EX-99.1 2 a19-6491_1ex99d1.htm EX-99.1

Exhibit 99.1

 

Innovative Therapies for Disorders of the Brain and Nervous System Discovering and Developing Novel Small-Molecule NMDAr Modulators Cowen and Company 39th Annual Health Care Conference

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Forward-looking statements This presentation has been prepared by Aptinyx Inc. (“we,” ”us,” “our,” “Aptinyx,” or the “Company”) and is made for informational purposes only and does not constitute an offer to sell or a solicitation of an offer to buy securities, nor shall there be any sale of any securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. The information set forth herein does not purport to be complete or to contain all of the information you may desire. Statements contained herein are made as of the date of this presentation unless stated otherwise, and neither this presentation, nor any sale of securities, shall under any circumstances create an implication that the information contained herein is correct as of any time after such date or that information will be updated or revised to reflect information that subsequently becomes available or changes occurring after the date hereof, except as required by law. This presentation contains estimates and other statistical data made by independent parties and us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. This presentation also contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to business, operations, and financial conditions of Aptinyx including but not limited to preclinical and clinical development of Aptinyx’s product candidates and the timing and reporting of results from preclinical and clinical studies evaluating Aptinyx’s product candidates. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “should” and “could,” and similar expressions or words, identify forward-looking statements. Although Aptinyx believes the expectations reflected in such forward-looking statements are based upon reasonable assumptions, there can be no assurance that its expectations will be realized. Actual results could differ materially from those projected in Aptinyx’s forward-looking statements due to numerous known and unknown risks and uncertainties. All forward-looking statements speak only as of the date of this presentation and are qualified in their entirety by this cautionary statement. Aptinyx undertakes no obligation to revise or update this presentation to reflect events or circumstances after the date hereof, except as required by law. 2

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POSITIVE HUMAN DATA in Phase 1 and Phase 2a clinical studies Clinical-stage biopharmaceutical company developing transformative NMDA receptor-modulating therapies 3 TARGETING RELEVANT DISEASE AREAS with significant unmet need & commercial opportunity ROBUST IP afforded through internal innovation and proprietary platform NEAR-TERM CLINICAL MILESTONES across multiple proof-of-concept studies and indications $ WELL-FUNDED AND BACKED by highly regarded healthcare investors PROVEN TEAM WITH EXPERTISE across pharma value chain PRODUCTIVE COLLABORATION with Allergan VALIDATED TECHNOLOGY with differentiated science and mechanism

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4 Affects up to 100mm people in the U.S. Current therapies have limited efficacy and substantial side effects Market leading therapies have significant drawbacks, yet have garnered >$5bn in annual revenues each Significant abuse liability Chronic Pain ~8.5mm people suffering from PTSD in the U.S. Caused by numerous trauma types and underdiagnosed Elevated suicide risk Often with simultaneous addiction or drug abuse Only 2 approved therapies – both approved 10+ years ago PTSD Affects up to 500k people in the U.S. 50% of those with Parkinson’s have some cognitive impairment Significant disease burden on patients and caregivers Only 1 approved therapy with limited efficacy in PD Parkinson’s Cognitive Impairment

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Modulation: A differentiated approach to targeting the NMDA receptor VS. 5 NMDAr-targeted drugs discovered to date (largely inhibitors, e.g., PCP, ketamine) have significant limitations

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Prolific output from Aptinyx small-molecule NMDAr modulator discovery platform Dozens of novel chemical scaffolds Novel, distinct, newly characterized binding domain High oral bioavailability and stability Diverse potency, activity, subtype selectivity, and pharmacology/biology profiles Composition of matter IP protection through 2034 and beyond Over 1,000 unique, small-molecule NMDAr modulators designed and synthesized NMDA Receptor 6

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Multiple clinical-stage development programs across various CNS indications 7 NYX-2925 NYX-783 NYX-458 AGN-241751 Painful Diabetic Peripheral Neuropathy Fibromyalgia Post-Traumatic Stress Disorder Parkinson’s Disease Cognitive Impairment Indication Est. U.S. Prevalence Next Milestone Phase 1 Phase 2 Phase 3 ~5.5mm ~5mm ~8.5mm ~500k Detailed Phase 2a data April 2019 Phase 2a data expected 1H 2019 Phase 2a data expected 1H 2020 Phase 1 data expected 1H 2019 Additional Program from Our Discovery Platform Indication Partner Details Acquired by Allergan via exercise of option under ongoing research collaboration. No further economic consideration to Aptinyx associated with future development. Major Depressive Disorder

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Increases non-REM sleep without impacting REM sleep Shows positive effects on pain processing and pain in patients with fibromyalgia and painful DPN NYX-2925 in Phase 2 clinical development for treatment of chronic pain Strong mechanistic rationale Safety and activity observed to date suggest NYX-2925 has therapeutic potential in chronic pain with a differentiated safety profile Sensory processing Learning & memory Shift in pain processing in people with chronic pain Clear clinical evidence of favorable safety and relevant activity 8 This common circuitry is also implicated in key comorbidities of pain such as MOOD and SLEEP Exhibits favorable safety, tolerability, CNS exposure, and pharmacokinetics Enhances NMDAr-mediated synaptic plasticity

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Exploratory biomarker and efficacy study of NYX-2925 in patients with fibromyalgia Primary endpoints known to be correlated with pain improvement and are a direct measure of drug effect 9 Aptinyx & U of M used fMRI to evaluate effects of NYX-2925 Building on prior work of University of Michigan Glutamatergic activity in insular cortex Connectivity between insular cortex and default mode network Evaluated effects of Lyrica® on brain activity, which identified key signatures associated with pain and pain reduction in fibromyalgia: Primary endpoints were objective imaging-based markers of central pain processing Strong correlation between these imaging markers and clinical pain symptoms Harris et al., Anesthesiology, 2013

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Significantly lower pain-evoked increases in posterior insula Glx Reduced connectivity between insular cortex and default mode network Significant reductions of Glx levels in dorsal anterior cingulate cortex Corresponding trends of improvement on clinical pain scores, cognitive impairment, fibromyalgia impacts, and mood NYX-2925 was well tolerated with no treatment-related serious adverse events reported NYX-2925 demonstrated effects on pain processing, pain, and other measures in patients with fibromyalgia Robust activity on objective imaging markers supports further development of NYX-2925 in fibromyalgia 10

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Phase 2 study of NYX-2925 in patients with painful diabetic peripheral neuropathy (DPN) 11 Placebo q.d. (n = 72) Inclusion/ exclusion eligibility Analgesic washout* Daily Pain Score NYX-2925 10mg q.d. (n = 77) NYX-2925 50mg q.d. (n = 77) NYX-2925 200mg q.d. (n = 74) *Patients were allowed to maintain stable dosing of 1 allowable concomitant analgesic Screening (2-4 weeks) Baseline (1 week) Treatment (4 weeks) Safety follow-up (1 week) Randomization eligibility Baseline pain score Monitored for AEs – no treatment Key objectives of the study: Evaluate safety and tolerability of NYX-2925 in a DPN patient population Assess the most active dose level across a 20-fold dose range Assess activity of NYX-295 across multiple endpoints relevant to chronic pain Identify key patient characteristics to inform inclusion/exclusion criteria for future studies

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NYX-2925 showed significant effects across primary and secondary endpoints in a highly relevant patient sub-population 12 Change in average daily pain vs. placebo (primary efficacy endpoint) Total efficacy population (N=300) Advanced DPN population (N=127)* *Post-hoc analysis of advanced DPN population includes patients who have had DPN for > 4 years

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Key findings provide scientific foundation for further development of NYX-2925 NYX-2925 showed excellent safety profile – AEs comparable to placebo and no SAEs Patients with advanced DPN showed the greatest treatment benefit Mechanism of NYX-2925 addresses the increasing central manifestation of pain perception and processing associated with the prolonged chronic pain these patients experience Patients with advanced DPN represented nearly half of the entire study population (N = 127) 50 mg identified as the most active dose level among the three doses tested Evidence of inverted-U-shaped dose response, consistent with previous preclinical and clinical data with this mechanism In patients with advanced DPN, effect of 50 mg dose was both clinically meaningful and statistically significant Week 4 change vs. baseline in average daily pain (on 10-point NRS) = 1.93 points Week 4 change vs. placebo in average daily pain (on 10-point NRS) = 1.21 points (p = 0.004) Effects were consistent across primary and secondary endpoints Effects were even more pronounced in patients not on a concomitant analgesic medication 13 Presentation of detailed results at APS Scientific Meeting in April 2019

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Favorable safety, tolerability, CNS exposure, and PK in Phase 1 2 approved SSRIs – approved 10+ years ago Limited efficacy – only targeting symptoms Burdensome side effects with current therapies NYX-783 in Phase 2 clinical development for treatment of PTSD Strong preclinical & early clinical evidence Robust and long-lasting activity in multiple preclinical models Clear mechanistic rationale Learning and memory dysfunction NMDAr crucial to learning and memory and fear extinction Significant unmet need Preclinical evidence and clinical safety profile indicate the potential for NYX-783 to address significant unmet needs in the treatment of PTSD 14 Contextual Fear Conditioning Model

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First-in-patient Phase 2 study of NYX-783 for the treatment of post-traumatic stress disorder 15 Data from this first-in-patient study expected 1H 2020 Screening Placebo non-responders Placebo non-responder criteria: CAPS-5 reduction from baseline <35% CAPS-5 score @ re-randomization >26 Stage 1 (4 weeks) Stage 2 (4 weeks) Placebo NYX-783 50mg daily NYX-783 50mg weekly Placebo responders Placebo NYX-783 50mg daily NYX-783 50mg weekly Placebo NYX-783 50mg daily NYX-783 50mg weekly Placebo Diagnosis of PTSD (DSM-5) CAPS-5 >30 PCL-5 >38 Primary analysis for efficacy CAPS-5 (Clinician Administered PTSD Scale – DSM 5th Edition) PCL-5 (PTSD Checklist – DSM 5th Edition) Evaluating effects of NYX-783 on PTSD symptoms Outcome of study to inform most appropriate dose regimen, enrollment criteria, and endpoints for future studies Sequential parallel comparison design

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NYX-458 in clinical development for treatment of Parkinson’s disease cognitive impairment Strong preclinical evidence in cognition and Parkinson’s disease models Clear mechanistic rationale NYX-458 enhances synaptic plasticity and LTP through NMDAr modulation NMDAr dysregulation and dysfunction caused by loss of dopamine neurons in Parkinson’s Substantial opportunity Significant unmet need Concentrated patient and prescriber base Attractive potential follow-on indications in a number of cognitive disorders 16 *MPTP is a neurotoxin employed to deplete dopamine-related neural cells -- similar to the way Parkinson’s disease does in humans Pronounced effects on cognition in preclinical models support development of NYX-458 in Parkinson’s disease cognitive impairment – Phase 1 healthy volunteer safety and PK data expected 1H 2019

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