Max-Planck Institute of Psychiatry

A study reveals new details about how ketamine works, paving the way toward the development of safe, effective treatments for depression. Ketamine, a well-known anesthetic used in smaller doses as a party drug, was hailed as a "new hope for depression" in a Time magazine cover story in 2017. Two years later, the arrival of the first ketamine-based antidepressant -- the nasal spray esketamine, made by Johnson & Johnson -- was applauded as the most exciting development in the treatment of mood disorders in decades. Yet the U.S. Food and Drug Administration still limits the spray's use. It is mainly given to depressed patients who have not been helped by other therapies -- in part, because the new drug's mechanism of action is insufficiently understood, leading to concerns over its safety. Today, a study published in Neuron reveals new details about how ketamine works, paving the way toward the development of safe, effective treatments for depression. The research was conducted at the Weizmann Institute of Science in Rehovot, Israel, and at the Max Planck Institute of Psychiatry in Munich, Germany, in collaboration with the Helmholtz Zentrum, Munich. Even though depression is on the rise in developed countries, taking a heavy toll in terms of human suffering and economic loss, there have been no major breakthroughs in the treatment of depression since the 1987 approval of the most famous antidepressant of all time, Prozac. Meanwhile, existing drugs bring no relief to about a third of depressed patients. Even when the drugs do work, they take four to eight weeks to take effect, a delay that can prove fatal in suicidal cases. That's precisely the reason for much of the excitement over ketamine-based therapies: They make people feel better within hours. Their antidepressant action then lasts for days after the drug itself has cleared from the body. Evidently, it's the body's response to ketamine, rather than ketamine itself, that produces the desired effect, but the nature of this response has until now been unclear. When scientists tried to clarify ketamine's mechanism of action in previous studies, they examined its impact on gene expression in brain tissues, but not in individual brain cells. This approach can miss crucial differences between different cell types. Recent technological advances, however, have made it possible to assess gene expression at an unprecedented level of resolution: that of the single cell. These technologies were employed in the new study, conducted under the guidance of Prof. Alon Chen, former managing director of the Max Planck Institute of Psychiatry and current president of the Weizmann Institute of Science. In this study, researchers led by Dr. Juan Pablo Lopez mapped out gene expression in thousands of individual neurons in the brains of mice that had been given a dose of ketamine. These neurons belong to networks that convey their signals by means of the neurotransmitter glutamate. Ketamine had been known since the 1990s to produce its effects by acting on such neurons -- this in contrast to older antidepressants, which mainly affect neurons influenced by serotonin. But since ketamine's effect persists long after it leaves the body, its action could not be explained by mere blockage of glutamate receptors on the surfaces of neurons. "We wanted to clarify the molecular cascade that is triggered by ketamine, leading to its sustained antidepressant effects," Lopez says. To this end, the scientists focused on the ventral hippocampus, a brain region that in previous studies had been associated with the antidepressant effects of ketamine. After mapping out gene expression in cells from this area of the mouse brain, the researchers identified a subpopulation of neurons with a characteristic genetic signature. Ketamine had increased these neurons' expression of a gene called Kcnq2, which encodes a potassium channel -- that is, a tunnel that opens up in the cell membrane, enabling the passage of potassium ions. Potassium channels play a central role in the life of neurons, maintaining their stability and preventing their excessive firing. In a series of elaborate experiments on the molecular and cellular levels, which included electrophysiological, pharmacological, behavioral and functional studies, the scientists confirmed their major finding: Ketamine exerts its lasting antidepressant effect by enhancing the Kcnq2 potassium channels in a certain subtype of glutamate-sensitive neurons. "In the past, other researchers used whole tissue samples, which are composed of different cell types, so ketamine's effects on specific cell types were averaged out," Lopez explains. The researchers then tested ketamine's effects in combination with an epilepsy drug, retigabine, known to activate potassium channels in the brain. When the drugs were given together, ketamine's antidepressant effects were significantly enhanced. "A single dose of retigabine was enough to amplify and prolong ketamine's antidepressant action in mice," Lopez says. "Not only that, ketamine produced the same benefits when given in smaller doses than usual, which may help reduce its unwanted side effects." Since both drugs already have FDA approval, the way is open toward testing their combined action in humans. According to the World Health Organization, depression afflicts nearly 300 million people worldwide; more than 700,000 people commit suicide every year. Yet despite decades of research, much remains to be learned about the neuronal mechanisms underlying depression and the ways of manipulating those mechanisms with drugs. By revealing a new mechanism of ketamine's action, the study may make it possible to expand the use ketamine-based drugs. This, in turn, might help these drugs fully deliver on their promise of providing new hope for depression. "In-depth knowledge of how antidepressants work might lead to a better understanding of depression and help improve existing treatments," Chen sums up. Prof. Chen's research is supported by the Ruhman Family Laboratory for Research in the Neurobiology of Stress and the Licht Family. He is the incumbent of the Vera and John Schwartz Professorial Chair in Neurobiology.

Benedikt von Braunmühl named new CEO Dr. Hans Eriksson appointed Chief Clinical Development Officer Dr. Franz Humer strengthens Board of Directors as Chairman Founder Prof. Dr. Dr. Dr. h.c. mult. Florian Holsboer to lead Scientific Advisory Board MUNICH, GERMANY / ACCESSWIRE / April 22, 2021 / HMNC Brain Health, a biotech company focused on the development of innovative and personalized treatments for depression and other neuropsychiatric disorders, enters a new phase of growth with a new leadership team. Benedikt von Braunmühl, formerly COO, Diagnostic Services of Medicover, will take over as Chief Executive Officer with effect of May 1, 2021. He will succeed the company founder Prof. Florian Holsboer who already stepped up to the Board of Directors and now also took over the lead of the Scientific Board. Dr. Hans Eriksson, most recently Chief Medical Officer at COMPASS Pathways, further strengthens the Executive Board as Chief Clinical Development Officer. Dr. Franz Humer, longstanding CEO and Chairman of Roche was appointed Chairman of the Board of Directors. In addition, Adalbert Freiherr von Uckermann, Managing Director of the Jahr Group, joined the Board of Directors as a member. Together with Prof. Holsboer and his co-founder, the entrepreneur Carsten Maschmeyer, the Board of Directors is now composed of four top-class executives. "Our projects are in a promising state of development and now is the right time to entrust the further steps towards market maturity to a new team that is ideally equipped for this task", said Prof. Holsboer. "Our new Chairman of the Board of Directors, Dr. Franz Humer, brings in decades of experience in the pharmaceutical and diagnostics industry as well as plenty of ideas and a unique network to build further partnerships for growth. As Head of the Scientific Board I remain committed to contribute my expertise with the final goal of making it a reality that patients with mental health conditions like depression can be treated with the right medication", Prof. Holsboer added. The new CEO von Braunmühl and Chief Clinical Development Officer Dr. Eriksson will form the Executive Board together with CFO Rainer Sturm. They are supported by Head of Operations Dr. Maximilian Döbler. "With Benedikt von Braunmühl, we have found an energetic and highly skilled new CEO to drive HMNC Brain Health forward", Dr. Humer said. "It is our priority to leverage HMNC Brain Health's potential to develop innovations and bring them to market successfully." "As a thriving company with a high-potential pipeline we're poised to fundamentally change the precision psychiatry market", said von Braunmühl. "Our company holds the key to much more precise treatment in indications with high unmet medical needs." HMNC Brain Health is a precision psychiatry pioneer addressing depression and other neuropsychiatric disorders as pressing medical challenges on global scale that translate into huge market potential. The company develops a unique pipeline for targeting both major depressive disorder (MDD) and treatment-resistant depression (TRD). HMNC Brain Health is located at one of the leading European biotech hubs in Munich and backed by renowned family offices. The company now enters the next stage of its development with a large-scale licensing and fundraising agenda. Benedikt von Braunmühl, CEO Benedikt von Braunmühl has more than 25 years of experience in business development, M&A, strategy, marketing, sales, and operations in the life-science industry. Most recently von Braunmühl served as Chief Operating Officer Diagnostic Services and member of the Management Board at Medicover AB, an integrated health care company. During his tenure with Medicover he prepared the company's IPO at the Nasdaq Stockholm as leader of the Diagnostic Division. His experience includes positions as Senior Vice President, Head of Global Commercial Operations and member of the Executive Committee at Qiagen and Regional Director Latin America of Novartis Vaccines & Diagnostics, as well as Chairman of the Supervisory Committee at Pathoquest S.A., a spin-off of the Pasteur Institute. Dr. Hans Eriksson, Chief Clinical Development Officer Dr. Hans Eriksson obtained his MD and PhD in Cell and Molecular Biology at Lund University in Sweden. He also holds an Executive MBA from Stockholm School of Economics. After clinical training in psychiatry, he served as Consultant Psychiatrist and Assisting Head of the Psychiatric Clinic at Lund University Hospital. During the last two decades, he has held several senior clinical development roles in the pharmaceutical industry, in Sweden, Denmark, USA, and the UK. His career moves prior to HMNC Brain Health included most recently serving as Chief Medical Officer at COMPASS Pathways and previously as Senior Director of Clinical Research at Lundbeck and Medical Science Director at AstraZeneca. He has worked on five late-phase clinical development programs for depression indications, three of which have resulted in regulatory approvals for Major Depressive Disorder. Dr. Franz Humer, Chairman of the Board of Directors Dr. Franz Humer is one of the most experienced leaders in the global pharmaceutical and diagnostics industry. In 1995, he joined Hoffmann-La Roche as a member of the Board and the head of Pharmaceutical Division, progressing to become Chairman and CEO in 2001, and between 2008 and 2014 the Chairman of Roche Holding Limited. He joined the Board of Diageo in 2005, became Chairman in 2008 and retired in 2016. Apart from HMNC Holding GmbH, Dr. Humer is Chairman of Neogene Therapeutics. He is a Board Director of Allogene Therapeutics, Cydar Medical and Emil Frey Holdings and an Advisor to Temasek Holdings, Letterone Healthcare and Breakthrough Properties. Dr. Humer earned a PhD in law from the University of Innsbruck, Austria, and an MBA from INSEAD in Fontainebleau, France. Adalbert Freiherr von Uckermann, Member of the Board of Directors Adalbert Freiherr von Uckermann has been the Managing Director of Jahr Group, Hamburg, since July 2020. He was a member of the management board of the multi family office HQ Trust between 2011 and 2020. His previous positions include the investment banks UBS Deutschland AG and Rothschild GmbH. In addition, von Uckermann was part of the project management team for the IPO of Deutsche Telekom AG and initially worked at Dresdner Bank AG after studying economics at Ludwig Maximilian University in Munich. Prof. Dr. Dr. Dr. h.c. Florian Holsboer, Co-Founder, Head of the Scientific Board, and Member of the Board of Directors Prof. Florian Holsboer is one of the most internationally renowned depression researchers. He was Director of the Max Planck Institute of Psychiatry for 25 years. Furthermore, he was the CEO of HMNC Brain Health from 2014 till the end of 2020. He is known for his discoveries about the connection between stress, depression, anxiety and sleep disorders, the laboratory diagnostic characterization of these diseases and their optimal treatment. He is one of the founders of personalized depression therapy, which, based on laboratory diagnostics, helps sustainably improve depression treatment. Prof. Holsboer is the author and co-author of over 1,000 scientific publications and is one of the most cited scientists worldwide. Carsten Maschmeyer, Co-Founder and Member of the Board of Directors Carsten Maschmeyer is a highly successful German entrepreneur, investor, speaker, and bestselling-author. Under the strategic umbrella of the Maschmeyer Group all his investment activities are combined. With his investment companies ALSTIN (Munich), seed+speed (Berlin), and MGV (San Francisco, USA) he engages in companies in sunrise industries and growing markets. Carsten Maschmeyer is also the inventor of independent financial consulting. The company he founded, he built up in record time into an international M-DAX group and sold it in 2007 to the largest Swiss life insurer. HMNC Brain Health HMNC Brain Health is a precision medicine pioneer in psychiatry based in Munich. Founded in 2010, the privately held biotech company combines the development of machine learning-enabled companion diagnostics with specific therapeutics to personalize the treatment of neuropsychiatric disorders with a focus on depression. The ultimate goal of HMNC Brain Health is to improve the lives of patients by developing highly disruptive solutions for their high unmet medical needs. The company strives to reduce not only the immense individual burden, but also the societal impact of these diseases. HMNC Brain Health develops patented genetic tests and combines those with innovative exclusively in-licensed medications, resulting in precise therapies for depression and other neuropsychiatric disorders. Media contact: Alexander Schmidt, GAULY Phone: +49 151 22 939 765 E-mail: alexander.schmidt@gaulyadvisors.com Dr. Franz Humer, Chairman of the Board of Directors, HMNC Brain Health SOURCE: HMNC Brain Health Benedikt von Braunmühl, CEO of HMNC Brain Health (starting May 1, 2021) View source version on accesswire.com:

March 24, 2021 20:05 UTC Phase 2 studies in fibromyalgia and painful DPN enrolling as planned – data readouts expected in 1H 2022 Phase 2 study in cognitive impairment expected to recommence imminently – data readout expected in 2H 2022 Reported data from Phase 2 exploratory study of NYX-783 in PTSD, supporting further clinical development – meeting with FDA to discuss future development path April 29, 2021 Strong cash position expected to support operations through multiple clinical data readouts and into 2023 Conference call today at 5:00 p.m. EST EVANSTON, Ill.--(BUSINESS WIRE)-- Aptinyx Inc. (Nasdaq: APTX), a clinical-stage biopharmaceutical company developing transformative therapies for the treatment of brain and nervous system disorders, today reported financial results for the fourth quarter and full year 2020 and provided updates across the company’s pipeline of novel NMDA receptor modulators. “Despite the COVID-19 pandemic, we are excited to be advancing clinical development across all four of our pipeline programs,” said Norbert Riedel, Ph.D., chief executive officer of Aptinyx. “The recent and upcoming recommencements of key clinical studies are a testament to the dedication of our team at Aptinyx, and I am grateful to all of my colleagues who have been instrumental in these efforts.” Dr. Riedel continued, “2020 was a very important year in further validating the novel mechanism through which our NMDA receptor modulators act. The results from our completed PTSD study enhance our understanding of the neurobiology of PTSD and the potential for NYX-783 to be a significant advancement in the field. We have observed the therapeutically relevant activity of our compounds across numerous studies, both in patients and in healthy volunteers. We believe the foundational data we have collected across our pipeline thus far have informed and de-risked the multiple Phase 2 studies that we expect to readout in the next 12-24 months. All of this progress sets us up nicely to bring much needed therapeutic innovation to multiple challenging CNS disorders in the years to come. And, with these important clinical milestones ahead, we are pleased to be in a strong financial position, with a cash balance that we anticipate will support our planned operations into 2023.” Pipeline Updates Chronic Pain Pipeline – NYX-2925 Aptinyx is developing NYX-2925 for the treatment of chronic centralized pain conditions. To date, NYX-2925 has been studied in more than 400 human subjects, including in three Phase 1 studies in healthy volunteers and two completed Phase 2 studies in patients with chronic pain. Across all studies, NYX-2925 has been well tolerated with no drug-related serious adverse events reported. Development in fibromyalgia: Following the completion of a successful Phase 2a neuroimaging biomarker study in 2019, Aptinyx initiated a Phase 2b study to evaluate NYX-2925 in patients with fibromyalgia. In March 2020, Aptinyx temporarily suspended enrollment of new patients in the Phase 2b study due to the COVID-19 pandemic. In September 2020, Aptinyx recommenced enrollment in the Phase 2b study with targeted protocol amendments designed to streamline enrollment and ensure safety of patients and study personnel amidst the ongoing COVID-19 pandemic. Study design: The study is a randomized, double-blind, parallel-design, placebo-controlled study to evaluate once-daily oral dosing of two dose levels of NYX-2925 (50 mg and 100 mg) compared to placebo in approximately 300 patients with fibromyalgia. The primary endpoint is the change in average daily pain score over a 12-week treatment period as reported on the 10-point numeric rating scale (NRS). Multiple secondary endpoints will be evaluated to characterize the effects of NYX-2925 across the broad array of symptoms experienced by patients with fibromyalgia. Enrollment to date has been consistent with the company’s plan and Aptinyx anticipates reporting top-line data from the study in the first half of 2022. Development in painful diabetic peripheral neuropathy (DPN): Following the completion of a Phase 2 study in 2019, in which NYX-2925 exhibited the strongest activity in patients with advanced DPN, Aptinyx initiated a Phase 2b study to support findings from the prior study. In March 2020, Aptinyx temporarily suspended enrollment of new patients in the Phase 2b study due to the COVID-19 pandemic. In December 2020, Aptinyx recommenced the Phase 2b study with targeted protocol amendments designed to streamline enrollment and ensure safety of patients and study personnel amidst the ongoing COVID-19 pandemic. Study design: The study is a randomized, double-blind, parallel-design, placebo-controlled study to evaluate once-daily oral dosing of 50 mg of NYX-2925 compared to placebo in approximately 200 patients with advanced DPN. The primary endpoint is the change in average daily pain score over a 12-week treatment period as reported on the 10-point NRS. Multiple secondary endpoints will be evaluated to characterize the effects of NYX-2925 across symptoms experienced by patients with painful DPN. Enrollment to date has been consistent with the company’s plan and Aptinyx anticipates reporting top-line data from the study in the first half of 2022. Publication of review article in Medicine in Drug Discovery highlighting preclinical data supporting the potential of NYX-2925 to treat chronic, centralized pain conditions: In January 2021, Aptinyx announced the publication of a recent review article in Medicine in Drug Discovery featuring data on its investigational novel NMDA receptor modulator, NYX-2925. The data span across numerous preclinical models and highlight the potential therapeutic benefits of NYX-2925 in treating chronic, centralized pain conditions. Psychiatry Pipeline – NYX-783 Aptinyx is developing NYX-783 for the treatment of PTSD. Across the completed Phase 1 and Phase 2 studies, including more than 200 human subjects combined, NYX-783 was well tolerated with no drug-related serious adverse events reported. Development in PTSD: In October 2020, Aptinyx reported results from a Phase 2a exploratory study of NYX-783 in patients with PTSD. The study was a double-blind, placebo-controlled, sequential parallel comparison design (SPCD) study in approximately 160 patients with PTSD. The study consisted of two four-week treatment stages, in which patients were randomly assigned to receive once-daily oral doses of either placebo, 10 mg NYX-783, or 50 mg NYX-783. This was an initial exploratory study and thus was powered based on clinical, and not statistical, considerations to detect signals of efficacy. Nonetheless, statistically significant separation from placebo was observed on some measures. Results: Clinically meaningful improvements from baseline were observed on the CAPS-5 Total score within four weeks in the 50 mg dose arm. Compared to placebo, a significantly greater proportion of patients on NYX-783 50 mg achieved a clinically meaningful improvement in CAPS-5 Total score in Stage 1 of treatment. Statistically significant improvement was observed on CAPS-5 Arousal and Reactivity score. Consistent improvements were observed across three of the four CAPS-5 symptom cluster scores, with statistically significant improvements compared to placebo observed on two of the four symptom clusters in Stage 1. Next steps: Aptinyx is scheduled to hold a Type C meeting with the U.S. Food and Drug Administration (FDA) on April 29, 2021 to discuss the future development path for NYX-783 in PTSD. Aptinyx expects to initiate a Phase 2b study in the second half of 2021, with a design consistent with that of a registration-supportive study and focused on evaluating effects on the CAPS-5 Total score. Data from the Phase 2a exploratory study will be presented at the 2021 Society of Biological Psychiatry (SOBP) Annual Meeting to be held virtually on April 29 – May 1, 2021. Neurology Pipeline – NYX-458 Aptinyx is developing NYX-458 for the treatment of cognitive impairment. In a Phase 1 study conducted in 62 healthy volunteers, NYX-458 exhibited a favorable pharmacokinetic pro was well tolerated with no drug-related serious adverse events reported. Development in cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies: In December 2019, based on positive preclinical data, including those from a highly translatable model in non-human primates, Aptinyx initiated a Phase 2a exploratory study of NYX-458 in patients with mild cognitive impairment associated with Parkinson’s disease. In March 2020, Aptinyx temporarily suspended enrollment of new patients in the Phase 2 study due to the COVID-19 pandemic. Following the suspension of enrollment, Aptinyx incorporated certain study design changes to improve study feasibility amidst the COVID-19 pandemic, simplify study execution, and optimize the potential for the study to detect signals of efficacy. Phase 2a exploratory study design: The Phase 2 study is a randomized, double-blind, parallel-design, placebo-controlled study to evaluate the safety and potential cognitive benefits of NYX-458 in patients with cognitive impairment associated with Parkinson’s disease or dementia with Lewy bodies. Patients with dementia with Lewy bodies have been included in consideration of the pathophysiology in common with Parkinson’s cognitive impairment – believed to be caused by increased levels of alpha synuclein, which, in turn, decreases NMDA receptor expression and activity. The study will evaluate daily oral dosing of NYX-458 30 mg compared to placebo over a 12-week period. The study is expected to enroll approximately 100 patients. The primary endpoint in the study is safety and tolerability. Secondary endpoints include multiple computerized neurocognitive assessments to evaluate the effects of NYX-458 on attention, memory, and executive functions. Exploratory endpoints include various clinical assessments to broadly evaluate the signals of efficacy of NYX-458 in patients with cognitive impairment. Next steps: Aptinyx expects to re-initiate patient screening and enrollment in the coming weeks and anticipates reporting top-line data from this study in the second half of 2022. Corporate Updates Harald Murck, M.D, Ph.D., joined Aptinyx as vice president, medical and pharmacovigilance: In January 2021, Harald Murck, an experienced drug development executive trained at the Max Planck Institute of Psychiatry, Germany, and a leader in NMDA receptor research since the late 1990s, began working with Aptinyx in the role of vice president, medical and pharmacovigilance. Andy Kidd, M.D., appointed president and COO: In December, Aptinyx announced the appointment of Andy Kidd, the company’s then-incumbent chief operating officer, to the role of president and chief operating officer. Strengthened the company’s financial position through a $48 million common stock offering: In early October 2020, Aptinyx announced the closing of a public offering of common stock with gross proceeds totaling $48 million, inclusive of the full exercise of the underwriters’ option to purchase additional shares and before deducting underwriting discounts and commissions and offering expenses. The offering included participation from new and existing investors. The company’s current cash balance, inclusive of the proceeds from the offering, is expected to provide financial support into 2023. Upcoming Milestones Recommencement of patient screening in Phase 2a study of NYX-458 in patients with cognitive impairment associated with Parkinson’s disease or dementia with Lewy bodies – First week of April 2021 Meeting with FDA to discuss development path for NYX-783 in PTSD – April 29, 2021 Presentation of detailed data from Phase 2a exploratory study of NYX-783 in PTSD at SOBP – April 29 – May 01, 2021 Initiation of Phase 2b study, with registration-supportive design, of NYX-783 in patients with PTSD – 2H 2021 Data readout from Phase 2b study of NYX-2925 in patients with fibromyalgia – 1H 2022 Data readout from Phase 2b study of NYX-2925 in patients with painful DPN – 1H 2022 Data readout from Phase 2a study of NYX-458 in cognitive impairment – 2H 2022 Fourth Quarter and Full Year 2020 Financial Results Cash Position: Cash and cash equivalents were $141.0 million at December 31, 2020, compared to $98.8 million at December 31, 2019. Collaboration Revenue: Revenue was $0.0 million and $1.6 million for the fourth quarter and full year 2020, respectively, as compared to $1.0 million and $3.7 million for same periods in 2019. Aptinyx’s revenue was derived from its research collaboration agreement with Allergan, now a wholly owned subsidiary of AbbVie, which came to its contractual conclusion during the third quarter of 2020. Research and Development (R&D) Expenses: R&D expenses were $6.8 million and $32.8 million for the fourth quarter and full year 2020, respectively, as compared to $10.6 million and $44.3 million for same periods in 2019. The decrease in R&D expenses during 2020 was primarily driven by reduced costs associated with the temporary suspension of enrollment across three Phase 2 clinical studies. General and Administrative (G&A) Expenses: G&A expenses were $4.8 million and $19.5 million for the fourth quarter and full year 2020, respectively, as compared to $4.5 million and $19.0 million for the same periods in 2019. Net Loss: Net loss was $11.5 million for the fourth quarter of 2020 compared to a net loss of $13.8 million for the same period in 2019. For the year ended December 31, 2020, net loss was $50.1 million, or basic and diluted net loss per share attributable to common stockholders of $1.02, compared to a net loss of $57.4 million, or basic and diluted net loss per share attributable to common stockholders of $1.71, for the year ended December 31, 2019. Conference Call The Aptinyx management team will host a conference call and webcast today at 5:00 p.m. EDT to review its financial results and highlights for the full year 2020 and to provide other business updates. To access the live conference call, please dial (833) 772-0394 (domestic) or (236) 738-2205 (international) and refer to conference ID 4846816. A live audio webcast of the event will be available on the Investors & Media section of Aptinyx’s website at . A replay of the webcast will be archived on Aptinyx’s website for 30 days following the event. About Aptinyx Aptinyx Inc. is a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of proprietary synthetic small molecules for the treatment of brain and nervous system disorders. Aptinyx has a platform for discovery of novel compounds that are believed to work through a unique mechanism to modulate—rather than block or over-activate—NMDA receptors and enhance synaptic plasticity, the foundation of neural cell communication. The company has three product candidates in clinical development in central nervous system indications, including chronic pain, post-traumatic stress disorder, and cognitive impairment. Aptinyx is also advancing additional compounds from its proprietary discovery platform, which continues to generate a rich and diverse pipeline of small-molecule NMDA receptor modulators with the potential to treat an array of neurologic disorders. For more information, visit . Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the company’s business plans and objectives, including future plans or expectations for NYX-2925, NYX-783, and NYX-458, therapeutic effects of the company’s product candidates and discovery platform, expectations regarding the design, implementation, timing, and success of its current and planned clinical studies, including providing updated guidance with respect thereto, the timing for the company’s receipt and announcement of data from its clinical studies, the timing and outcome of discussions with FDA and other regulatory agencies, expectations regarding its preclinical development activities, expectations regarding its uses and sufficiency of capital, the company’s growth and the anticipated contribution of its executive officers and management to its operations and progress, and its expectations regarding its uses of capital, expenses, future accumulated deficit and other fourth quarter and year end 2020 financial results, and the effect of the COVID-19 pandemic on the foregoing. Risks that contribute to the uncertain nature of the forward-looking statements include: the effect of the COVID-19 pandemic on our business and financial results, including with respect to disruptions to our clinical trials, business operations, and ability to raise additional capital; the success, cost, and timing of the company’s product candidate development activities and planned clinical studies; the company’s ability to execute on its strategy; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time‑consuming, and inherently unpredictable; regulatory developments in the United States and foreign countries; the company’s estimates regarding expenses, future revenue, and capital requirements; the company’s ability to fund operations into 2023; as well as those risks and uncertainties set forth in the company’s most recent quarterly report on Form 10-Q and subsequent filings with the Securities and Exchange Commission, including our upcoming Annual Report on Form 10-K for the year ended December 31, 2020. All forward-looking statements contained in this press release speak only as of the date on which they were made. Aptinyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. APTINYX INC. CONDENSED BALANCE SHEETS (in thousands) (Unaudited) Assets December 31, 2020 December 31, 2019 Current Assets: Cash and cash equivalents $ 141,028 $ 98,849 Restricted cash 179 179 Accounts receivable 257 444 Prepaid expenses and other current assets 8,140 5,637 Total current assets 149,604 105,109 Property and equipment and other long-term assets 1,002 1,370 Total assets $ 150,606 $ 106,479 Liabilities and stockholders’ equity Current Liabilities: Accounts payable $ 1,209 $ 1,555 Accrued expenses and other current liabilities 3,374 3,341 Total current liabilities 4,583 4,896 Other long-term liabilities 114 272 Total liabilities 4,697 5,168 Stockholders’ equity 145,909 101,311 Total liabilities and stockholders’ equity $ 150,606 $ 106,479 APTINYX INC. CONDENSED STATEMENTS OF OPERATIONS (in thousands, except per share data) (Unaudited) Three Months Ended December 31, Year Ended December 31, 2020 2019 2020 2019 Revenues Collaboration revenue $ — $ 918 $ 1,564 $ 3,669 Operating expenses Research and development 6,786 10,598 32,835 44,330 General and administrative 4,775 4,533 19,494 18,952 Total operating expenses 11,561 15,131 52,329 63,282 Loss from operations (11,561 ) (14,213 ) (50,765 ) (59,613 ) Other income 73 435 712 2,203 Net loss and comprehensive loss $ (11,488 ) $ (13,778 ) $ (50,053 ) $ (57,410 ) Net loss per share - basic and diluted $ (0.20 ) $ (0.41 ) $ (1.02 ) $ (1.71 ) Weighted average shares outstanding - basic and diluted 58,882 33,692 48,866 33,556 Source: Aptinyx Inc.