Cyclerion Therapeutics, Inc. (CYCN) Earnings Call Transcript & Summary

Hello, everyone. Good afternoon, and welcome to the 39th Annual JPMorgan Healthcare Conference. My name is Bedir Shather. I'm a Vice President in the Healthcare Investment Banking team here at JPMorgan. We're super excited to be having our next session with Cyclerion. And I'm going to hand it over to our next presenter, Peter Hecht. But before we do that, I just want to make sure that I've reminded everyone that we have a Q&A session at the end of this prepared remarks session, and you should be able to submit questions through the submit a question link, which is a blue bar on the page. And so with that, I'll hand it over to Peter.

Thank you, Bedir. And thank you to not only yourself, but to your whole team. It's been a great week for us. It's been a really terrific opportunity to participate in the conference and to share our excitement for our mission to develop treatments that restore cognitive function. And if you don't mind lingering briefly on Slide 2, you all can control the slides yourselves. You'll see on Slide 2 that we're a public company, and you'll appreciate that I'll be making forward-looking statements. And then if you can turn to Slide 3, you'll see that we believe that we have, in 6463, a very special drug that our drug hunters are developed, and that it has the potential to really make a huge difference in the lives of patients suffering from cognitive impairment and in the lives of their loved ones and caregivers as well. And we believe it can drive a quite special investment return as well. 6463 is the first in a class of molecules that targets a keynote in a fundamental CNS signaling network. And it's the first to be developed that crosses the blood-brain barrier and works on a core node in the central nervous system that controls multidimensional pharmacology. We've seen really a very promising pharmacology so far in the studies that we've done in the clinic as well as in preclinical studies. And I'll take you through that. We've most importantly seen rapid improvement in biomarkers that are associated with cognitive impairment, and those are across a range of different outputs from this key node in the pathway. And we're using the biomarkers that we have and a guided development strategy to move as quickly and efficiently as we can and to advance through targeted patient populations and to understand the molecule as well as we can, as quickly as we can so that we can unlock value. If you'll turn to Slide 4, please. You can see that we believe that this really has an opportunity to impact a very broad range of CNS diseases. Because of the multidimensional pharmacology, we think it can be used over time broadly. There's very extensive data in the literature and results from our labs as well and also powerful human genetic and network analysis that drove us to focus first on the 2 core areas on the left. These are subsets of selected patients in the neurodegenerative space in Alzheimer's disease with vascular features and a subset of a rare disease in mitochondrial genetic diseases called MELAS. And we'll talk extensively about both of those. Again, over time, we believe that this multidimensional pharmacology has a potential opportunity in a broad range of CNS disorders in neurodegenerative diseases, broadly in Alzheimer's, in genetic -- neurodegenerative diseases like frontotemporal dementia, in some neuropsychiatric diseases. In particular, in schizophrenia and potentially in movement disorders like Parkinson's as well. If you can turn now to Slide 5. Let me tell you a little bit about 6463 and the mechanism. It modulates a key note in, as I said, a fundamental CNS signaling network. It's the first of the blood-brain permeable positive allosteric modulators of soluble guanylate cyclase. As you can see from the figure on the left, soluble guanylate cyclase is the receptor for nitric oxide, which is a very important signaling molecule in the body. It's a gaseous signaling molecule. And 6463 is an endogenous amplifier of that signal. And importantly, because spatial control is so important in signaling and especially in the brain, it's critical that this works really in situ in the right site of action. And that leads to production of cyclic GMP, another key signaling molecule in the body. And that leads to activation of downstream targets. And there is a series of networks through this key node. And we've seen, again, both in terms of a very large body of academic research that demonstrate the critical roles in this network of neuronal function, neuroinflammation, bioenergetics and vascular function. And that all has been both validated and extended through the preclinical work that's been done in our labs and in others as well. So we've been very pleased to be able to confirm and extend those and on the basis of the weight of all of that data. If you'll turn to Slide 6 now, we've advanced the compound through a development program that works to both move rapidly and reduced risk as effectively as we can. I think we all know the history of CNS drug development, and that points out the many challenges and risks in the field, also the enormous need for better therapies and the benefit that good therapies can bring. If you look, starting from the left and the right, we've been taking a stepwise journey to try to -- as quickly and nimbly as we can, understand the molecule and understand its attributes and get it into the best patient population as quickly as we can. So on the left, you can see a summary of what I was describing from both the pharmacological profile that we've seen in those 4 key downstream nodes in the network. We've seen very good drug-like properties from this molecule in terms of pharmacokinetics and pharmaco distribution. It's a nice oral once-a-day pill, it's convenient and simple to synthesize. This was discovered by our wonderful chemistry team. And we have intellectual property very broadly across the space. And we saw, to our great pleasure, the ability for this team to crack the code and get a very good CNS exposure. So on the basis of all of that, we moved the compound into Phase I. Given that it was a first in this mechanism into the CNS, we did a quite extensive Phase I program with single ascending dose, multiple ascending dose and a food effect study in 110 subjects. And saw, again, a very good safety and tolerability profile and similar PK PD. In other words, nice once-a-day dosing, good evidence of engagement with the target that we're seeking the soluble guanylate cyclase and a good therapeutic index for selecting our dose. And in addition, we saw the kind of exposure that we were looking for that we had seen in preclinical as well. On the basis of that, we went into a translational pharmacology study. This is in healthy subjects, but older subjects, over 65, we thought we'd enrich for a larger therapeutic index to give us a chance to look at some of the potential markers of aging and cognitive impairment that we expected to see based on the literature and the preclinical data. And I want to spend the next 4 or 5 slides focused on what we've seen from that study because I think it's really quite encouraging. So if you can turn now to Slide 7. This is a summary of what you'll hear in the next few slides. Across a range of biomarkers, each of which is biologically associated with aging or cognitive impairment. We saw rapid and persistent improvements in those biomarkers. And this is in a quite small and quite short study. This is 24 healthy elderly subjects. It was a 15-day study. So to be able to see such robust signals in these markers, in such short study in a small patient number gave us cause for real encouragement. I think also the robustness of the signal, the fact that we see not only the particular biomarkers that I'm going to tell you about, but associated markers in the various studies that we did, all moving in the right direction. Suggests to us, again, sort of on the weight of evidence, a very encouraging read. And I guess to put that a different way, there's nothing going in the wrong direction, which is also very nice to see. All of these also were more pronounced in the older subjects in this study. And these are all biomarkers that are linked to aging or to Alzheimer's disease and dementia. So we'll go through each of the 4, 1 at a time, but that's the summary. So now with that, let's go to Slide 8 and look at quantitative EEG. So I think mostly you guys are aware of qEEG. It measures brain waves and electrical activity in the brain. And we saw really a very clear signal in alpha power, and a very good trend in gamma power, both posterior and anterior gamma power. And this alpha signal was clear and sustained over many hours in the -- on the 15th day when we measured. It was, as I said, more pronounced in elderly. You can see on the left, this is a top-down schematic of aggregated patients or subject's skulls head down nose up top. There's a quite pronounced effect versus placebo or versus baseline in the posterior alpha. That's in the occipital zone. And occipital alpha emerges from the signaling circuit between the cortical and the thalamic neuronal networks. And it's thought to be involved in coordination in that circuitry. And slower and lower amplitudes are associated again with aging and are one of the earliest diagnostics in Alzheimer's. So this is one where when we showed this to key opinion leaders in the field, there's been universal enthusiasm. And again, I think the strength of the signal and the robustness in a small short study makes us quite encouraged. The other powers, gamma and so -- and all, again, go in the right direction and give us further support. You're going to hear the same themes as we go through. So let's go to Slide 10. And if you look there, this is an aspect of event-related potential study that was done with these subjects. This is an auditory event-related potential. And the mismatch negativity latency was substantially improved. It was a significant improvement. That's a quite tight measure in these subjects. And the latency tends to get longer over aging and in neurodegenerative diseases with cognitive impairment, both with Alzheimer's and with schizophrenia and cognitive impairment schizophrenia for instance. And if you look on the right, you can see that the improvement is more pronounced in the elderly subjects. Here, we've shown an idealized schematic of the data, but that's the actual data in the background. So -- and that's also significant. So now on Slide 10, you'll see, again, this is a measure called saccadic eye movement. It's an objective functional measure associated with cognition. They're the short, fast simultaneous tracking that your eyes do together around visual movement. And it's reflective of attention on an aspect of cognition. And again, aging is associated with longer reaction times and slower velocities. We saw -- you can see here with the data, a significant decrease in the saccadic reaction time. And so then if you turn now to Slide 11. This is a panel of biomarkers where we looked in the cerberospinal fluid of the study participants. And we observed intriguing improvements in a host of biomarkers. And I want to focus on the top 2, but I do want to encourage you to observe the directional trends. Again, here, we're showing the example. But this is the sort of thing we're seeing in the other measures as well, sort of the bulk movement in the right direction. And these are frequently involved in similar biological networks. And in this particular case, the top 2 alpha-2-macroglobulin, that's a protein whose levels predict cognitive decline and development of Alzheimer's disease. And it's thought to be involved in some way in tau hyperphosphorylation and complement C3, a central element of the complement cascade also is elevated. And it also is known to both co-localize with A-beta plaques and tau tangles. And it's known to be also involved in synaptic remodeling of plasticity and thought to be involved in degeneration in Alzheimer's and maybe in schizophrenia as well. So again, summarizing the last 4 slides, I think we found it quite remarkable to see such clear and robust signals of drug activity in a short study in relatively few patients. To see signals across measures of neuroinflammation and neuronal health and neuronal function that we believe are potentially different domains of the downstream network from this key control node is consistent with the central role that we believe the target plays and is, again, consistent with the polypharmacy that we think we may be able to hit. And again, everything's pointing in the right direction, nothing in the right wrong direction, which, in these early studies, particularly with the novel mechanism, is encouraging, again, with very good safety. So let's move to Slide 12, please. What we've done -- so now I want to bring you back to the development strategy. What we're doing is applying those accumulated learnings from the preclinical data that we had generated in the literature from the single multiple-dose Phase Is, from the Phase II -- the Phase I translational pharmacology study and the biomarker activity we've seen and the very good safety and tolerability that we've seen to date. And we're aggregating all of that and moving really rapidly ahead to the first 2 exploratory studies. These are both studies where we're working in focused patient subsets. And we're hoping that getting into the patient populations, we can both begin to evaluate disease symptoms and also where the various biomarkers and other symptoms have a larger therapeutic range and may amplify the signals we've already seen. The 2 initial indications that we're focusing on are subset of Alzheimer's called Alzheimer's with vascular pathology and MELAS. Both are characterized by a strong scientific rationale, by focused patient populations. And in both cases, by very large unmet patient needs. So let's spend the next few slides on both of those studies. If you can turn with me to Slide 13, please. We'll start with ADv and describe what that is. It's a defined set of patients at the intersection of Alzheimer's and vascular dementia. It's an area of extremely high unmet need, given the patient symptom burden and the lack of approved therapies. Given what's known about the role of nitric oxide and related vascular inflammation, neuroinflammation, neuronal dysfunction, we're quite excited to evaluate 6463 as a potential treatment for this. You'll see today, we're working to study in a relatively small -- relatively short study so that we can try to get after these endpoints quickly and reduce risk as well as we can. And as we move forward, we'll look to do longer symptomatic trials focused on cognition as an endpoint with that as potential approval. And over time, we hope to expand out into both broader areas in dementia and potentially in outcomes. So if you'll go with me to Slide 14, here's a quick summary of the study design. We've taken a little time to incorporate the exciting findings that we had from the translational pharmacology study and also to extend the study to a longer 12-week design based on the potential that we'd really be able to start seeing patient symptoms. And we were able to get longer [indiscernible] coverage to do so. And so we're submitting the IND, and we're on the verge of doing so. And we'll start up as soon as possible follow getting the idea. We say we're expecting to initiate that mid-year. And if you look at the enrichment strategy, again, we're insisting on confirmed Alzheimer's pathology, at least 2 cardiovascular risk factors. And small vessel disease on the MRI, and we're looking in patients with mild cognitive impairment of 20 to 26. Okay. Turn now to Slide 16, and let's talk about MELAS. MELAS is a serious rare disease. It has, again, associated symptoms that are diseases -- symptoms that are associated with NO deficiency. There are no approved treatments for this disease. Patients with MELAS experience metabolic dysfunction. It manifests in CNS symptoms as well as peripheral symptoms. And the way 6463 both penetrates the CNS and has systemic exposure makes that drug potentially very appropriate for this disease. Mitochondrial diseases like MELAS are complex and heterogeneous, and we should acknowledge that drug development has historically been very difficult in this space. And the patient need is dire, and we find the biological rationale quite compelling. So we're starting an exploratory study that aims to mitigate that risk and also allow us to begin to understand whether our drug can help these patients. And we're trying to balance both. If you'll turn to Slide 16, with a study design that we're quite pleased by. It's a 29-day study. It's open-label in up to 20 adults. I mentioned the heterogeneity in mitochondrial diseases. We're working to mitigate that 2 different ways. One is in patient selection. We're insisting that patients, if you look at the enrichment strategy, have all 3 of both genetically confirmed mitochondrial disease with the MELAS mutation, clear Neurological features of all of the aspects of MELAS and elevated plasma lactate as a biomarker of active disease. And so that should enrich for subset of patients that we think we're most likely to have an impact with. I think also in terms of execution, we're doing everything we can to minimize risk and maximize success by working with the best people and the best centers in the field. We're working in 5 of the best clinical centers and with the top clinicians at each of those centers in this area, and they've been very engaged and they're very enthusiastic with us about this study. This study is underway. We're expecting data mid this year. Okay. Turn to Slide 18 (sic) [ Slide 17 ] . Okay. I've been completely focused on 6463. And I hope you can sense the enthusiasm for the data we have to date and the promise that we believe we can uncover for 6463 going forward. I'd like to quickly whet your appetite on the idea that there's more coming from our great team. We've -- de-leveraging the deep expertise and the accumulated knowledge of our drug hunters to create and bring forward some additional, highly differentiated drug candidates. I don't want to go too deep today given the time, but I do want to give just a couple of examples of some cool data. If you look on the left, this is one example where you can see the FMRI pattern of activation of a subset of areas in the brain of a rat upon dosing of 6463. And then you can see an example of a different compound a with quite distinct areas of the brain being activated. This is despite the fact that the receptor that STC that the target for 6463 is ubiquitously expressed in the brain at quite high levels. So a broadly distributed target, a small molecule getting into the brain, but working -- or at least activating different parts of the brain. This is, I think, pretty interesting. A different example on the right of a compound where we're seeing a relative increase in the ratio of CNS exposure over the peripheral exposure in the plasma. This is all very elegant chemistry and pharmacology, again, based on the knowledge and experience of our team. So these sorts of different compounds may be useful for different diseases or in different situations, more to come. But we're excited about what we have coming. If you can turn now to Slide 18. This summarizes, in a pipeline view, what I've been telling you about. We're very focused on delivering value in 6463. We think the molecule has quite exciting attributes and we've initiated the study in ADv and in MELAS. And we have next interesting program coming with more to unveil during the course of 2021. On Slide 19, different way of looking at the same thing. I think I've covered the clinical and pipeline milestones for you there. I should mention that we have a legacy asset that we believe could play an important role in the treatment of kidney disease. And we both want to maximize its value for our shareholders, and we also want to maximize its value for patients. And we're in discussions to get that into the hands of the best partner we can to have that partner take it forward and maximize its value. That's the top bullet under partnerships there. And the second bullet on that CNS network, I would say, we have quite a large number of individuals in and associated with our company with real depth and world-class expertise in CNS. But we recognize we're relatively new as a company and the -- new in the space. We don't have much presence, and we need to grow our presence and our expertise, both internally and externally, and that's a very high priority for us. I've seen in the past that there's nothing like data great compounds attract, attention and assets and resources. But I think there's a lot we can do to make our own luck. So we're very focused on that. And I should say that we're starting 2021 with just under $68 million (sic) [ $58 million ]. And we've worked as a team to very substantially focus our efforts on the core areas that I've discussed with you just now. And we've reduced our burn quite dramatically over the past few months, and we feel good about our cash position. If you'll turn to Slide 20. I just want to conclude by thanking you for time and attention and encouraging you to reach out either now with questions or afterwards to learn more. We're -- I think you can tell that we have tremendous passion for the mission we described and the opportunity to help patients. So please come find us. With that, Bedir, we can bring up the rest of the team and see what questions there are.

Yes, sure. And thanks for the presentation. Peter, do you want to introduce the rest of the team on the call before we move into questions?

Sure. Chris Wright, our Chief Medical Officer; Andy Busch, our Head of our Research and Innovation, Chief Scientific Officer; Anjeza Gjino, our CFO; and Cheryl Gault, our COO, are along with us on the call. And we've had lot of practices. We're well pride. We're ready for you.

Okay. Awesome. So just to remind everyone, you can submit a question through the blue button online. I'll kick us off.

So interesting discussion, Peter, on the 6463. I wonder if you could kind of give us a little bit more information around the translatability of the biomarkers you mentioned from the preclinical to the clinical sensing and ultimately into the -- well treating patients in the clinic?

Yes, super. Maybe let's break that into a couple of parts. Chris, maybe if you could talk a little bit about the clinical evidence and how we're using that in our ADV study? And then maybe, Andy, you could talk a little bit about the connection into the -- from the preclinical to the clinical.

That sounds great. So as Peter outlined, we saw some really interesting findings, particularly kind of on our electrophysiologic measures. So on EEG and also on the ERP, the mismatch negativity or N200. And so we're excited to take a look at those in our ADv study. Those are measures that you can repeat on multiple visits and increase your power and chance to [indiscernible] a difference. And we know that both those measures are impacted in aging and Alzheimer's disease, and in some cases, actually predict whether patient with mild cognitive impairment would go on to get Alzheimer's disease. So we're excited to look at those electrophysiologic measures, in particular, and we're focusing on those as endpoints in our upcoming ADv study. The other area that's kind of really interesting and it's a bit new that Peter mentioned was around the biomarkers, the CSF biomarkers. So it's known that those -- the biomarkers, A2M and complement are associated with the Alzheimer's disease and cognitive impairment and also with some of the more traditional neuropathologic features of the disease, such as the level of phosphotal and A beta. So this gives us quite an interesting opportunity to look at the impact of our molecules on these biomarkers, which are known to be impacted in Alzheimer's disease. And also to see whether we have an impact on measures of tau and A beta in the CSF. So those are 2 sort of focused learnings that we've attained from our transitional pharmacology study, which we'll be applying in our ADv study.

So maybe adding the translatability. Obviously, there's a scientific rationale that through protein kinase G, we phosphorylate creat, which has obviously known, and we've also shown that neuro anti neuroinflammatory aspect, and we've shown that in preclinical models before we went into the translation of pharmacology study, both in rat brain tissues as well as in mouse microglial cells. We could show that LPS-induced increase of inflammatory markers could be nicely handled by 6463 exposure. As a consequence, we actually looked at a whole battery of inflammatory markers in the CSF, and we could show, as Peter said in his presentation on several significant effects, on a number of them, very nice trends of reduction, and none of those inflammatory markers went in the -- what we would consider the wrong direction. And I think Chris made it quite clear that those inflammatory markers, we looked at were also nicely aligned certain -- around certain networks, around the complement pathway, CNS signaling pathway and the extracellular matrix pathway, which certainly increases our confidence that they can be involved in the pathophysiological relevance in different diseases.

Just piggybacking off that. These biomarkers that you've outlined in the presentation, how have other maybe standard of care drugs or drugs in development impacted those biomarkers? Or how should we think about sort of competitive products and their impact on these in healthy subjects?

Chris, I think that's probably your zone.

Sure, sure. So there's quite a bit of evidence in Alzheimer's disease. If you look at the effects of different drugs on alpha and gamma, there's known responses to drugs like Aricept, for example. So we know that some of the approved drugs and also some experimental medicines can have an impact on those EEG measures. And so that's a nice sort of precedence or it just gives us -- we think that we'll be able to -- if we see changes in those measures, that will provide us with some good insights into whether our 6463 has similar effects of either approved drugs or others that are being investigated. And that's the same thing for ERP as well. So there's some interesting findings in ERP, event-related potential showing modulation of event-related potentials by medicines that are either approved or that are in development. So I think there's a number of areas of precedents there so that if we saw effects, we can increase the likelihood that we'd have a meaningful clinical effect in a longer-term study.

Thanks for that, Chris. In your translational pharmacology study, you noted you didn't see any effects on cerebral blood flow and bioenergetics. Is this a function of the fact that we were treating healthy subjects? And do you expect to see an effect once we go into the Alzheimer's disease patients with the vascular pathology or the MELAS patients?

Sure. So yes, I think to your point, what we saw in the traditional pharmacology study was that there was not an effect on blood flow based on FMRI or MRI ASL. And we think that after talking with a number of KOLs about this, the sense was that the -- in healthy volunteers, in particular, the control of strive blood flow is very strong. And that -- you might be more likely to see an effect in a setting where you have a more severe reduction in flow and a broader dynamic range. And we did see some effects at higher -- so in individuals that had lower baseline levels, they may have greater responses. So it's kind of aligned with that. And so we're excited to see what we might find in the Alzheimer's population, given the greater degree of vascular pathology there. From MRS perspective, we didn't see many changes there, and there's not a lot of literature around that. And so we've focused our -- narrowed the focus to primarily looking at different elements of blood flow versus metabolism, at least for ADv.

And maybe let me add, Bedir. That also was actually quite nice translation of what we saw preclinically because preclinically, we saw only with acute IV experiments with high doses or in L-NAME treated rats and animals, which, of course, had a complete inhibition of the NO pathway. We saw a nice effect on the blood flow with the compound indicating that indeed, you need either very high dose or the pathophysiology in the -- going in the wrong direction to have the effect in chronic administration, healthy animals, we did not see an effect on cerebral blood flow. So that fits actually quite nicely to what Chris has described, what we've seen in the translation of pharmacology study.

It's very helpful. One other aspect I wanted to kind of hone in on was this idea, which you mentioned in your presentation of kind of an efficient path of development through these biomarkers. Can you maybe -- and kind of reducing clinical risk, and maybe we've answered some of these questions. But can you maybe elaborate on that a little bit more for the audience in terms of how you -- how much more efficient will -- what is this approach relative to what maybe you might have done? Had you not explored biomarkers initially in healthy subtest?

Chris, I think you probably worker for this one. I know anything, but I probably heard it. Go for it.

Sure. So I think it's really nice about this approach or one of the reasons we moved forward with it is that, it's not [indiscernible] the direct. So like along the way, we're getting information that changes how we design the next study. And we think that, that's going to increase the likelihood of success for that next study because we didn't know for sure that we were going to see these strong effects on alpha. And now we have a great measure that we know is associated with aging and Alzheimer's disease that we can evaluate in a patient population to understand if we're having an effect on that. And that will tell us we're sort of hitting our mechanism in that particular disease. And it's the same thing with the biomarkers. There's a bunch of different biomarkers you could look at. We actually found that 2 of the ones that are most commonly found to be affected in Alzheimer's and where there's a lot of literature support are ones that we've had an impact in our healthy elderly. So we're taking those forward into the next study. And we may not have done that or been able to do it in such a focused way had we not done those initial experiments. And then the idea of the ADv study is now to get through understanding of effects on cognition or disease modification, that may require a very large and long trial. So we can kind of get a sense of are we likely to have effects in those longer and larger trials if we see effects in this shorter and sort of more efficient trials on these key biomarkers where we see our drug hitting the target and having it move in the proper direction. And we know that those targets are associated with Alzheimer's and aging. So if we can sort of reverse those or improve them, we think that would give us a much better chance of seeing an effect in the larger, longer study which would be more of a registration-type study.

Great. And so just to close out, you mentioned on your Alzheimer's disease study or -- maybe it was sorry, the MELAS study, some of the partners and collaborators in terms of the academic collaborators. What about in the Alzheimer's study? Which sort of academic centers are you collaborating with on that study? And then a second question would be, how large are those 2 studies going to be from a sort of patient numbers perspective? And how is the enrollment going on the new apps?

Super. Chris, I think that's you too.

Great. So maybe I'll start with the enrollment and the size question. So as Peter mentioned, for the MELAS study, we have -- we're looking to enroll up to 20 patients to try to get 12 completers. So minimum 12 and most of it would be 20. And so it's a relatively small open-label study, and we're currently just in the early phases of enrollment. So we can give you an update on that as that proceeds. For the ADv study, that's not anticipated to start until the middle of this year. And so we're in the process of completing the protocol and filing an IND in this area. So we haven't yet disclosed the end for the study. We're in the process of completing the protocol and doing some power calculations now. So we're still -- that's still a work in progress, but we're quite far along in the study design. And we have engaged with a number of experts in the area. And you may have heard in some of our earlier investor conferences, we have a number of advisers from MGH and from BU, from University of Calgary, that are all experts in the area that are working with us and helping us to design our protocol. So we haven't chosen all the sites yet because we still have 3 months before we start. But we're working through that as we speak.

Great. Well, so that concludes the questions that I had. And I just wanted to congratulate you guys on the data to date with 6364. And we look forward to -- sorry, 6463. We look forward to 2021 and what hasn't stopped you guys. So congratulations and thank you very much.

Thank you very much, Bedir. And just in closing, let me thank all of you for the time and attention and for joining us in this time, and thanks again to morgan -- JPMorgan crew. And for those of you that are interested, please reach out. We've got a -- I think you can hear a great drug and a great platform, a terrific team and a lot of passion. I think we've got a substantial investment opportunity, too. So whether you're a collaborator or an investor or a potential employee, come find us, we'd love to talk to you. Thanks.