Aptinyx Inc.

Good afternoon and welcome to the APTINX fourth quarter and year end 2020 financial results conference call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open up the call for your questions. Please be advised that the call is being recorded at the company's request. At this time, I would like to turn the call over to Nick Smith, Vice President of Corporate Development and Investor Relations of APTINX. Nick, please proceed.

Good afternoon, everyone, and thank you for joining us on today's call to discuss Aptinix's fourth quarter and year-end 2020 financial and operating results. Our press release describing financial results and business highlights is now available on our website. On today's call, Norbert Riedel, our Chief Executive Officer, will discuss our business and clinical development progress, and Ashish Khanna, our Chief Financial Officer and Chief Business Officer, will review our financial results. Additionally, for the Q&A portion of the call, we're joined by Andy Kidd, our President and Chief Operating Officer, Catherine King, Senior Vice President of Clinical Development, and Harold Merck, Vice President of Medical and Pharmacovigilance. I'd like to remind everyone that statements made during this conference call will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties that can cause actual results to differ materially. Any forward-looking statements are made only as of today, and we disclaim any obligation to update these forward-looking statements. Please see the forward-looking statements disclaimer in our financial results release issued this afternoon and the risk factors in the company's current and subsequent filings with the SEC. It is now my pleasure to turn the call over to Norbert.

Thank you, Nick, and good afternoon, everyone. We appreciate you taking the time to join us on today's call. We are excited to talk with you today, following what was a productive, albeit challenging year for us at Aptinix. Despite the global COVID-19 pandemic, our team remained focused on responsible decision-making and first-rate execution. And as a result, the past year has been marked by several important achievements in advancing our development programs. Among the key highlights of the year was the data from our Phase II exploratory study of NYX783 in post-traumatic stress disorder, which we reported in October. We are truly encouraged by the early results with NYX783, particularly at a time when mental health is at the forefront due to the trauma, isolation, and loss being experienced by so many. Our Phase IIb studies of NYX2925 in chronic pain resumed late last year, and the early metrics of execution and enrollment are looking very positive. Our clinical development efforts with NYX458 in cognitive impairment presented even greater challenges due to the pandemic, given the vulnerability of this patient population. However, we will be recommencing this study in the coming days, and will then again be enrolling patients in each of the Phase II studies that we have suspended last year. We are keenly focused on executing these studies in a safe, durable, and efficient manner to complete them expeditiously, with particular attention to the quality of the data coming out of each study. This execution will lay the foundation for four Phase II study readouts with our novel NMDA receptor modulators beginning in the first half of 2022. All this important work, perseverance, and attention to detail is only possible with a dedicated and resilient team. I am very proud of the team members we have here at Aptonyx, all of whom are very passionate about our mission to improve the lives of patients who are suffering from challenging CNS conditions. We have a strong cash position with over $140 million at the end, which we expect to fund our operations for multiple phase two study readouts and into 2023. Let's discuss each of our development programs, starting with NYX 2925, our clinical stage development candidates under evaluation in two centralized chronic pain conditions. Fibromyalgia and Painful Diabetic Peripheral Neuropathy, or DPN. Following the pause in enrollment in both the Fibromyalgia and DPN studies due to the escalation of the COVID-19 pandemic last March, we reinitiated both of them towards the end of last year. While we have incorporated certain targeted protocol modifications to facilitate durable study execution, and ensure the safety of patient and study personnel against the backdrop of COVID-19, the key elements of the Phase II study design have not changed. In fibromyalgia, we are evaluating the effects of daily dosing of 50 milligrams and 100 milligrams of NYX2925 against placebo in a 12-week study. We expect to enroll approximately 300 patients in this study. In DPN, we are evaluating the effect of 50 milligrams of NYX2925 against placebo, also over a 12-week treatment period. In this study, we expect to enroll approximately 200 patients with advanced DPN. The primary endpoint for both studies is the change from baseline on the average daily pain score as measured by the 0 to 10-point numeric rating scale. So far, we are pleased that enrollment in both studies has been tracking in line with our expectations. Based on this steady execution and enrollment progress, we anticipate reading out data from each of these chronic pain studies in the first half of 2022. Let's move now to NYX783, which is in development for the treatment of post-traumatic stress disorder. In October, we announced positive results from our Phase II exploratory study in patients with PTSD. In this study, NYX783 demonstrated clinically meaningful effects on multiple efficacy endpoints after four weeks of treatment. Importantly, the signals we observed were very consistent with our understanding of the mechanism of NYX783. The study evaluated two doses of NYX7A3 against placebo in 153 patients over four weeks. The effects were measured on the CAHPS5, which is a holistic evaluation of the range of symptoms experienced by people with PTSD. As this was an exploratory study, and the first time NYX783 was evaluated in patients with PTSD, we were focused primarily on evaluating parameters that would inform our design of future well-powered studies, including the safety and tolerability profile and the degree to which NYX783 exhibited efficacy signals across an array of endpoints. We are encouraged by the data we obtained from this study and believe that NY783 has the potential to become a new therapeutic option in an indication that has not had a new target proved in over 20 years. As we look ahead to future clinical development, we will build on the following key observations from this first study. On the CAHPS 5 total score, we saw a clinically meaningful improvement from baseline with the 50 milligram dose. Importantly, looking at responder rates, a significantly greater proportion of patients receiving 50 milligrams achieved a clinically meaningful improvement on the CAHPS 5 total score compared to the placebo group. These observed effects on the CAHPS 5 total score were driven by consistent and robust improvements from baseline across three of its four symptom cluster scores. NYF783 exhibited a very favorable safety profile with no drug-related serious adverse events and an overall adverse event profile that was in line with placebo. We also learned about certain patient characteristics that appears to influence the overall response to NYX783, which we will incorporate into the design of the next study. These promising signals, which we have seen with four weeks of treatment, provide us with confidence to move forward in this indication. We are pleased that these data have been accepted for presentation at the upcoming Society of Biological Psychiatry annual meeting scheduled to take place virtually April 29th through May 1st. In addition, we have been granted a Type C meeting with the FDA on April 29th to discuss the design of the next study and the path to an NDA in PTSD. While the specific study design details have not been finalized, we expect the next study to be a Phase IIb study with a registration-supported design focused on the CAHPS 5 total score, consistent with other pivotal studies in PTSD. We plan to commence this study in the second half of this year, and we will provide more details at the appropriate time. I am pleased with our progress with NYX783, and maybe most importantly, The data from this Phase II study now provide a third clinical validation of the activity of the novel NMDA receptor modulators from our platform. Across two chronic pain studies and this PTSD study, we have seen that compounds from our platform show improvements on validated clinical endpoints, giving us a solid foundation to confirm these signals in larger more conclusive clinical studies. Let's now discuss relevant updates on NYX458, which is in development for the treatment of cognitive impairment. Following the suspension of our Phase IIa study last March, I am pleased to report that we are now just days away from recommending patient screening in this study. We have incorporated several targeted protocol changes designed to simplify study execution and optimize our chances for detecting signals of efficacy, while, of course, ensuring the safety of patients and study personnel. This Phase II study is a randomized, double-blind, placebo-controlled study to evaluate the safety and potential cognitive benefits of NYX458 in approximately 100 patients. Recall, when we initially started this study, we were enrolling patients with mild cognitive impairment in Parkinson's disease. We are now expanding this patient population to also include mild dementia in Parkinson's disease and dementia with Lewy bodies. It is recognized that these diagnoses represent a continuum with the same alpha-synuclein-related pathophysiology which we believe NYX458 is well-suited to address. In particular, alpha-synuclein buildup has been implicated as a causal factor for cognitive impairment. And further, it has been demonstrated that increases in alpha-synuclein levels reside in decreased NMDA receptor expression and activity. We therefore believe the enhancement of NMDA receptor activity with NYX458 has the potential to address this cognitive impairment. The study will involve two treatment arms, daily dosing of either 30 milligrams of NYX458 or placebo, and will evaluate the safety, tolerability, and cognitive effects on patients over a 12-week period. This is our first study of a new mechanism in patients with cognitive impairment, and it is critical for us to explore multiple cognitive endpoints to characterize the activity of NYX458. Accordingly, we will leverage multiple computerized neurocognitive assessments to evaluate the effect across the key cognitive domains impaired in this patient population. Following significant progress over the last few months, we are pleased to be hosting a virtual investigative meeting March 26 and will then begin screening and enrolling patients. We have received good initial feedback from clinical study sites on the changes we are incorporating and anticipate reporting data from this study in the second half of 2022. To summarize, I'm immensely proud of the way our team has navigated the challenges of the past year. The data we read out in 2020, combined with the tremendous work to get our preclinical studies back up and running, have enabled us to advance our development efforts across each of our programs. With that, I will now hand the call over to Ashish to discuss our full year 2020