Ladies and gentlemen, thank you for standing by. Welcome to the Omega Therapeutics investor conference call. At this time, all participants are in listen-only mode. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at Omega's request. I would now like to hand the call over to Eva Stroynowski, Vice President, Investor Relations and Corporate Communications at Omega Therapeutics. Please go ahead. Good morning, everyone, and thank you for joining us today to discuss preliminary data from the ongoing MYCHELANGELO I study. As a reminder, we will be making forward-looking statements during today's presentation. These statements are subject to risks and uncertainties that may cause actual results to materially differ from those forecasted. Important disclosures about these statements and risks can be found in our most recent Form 10-Q on file with the SEC and available at sec.gov. I'm joined on today's call by Mahesh Karande, our President and Chief Executive Officer, and Thomas McCauley, Omega's Chief Scientific Officer. Following introductory remarks and a review of today's clinical update, we will be joined by Dr. Gerard Evan, one of the world's foremost experts on the biology of c-MYC, for a moderated Q&A session. Mahesh will then provide closing remarks and open the call for Q&A with management. Now, I'd like to turn the call over to Mahesh. Thank you, Eva. Good morning, everyone, and thank you for joining us. Turning to slide five. Omega was founded in 2017 by Flagship Pioneering with the explicit intent to truly understand epigenetics at a level no other company has ever been able to, and co-opt this fundamental mechanism of nature to create a unique drug development platform. That's precisely what we have done, and today we are presenting preliminary data from the initial 2 dose levels of our ongoing trial for our lead candidate, OTX-2002. I'm incredibly excited by these early data, which show the first known clinical observation of epigenomic control of gene expression using a programmable mRNA development candidate. These results showed OTX-2002 achieved direct targeting and therapeutic control of c-MYC, a historically undruggable target in all eight of eight patients treated so far. Controlling c-MYC expression pre-transcriptionally holds tremendous promise, not only for this important target, but also other intractable genes. We believe that these findings establish clinical proof of platform for Omega, showcase the tremendous potential of controlled epigenomic modulation with programmable mRNA candidates, and support the potential of epigenomic controllers as the next promising class of innovative therapeutics. We believe this marks a new era of therapeutic development, and we are incredibly energized by the possibilities that lie ahead. Taking a step back, as we think about the landscape of drug development, there has been incredible innovation over the past few decades. Yet despite this, significant challenges remain unaddressed with existing modalities. Whether it be small molecules, dependence on druggable target structures, therapeutic proteins, restriction to cell surface agents, or non-coding RNA gene therapy and editing's narrow range of applicability and safety challenges, it is clear that a completely new approach is needed to help address these limitations. This is where pre-transcriptional control of the epigenome comes in and offers distinct advantages. Targeting upstream enables our epigenomic controllers to bypass the traditional requirements of protein structure activity relationships and is applicable to nearly any gene, irrespective of the structure of chemistry of the target. Such an approach also opens the door for accessing targets historically considered undruggable or difficult to reach and where prior therapeutics have been unsuccessful. Importantly, we can regulate expression up or down in a non-binary or on-off manner, and do so without making edits to the underlying nucleic acid sequences, thereby preserving genomic integrity. Taken together, we believe this approach has the potential to treat nearly any human disease. Moving to slide seven. Let me explain how we do it. Our OMEGA platform engineers programmable mRNA therapeutics designed to precisely target and controllably modulate gene expression at the pre-transcriptional level. First, let's talk about the fundamental biology. We have figured out nature's control and filing system for genes and their regulators. Each individual unit within this system is an insulated genomic domain, or IGD, that contains genes and their regulatory elements. Each IGD acts as the fundamental transcriptional control unit for single or multiple genes it contains. Gene expression is controlled by epigenetic marks made at the regulatory elements. This control system is evolutionarily conserved across mammalian species and almost fully conserved between non-human primates and humans, making translation easier. We have delineated this system of approximately 15,000 IGDs across the human genome and have created a proprietary database of the thousands of unique regulatory sequences, which we call EpiZips or epigenomic zip codes, which we use as precise drug targets. We then engineer bespoke epigenomic controllers that we rapidly and rationally design. These mRNA therapeutics enter the cell, engage the ribosomal machinery, and home into the target EpiZips to apply the intended epigenetic marks, resulting in desired down or upregulation of gene expression. Our investigational controllers are designed to be highly specific in terms of targeting, tuning the level of gene expression as needed, as well as for sustaining the duration of effect, depending on the target disease profile. Underpinning all of this, we have powerful computational genomic and data science capabilities, all powered by AI. This allows us to prospectively design and test our controllers rapidly, leading to potentially compressed timelines to development candidates and INDs. For example, our first program in hepatocellular carcinoma took us 27 months from scratch to getting an IND cleared. Turning to slide eight. As you can see, our platform has generated a robust pipeline of epigenomic controllers across a diverse range of disease processes and therapeutic areas. OTX-2002 is our first program in the clinic and is designed to down-regulate MYC expression for the treatment of hepatocellular carcinoma. Let's talk about MYC, the holy grail of master oncogenes on slide nine. MYC is a canonical oncogene involved in cancer growth and immune evasion in a majority of human cancers. Dysregulation of MYC is strongly correlated to aggressive or high-risk metastatic disease and poor patient outcomes. To date, it has been considered undruggable due to the inability to directly target it, because of its highly disordered protein structure. Additionally, MYC autoregulation makes downstream control at mRNA or protein level virtually impossible. This is why you should not completely turn off or eliminate MYC, because normal cells require a certain basal level of MYC to function. By going straight to the epigenome and pre-transcriptionally targeting the MYC-specific IGD, we have the opportunity to controllably down-regulate MYC to the right levels and not just turn it off completely. OTX-2002 is our first program to target MYC and is in development for the treatment of HCC, where 70% of cases are associated with MYC overexpression. Behind it, we have a second program, OTX-2101, which is currently in IND-enabling studies for non-small cell lung cancer. Shown here on slide 10 are preclinical data showing the mechanism of action for OTX-2002 and our epigenomic controllers more broadly. At a high level, the controller behaved exactly as designed. In the first two images on the left side of the slide, you will see in vitro demonstration of OTX-2002's highly specific on-target engagement and intended epigenetic state change at the target genomic loci. In the third image on the bottom left, these in vivo data show that when OTX-2002 methylated the MYC-specific IGD at the target EpiZips, we saw the corresponding reduction in MYC mRNA gene expression. On the right-hand side of the slide, these actions ultimately translated to the desired changes at the protein level in vivo and robust inhibition of tumor growth in preclinical models. With today's update, we have clinically recapitulated the first three items, which we believe demonstrate early proof of concept of this novel mechanism and gives us confidence that our program may ultimately lead to anti-tumor activity in patients. Moving to slide 11. Today, we announced preliminary phase I monotherapy data for OTX-2002 from the initial 2 cohorts of our ongoing trial. Even at these initial doses, we are thrilled by the results seen to date in all eight out of eight patients, and believe we have now demonstrated the promising clinical potential of OTX-2002. At a broader level, we believe these findings have important implications for Omega, establishing clinical proof of platform and validating the potential of epigenomic controllers as a new class of programmable mRNA medicines that have therapeutic potential to treat nearly any human disease. With that, I would now like to invite Thomas McCauley, our Chief Scientific Officer, to review the data that we have generated thus far. Tom? Thank you, Mahesh. Turning to slide 13, here we show the schematic of the MYCHELANGELO I trial design. This global two-part study is designed to evaluate OTX-2002 as a once every two-week intravenous treatment in both monotherapy and combination settings. Outlined in green is the monotherapy dose escalation portion of the trial, where the preliminary data we're sharing today is from the initial two cohorts. Our dose escalation utilizes a classic 3 + 3 trial design and includes enrollment of patients with HCC and also other solid tumors known for association with the MYC oncogene. We are currently actively enrolling in Cohort 3 and will be enriching for HCC patients going forward. Slide 14 provides an overview of the demographics for patients enrolled in the first two dose cohorts. Patients in dose level 1 received 0.02 mg/kg of OTX-2002, and patients in dose level 2 received 0.05 mg/kg. As this is a first-in-human trial investigating an entirely new modality, we intentionally designed our study to initially evaluate low doses in order to understand the safety and tolerability of our drug as we escalate up to dose levels where we hope to see antitumor activity. There were a total of eight patients enrolled across the initial two dose cohorts. Three of these had HCC, while other tumor types included colorectal cancer, cervical cancer, and sarcoma. These patients had received extensive prior therapy with an average of four prior lines, and included chemotherapy, tyrosine kinase inhibitor therapy, and checkpoint inhibitor therapy. As of the data cutoff of September 18th, up to 10 doses were administered to patients, with an average of four doses received, and one patient with HCC in dose level 2 remains on treatment. Of note, even in this heavily pretreated salvaged population, we saw an encouraging safety profile. Treatment was generally well-tolerated, with no dose-limiting toxicities observed, and the majority of adverse events were grade 1 or grade 2. The most common treatment-related AEs were infusion-related reactions, including things like fever and chills. These reactions primarily occurred during the initial dose and decreased in frequency with subsequent administrations. Importantly, there were no dose interruptions or modifications necessary due to treatment-related adverse events in either cohort. Following the end of the dose-limiting toxicity surveillance window for Cohort 2, there was one grade 4 serious adverse event of AST elevation reported in a single patient. This event was transient in nature and resolved within four days, with minimal intervention consisting of only supportive care. There has been no clear etiology or causality determined for this event, and we do not believe it is due to the study drug. While our pharmacovigilance evaluation continues, we believe there is a strong rationale for this event being related to the patient's underlying disease. Overall, we are highly encouraged by the emerging safety profile observed for OTX-2002. Turning to slide 15, we were pleased to have seen a predictable and consistent PK profile, which closely mirrors what we saw in our preclinical studies. There was a low degree of variability in the PK profiles of both the LNP and mRNA components, which were consistent both within and between patients, as well as across dose levels. In addition, the drug product was cleared rapidly from systemic circulation, as expected, with no accumulation observed after repeated doses. Importantly, there were low levels of immune response, with no related adverse events or impact on PK observed. I'll note here that based on our preclinical data and modeling, the doses selected for dose levels 1 and 2 were below the predicted range in which we would expect to see antitumor activity. As I mentioned earlier, the dose escalation portion of this study is ongoing, and we have recently begun enrolling patients into the third dose cohort. Moving now to slide 16, we show that following administration of OTX-2002, we observed highly specific target engagement and the intended epigenetic state change at the MYC IGD, shown here by robust on-target increase in MYC methylation signal as measured by cell-free DNA. The increased methylation signal was durable, persisting throughout the two-week dosing interval. Impressively, these results were observed for all eight patients across dose levels 1 and 2. Next, on slide 17, we show the downstream effect of these site-specific epigenetic changes on MYC gene expression. As you can see, treatment with OTX-2002 led to rapid, robust, and durable downregulation of MYC expression in all eight patients, with mean reductions in MYC mRNA levels of close to 50% for both doses. Importantly, the methylation increase and resulting MYC downregulation observed clinically were within the ranges that led to robust antitumor activity in preclinical models of HCC. This fidelity of translation from preclinical data to clinical performance gives us confidence that OTX-2002, at the right dose level, could ultimately lead to antitumor activity and clinical benefit for patients. I'll pause here to underscore the implication of these results because it's easy to overlook when focusing just on the data at this level of detail. To take a step back and put these results in perspective, to our knowledge, this is the first clinical observation of the specific and controlled epigenomic modulation of a disease-associated gene. In particular, it shows that we've directly targeted and tunably downregulated MYC, a pan-essential oncogene that until now has been considered undruggable and is known to be implicated in HCC as well as many other human cancers. Now I will pass the call back over to Mahesh. Thank you, Tom. I echo your remarks on our tremendous excitement around this preliminary data. Taken together, these results showcase the promising potential of OTX-2002 and controlled epigenomic modulation. While today's focus is on the early clinical and translational data, I want to comment briefly on the question everyone always asks: What about efficacy? At these early doses, we would not have expected to see antitumor activity. That said, I can share an anecdote on the single HCC patient from dose level 1. This patient was heavily pretreated, with stable disease being his best response prior to joining our study. As he got onto OTX-2002, he reported improvement in his symptoms and well-being to his clinician. At his 12-week scan, his tumor enlarged by more than 30%, and his AFP levels increased tenfold from baseline. Having shown progressive disease by RECIST 1.1 criteria, it would be customary to discontinue study drug at this point. However, his physician felt that the patient was still deriving clinical benefit and kept him on therapy. At his subsequent scan, we saw a dramatic impact on his overall tumor size and AFP levels, both decreasing to levels near baseline. Now, we know this observation would not qualify as a response, given the patient had already progressed, but we do find this clinical occurrence interesting, particularly in the context that OTX-2002's profile may ultimately show that it takes multiple dosing cycles to generate the full clinical benefit of MYC downregulation. The patient ultimately had a new lesion identified and stopped treatment. Of the other patients in the trial, we have one HCC patient still on treatment at dose level two. He just recently had a six-week scan and showed stable disease. We acknowledge that these are still early days, and it would be premature to infer any conclusions from these findings. However, in context of the compelling translational data showing OTX-2002 performing exactly as intended, we are highly encouraged that we are on the right track. Moving to slide 18. We are energized by the data generated thus far, in which OTX-2002 showed an encouraging safety profile, conferred the intended epigenetic changes at the expected IGD, and led to rapid, robust, and durable downregulation of MYC expression in all eight patients. We believe this marks a pivotal moment for Omega and for the field of genomic medicine. We have taken the first epigenomic controller into humans and shown that it is safe and functions as it was designed and engineered to do. We continue to advance OTX-2002 in development and are actively enrolling patients in Cohort 3. We look forward to sharing additional updates as we progress through the trial. Now, I would like to invite a highly regarded professor and leader in the field of MYC biology and cancer research to share his perspectives. Dr. Gerard Evan is a professor of cancer biology at King's College London, and the Principal Group Leader at the Francis Crick Institute in London. He was formerly the Sir William Dunn Professor of Biochemistry and Head of Department of Biochemistry at Cambridge. His distinguished career also includes election to the European Molecular Biology Organization, the Royal Society's Napier Research Professorship, and Fellowship of the Academy of Medical Sciences. His research is focused on determining the molecular basis of cancer, and he's a world-renowned expert in oncogenes and specifically c-MYC. Thanks for joining us, Gerard. Oh, it's a pleasure, and thank you for the introduction. First off, can you tell us about the MYC oncogene? Why is it important in cancer, and why, historically, has it been so challenging to target? Yes. Well, it, it encodes a transcription factor, which is a master controller of many genes, perhaps thousands of genes. And it appears to be the sort of single go, no-go decision-making transcription factor that regulates all the transcriptional processes that together cells need in order to proliferate, talk to each other, to run the cell cycle, change the metabolism, and so on and so forth. And because of this, it, it appears to be non-redundant, which makes it, of course, an excellent target in principle, because there's no way around the need for it in cells, certainly in proliferating cells. So, the concerns... it's, it's been a, an attractive target for decades, but nobody's really has been able to develop a, a way of, of regulating it or inhibiting it. Actually, initially, it was thought that this wouldn't be a very good idea. There were concerns about potential toxicity in normal proliferating tissues, although the actual side effects are minimal. We may come back to that. Then there was this issue that it wouldn't kill tumor cells. Since it was involved in driving tumor cells to proliferate, if you inhibited it, it would just stop the tumor in its tracks, but it wouldn't make the tumor go away. This also turns out not to be the case, and maybe we'll come back to that later. It turns out that actually, when you do inhibit MYC, it activates a cellular and tissue program which causes regression of tumors. In fact, it looks like you don't even need to inhibit MYC completely. In fact, it may not be a good idea to do that. It's far better to blunt it, and that seems to be all that's needed in order to trigger the death of tumor cells and also to act as a prophylactic agent. If you dampen it, there are animal models where you damp down the level of MYC partially, about 50%, and those animals seem to be free of cancers for the rest of their lives. So it's something that needs to be finely tuned, but seems to be a very, very good target in principle, and who knows, now, a very good target in practice. Great. That's, that's great to hear. So then, you know, given that, what are your thoughts on the pre-transcriptional approach to control epigenomic modulation?... in build of MYC, could it represent a more effective and safer way to target MYC? Yes, I think what we really are looking for is a way to tune down MYC, not to what, turn it off completely in a sort of binary way, and which you would get with other techniques, perhaps, you know, like gene editing or siRNAs. They'd be, if they would wipe out MYC completely, and that might cause problems and is not necessary. But one of the problems with MYC, of course, has always been that it's an intrinsically disordered protein, so it's not been amenable to the usual type of let's, get a, an inhibitor design that fits into a cavity in the, in the protein and stops it working. It's not like that. So everyone's been forced to think about other inventive ways of inhibiting MYC. The problems with MYC are, it's got a very short half-life and the RNA and the protein level. So, the problem is... Why is that a problem? Well, the problem is that if you inhibit MYC RNA, it's turned over very rapidly, and if you inhibit MYC protein, it's also turned over very rapidly. So it might be difficult, probably would be difficult, to get a persistent down regulation of either the RNA and the protein. So one way around this is to inhibit the factory that makes it, the machinery that makes MYC in the first place. The genes that regulate it, turn them down, and then you don't get any MYC RNA or MYC protein. So the most Omega approach seems to me here to be sort of fundamentally different. Instead of attacking, as I say, the factory output, you shut down the factory itself, and it takes down the means to make MYC rather than block it upstream. I think this is quite a revolutionary approach and not been tried before, and sounds to me like the way to do it. So then, Gerard, having seen the update today from Omega, could you share your perspectives on the early clinical data generated thus far? Yes. Well, it looks quite remarkably optimistic, I would say. I mean, we used a dose that was not ever thought to be perhaps clinically efficacious, but nonetheless, what we know is there are minimal side effects. There's great PK. I mean, the drug seems to stay around for seven to 14 days. And albeit with low dosage, this dosage is able to induce methylation, which is a means of silencing the promoter of MYC. It induces methylation, and that persists out to 14 days with suppression of the MYC RNA in patients. So I think this is pretty amazing. And the level of repression of MYC expression is about, I think, between 30% and 70%. It varies a little bit from patient to patient, I guess, but that's probably in the range where we want it, in order to be able to, as I say, tune down MYC rather than just shut it down. Yeah. So, you know, I think that segues well into my next sort of question and the thought that I had, right? What level of MYC downregulation do you believe is needed to prompt tumor cell death? And then, these data, as you just, you know, outlined, in your mind, do these indicate that OTX-2002 is approaching those necessary therapeutic levels? Right. Well, in absence, of course, human data, we don't really know how low you would need to go with MYC expression in a human being in order to wipe out its oncogenic functions, but we do have a very good idea in mouse models. It's possible to generate mice which have diminished levels, hypomorphic levels of MYC, either because you've damaged the existing enhancer elements, or we made a mouse, which is a switchable hypomorph, where we can damp down the level of MYC to 50%. It turns out that this 50% reduction makes a huge difference in the ability of MYC not to support normal tissues, but to support neoplastic tissues. These mice really seem to show lifelong immunity from most types of cancer. Certainly, it's been done, I think, with cancers of the GI tract and cancers of the lung and cancers of the pancreas. So from that limited animal preclinical data, it would seem that actually, the diminishment of MYC levels that you're achieving with OTX-2002 is right, smack in the right territory for the way that you would want the drug to work in order to have a therapeutic effect on patients with cancer. So very encouraging, I would say. So that's great to hear, Gerard. And, you know, we talked about the optimism that you shared about OTX-2002. We share that same optimism, not only for the development of this particular drug, but also for the platform and for patients, obviously. So let me step back. So you are one of the world-renowned experts in the field of epigenetics and oncology. You know, when you put these data in context of that, what are the potential implications from these data and from this approach to the broader field of epigenetics and oncology? Well, how high is the sky? I would say. I mean, we know now that epigenetic mechanisms underlie many pathologies, from cancer to predispositions to cancer, to inflammatory disease, degenerative diseases, and even infectious diseases and aging. And we don't really have many tools. We've got tools that inhibit the switch gear of the epigenome, enzymes that mark genes as open and closed and very something. But to be able to go in there and, as it were, surgically modify individual bits of the epigenome- ... I think opens up the many, many possibilities, very many exciting possibilities. It's quite a jungle out there at the moment, but as our knowledge about how the epigenome is regulated and specifies phenotypes in cells and tissues, I think that the tools like yours are going to be invaluable in, as the case, surgically going in there and modifying the things that cause diseases. I think the future looks pretty bright, and there's an interesting treatment landscape ahead. Well, Gerard, thank you. Thank you very much for your time today and for providing your valuable insights. My pleasure. Before opening the call to Q&A, I would like to take a moment to share my perspectives on this data set and its implications for Omega. We believe today's update underscores that OTX-2002 has the potential to be transformative therapy and that these data firmly establish clinical proof of platform. The fidelity of translation from preclinical models to the clinical setting further validates our Omega platform, and we believe, de-risks our other pipeline programs. With the potential to treat a broad range of diseases, including those with historically intractable targets, we believe we have unlocked tremendous value for Omega, and we are incredibly excited by what's to come. We look forward to updating you on our progress as we continue on a pioneering journey to develop a new class of medicine that leverages precision epigenomic control to treat or cure diseases. Now, I'd like to open up the line for questions. Operator? To ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. The first question comes from Roger Song with Jefferies. Your line is open. Great. Congrats, the data, first of all, thanks for taking the question. A couple from us. The first one is very interesting. You say at the lower dose, you don't expect to see this PD effect reaching the designed kind of, or desired kind of level. And also you mentioned as you dose higher, you expect to see potentially will have the clinical activity. How should we understand with the higher dose, maybe greater PK will translate into better clinical activity with the desired PD effect already reached at a certain level? Thank you. Roger, thanks for the question. The way that I would think about this is that as we are escalating to higher and higher doses, we're transfecting more and more target cells, right? Which will have the desired effect, you know, in the target cell population, which should drive efficacy. What we're seeing currently, both in terms of, you know, on the PK side and on the methylation side, for example, we are measuring that in blood and in cell-free DNA, which are both, you know, influenced by a number of parameters, including that transfection rate. And so you would expect to see the sort of dose proportional increases that we see there in the PK and in the methylation measures. However, for the MYC gene expression, which we're measuring in exosomes, that doesn't show the same sort of dose response, and that's not unexpected in the sense that it's because of how we are measuring MYC expression in exosomes, which are shed by tumors in the liver, certainly, but also by healthy cells throughout the body. And so as the vast majority of those cells are healthy and express low levels of MYC, you know, it's our belief, you know, based on the data, that what we're seeing is a blunted signal based on that large background and relative to what you would see in a concentrated sample of tumor cells, which we expect to see when we'll be able to take biopsies from the liver itself. Yeah. Thanks, Tom. And, hey, you know, one thing that I would like to add, that everything that Tom said, right? You know, the interesting thing, Roger, is that, you know, at these doses, we see this exact pattern in all eight of eight patients. So, you know, that tells us that this is probably working in the right way. Please stand by for our next question. The next question comes from Salveen Richter with Goldman Sachs. Your line is open. Good morning. This is [Anomit An] for Salveen. Just wanted to follow up on the previous question on measuring MYC, MYC expression from exosomes. Just wondering if you believe that you're seeing a blunted signal, what do you think is the actual levels of MYC mRNA levels following OTX injection? And then, I guess, could you help us understand the durability profile in the context of DNA methylation, as we know that DNA methylation is a little bit more stable than other types of epigenetic modifications? Thank you. Sure. Happy to address both of those. In terms of the level, you know, from our preclinical data, where we were directly looking at, you know, at the cellular level in xenograft models as well as in human cells, we would expect to see the higher levels of MYC downregulation than what we're measuring here, where, as designed, this molecule is intended to tune down MYC expression anywhere between sort of 70%-90% or so percent, which is exactly the target range that you want to be in, you know, following on Gerard's remarks, in terms of the amount of downregulation that we need to hit. With respect to durability, as you mentioned, methylation can be a long-lived sort of epigenetic mark. In this case, as we, you know, in cells in which we're seeing significant methylation, you know, we are downregulating MYC and inducing apoptosis in a large fraction of those. And so those cells would be cleared. And so the sort of diminution of signal that you see over time really is very likely turnover of those transfected cells. Yeah. Yeah, and I think, [Anomit], I think that's a great question. Look, I think, you know, importantly, this is behaving as designed. And also from a preclinical work, I think the most important thing is the signal being blunted. It's still showing upwards of 50% downregulation at the right time, right? Which is what you want. You know, as you heard Gerard speak about it as well, as well as all the work that we have done preclinically. And, you know, that's what we expect eventually to get to beyond 50% in that, in that range that, you know, anywhere from there to what we have designed the drug for. That should be efficacious in our expectation and what the preclinical work that we did. Great. Thank you so much. Please stand by for our next question. The next question comes from Keay Nakae with Chardan. Your line is open. Keay, your line is open. Hello, can you hear me? Yes, Keay. Yes, we can hear you. Yeah, thanks. Tom, Mahesh, so based on your preclinical work, you know, if you're seeing a nice translation thus far at these first two subclinical doses, you know, what should we start to see, or when should we start to see an effect on tumors? Is it dose three? Is it dose four? So that's question one. Yeah, thank you for the question, Keay. So we are, you know, very excited to have seen, as you said, at these low doses, these pharmacodynamic signals, below, again, below where we would have anticipated to see real anti-tumor activity, based on our preclinical data. You know, as we continue to dose up, you know, we would expect to see clearer signals of efficacy, as, you know, tracking our PD signals. However, one thing I would note is this, you know, this stage of trial that we're in currently is early, right? And we're focused initially on characterizing, you know, safety and tolerability. And, you know, to that point, most of the patients that have been enrolled so far are quite late stage and heavily pretreated, and, you know, with a range of different tumor types. And as such, it's often challenging just based on the severity of their underlying disease, for them to remain on the trial long enough to realize the benefits of cyclic therapy. And so we would expect, you know, that as we continue to escalate and also move into the expansion phase of the trial, you know, where we would expect to see sort of second line and, you know, healthier patients overall, that, you know, that would be a more ideal place to really see efficacy. Right. So appreciating the nature of the disease of the patients coming in the study at this point, you know, how far out, how many cycles do you think you need to see at those dose level 3, 4, to see the tumor response? And then separately, how difficult is it currently to find those patients to get them into the study in the first place? Thanks. No, thank you. So, to the first part of your question, I mean, if you, you know, if you think about the landscape of, you know, both targeted agents as well as chemotherapeutics, I mean, generally speaking, you know, most agents, you need to be on therapy for somewhere between four and six months on average, you know, to reach sort of maximal benefit. You know, so certainly we would hope to be, you know, in or, or perhaps better than that range, but certainly that. I think that's a reasonable ballpark. With respect to the second part of the question about the availability of patients that sort of fit our phenotype, you know, we have a number of, you know, 15 clinical sites open at this point, in both the U.S. and Asia. And so we, you know, we actually have a sort of pent-up demand in terms of patients for enrollment in the trial. Yeah. And I think, Keay, just to add to that, right, I mean, I think like Tom said earlier, that in this part of the trial, you are definitely going to be able to enroll only those patients who have failed multiple therapies, and only later on as we, you know, expand as well as, as we do our combination studies, that's when we will get those patients. That's how clinical trials run. Okay, very good. Thanks. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. Please stand by for the next question. The next question comes from Catherine Novack with Jones Research. Your line is open. Catherine, your line is now open. Catherine, your line is now open. At this time, I am showing no further questions. I would now like to turn the call back to Mahesh Karande for closing remarks. Thank you very much, Michelle. Thank you everyone for joining us today. We are very excited about this preliminary data, which only strengthen our belief in OTX-2002 and our unique epigenomic platform. Please reach out to the company if you have any additional questions. Have a good rest of your day. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.