Pipeline

Aptinyx’s Development Pipeline

Aptinyx’s proprietary chemistry platform has yielded numerous small-molecule modulators of N-methyl-D-aspartate (NMDA) receptors. While all of the product candidates from our discovery platform modulate NMDA receptors, each one is a distinct chemical entity with unique pharmacologic properties. We evaluate the therapeutic implications of variations in these properties by interrogating our molecules across different preclinical models of brain and nervous system disorders. The data we collect from these preclinical studies indicate which molecules are better suited for different indications and inform our development decisions accordingly.

A number of these molecules have advanced into clinical development as product candidates for the treatment of various brain and nervous system disorders. In studies to date, they have demonstrated high oral bioavailability, diverse NMDA-receptor subtype binding profiles, and differentiated activity. Aptinyx’s product candidates bind within a previously uncharacterized binding domain, or “pocket,” on the NMDA receptor to modulate NMDA-receptor channel opening and enhance synaptic plasticity. This mechanism is distinct from any other therapies, emerging or marketed, for multiple challenging neurologic disorders.

Pipeline of novel oral NMDA receptor modulators discovered from Aptinyx’s proprietary chemistry platform

Compound

Indication

Pre-IND

Phase 1

Phase 2

Phase 3

NYX-2925

NYX-783

NYX-458

Painful Diabetic
Peripheral Neuropathy

Fibromyalgia

Post-Traumatic Stress Disorder

Parkinson's Disease
Cognitive Impairment

Additional Programs from Our Discovery Platform

Compound

AGN-241751

Indication

Major Depressive Disorder

Partner

Allergan

Details

in May 2018, Allergan exercised an option under our ongoing research collaboration to acquire AGN-241751. We will receive no further economic consideration from this product candidate.

NYX-2925

NYX-2925 is a novel, oral, small-molecule NMDA receptor modulator in development for the treatment of chronic pain. NYX-2925 is currently being evaluated in multiple Phase 2 studies in patients with fibromyalgia and painful diabetic peripheral neuropathy (DPN).

NYX-2925 works by enhancing synaptic plasticity, a mechanism uniquely suited to addressing chronic pain. It is established that, when pain becomes chronic, it can become a largely centralized disorder mediated by central learning and memory processes. We believe NYX-2925, by enhancing neural cell communication, has the potential to address a wide range of chronic pain conditions, including fibromyalgia, painful DPN, and other centralized chronic pain conditions.

In clinical studies, NYX-2925 has been shown to have activity that affects central pain processing, resulting in alleviation of pain and other symptoms associated with chronic pain conditions. In preclinical models of numerous neuropathic pain conditions, NYX-2925 has shown robust analgesic activity. Across these preclinical studies, as well as in Phase 1 and Phase 2 clinical studies, NYX-2925 has exhibited a favorable safety and tolerability profile across a wide dose range. In April 2019, we reported detailed results from a Phase 2 study in patients with painful DPN, demonstrating robust analgesic activity in patients with advanced (more chronic) DPN. In early June 2019, we reported positive top-line data from a Phase 2 study of NYX-2925 in patients with fibromyalgia, demonstrating significant effects on both biomarkers and patient-reported outcomes. In the second half of 2019, we expect to initiate a larger 12-week Phase 2 study in patients with fibromyalgia which will evaluate patient-reported outcomes as the primary endpoint.

The U.S. Food and Drug Administration has granted Fast Track designation to the development of NYX-2925 for the treatment of neuropathic pain associated with DPN. We believe the therapeutic profile of NYX-2925 will allow us to expand the development of this molecule into multiple other chronic pain conditions.

See the Clinical Studies page to learn more about ongoing studies with NYX-2925.

NYX-783

NYX-783 is an NMDA receptor modulating small molecule in clinical development as a therapy for post-traumatic stress disorder (PTSD).

As learning processes are involved in fear extinction, NYX-783’s mechanism of enhancing synaptic plasticity and facilitating learning is highly relevant in PTSD. NYX-783 has demonstrated robust and long-lasting effects in preclinical models of depression, learning, and fear extinction, as well as a favorable tolerability profile. These findings suggest NYX-783 may target the underlying cause of PTSD, not simply palliate its symptoms.

NYX-783 has been evaluated in a Phase 1 clinical study in healthy human subjects and was well tolerated across a wide dose range. The U.S. Food and Drug Administration has granted Fast Track designation to Aptinyx’s development of NYX-783 for the treatment of PTSD.

NYX-458

NYX-458 is an NMDA receptor modulating small molecule that we intend to develop for the treatment of cognitive impairment associated with Parkinson’s disease.

While motor symptoms are the principle symptoms of Parkinson’s disease, many people with Parkinson’s also suffer from cognitive impairment. It is believed that the loss of dopamine neurons and the associated downstream changes, including dysregulation and dysfunction of NMDA receptors, leads to impairments in multiple cognitive domains. We believe, through its modulatory approach, NYX-458 has the potential to correct the function of NMDA receptors and address the cognitive symptoms in people with Parkinson’s disease.

In preclinical studies we have observed robust, rapid, and sustained effects of NYX-458 on cognitive deficits – Across a number of assessments in a non-human primate model that mimics Parkinson’s disease, and uses measures that are highly translatable to human studies, administration of NYX-458 resulted in a reversal of cognitive impairment and, on some measures, restored performance back to baseline levels.

NYX-458 has been evaluated in a Phase 1 clinical study in healthy human subjects and was well tolerated across a wide dose range with a dose-proportional and predictable pharmacokinetic profile.

Platform

Aptinyx has a robust and growing chemistry platform, enabling discovery and design of small-molecule compounds that elegantly modulate the NMDA receptor. The company has developed a discovery screening and profiling process to rapidly assess the binding and functional properties of these NMDA receptor modulators. To date, Aptinyx compounds have shown activity in a number of preclinical models of depression, neuropathic pain, migraine, PTSD, neuroprotection, cognitive function and impairment, and sleep, among others. Aptinyx is rapidly progressing the most promising of these drug candidates in preclinical and clinical development.