elaborated on the data and emphasized that in Stage 1, two-thirds of the patient population was randomized into placebo. As the trial moved into Stage 2 after four weeks, all of the patients in the original drug arm were placed into placebo, and the original placebo group was divided into responders and non-responders. Each group was then randomized for the next four-week period to receive placebo, the 10 mg dose or the 50 mg dose at a 2:1:1 rate.
Aptinyx scientists stressed on the call that this ensured no individual received more than four weeks of treatment at any point.
SVBLeerink’s Marc Goodman pegged this as a good sign for Aptinyx, writing to investors:
The stock has been in the “penalty box” since the negative Phase 2 readout of its leading asset NYX-2925 in painful diabetic peripheral neuropathy over a year ago, which has resulted in increased investor skepticism regarding its NMDA modulation platform, so this is very welcome news which should help rejuvenate confidence in this MoA. Given how negative investor sentiment has been, we are not surprised to see the stock up >80% in after-market trading.
Extinction learning itself is a psychological phenomenon that’s used to recondition the brain in response to certain stimuli. Specifically, it refers to the decreasing response to a known stimulus when it’s presented without reinforcement. Think Pavlov’s dog: after the dog was trained to salivate at the sound of a bell, Pavlov began ringing the bell without giving any food. Soon, the dog stopped salivating.
Similar methods are used to help PTSD patients disassociate from their fears. NYX-783 boosts this activity, Aptinyx says, modulating the NMDA receptor to drive activity to portions of the brain where patients have altered connectivity when recalling traumatic events.
Monday’s news could mark the start of a turnaround for the biotech after their program for diabetic peripheral neuropathy flopped hard back in January 2019. The former lead candidate, another NMDA receptor modulator, failed to meet the primary endpoint in a Phase II in any of the three doses being tested, sending their stock price plummeting 70%. After making its public debut in June 2018 at $20 per share, Aptinyx has traded below $6 ever since that bust.
PTSD has proved a notoriously tough indication to crack, and NMDA programs tested in other fields have not seen much success either. Allergan bought out Naurex for $560 million several years ago hoping to utilize its experimental NMDA drugs to treat depression, but that led to a Phase III dud in March 2019.