Aptinyx Inc.

Good afternoon and welcome to the Aptinex first quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode. Following the formal remark, we will open the call for 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 corporate development and investor relations at aptinix nick please proceed thank you operator good afternoon everyone and thank you for joining us on today's conference call to discuss aptinix's first quarter 2021 financial and operating results our press release describing financial results and recent highlights is available on our website Today on our call, Norbert Riedel, our Chief Executive Officer, will review our business and clinical progress, followed by Ashish Khanna, our Chief Financial Officer and Chief Business Officer, who will review the financial results. In addition, Andy Kidd, our President and Chief Operating Officer, and Catherine King, our Senior Vice President of Clinical Development, and Harold Merck, our Vice President of Medical and Pharmacovigilance, are with us for the Q&A portion of the call. Before we begin, 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. Norbert, over to you.

Thank you, Nick, and good afternoon, everyone. We appreciate you taking the time to join us on today's call. Before we delve into our clinical programs, I would like to share with you that we have recently announced the appointment of Dr. Joan Miller to our Board of Directors. John brings extensive experience in academic and medical leadership, clinical development, and clinical research to our board, and we are excited to have her join us as we progress into later stage clinical development. Related to our clinical programs, although it has only been a few weeks since our last business update call, we have made important progress across each of our four programs. As you recall, we currently have three Phase II clinical studies underway, one in painful DPN, one in fibromyalgia, and one in cognitive impairment. Our teams have been executing diligently on patient enrollment in these studies, and I'm happy to report that each of these studies is tracking very well. We also have been keenly focused on moving our PTSD program toward initiation of a phase 2b study with the design intended to be registration supportive in this indication. These past few weeks in particular have come with a number of positive developments for our PTSD program. So I will start with those updates for NYX783. In late April, we presented additional data from our initial exploratory PTSD study at the annual meeting of the Society of Biological Psychiatry, or SOBP. These data provide insights from stage one of the study, which was a four-week treatment period that included all patients in a double-blind, randomized, parallel design, most consistent with and informative of our next study. we reported that a significantly greater proportion of patients achieved a clinically reliable change in the 50 milligram treatment group compared to placebo. The reliable change index is defined as an improvement of 13 points or more on the CAHPS 5 total score and is a recognized metric for determining real effects as opposed to effects driven purely by variability. Our SOBP presentation also highlighted that when accounting for baseline imbalances across groups in the patient's time since trauma, the percentage improvement on the CAHPS 5 total score for the NYX78350 milligram group separated from placebo by a statistically significant margin. These additional analyses reinforce our confidence in the therapeutic potential of NYX783 in the treatment of PTSD. Also in late April, we met with the FDA for a Type C meeting to discuss the future development path in PTSD and to review the key design parameters of our planned Phase IIb study. It was a positive meeting during which the agency provided us with valuable input on a variety of study parameters, and we are in the process of finalizing the details of the protocol for the upcoming study accordingly. As we have laid out at a high level in our public presentations to date, this study will involve an evaluation of 8 to 12 weeks of daily dosing of NYX783 compared to placebo in a randomized parallel design with the CAHPS 5 total score as the primary endpoint. We will be proceeding with that design and, accordingly, if the data are positive, we believe the study has the potential for consideration by the agency as one of the two well-controlled studies required in support of an NDA. Of course, that will be a matter for review by the agency follow the completion of the study and review of the data. We plan to provide greater details on the study design and continue to anticipate that we will commence this Phase IIb study in the second half of this year. Let's briefly discuss NYX2925, which is in Phase II clinical development across two chronic pain indications. In painful diabetic peripheral neuropathy, and in fibromyalgia. I am glad to report that we have made excellent progress in both studies, and we continue to be on track towards our enrollment goals and our projected data readouts in the first half of 2022. We appreciate the continued engagement from the investigator sites and patients involved in these studies. Let's move now to NYX458, our product candidate in development for the treatment of cognitive impairment. We recently announced that we have recommenced an exploratory phase two study in patients with cognitive impairment associated with Parkinson's disease and with dementia with Lewy bodies. This is the first time NYX458 is being evaluated in patients with these diseases. This exploratory study is designed to detect the signal of therapeutically relevant activity of NYX458 and to assess its tolerability profile in this patient population. This is a double-blind, randomized, parallel design study and is expected to enroll approximately 100 patients to receive daily dosing of either 30 milligrams of NYX458 or placebo over a 12-week treatment period. Given the novel mechanism of NYX458, we are evaluating multiple cognitive endpoints in this study in order to characterize the activity across attention, memory, and executive function. I am pleased with our progress so far, and we expect to be able to report data from this study in the second half of 2022. With that, I will now turn the call over to Achish to review our first quarter financial results.

Thanks, Norbert. As we make progress across each of our programs, we are fortunate to be supported by a strong cash position. We anticipate our current cash will fund our operations into the year 2023, enabling readouts from multiple Phase II clinical studies along the way in 2022. Specifically, beginning with the balance sheet, We ended the first quarter with $146.8 million in cash and cash equivalents compared to $141 million at the end of 2020. Revenues for the first quarter were $1 million compared to $0.8 million for the same period in 2020. These revenues were related to our research collaboration agreement with Allergan, now a subsidiary of AbbVie. The collaboration agreement has come to its predetermined contractual conclusion, and accordingly, we expect no future revenues associated with it. The majority of our spend was focused on research and development related to our ongoing clinical studies across chronic pain and cognitive impairment. R&D expenses were $10.3 million for the first quarter compared to $11.5 million in the same period in 2020. We expect R&D expenses to increase throughout 2021 on account of our three ongoing clinical studies, as well as our planned Phase IIb study of NYX783 in PTSD. We reported G&A expenses of $5 million for the first quarter, compared to $4.9 million for the same period in 2020. Finally, our net loss for the first quarter was $14.2 million, compared to a net loss of $14.7 million for the same period in 2020. I'll now turn the call back over to Norbert. Thank you, Ashish.

This is an exciting period of time for Apptenix. With our three ongoing studies progressing very well, and with another PTSD study to be initiated in the coming months, this year and next will be critically important for us as we seek to bring better therapeutic options to patients in need. We feel confident that our focus on execution across our clinical programs, along with our strong financial position, will enable us to achieve multiple potentially catalytic milestones within the next 12 to 18 months. We will be happy to begin taking your questions now. As we field the questions, I'd like you to keep in mind that we will be limited in how much we can talk about our next PTSD study as we are still awaiting the minutes of the meeting. With that said, I'll open it up for Q&A now.

Thank you, sir. As a reminder, to ask a question, you will need to press star 1 on your telephone keypad. Please limit your question to just one question so that we could... so that all participants can ask a question. Please sign by while we compile the Q&A roster. Our first question comes from the line of Myles Minter from William Blair. Your line is open.

Myles Minter Hey, thanks for taking the questions and congrats on the SBA meeting. My first one is just on the SABP data. and the correlation that you saw between enhanced efficacy with the 50 milligram dose in patients that had a more recent traumatic event setting off their PTSD. I guess, given you have those learnings now, how are you thinking about incorporating those into the trial design? Would that be something in the inclusion exclusion criteria for that trial or would it be something more like a pre-specified analysis where you might want to stratify those patients once you have the data set thank you my that's a terrific question i'm going to have andy kick it off with giving you a sense of where how we are thinking about that at this point

Yeah, thanks, Miles. Good question. You know, like Norbert said, we can't sort of be definitive about this. I think one thing we would say on this specific question, though, you know, is our preference would probably be to avoid entirely excluding patients with a longer time since trauma, and we'd probably be looking to other ways to incorporate that learning. But we can be more specific once we've finalized the study design. I think that's the only point we'd want to make right now.

Okay, fair enough. And then we've been talking to a few clinicians. I think the clinically meaningful improvement on the total CAHPS5 is 10 points from baseline with the treatment. You definitely saw that in the SPCD trial. But they also made a comment on four points over placebo. I guess does that kind of jive with what... you would anticipate being clinically meaningful over placebo? And I guess the obvious question would be, you expect to obtain that going from four weeks of therapy to eight to 12 weeks, like you're stipulating?

Yeah, I think that's roughly right, Myles. I think we would expect to see perhaps continued improvement over the course of four weeks to eight weeks, as well as a few other factors, I think, again, which we can get into more in the detailed study design that might help us out, as well as obviously the study being larger. So yeah, I think that's fair.

Okay. But just to be definitive, you'd agree that a four-point move over placebo would be the clinically meaningful threshold here?

I think it's in the right direction, but I don't think we'd be pinned down to that exact number. Again, as we design the study, we'll think about specific effect size that we're looking to see and that we're powered to show and so forth. And again, we probably can be more specific down the line.

Okay, cool. And my final question is, congratulations on Joan Miller on the board. That's a great appointment. She obviously has extensive expertise in ophthalmology. So maybe this is a broader question, but it does beg the question whether you're going to potentially look at expanding the NMDA modulator platform into ocular indications. Is that something you're thinking about, or am I completely on the wrong, out of the ballpark on this one?

No, so I think really our excitement about Joan joining the board is really her extensive academic and medical leadership experience that we pointed out in the press release, as well as her involvement in clinical development and clinical research, all the way to basically having been instrumental in getting the first therapy approved for AMD. So that is terrific. I think, as we have communicated before, that there are numerous other areas in which NMDA receptor biology is relevant. and shown to be involved in various diseases beyond what we currently have on our plate. But for now, we will stay the course with the indications we are in and see where we go from there. And when the time comes to basically extend our scope, I look forward to Joan being a key contributor to actually help assess what makes the most sense and how to go about it.

Once again, as a reminder, please limit your questions to one to allow other participants to ask a question. Our next question comes from the line of Charles Duncan from Cantor Fitzgerald. Your line is open.

Yeah, thank you, Norbert and team. Congrats on the progress in the quarter. I did have a question I wanted to follow up on, on the PTSD program, 783. I guess I'm wondering, you mentioned having a positive type C meeting. Can you provide any color? I know that you're waiting for the meeting minutes, but any key takeaways that you consider positive? Was it positive with regard to the agency's awareness of the challenge of PTSD or the mechanism of 783 that could be differentiated or some design feature that you want to point to. And then I did want to ask you, recently the MDMA trial has been read out, and I'm wondering if there are any new kind of thoughts that you have on PTSD and the opportunity there given the MDMA results. Thanks.

Terrific. Thank you, Charles. So, look, the Type C meeting was very positive in that I think there is a clear acknowledgement and recognition that PTSD is a significant challenge we have for which there are very limited treatment choices. And I think that is in support of new mechanisms and new approaches to finding ways to actually serve sufferers from PTSD much better. I think it was also positive in that what we had communicated before as the outline of our study is indeed roughly how we will go about it. And as we pointed out, There will be details and nuances to that that we will communicate at the right time, but I am pleased that what we outlined and communicated before is very much in line with what that Phase IIb study is going to look like. On the MDMA results, I think that's actually very, very encouraging for a number of reasons. First and most importantly, it looks as if it truly makes a very meaningful difference to patients who have actually been treated with MDMA compared to placebo and CBT. And what I like about it is that in our definition of what the mechanisms are that need to be active here in the treatment of PTSD, it truly is about plasticity changes. It's basically, I would say in crude terms, a reset of the cognitive networks, and I believe that Our mechanism of NMDA receptors and plasticity enhancement works along those lines, as we have shown. And I very much like that mechanism and the superb safety profile and tolerability profile that comes along with that, that we have now established with three of our compounds in pretty large numbers of either healthy volunteers or patients. So I think that differentiates us. That's why we are really excited about where we go about and how we go about PTSD and other indications.

Yeah, I was hoping you'd make that mechanistic connection, and I appreciate you taking my multi-part but single question. Thanks, Norbert.

If you have another one, I'll let you sneak it in now, Charles.

I have many, but I want to be respectful of the other people on the call.

All right. Maybe when we have time at the end, you get back in the queue.

Yeah.

Yeah.

Thank you.

Our next question comes from the line of June Lee from Thruway Securities. Your line is open.

Hello. Believe me, you're listening in for June. Thank you for taking our questions. Regarding the phase 2B trial for 783 in PTSD, what proportion of civilian and military PTSD patients will be enrolling, if you could give us some comment on that? And how do you think these will relate to moderate versus severe PTSD at baseline? And do you expect that similarly to 2925, where you saw bigger effects on advanced DPN patients, there will be a larger benefit of 783 also in patients suffering from severe PTSD or having PTSD for a longer period.

Okay. Let's see how we can tackle this as a team. So I'm going to just get to your part of the question that relates to the DPN study and patients with more established longer duration of disease. I just made the comment to Charles that we are looking at this from a point of view of plasticity changes. And in DPN, of course, the disease, the neuropathy starts in the periphery, but over time, it manifests itself centrally and does cause changes in how pain is actually perceived and processed. So mechanistically, it makes perfect sense that advanced patients, those that have suffered from the disease for a longer time, have a more pronounced manifestation of the pain perception and processing issues in their brain, which is why we actually rely on the earlier study we have done by saying mechanistically it makes sense to have the current phase 2b study be focused on patients that have had a longer duration of disease. I think that answers your DPN question. Let me have Andy give a try to the PTSD study, but as I said already, as it relates to patient numbers, size of trial, and parameters as such, we will not and cannot comment on that until we actually are, first of all, in possession of the minutes of the meeting and have further designed and finalized our study design, okay?

Yeah, thanks, Robert.

I think the one thing we can reiterate, because we did make the point that the study design we had outlined to you in prior calls and so forth is still the direction that we are heading, that we still, as we said before, plan to enroll a fairly broad PTSD population. And our general philosophy would be to try to include as representative a patient population as possible of the entire PTSD population. patient group. But beyond that, I think at this point, we can't comment more. Obviously, there will be some specific inclusion-exclusion criteria we will apply, and I think we can comment more on those once we finalize the study design.

Thank you. And very quickly, Samar, in 458, where you showed a doable benefit on this acute injury NHP model of Parkinson's, how do you think this would translate to a disease setting where you expect less NMDA receptor expression?

Okay. If I understand your question right, you are asking a mechanistic question as to how 458 goes about in our, actually, view of the data about its potential therapeutic benefits in cognitive impairment. And I'm going to have Harald actually address that question. Harald, if you wouldn't mind following up, please.

Yeah, of course. I mean, one of the observations which led us first and foremost to basically combine the indication of Parkinson's disease dementia and dementia with Lewy bodies is that they have a similar pathophysiology, which is based on an increase in alpha-synuclein, which is really the basis of both of these disorders. and it is known from preclinical studies that alpha-synuclein leads to a downregulation of NMDA receptors. It has been demonstrated in a number of animal models. We have our own data on the effect of NVX458 where you actually see that This is a compound which upregulates an NMDA receptor. So in a very mechanistic way, we have the working hypothesis to say that we are basically reversing the downregulation which is induced by iposinuclein and expect to see beneficial clinical effects by this fairly simple, if you want, reversal of the pathology. As I said, that's a working hypothesis. It's based on animal data, but I think this is as strong as it gets in this space of science.

Our next question comes from the line of Laura Chico from Wedbush. Your line is open.

Good afternoon, and thanks for taking the question. I will try to focus it to just one. And I'd actually like to ask one on 2925 and the fibromyalgia study. So there was recently a published study on fibromyalgia that examined weather sensitivity trends in a relationship to NRS scores. So it was interesting that nearly two-thirds of the subjects were deemed to be sensitive to weather and ended up having worse NRS scores. Just looking at the geography for the Phase II study for 2925, you've got a pretty diverse sampling here across different U.S. regions. And just wondering if you could talk to, A, maybe your thoughts on how you might be controlling for that variable in the study, but also, B, just remind us about any powering assumptions on the primary endpoint. Thanks very much.

Great. Thanks, Laura. Catherine, would you like to take that question and share your thoughts?

Yeah, I think as you notice, we've got a diverse and kind of wide geographic spread of our sites. So I think with respect to that impact, we certainly could look for it, but would also expect that with enrollment across that wide variety of sites, that it shouldn't dramatically impact our results. We should still have results that are interpretable in a general sense. I guess also just to say, if this is something experienced by fibromyalgia patients, we'd want to account for it in any therapy that we bring to market as well. So it'll be interesting to explore it as we go.

I believe this has also been noted in diabetic neuropathy and other kinds of chronic pain. It's not, I think, that uncommon or unique to fibromyalgia. And, you know, I agree with Catherine that, you know, we have the appropriate, I think, geographic spread and powering of the study to cope with it.

Our next question comes from the line of Mark Goodman from SVB Learing. Your line is open.

In orbit, I was hoping you could give us some color on the enrollment for 2925 and the studies. I mean, any type of... Color would be helpful. Dropout so far, anything? I mean, where are we in the process? Thanks.

Great, Mark. Thank you. You know from previous communications that we don't actually offer any specific details on enrollment of our studies. I can share with you that as we design studies and basically map them out with respect to size as well as timeline, we take into account numerous parameters, including dropout rates and the like. And as I made my comments in the prepared remarks, we are, much to my delight, on track with enrollment and confirming that the readout of our data is in the first half of 2022. And so you can deduct from that that we are satisfied and pleased with the trial and how the trial is actually conforming to what we had set out to be the likely parameters of the study. But that's typically where I limit it to discussing our studies as they are ongoing studies. So far, so good.

And then just a clarification on one other thing, the Parkinson's and the Lewy body patients that you're enrolling, I think you said it was 100 in total Will this be pre-specified for both groups, and are you trying to do half and half, or are you just taking all comers and either? How is this working?

Yeah, Mark, so we are not pre-specifying or stratifying in a particular way. And so, you know, it's likely, based on what we know about patient numbers and about the extent to which, you know, those patients are diagnosed and likely to seek entry into clinical trials, that it will probably be a mixture of all of the three of Parkinson's, MCI, Parkinson's disease, dementia, and dementia with Lewy bodies. So, yeah, we expect a mixture, but we haven't got any stratification.

Thanks.

Our next question comes from the line of Ritu Baral from Collin. Your line is open.

Good afternoon, guys. Thanks for taking the question. I understand that you haven't nailed down the final design of the Phase III PTSD study, but as you think about Phase III Study 1, versus phase three study number two, is the FDA sort of generally in alignment that the two studies can essentially be identical? Do you think that you might have sort of orthogonal populations that you might want to investigate separately? Could you address that? And then I've got a very quick follow-up.

Yeah, Ritu, that can address that for sure. And we should clarify, it's a Phase 2b study, and so we've not had an end of Phase 2 meeting. This is a Type C meeting. I think when we say that we believe that this study, if positive, could be used to support registration and could potentially be a pivotal study, As Norbert said in his remarks, that's very much a matter of future FDA review. We certainly want to design the study to allow for that possibility, but it would be a matter for FDA and what the data say. If that's the case, then we expect complete one further pivotal study, but I think that's also what that would exactly look like is part of what we would wait until we have FDA minutes and until we finalize the study design to comment on any more.

Got it. And then just on your 458 cognitive study, you mentioned you're looking at multiple cognitive endpoints, attention, memory, and executive function. How do you prioritize those three? Some of your competitors with different mechanisms also looking at Parkinson's cognition seem to be focusing more on executive function. And I guess I'm wondering if that's based off of guidance or communication or KOL opinions.

So first of all, as we point out, it's an exploratory signal-finding study. So we basically want to give us the opportunity to look across multiple neurocognitive results in no particular prioritized order. We know from 458, from the preclinical studies we have done, that it is very much a compound active across the domains we are talking about, executive function, cognition, learning. And that's what we actually want to confirm so that we can then use that information for the next study just like we have done in the other indication. to be much more targeted as to what specifically we would then be looking for. So here we give ourselves the opportunity to be broader without prioritizing any particular endpoint per se.

Maybe just that the competitor that you're referring to has made a comment, I think, that they were expecting to see more of an improvement on executive function and not perhaps so much on attention. We don't sort of exactly know what data may have informed that expectation. I think if you recall, our preclinical data that we achieved in a model in non-human primates, the MPTP model, generated really robust findings across relevant cognitive domains. And so we have no prior such expectation. And that's why we are studying all of these different cognitive domains, utilizing the different endpoints and cognitive tests in the different areas. And we will see what the data says.

Great. Thanks for taking the question.

Our next question. Our next question comes from the line of Gary Nachman from BMO Capital Markets. Your line is open.

Thanks. Good afternoon. Just following up on 458, just remind us why you're just using the 30 milligram dose. Do you think there's a chance that you would need to change the dose at some point down the road, depending on the outcome of the study? And then while you're focused initially on Parkinson's and Lewy body dementia, what are other cognitive dysfunction indications that it could potentially inform you on once you have that data in hand? Thanks.

Great. Thank you, Gary. So I'll take the first part of your question. Gary, I think I mentioned before that we do very extensive preclinical work in looking at dose ranges as to where we see the most effective dose of our compounds. And we then confirm the presence of compound in healthy volunteers in phase one to make sure we can correlate brain exposure to the preclinical models. We have now done studies in fibromyalgia, in DPN, and in PTSD. And I can say with truly a level of satisfaction that we have been pretty much right on target picking the right dose or predicting the dose that would be the most effective dose in the ranges we have looked at. So here we have a pretty high level of confidence that the 30 milligram dose is the right dose to do this exploratory study. But without a doubt, we will in future studies do dose ranging as well, which we would do for our own benefit and also because it is a likely requirement that the agency would have. But there's no reason to burden this first exploratory signal-finding study with dose ranging on top of just the signal detection we want to see. And then there was a second part to your question.

Yeah, I'll repeat it if you need me to. Yeah, just the data that you'll have on the Parkinson's and Lewy bodies, dementia patients, yeah, how is that going to inform you for other potential cognitive dysfunction indications?

Yeah, I think generally, you know, and I think Harold ran through the mechanistic rationale earlier that in Parkinson's disease, you know, part of the neurodegenerative process results in reduced NMDA function, but that's not unique to Parkinson's disease. You know, quite a few different causes of cognitive impairment involve impaired NMDA function. And so I think once we have clinical proof of concept in this area, we've always thought that we had broad applicability in multiple different causes of cognitive impairment. And I think that remains our plan. OK.

Thank you.

Thank you.

Our next question comes from the line of Chris Raymond from Piper Sandler. Your line is open.

Hi, this is Allie for Chris today. Thanks for taking the question. So on the 783 data at SOBP, it was really helpful to see the additional analyses adjusting for baseline imbalances in time since trauma for stage one of the trial. Just wondering if you've run that analysis on patients in stage two of the trial and if we can expect to see that or any other additional analyses presented at some point. And then just related to that, hoping you could characterize the kind of feedback from the PTSD physician community since presenting the data at SOBP. Just any color on what most stood out to docs on the data itself or the mechanism of 783 or other aspects of the program. That would be helpful, too. Thanks.

Thank you, Ellie. Great questions. I'm going to have Harold actually provide you with the answers because he actually if the one who actually presented the data and was there at the SOBP meeting. So, how about if you could tackle that one?

Yeah, of course. I mean, just to say, if you want, adjustments of the analysis were really motivated by the data as they fell, if you want. So there's some randomness, of course, from a baseline perspective. You don't know, particularly in a smaller study, what the specific characteristics are. And as we presented on our poster, there was a significant imbalance regarding baseline severity on the CAHPS-5 and also the time since trauma. So this basically motivated us to do this additional analysis, which is, I think, scientifically the right thing to do. We want to make sure that you compare efforts with efforts and not with anything else. Regarding the stage two, we are in somewhat... Yeah, unfortunate situation that a much smaller number than originally anticipated ended up in stage two, which basically makes stage two much underpowered in order to come up with any conclusive results. We also didn't look for imbalances in stage two because we compared 11, 12 subjects who were actively treated with, I think, 16 subjects in the placebo group, this is just not meaningful, whatever would have been the outcome of this analysis. Regarding additional analysis, we wouldn't exclude that we are doing any additional post hoc analysis based on new evidence. Sometimes a nice publication comes out, you want to verify if you see the same thing. But I would say that at this moment in time, the bulk of the analysis has been done. And I would say to our satisfaction, we understand the data structure quite well and move forward with this justification based on the data.

And Ellie, to your second part, maybe I kick it off. So mechanistically, what we target with 7A3 is really a hypofunction in the prefrontal cortex of NMDA receptor activity and what is well known to be a conditioning to a fear that really describes PTSD and why people suffer from PTSD because they can't properly extinguish that fear and consolidate that fear extinction. And we have shown preclinically that 783 is indeed active in the area of fear extinction, accelerated fear extinction, as well as consolidation. So we believe that this is a more mechanistic rationale that addresses the underpinnings of PTSD compared to the only two other approved therapies in PTSD today which are both SSRIs and of course helpful when you have symptoms of depression as an example, but they don't really get to the underlying root cause of what makes a distinction between people suffering from PTSD and people who extinguish a trauma without becoming PTSD sufferers. That's important to keep pointing out. Harald, I don't know if you have feedback from KOLs that we want to actually

Yeah, to be quite honest, there was not that much feedback. As you know, this was a virtual conference. It was somewhat difficult to get into contact with people. We got ourselves quite a bit of feedback by getting in touch with KOS, but really nothing specific regarding our data.

Does that answer your question, Elie?

Our next question comes from the line of Selvaraju from HC Wainwright. Your line is open.

Hi, team. This is Mazan from Selvaraju. Thanks for taking our question. So I was thinking about NYX783 and came across a negative allosteric modulator owned by Novartis. They've licensed it from Cadent Therapeutics. It's MIJ821, and they're showing safety and efficacy in treatment-resistant depression. Wondering if you're tracking this and if this could pave a precedent for a TRD indication for NYX783. Thanks for taking that question.

Yeah, we're certainly aware of that program, and we followed a cadence and partnered with Novartis and then were acquired. So we definitely follow it. It might be worth a little just refresher on the history of our program and where treatment-resistant depression has played into that. Yeah, hi, Maz.

This is Ashish. You will recall that Aptinix, of course, was spun out of our predecessor company, Norex, as we sold Norex to Allergan back in 2015. The impetus for that sale was Allergan's interest in the data we had generated on earlier chemistry, peptide chemistry, IV-administered therapeutics for the treatment of depression, major depressive disorder, and TRD. We had multiple large, well-controlled Phase II studies across two different peptides, IV-administered peptides, demonstrating compelling effects in depression. As part of that deal, Allergan and we engaged in a research collaboration around our Aptinix spin-out that does put some field restrictions on Aptinix, and included in those field restrictions is the area of depression. And so we will not be going into major depressive disorder in the near term.

Thanks for connecting the dots there. I'll get back in the queue.

Our next question comes from the line of Jessica Fay from J.B. Morgan. Your line is open.

Hi, this is Daniel for Jessica. Thanks for taking our question. One quick question here. We have heard about the impact of COVID on enrollment in other ongoing Phase II DPM studies. I know you mentioned the pre-prepared remarks as well as in the Q&A that you remain on track for the studies to read out in first half 2022. So curious how much of an impact have the amendments you have made helped with enrollment?

Yeah, great question. Thanks, Danielle. Catherine, I want to hand it to you to just give a quick update.

Yeah, I think we continue to monitor the impact of COVID on our trials. We're happy with the way things are progressing and, you know, manage issues as they come up, but we remain on track as we've described. Thank you.

Our next question comes from the line of Charles Duncan from Cantor Fitzgerald. Your line is open.

Charles, are you there?

Yep. Yeah, I am. I was on mute talking to myself. Sorry about that. Thanks for taking the follow-up. I did have a question on 458. Actually, I'll ask two questions so they're not multi-part. One is on the planned PD and DLB study that you're pursuing. For the PD patients, are these pre-dopamine therapy patients or are they on stable background? And I guess I'm wondering how you think PD cognition shows up relative to, say, movement disorder within that.

Great. I'm glad you took the opportunity, Charles, to follow up, because we have the time to do so. Harald, I'm going to hand that to you.

Yeah, so indeed these are patients which have to be on a stable medication. They can be treated as they would do, but they have to be stable. These patients can have movement disorders, but we have an exclusion to that regard that people who have movement disorders which will then touch here with the cognitive assessments just from the motor aspects would not be allowed to participate. So the general focus is on cognition, but, of course, you have to make sure that there is no interference, if you want, so between the motor dysfunction and just the capability to participate in those tests. So medication should be stable, but are actually broadly allowed.

Okay. That's helpful. And then just kind of a perspective builder follow-up to a previous question. on how big 458 could be or the mechanism, how broadly applicable it may be. And I guess beyond just highly prevalent disorders, it seems like there are some neurodevelopmental disorders that are driven by alpha-synuclein, and yet those disorders are really hard to treat, and patients may benefit for a long time, such as Gaucher or GBA disorders. associated Parkinson's. I'm wondering if you have any sense of maybe going to a more rare disorder paradigm once you see a signal, if it's positive, with 458 and PD.

Yeah, that's great. Thank you, Charles. I think that as we typically go about it, let's establish that we have a reliable signal or set of signals. And then I think we are very open-minded to asking what else should be targeted. I like the idea of rare diseases, of course. And so that goes back to the question of how broad can this mechanism be? And we would certainly look at diseases where a correlation is likely between NMDA receptor dysfunction and cognitive impairment across the board of those that you also mentioned a moment ago.

Okay, maybe I just can. Yeah, all right, go ahead. Sorry about that. So, I just want to say it is indeed a very broad mechanism in that regard that inflammation in general terms leads also to a downregulation of NMDA receptors. Even things like diabetes lead to a downregulation of NMDA receptors. So, I think mechanistically that would be the place to look at because that's what we believe we will be able to reverse. So, but indeed it's a fairly generalizable mechanism with much more implications.

Look forward to the signal next year. Thanks.

Thank you.

We have a follow-up question coming from the line of Ram Selvararaju from HC Wainwright. Your line is open.

Hi, this is Mazan again. Just a quick follow-up regarding NYX 458. I was wondering if you're aiming to coincide the data readout, you know, later this year with a specific conference in mind?

The data readout is actually the second half of next year, to be clear. And yeah, I would say very much like we just did with SOPP, we will look for the appropriate medical or scientific symposium that is suitable for the data presentation and discussion. But we are still quite a distance away from the data readout. So let's see where we come out and what then is sort of like the logical set of conferences we should consider.

All right, thanks very much.

Yep, you're welcome.

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