Syndax Pharmaceuticals, Inc. (SNDX) Earnings Call Transcript & Summary

Hey, everyone. Thank you for joining us here at the Goldman Sachs Global Healthcare Conference. I'm really, really excited to be joined by the whole team from Syndax Pharmaceuticals to give us an update on kind of an interesting first half of the year heading into hopefully even more interesting second half of the year.

So let's get started with the kind of big picture view. So team, if you could you then walk through kind of the current Syndax clinical pipeline focusing both on ongoing and kind of planned clinical trials given where you are today?

Yes, Madhu. First, thanks so much for inviting us to participate. It's great to see you in your new assignment. We currently have 2 programs in clinical development, 5613 and axatilimab. 5613 is our Menin MLL inhibitor for which we were the first to validate this target for the treatment of acute leukemias. We presented interim data from the ongoing Phase I AUGMENT-101 study back in April of this year, and we anticipate initiating the Phase II portion of that trial very shortly. We also expect to initiate some studies in combinations with standard of care later this year as well. Axatilimab is our CSF1R monoclonal antibody in development for the treatment of chronic graft versus host disease. And potentially other monocyte macrophage driven diseases. Last December at ASH, we presented our Phase I data in chronic graft versus host disease, again, validating the use of this mechanism against fibrotic diseases. And we recently initiated a randomized pivotal trial for which we anticipate to have top line data in 2023.

Excellent. So why don't we started after that broad introduction by focusing it on the menin-MLL program, 5613. For MLL-rearranged NPM1 mutant blood cancer. So to begin with, why don't we start by walking through the mechanistic rationale for targeting menin-MLL in these specific subsets of blood cancers?

Yes. Sure. So let's start with the MLL-r story. So it's probably more than 30 years ago, people noticed that there was a recurring chromosomal translocation involving 11q in a number of leukemias. Over time, people were able to identify what that translocation was and that translocation resulted in the formation of a novel fusion protein, which is known as MLL-r, MLL rearranged. And it's called that because the left-hand side of that fusion protein always comes from a protein called MLL-1. The right-hand side of the fusion protein comes from a variety of different donors, but it was pretty clear that this fusion protein was driving transformation. Over time, people figured out how this fusion protein drives transformation. In order to do so, it has to bind to a protein, a scaffolding protein called menin. And if you block the interaction of the fusion protein with menin, the fusion protein can no longer transform cells. The transcriptional activation that it drives is turned off and [indiscernible] or differentiate. It then became clear that in NPM1 leukemias, this exact same pathway was operative and using a combination of genetic and pharmacologic experiments, people have shown that, again, this interaction of menin with the amino terminus of MLL-1 is required for NPM1 transformation. And our small molecules are able to preclinically and now we've shown clinically inhibit transformation and provide a therapeutic benefit.

Okay. Great. So following from that, could you walk us through what are the existing treatment options in this subset of leukemias, particularly starting out in the kind of relapsed refractory setting?

Right. For both NPM1 and MLL-r, in either case, are there any agent specifically targeted for these populations of patients. So today, they're generally treated like any other acute leukemic patient. They're in the first-line setting, they all get induction chemotherapy. If they're fit for chemotherapy or they may receive a hypomethylating agent in combination with venetoclax, if they're not a candidate for induction chemotherapy. Once they relapse, unfortunately, the options are really quite limited for these patients. There have been attempts to try to treat them with salvage chemotherapy and unfortunately, they generally do quite poorly. In the case of NPM1 occasionally, you will see patients -- the tumor will have a co-mutation. So in addition to the NPM1 mutation, they may have another mutation and in those cases, the patient may be treated with an agent that targets that co-mutation, such as FLT3 or IDH1 or IDH2.

So to that end, when you think about these kind of co-mutant NPM1 mutant leukemias, like how much dependency is there for anyone mechanism? We might get into that later on when we discuss NPM1, [indiscernible]. How do you think about dependency on one pathway versus multiple pathways and how that could impact therapy in that setting?

Right. So in a variety of preclinical experiments that have been done using leukemia is derived from patients, so-called patient derived xenograft. At least in the case of NPM1 and menin, it doesn't seem to matter what these additional mutations are. So there have been patient-derived xenografts Scott Armstrong's lab has described that have an NPM1 mutation and the FLT3 mutation and the DNMT3A mutation and those tumors are sensitive to menin inhibitors, presumably working through the NPM1 abnormality. So it would appear not fully proven yet, but it would appear that NPM1 seems to be the key driver, even though there are other mutations present.

Okay. So given that context, can you also kind of walk through what you think are the really critical clinical endpoints for kind of assessing efficacy in relapsed/refractory, MLL rearranged and NPM1 mutant leukemia?

Sure. So there's -- I would split your question to clinical endpoints and regulatory endpoints. From a clinical point of view, the goal -- the treatment of any leukemic is to try to get the patient into remission, to try to eliminate their leukemia, and that's what we refer to as a complete response, where either looking under a microscope or using much more sensitive test, you can see that there is no leukemia in the patient. And that's clearly, the clinical treatment goal. From a regulatory point of view, that ability to get rid of the leukemia is part 1 of the regulatory endpoint. The second part is does their blood count -- do their blood counts come back to normal. So this is what's known as CR or CRh. CRh is, their blood counts are at least half normal. And in that case, that means the patient is unlikely to be receiving transfusions. They're unlikely to be suffering from an opportunistic infection. And for the most part, have been palliated from their leukemia. So the so-called CR, CRh is a regulatory endpoint. The other point in these relapsed/refractory patients is, of course, to try to get that leukemia down to a point where not only is it not detectable, when you look at the bone marrow under microscope, but it's not detectable when you use much more sensitive assays, and this is what's referred to as minimal residual disease, MRD or some people call it measurable residual disease. If there is no measurable residual disease, that also is quite an important clinical endpoint in the relapsed/refractory setting, that's not recognized as a regulatory endpoint, but is a clinical endpoint. And then, of course, in the relapsed/refractory setting, there are if you do randomized trials, there's the ability to show that your drug improves overall survival, which is, again, important clinically and from a regulatory point of view.

That's great. So with all of that context in mind, why don't we start walking through the existing Phase I data you all have presented for 5613 in these 2 different settings, in MLL rearranged disease and in NPM1 mutant leukemia?

Yes. So let me just give a little bit of context as we go into this. So in November of 2019, we started a Phase I trial in relapsed/refractory acute leukemia. So at that point, it was an all-comers trial. The patient did not have to have either MLL-r rearrangement or NPM1. It was any patient who had relapsed refractory, either AML or ALL, regardless of the gene profile of leukemia. It's a Phase I dose escalation trial with the primary objective of defining the recommended Phase II dose. And I would just make a couple of points of how this trial has unfolded since November of 2019. The first thing is that given the exquisite selectivity of our compound, our GLP tox data was quite clean, which allowed us to start dosing essentially at a therapeutic dose. So the second patient enrolled in our trial and the very first patient with an MLL-r rearrangement ever treated with our drug at a rapid, deep, MRD-negative durable complete response with full count recovery. So we started the therapeutic doses. And I point that out because one [ worries in ] contrast when you're starting at a dose that's, let's say, 5 to 10-fold lower than your efficacious dose, that generally is an indication that there might have been significant toxicity seen in the GLP tox studies at potentially subtherapeutic exposures. So our recommended Phase II dose, which we've now identified, is the second dose level in [ RMA ] and the first dose level on [ RMV. ] So I think that speaks to how clean our compound is. The second thing, as I mentioned, this was initially an all-comers trial, but because of the efficacy we were seeing so early in the trial, we rapidly focused enrollment only on patients with MLL-r and NPM1 leukemias. So the data set that we presented back in April was 43 patients, of which the vast majority had the specific genetic abnormality that we're interested in. So it is a Phase I trial, and yet we have 31 evaluable patients who have the genetic abnormality of interest. And the last part of course, I'd just point out, this is a Phase I trial. So the patients on average had 3 prior lines of therapy, about 40% had relapsed after a bone marrow transplant, which is a very negative prognostic sign. And almost 60% had previously received venetoclax. So these are very difficult-to-treat patients, and yet we showed that 15 of the 31 evaluable patients or 41% who are eligible for efficacy assessments had an overall response, which again means their leukemia had gone away regardless of the amount of blood count recovery. And we also indicated that 10 of those 15 or about 2/3 of those responders had MRD-negative responses, which, again, we talked about earlier, as a very important clinical endpoint. Four of the patients actually were able to go on to a bone marrow transplant, which is the only potential curative regimen for these patients today. Seven of the 15 responders, or about 23%, had significant blood count recovery that met that criteria for CR, CRh that we talked about earlier as the regulatory endpoint. There are 2 patients at the time that we presented who had not had full recovery but are still on treatment, and we're waiting to see if they recover further. So we've seen responses both in MLL-r and NPM1 in AML and in ALL and that's sort of the top line, I would say, in terms of the efficacy we've seen in the Phase I trial.

Okay. Cool. So to that end, you mentioned that CR, CRh kind of standard. So have you all broken out the CR,CRh rate, particularly in certain patient subsets? Like what is the CR,CRh rate in MLL-rearranged leukemia? What is the CR,CRh rate in NPM1 mutant leukemia?

No, we have not provided that breakdown at this point. Again, these are -- although it's a pretty big Phase I sample, still a relatively small number of patients. We did -- when we presented the data, Dr. Eytan Stein from Sloan Kettering actually presented the data, walked through a couple of patients vignettes. And one of those patients was a patient who had primary refractory NPM1 disease, who had an MRD-negative complete response and went on to bone marrow transplant. So I think we're seeing good activity both in MLL-r and in NPM1.

Okay. And I remember that you also updated the data from your initial presentation of it in April and which you highlighted potential deepening of responses. So to what extent do you expect that kind of trend to continue where potentially you could have patients who might have been responders, but not CR,CRh levels who could deepen into CR,CRh with longer drug exposure?

Yes. So again, as I pointed out, the primary clinical goal here is try to get the patient into a CR, which means eliminate the leukemia. And as I pointed out, that of the patients who had responses, 2/3 of them have MRD-negative complete responses. So if you have a patient who has MRD-negative response and their blood counts haven't fully recovered, that may have as much to do with their bone marrow reserve as it has to do with anything else because essentially the leukemia is really not suppressing that any longer, you've eliminated it. How long it takes for people's blood counts to recover is something that we're continuing to understand as we explore this drug. We have a small number of patients at this point. So we don't know exactly how long. And again, it may depend in part on prior therapies and their bone marrow reserve. So we'll continue to characterize that as we further develop the drug.

Okay. Great. So with that context in mind, another consideration has been kind of raised for 5613, and you referenced it a little bit earlier, is the emergence of QT prolongation events on therapy. Could you please walk through the observations that exist to date, kind of how the QT event has been managed? Maybe more practically how we should think about them on a move forward basis?

Yes. Sure. So let me first start off by saying that 5613 has been extremely well tolerated. No patient has discontinued for a drug-related adverse experience so far in our Phase I experience. We've seen really no other adverse experiences aside from this QT prolongation, which we'll talk about, at any of the doses we've explored. We have not seen any evidence of drug-induced pancreatitis or rash or thrombotic events or other non mechanism based toxicities. QT prolongation is really the only drug-related adverse event that we've observed. And at the recommended Phase II dose, we see about 9% of patients have a grade 3 QTc prolongation. There are some patients who also have either grade 1 or grade 2. What I would say about the QT prolongation is it occurs -- it's an easily monitorable adverse experience. We get EKGs. It's asymptomatic. The patient doesn't know that they have it. We've seen no clinical sequela of this, and it's rapidly reversible. In the patients who have a grade 3 QT, what we do is to pause dosing, the QT reverses quickly. We've dosed reduced the patients. And as you've seen in our presentation, a number of those patients have gone on to have very nice, durable responses. So it seems to us to be quite easily manageable. The leukemia doctors that we've spoken to about this are quite comfortable monitoring this. Again, it's a routine electrocardiogram. If they see it, they may need to dose reduce the patient, but it doesn't seem to, in any way, limit the ability of the drug to work.

I mean, to that end, are there good examples in kind of prior kind of leukemia experience of managing QT prolongation events that have demonstrated the ability to kind of readily manage it, both the later clinical development and more in preclinical practice?

Sure. I mean, there's actually a number. So for gilteritinib, which is a FLT3 inhibitor, has -- there's been observations of QT prolongation with that drug. It's been -- physicians are quite comfortable managing it. Ivosidenib, which is an IDH1 inhibitor also there's been observed QT prolongation. Physicians are comfortable managing that. There are other drugs that are not in the AML space that also have this. But it is something that oncology physicians have seen. And again, the conversations we've had with them is they're very comfortable monitoring for it and managing it.

Great. So with all of this information from the Phase I, it's obviously a work in progress in hand, can you remind us about your plans you have for the Phase II arm of the study and how we should think about how the kind of Phase II cohorts will practically work?

Sure. So we're very close to finalizing our recommended Phase II dose, and then we'll open up our Phase II portion of the trial. The Phase II portion has 3 parallel single arm trials, one in MLL-r AML, one in MLL-r ALL and one in NPM1c AML. So these are 3 parallel trials that are essentially independent of each other. They enroll -- they may enroll at different rates. If all 3 of them are positive at the same time, we could potentially file with all 3. If 1 of them enrolls faster than the other and is markedly positive, we can enroll with just one. So they're parallel Phase II trials. As we talked about earlier, our anticipation is that the endpoint of interest here will be the CR plus CRh and added to that other evidence of palliation such as lack of infections, lack of transfusions, et cetera, the transfusion independence. So those studies should start-up quite soon. We're, as I said, in the final stages of finalizing that recommended Phase II dose, and then we'll be opening those 3 parallel cohorts.

Okay. So when you kind of put all of the data together, what altogether gives you like unique confidence in the monotherapy utility at 5613 and these kind of subsets of relapsed/refractory leukemia?

Yes. So look, I think it's important that you emphasize the word monotherapy. So many times we've seen now recently in oncology drugs that -- the evidence of their efficacy comes from combination studies, which can be a little bit more difficult to interpret. This is not hard to interpret. We're giving monotherapy drug to patients who have relapsed/refractory disease. We're seeing MRD-negative complete responses, durable, both in the case of MLL-r and NPM1. So I think the data speaks for itself. We're quite confident that the drug works for these leukemias.

Okay. So following from that, is there a sense that there could be more monotherapy utility in, say, MLL-rearranged versus NPM1 mutant disease, like how do you think about the kind of relative activity of 5613 in these patient populations?

Yes. So again, the sample size that we've explored so far in NPM1 is a bit smaller. But I would again say that we're quite confident that the efficacy is going to be comparable. Again, if you -- one of the patients that [ Eytan ] presented, a patient with primary refractory disease, did not respond to chemotherapy, went on to our drug, this is an NPM1 patient and had an MRD-negative complete response and went on to transplant. So that's a good indication that the drug works well in NPM1 leukemia. In MLL-r, we have a larger sample size. And clearly, we're seeing a deep MRD-negative responses. So I think our level of confidence is comparable for both MLL-r and NPM1.

Okay. And so kind of to wrap up the discussion of menin-MLL, can you remind us when we can expect the next data update from the Phase I study, given that the Phase II is going to be kind of playing along for a while?

Right. So we don't anticipate -- we anticipate that at a scientific congress, probably the end of the year, there'll be an update on the Phase I trial. We will try to give a little bit of an update after we have our FDA meeting just to clarify for people, what actually is the recommended Phase II dose and to clarify that we now have buy-in on that from FDA, what the endpoints are, what the sample size is for the Phase II. So we will probably communicate some information after our FDA end of Phase I meeting. But the next big update on the data itself would likely come at a medical conference at the end of the year.

All right. So shifting gears over to axatilimab in chronic graft versus host disease. Why don't we start by discussing kind of the pathogenesis of chronic GVHD and how the disease is currently managed, particularly in kind of -- after the initial lines of therapy?

Sure. So graft versus host disease is, as the name implies, the graft starts to attack the host. So these are patients who have undergone a bone marrow transplant. And so we take bone marrow from a donor and put it into a patient with leukemia, that bone marrow transplant is foreign, it's the graft, and it recognizes the patient as far and then starts to attack various organs in the body, primarily because the acute phase of this is driven because of the HLA mismatch. A subset of the patients who develop acute disease will go on to develop chronic disease. And the chronic disease is essentially, in a way, an autoimmune disease, but it's caused by this foreign graft that is now attacking the body. It's managed today primarily with steroids and a number of off-label therapies. There's really only one today approved drug for this, which is ibrutinib. There is no really defined treatment algorithm. And really before the last 5 years, physicians really didn't have a lot of data on which to drive their treatment decisions. There's a high 5-year mortality rate in chronic graft versus host disease. And patients are chronically sort of cycling through potential options until they pass away. As we -- I mentioned, ibrutinib is approved, 2 drugs, ruxolitinib from Incyte and belumosudil from Kadmon are currently under FDA review for chronic graft versus host disease and could become a major part of the treatment paradigm for roughly 14,000 patients or so who suffer from this in the U.S., but it is clear to us that additional therapies are needed, and we're quite excited about what we're seeing with the chronic graft versus host disease.

So kind of paralleling our discussion of 5613 in leukemia, what would you say the key endpoints for thinking about efficacy in chronic graft versus host disease?

Right. So the chronic graft versus host disease, there is a guidance document in -- 2014 NIH consensus guidance document that talks about assessing response. And chronic graft versus host disease can manifest in multiple organs across the body. So you can see it in the skin, in the liver, in the lung, in the eyes, in the mouth, in the GI tract. And for each one of those organ systems, there are specific criteria about what is a partial response in that organ system or a complete response in that organ system. If every organ system has a complete response, then the patient is scored as having a complete response to their chronic graft versus host disease. If one or more organs has a partial response and no other organ has a worsening than the patient is scored as having a partial response to their graft versus host disease. So that gives you some sense of how this disease is assessed. And the 2014 guidelines talk about overall partial response and overall complete response. There is a guideline that looks at the response rate at 6 months of therapy. And so that is, again, trying to get at this question of durability of the response.

Okay. So kind of -- with that information in mind, can you also kind of similarly to menin-MLL walk with us to the mechanistic rationale for going after the CSF1 receptor with axatilimab to treat GVHD?

Right. So as I said, the acute phase of this is -- appears to be a T-cell or B-cell driven disease. But as the disease migrates into more of a chronic phase, it's clear from a number of preclinical experiments that the monocyte macrophage is now coming in and there becomes a chronic fibrotic inflammatory condition driven by those cells. And there was -- there have been a series of preclinical experiments done testing CSF1R antibodies -- which CSF1 is a molecule that drives the proliferation and differentiation of monocyte macrophages. And we know that if you block CSF1, it's one of the major growth factors for those cells. And so you essentially deplete them because they don't -- no longer have a growth factor. And there were preclinical data that showed in animal models of chronic graft versus host disease that you could either prevent or treat the disease with an antibody against CSF1R, which essentially blocks the ability of CSF1 to act as a growth factor for monocytes and macrophages. So that was the rationale that led us to test this in patients with this disease.

Great. So with all this information in hand, would you walk through the existing kind of Phase I data you'll have for axatilimab in GVHD?

Sure. So last December at ASH, we presented the Phase I dose escalation trial. This was a trial where we started at lower doses of axatilimab and escalated to increasing doses in a sort of standard dose escalation done in patients with chronic graft versus host disease, who were refractory to ongoing therapies. And what we saw was that at the -- and actually, all the doses we tested, we saw efficacy seemed to be best at the 1 milligram per kilogram dose. As we went higher on that, we did start to run into what are known mechanism based toxicities of this mechanism. And so we think the 1 milligram per kilogram is sort of the optimal dose. We also opened up a Phase II expansion cohort at that 1 milligram per kilogram dose. And so we've recently announced that we've completed enrollment of that cohort. So we anticipate that potentially at the end of the year, again, at a medical conference, we will be able to present the 23 patients who were treated at the 1 milligram per kilogram dose, as well as an update on the 17 patients treated in the Phase I portion of that trial to give people, hopefully, a pretty good insight into how that 1 milligram per kilogram dose will behave both from an efficacy and from a long-term safety point of view.

So to that end, when we think about the kind of on target tolerability questions that you got to -- saw in the data from last December, kind of very -- almost similar to the QT question, in menin and how do you think about how that's practically managed by physicians, the kind of enzyme signals that are observed and how that could be practically assessed in the course of -- giving a drug like axatilimab?

Yes. So this -- in this case, it is an on-target, on-mechanism, effect of this mechanism, where you see a depletion of a specific form of monocyte macrophage known as a Kupffer cell that exists in the liver. And those Kupffer cells, part of their job is to is to sort of be the garbage can, if you will, cleaning up any debris that comes about just from the natural turnover of cells in the liver. When you deplete those Kupffer cells, you're not clearing the debris quite as well. And so you see liver function test levels increase a bit. Our physicians who have been treating patients with the CSF1R antibody have become very attuned to this. It turns out that those LFT abnormalities are transient and usually just resolved back to normal with continued therapy. And so I think the physicians have become very, very comfortable, just treating right through any LFT abnormalities that they happen to see. The other on-mechanism toxicity that has been reported with this mechanism is swelling around the eyes, so-called periorbital edema. We actually don't see very much of that in this population at the 1 milligram per kilogram dose. But again, that is -- it's not -- it doesn't in any way affect vision. It's really just a more of a cosmetic thing and again, does tend to resolve as you continue to treat.

Excellent. So with all this in hand, walk us through the design of the AGAVE trial, your pivotal trial in graft versus host disease? And how you think about it versus some of the other studies you mentioned, like the ones for ruxolitinib and the ones for the Kadmon compound?

So the AGAVE trial is a 3-arm randomized registration trial. The 3 arms are the 1 milligram per kilogram, which I've mentioned, we believe, is -- will likely be the label dose and is where we saw, we think, good efficacy and safety in the Phase I and Phase II. We're also setting a lower dose of 0.3 milligrams per kilogram. This was at the request of the FDA to sort of ensure that we are at the lowest dose to give maximal efficacy. And then we have a third arm, which is 3 milligrams per kilogram given once a month, which is an exploration of whether a more practical regimen might be useful to patients. So those are the 3 arms. They essentially run in parallel, and we look for efficacy, again, using the 2014 consensus -- NIH consensus criteria for efficacy and standard safety parameters. The trial is actively enrolling now. And the guidance we've given is that we anticipate top line data in 2023.

Okay. So 2 questions that are tied together, how do you think about axatilimab's positioning in chronic graft versus host disease? And I guess, kind of tracking against that, I mean [indiscernible] kind of your perspective [ on data that ] you have like deep views on these. But like, what the heck is going on with the extended reviews, both of ruxolitinib and the Kadmon compound, given they've already completed studies very similar in structure to AGAVE.

Yes. So let me take the last question first, simply to say, I have no idea. I do not -- I don't know whether there's a common theme in the 2 of those studies or if there are unique features to each company. So I really can't make any comment on that. I think in terms of how we see this going into the landscape, the data I've talked about that we presented at ASH, these were patients who had 4 or 5 prior therapies, and we're seeing a very high response rate. So we think that in the trial -- the AGAVE trial, patients will have relapsed after 2 prior therapies. So again, we're confident that we're going to see good efficacy. And we think it will find an important place in the treatment of chronic graft versus host disease. It's the only agent in development right now that is specifically targeting the monocyte macrophages which, as I mentioned earlier, we believe, really is the core of the chronic phase of the disease, particularly the fibrotic component of it. So based upon the trial that we're doing now, we would anticipate that patients will have had 1 or 2 prior therapies before they go on to our drug, at least at the initial launch. Obviously, it would be -- it would make sense to study the drug in earlier lines of therapy as well, potentially even to see if you -- I mentioned earlier that in the preclinical models, you could prevent graft versus host disease. So there could be a study somewhere down the road where we asked, could this prevent the occurrence of disease completely, so that patients don't have to suffer through this.

So to that end, when you look at the kind of preclinical models that exists for chronic GVHD, is there a kind of rationale for specifically combining axatilimab with, say, a JAK inhibitor with a ROCK inhibitor, like is there kind of a combination strategy that emerges from that preclinical data that kind of would make sense to explore?

Yes. And I do -- again, as I pointed out, I think the other agents are mostly hitting B cells and T cells. And this is the only one really hitting the monocyte macrophage lineage. So it does make sense mechanistically that if you hit both of those pathways in combination, potentially even early in the treatment, you could prevent or clearly significantly ameliorate the disease.

Okay. Great. And so stepping back, I know kind of you discussed recently the idea of other potential indications for axatilimab to be [indiscernible]. Like how are you thinking about that now? What are you thinking about it as the broader opportunity for axatilimab and other kind of monocyte macrophage-driven conditions?

Yes. We've got a pretty comprehensive review of conditions that the science would suggest are driven by the monocyte macrophage and again might be amenable to this blockade of CSF1 as a way of depleting the monocyte macrophages. You may have seen that we received orphan designation for interstitial pulmonary fibrosis, which is an entity that the science, I think, is pointing to as one that may be amenable to this mechanism. There are a number of others, respiratory diseases and skin diseases, like we've seen in the chronic graft versus host disease, where we've seen these remarkable responses to skin disease. So there is a number of those. And I think as the year goes on, we'll talk about trials that we'll be undertaking in those -- in one or more of those indications.

Great. So shifting gears over to the balance sheet. Could you remind us of the company's cash runway kind of -- and what development plans that runway assumes?

Sure. Thanks, Madhu. So just as a reminder, we ended the first quarter with $271 million on the balance sheet. As we mentioned back during our earnings call, that runway takes us into 2023 and importantly, covers the full development costs for both 5613 and axatilimab to their first indications, all the way to registration. It also gives us flexibility on balance sheet to pursue some incremental business development and also start some of the activities that Briggs discussed potentially combination studies and some other activities.

Okay. Great. So we'll conclude with the question we ask every company when we have these presentations, which is quite simply, what is the reason to own Syndax shares in the next 12 months?

Yes. So as -- I like to do the question as why not? It's a -- look, we think it's a very exciting time for our company. We have 2 programs in registrational studies with the potential to file both in just a couple of years. And at this point, we have a market cap of less than $1 billion. We think there's a lot of untapped value there. And we think over the next 12 months, we've seen multiple opportunities for the stock to better reflect the value of these very meaningful market potential of our pipeline. We expect to, as I talked about earlier, have a clear path on expanding 5613 into combination studies. We'll talk about additional data from the Phase I trial. We'll talk about the FDA meeting and what the Phase II study is going to look like for axatilimab. I think we've mentioned that the data at the end of the year should significantly derisk the registration program there. And then again, you said over the next 12 months, within the next 12 months, we may actually have pivotal data from one or more of the cohorts in the menin program as well. So we think it's really a quite exciting time. And as Daphne pointed out, we do continue to look for potential business development activities, and that could end up on the radar screen as well. So we think it's a terrific opportunity for investors to get in low and do quite well.

All right. Excellent. Well, thanks so much to the team from Syndax Pharmaceuticals. We look forward to seeing how things move forward. And thanks, everyone, for joining us today.

Thank you, Madhu.

Thank you, Madhu.

Thank you, guys. Bye.