Thank you for standing by, and welcome to the Syndax Second Quarter 2021 Financial Results Conference Call. . As a reminder, today's conference call is being recorded. I would now turn the conference over to your host, Melissa Forst with Argot Partners. You may begin.

Thank you, Valerie. Welcome and thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax's second quarter 2021 financial and operating results. With me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer; and Daphne Karydas, Chief Financial Officer. Also joining us on the call for the question-and-answer session is Michael Metzger, President and Chief Operating Officer; Dr. Michael Meyers, Chief Medical Officer; and Dr. Peter Ordentlich, Chief Scientific Officer. This call is being accompanied by a slide deck that has been posted on the company's website, so I'd ask that you please turn to the forward-looking statements on Slide 2. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements represent the company's views as of today, August 9, 2021, only. A replay of the call will be available on the company's website at the conclusion of the call. And with that, I'm pleased to turn the call over to you, Dr. Briggs Morrison, Chief Executive Officer of Syndax.

Thanks very much, Melissa, and thank you to everyone joining us on today's call and the webcast. Slide 3 provides a high-level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before. We have continued to make great progress in both of our clinical programs during the second quarter of this year. AUGMENT-101, our Phase I/II trial of SNDX-5613, our selective menin inhibitor, is progressing as anticipated with a meaningful FDA meeting coming up this quarter. Today, we are announcing that we are initiating 2 trials that capitalize on the favorable combinability profile of 5613 and importantly, one of the trials represents our first opportunity to move into the frontline therapy of AML. For axatilimab, our antibody against CSF-1R, enrollment is ongoing in our pivotal AGAVE-201 trial. We, therefore, remain on track to have 2 registrational programs ongoing this year for 2 first-in-class and potentially best-in-class medicines for 2 areas of important unmet medical need. Thanks to the support of our many committed investors, we are well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline. Let's now turn to Slide 4, and our recent data disclosure from the Phase I portion of the AUGMENT-101 trial of SNDX-5613 for the treatment of leukemia. As we noted in our recent data disclosure, in our Phase I trial, 5613 has been well tolerated over multiple cycles with no patient discontinuing for a drug-related adverse event. We were, of course, excited to have also observed clear evidence of monotherapy activity in this population of patients with relapsed or refractory acute leukemia with either MLLr or NPM1c mutations with most responders achieving MRD-negative status. Our pharmacodynamic data confirmed the mechanism of action. And perhaps most importantly, we had identified a candidate recommended Phase II dose that met all of our prespecified criteria. We also previously communicated that we were exploring intermediate doses that represent an increase in dose over the candidate recommended Phase II dose. Since our last call, we have now completed our review of the initial results from the intermediate doses, which are 276 milligrams twice a day in Arm A and 163 milligrams twice a day in Arm B. These intermediate doses have also met all of our prespecified criteria for a recommended Phase II dose, and therefore, we have updated our recommended Phase II dose selection. On Slide 5, we include the DLT results in the dose-selection portion of the trial. In Arm A, you see we have moved from 113 to 226 to 339 and finally, to 276 with no DLTs observed at the intermediate dose level of 276. In Arm B, we moved from 113 to 226 and finally to 163 with, again, no DLTs at the intermediate 163-milligram dose level. Both 276 in Arm A and 163 in Arm B have been well tolerated and now represent our nominated recommended Phase II dose. As you may recall, the only DLT we have seen with 5613 is Grade 3 QTc prolongation, and we did not see that in the 276 Arm A or the 163 Arm B cohorts. We attribute this to efforts we have made with our investigative sites to implement simple clinical measures to minimize the incidence of QT prolongation. I, again, want to reinforce why we are so excited about what we are seeing in our Phase I program. Let me first remind everyone that this is a Phase I trial, patients had received on average 3 prior therapies. About 40% of patients had relapsed after a bone marrow transplant, which is a very negative prognostic sign, and almost 60% had previously received venetoclax. These are very difficult to treat patients, and we were delighted to see a 48% overall response rate, a 23% CR/CRh rate and 67% of the responses achieving an MRD-negative stat. Every physician currently treating acute leukemia who has reviewed this data with us has been excited by the efficacy we are seeing. We are aware of the regulatory precedents for the approval of novel targeted therapies for patients with relapsed/refractory acute leukemia. And while there are no guidelines on a specific rate that is required for approval, we have previously pointed out the rates that were reported for recently approved FLT3 and IDH inhibitors that suggests that a CR/CRh rate above 20% has been acceptable to FDA. The Phase I data we have generated from around 50 patients treated in our ongoing AUGMENT-101 trial gives us confidence that 5613 will achieve that level of efficacy or better in our Phase II trial. Slide 6 shows our go-forward plans for 5613. We had the option to initiate the Phase II portion of AUGMENT-101. As previously communicated, we have our updated recommended Phase II dose. However, our clinical and regulatory team decided not to start the Phase II portion at risk and instead decided to first garner endorsement from FDA regarding our recommended Phase II dose selection. This decision was in keeping with the excellent working relationship we've established with the agency and are being awarded Fast Track Designation. The end of Phase I meeting is anticipated to occur this quarter, as we have previously communicated, with the Phase II portion to open soon thereafter. While we have not officially started the Phase II expansion portion of the trial, we are continuing to enroll additional patients at our proposed recommended Phase II dose and have FDA agreement that these newly enrolled patients may be included in our Phase II expansion cohorts pending, of course, their approval of our recommended Phase II dose. We anticipate presenting a full and substantive update of AUGMENT-101 at a medical conference at the end of this year. We will have treated over 40 patients with either MLLr or NPM mutations and anticipate having a relatively mature data set. To date, we've only shown the CR/CRh rate for our Phase I population as a whole, but we are excited that at the end of the year, given this larger and more mature data set, that we will be able to break out the CR/CRh rate for MLLr versus NPM1. We will also present a promising first look at the durability of the CR/CRh responses, which is an important aspect of the efficacy of 5613. We believe these updates at a medical conference at the end of the year will be important and could meaningfully address key aspects of the 5613 profile. As I've mentioned previously, the Phase II portion of the trial will enroll 3 distinct expansion cohorts, patients with MLLr ALL, patients with MLLr AML and patients with NPM1 mutant AML. The Phase II portion will enroll both pediatric and adult patients, thereby providing us a potential path to regulatory approval with a broad label, including both adults and pediatrics. I should note that the results are positive. This Phase II portion of AUGMENT-101 could potentially support a regulatory filing, given existing regulatory presence. We look forward to soon finalizing the details of the trial with FDA and believe we could potentially have top line data for one or more of the cohorts sometime next year. Over the last period, we have also been conducting extensive research into the broad landscape of clinical opportunities for 5613 beyond the initial approval in relapsed/refractory acute leukemias, as illustrated on Slide 7. Our goal as a company is to be first to market in relapsed/refractory disease and then be first to garner additional value-driving indication. Today, we are announcing our first steps towards building out the 5613 franchise. Our scientists, in collaboration with scientists at MD Anderson, have recently published preclinical data that supported the use of our menin inhibitor in combination with venetoclax. The reference is provided on the slide. The Leukemia & Lymphoma Society, otherwise known as LLS, is sponsoring an umbrella trial that they call Beat AML. They have been assessing potential menin inhibitors to include in the trial, and based on the strength of our data, have selected 5613 as the first menin inhibitor to be tested as a specific targeted therapy for patients with MLLr or NPM1 AML. The collaboration we have agreed to with them will test 5613 in combination with venetoclax and azacitidine in newly diagnosed AML patients that are unfit for induction chemotherapy and will consist of a Phase I and a Phase II/III trial, which potentially could serve as the basis for regulatory filing. Our scientists have also generated preclinical data that supports the use of a menin inhibitor in combination with chemotherapy. As a result, we are also initiating a second Phase I trial exploring 5613 which will be called AUGMENT-102, in combination with standard salvage chemotherapies used for pediatric patients with either ALL or AML. We anticipate announcing additional trials over the remainder of the year that will further build out the 5613 franchise. Let me now turn to Slide 8, on axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF-1 receptor. As you know, we presented our Phase I chronic graft versus host disease data at ASH in December of last year. You may recall that we had opened a Phase II expansion cohort at the 1 milligram per kilogram dose. And as previously announced, that cohort has now been fully enrolled. Later this year, we anticipate presenting the full updated data from both the 17 patients from the Phase I portion of the trial as well as the 23 patients enrolled in the Phase II expansion cohort at the 1 mg per kg dose. I should emphasize that our base case assumption is that this 1 mg per kg dose will be our label dose and hence, the Phase II expansion cohort data is quite relevant as a derisking event to the eventual outcome of our pivotal trial. Slide 9 is our pivotal trial for axatilimab in chronic graft versus host disease. This trial is the axatilimab for a graft versus host disease trial called AGAVE-201. The trial is enrolling patients with chronic graft versus host disease whose disease has progressed after 2 prior therapies. Patients must be at least 6 years of age and have met overall entry criteria. This is a pivotal dose-ranging trial in which patients will be randomized to 1 of 3 treatment groups, each investigating a distinct dose of axatilimab given either every 2 weeks or every 4 weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft versus host disease. Secondary endpoints will include duration of response and validated quality of life assessments using the Lee Symptom Scale. Enrollment to the study is underway, and we are on track to deliver top line data in 2023. We believe that chronic GVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from chronic graft versus host disease in the U.S. today. With the most recent pivotal results from both Incyte's Jakafi and Kadmon's belumosudil and the recent approval of belumosudil, we will soon see commercial launches that will begin to delineate the commercial opportunity in chronic graft versus host disease. Despite recent advancements in this area, to our knowledge, axatilimab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. We believe the data generated to date with axatilimab suggests it has the potential to play an important role in the treatment of chronic graft versus host disease both as monotherapy and, given its safety profile, in combination with complementary medicines. We've also been working extensively with experts in the field of fibrotic diseases and have, on a strong consensus, that the scientific rationale for the efficacy of axatilimab in chronic graft versus host disease supports its potential in a wide variety of fibrotic diseases such as idiopathic pulmonary fibrosis and scleroderma. We're actively evaluating options by which to build out the axatilimab franchise beyond chronic graft versus host disease and to take advantage of what we believe are a significant set of opportunities that could materially enhance shareholder value. As we have previously communicated, we obtained Orphan Drug Designation from FDA for the use of axatilimab in IPS. And finally, on Slide 10, we summarized the transactions that led to the acquisition of the 5613 and axatilimab programs. We believe these transactions underscore our robust capabilities to evaluate and identify high-value differentiated assets as well as the clinical development expertise to bring these compounds through key value inflection points. We anticipate we will be able to continue to expand our pipeline through product acquisitions or in-licensing of quality differentiated assets, and we expect to remain among the preferred partners for such transactions. I'll now turn the call over to Daphne to review our financial results.

Thank you, Briggs. The results of our operations for the second quarter of 2021 and the comparison to the prior year quarter are included in our press release, so I won't repeat them in these remarks. Additional financial details are available in our first quarter report on Form 10-Q, which was filed earlier today. I would like to point out that our net loss for the quarter was $22.9 million, or $0.44 per share, compared to the $17.1 million, or $0.42 per share, for the same period last year. This net loss for the second quarter was below the guidance of $35 million to $40 million of total operating expenses for the quarter, due primarily to the shifting of timing for some CMC activities which shifted into the second half of this year. Turning to Slide 11. We ended the second quarter with $253.1 million in cash and cash equivalents and 51.9 million shares and prefunded warrants outstanding. This cash balance provides us cash runway into 2023 and importantly, covers the development costs for both our lead programs to achieve our corporate objectives and milestones during this period. Looking ahead, I'd like to provide financial guidance for the third quarter of 2021. For the third quarter, we expect R&D expenses to be $25 million to $30 million and total operating expenses to be $30 million to $35 million, including approximately $2.5 million of noncash stock compensation expense. Full year 2021 guidance remains unchanged, and we continue to expect R&D expenses to be $90 million to $100 million and total operating expenses to be $110 million to $120 million, including approximately $2.5 million of noncash stock compensation expense per quarter. With that, I would like now to turn the call back over to Briggs.

Great. Thank you so much, Daphne. Let me close the call by again noting that we have begun the registrational trial for axatilimab in chronic graft versus host disease and are on track to start the registrational program for SNDX-5613 shortly. This management team has been focused on obtaining regulatory approval for drugs that extend and improve the lives of people with cancer and other diseases, and we consider having 2 ongoing registration programs as a major achievement. We are also very excited about the broad franchise opportunities for both programs beyond their initial registration indication. We believe 5613 could have broad utility across a wide range of clinical settings in acute leukemia, and we are excited to be announcing our next steps in building out the SNDX-5613 franchise. Axatilimab also holds the promise of a broad franchise opportunity, both in chronic graft versus host disease and across a broad range of fibrotic disease. We are comfortable given our cash on hand that we have the financial resources to aggressively advance our programs and achieve key upcoming milestones. We remain optimistic that we can continue to identify and bring in novel molecules to deepen our portfolio. We have a proven track record of delivering on this pillar of our corporate strategy, and I believe this is a core strength of our company. As always, I'd like to thank the wonderfully talented team here at Syndax, our collaborators and most importantly, the patients, trial sites and investigators involved with our clinical programs. In addition, I'd like to thank our committed long-term investors, who are helping us build this great company. With that, I'd open the call for questions.

. Our first question comes from Phil Nadeau of Cowen and Company.

A few from us. Just first, would you be willing to disclose the AUC or time above the IC90 for the recommended Phase II doses? Second, will the updated data at year-end include those phased -- the initial experience from the recommended Phase II doses? And then third, what clarity do you hope to get from the FDA meeting?

So Phil, I think your first question, if I heard it correctly, you wanted to know the AUC and time above IC90 for the intermediate doses?

Yes, if you'd be willing to disclose that.

Yes. I think we're going to. I just don't know that off the top of my head. So let me dig into that, and we can get back to you on that. Your second question was at the year-end, would we also have data from the intermediate doses, is that right? And the answer to that is yes. And then the FDA meeting, there are sort of 4 things that we'd like to get some agreement on. Number one, of course, is the recommended Phase II dose. Number two are the endpoints. We are pretty clear that at CR/CRh complemented by information on transfusion independence or infections or other palliative endpoints. Number three is the sample size, how many patients do we need to enroll? And number four is some endorsement that if the data is positive, that these Phase II expansion cohorts could be registrational. So those are some of the things that we want to get in our conversation with them.

Our next comes from Yigal Nochomovitz of Citigroup.

This is Ash Mubarak on for Yigal. Congrats on all the progress. I guess my first one will be on the venetoclax combo. Is it correct to think that there may be an exposure or PK extension benefit for 5613, given that venetoclax is a CYP3A4 inhibitor? And maybe how does that affect the need for 2 different doses depending on CYP3A4 usage? And I guess how are you thinking about the dosing strategy with venetoclax generally?

Right. So just to clarify, venetoclax actually is not a CYP3A4 inhibitor. Venetoclax is metabolized by CYP3A4. So if you look at the venetoclax label, what you'll see is that if you give venetoclax in combination with another drug, that inhibits CYP3A4. There's a dose adjustment for venetoclax, just as we anticipate there is for 5613. So venetoclax should not inhibit the metabolism of 5613, and 5613 should not affect metabolism of venetoclax. So we're pretty optimistic that the combination of 5613 plus venetoclax azacitidine, we should be able, given the safety profile of 5613, to be able to get full doses of both our drug and Vanesa in the triplet.

Okay. I guess my second question would then be on axatilimab and maybe how you're thinking about the evolving landscape, especially with the recent approval of belumosudil and the recent PDUFA extension for ruxolitinib. It sounds like the FDA is being cautious with the JAK. So I'm just kind of wondering how you and maybe physicians for GVHD are perceiving that.

Yes. I mean the initial data we presented at ASH last year, we were quite encouraged to see efficacy from axatilimab in patients who had previously received rux or had previously received belumosudil. So we think there is an evolving now sort of approval landscape for drugs in chronic graft versus host disease. And we think that axatilimab will provide a complementary mechanism that, again, either as monotherapy in patients who have received other therapies or in combination with some of these emerging therapies, we think offers a very promising opportunity for those patients.

Our next question comes from Joel Beatty of Baird.

Congrats on the progress. So it's great to see that there's no dose-limiting toxicities or Grade 3 QTcs in the expansion or any intermediate doses. I think in the prepared remarks, you mentioned that, that may be attributed to efforts at clinical sites to minimize those. Could you tell us more about those efforts?

Yes. Sure, Joel. So the observation has been made by some of our investigators and our clinical staff that a little more, I should say, aggressive correction of electrolytes which, again, is this oral supplementation. It's not very complicated. It's a very straightforward thing. But rather than having patients who have their electrolytes in the normal range, the observations some have made is if you can keep patients in the high normal range, you tend to see less QT prolongation from any agent that is known to cause QT prolongation. So we've been working with the sites to help them with that and educate them on that, and it seems to be paying off. Again, it's pretty straightforward. It's just oral supplementation of their electrolytes. But once we get them into the right range, they do seem to be, again, small number, they do seem to be seeing less QT prolongation.

Great. And then maybe one more question. It's on the Beat AML trial that was announced today. Could you tell us a little bit more about the trial design? And it sounds like there may be multiple phases to it. I guess I'm curious, is there a point in time where there may be a go/no-go decision that may be made for you to decide whether the drug continues or not? And if so, what could that decision be based on?

Yes. So it's a program that essentially we have collaborated with the Beat AML team. The first part, of course, is just is a Phase I to Ash's earlier question of can you get -- what is the right dose of the triplet for each of the agents in the triplet? So that's the Phase I portion. Once we have confirmed that 5613, we have to know the right dose to give a Vanesa, then it goes into a randomized trial of Vanesa versus Vanesa plus 5613. And we'll say more in the future, Joel, about exactly what those -- the go/no-gos are from Phase II to Phase III, but it is sort of set up as sort of -- the initial thought is it'll be a seamless Phase II/III, and there will be a go/no-go, which we'll say more about in the future.

Our next question comes from Peter Lawson of Barclays.

Just on -- as we think about patients rolling over to the Phase II pivotal for your menin inhibitor, how many patients do you think you could have as the Phase II pivotal starts?

Yes. So again, Peter, remember, we had said we could potentially -- what the agency has said is as you continue to backfill cohorts where you've already seen efficacy, those could count. We haven't really said yet how many patients those are, but it just gives you a little bit of a head start as we head into the Phase II. But again, we don't know the final number of patients to be enrolled in the Phase II. So hard to say exactly what the percent of the total Phase II population that represents.

Got you. And then on AUGMENT-102, what chemotherapies are you looking to combine with?

Yes. Michael Meyers, are you on? Can you say more about that? I don't know if Michael is still on.

Sorry, I had trouble getting myself off mute. So yes, Peter, what we were going to combine with would be 2 different regimens that are typically used in relapsed/refractory AML, one being a FLAG-based regimen for AML and then the other would be a 4-drug regimen typically used in ALL.

Okay. And then I guess the final question would just be about other frontline trials that you want to run to and nice to see the one that's about to start, but are there other ones you want to run frontline? And would that go through academic, pharma or non-for-profit organization?

Yes. So we -- I think as we've talked about before, we've been doing quite a bit of work trying to understand what are the various development opportunities. Obviously, a combination with Vanesa, we think is timely and important given its increasing use of standard of care in patients who are not candidates for induction chemotherapy, combining with so-called 7+3 in patients who are candidates for induction chemotherapy also makes sense. And then there are other aspects of the program that we'll be saying more about as the year progresses.

Our next question comes from Justin Walsh from B. Riley Securities.

I have a couple on the Beat trial. So I guess the first is, is there a possibility that a competitor menin inhibitors could get added to that or is it most likely 1 drug from a single class? And then the other question related to Beat is, are you guys actually running the trial yourselves? And how much control do you have over those data releases?

Yes. So the first question, I think we probably have to defer to the LLS team. I don't believe in the arrangement we have with them that they can't include another menin inhibitor if they wish to. I don't -- that's about all I can say. I don't know if they wish to. And then the second question is part of the reason of working with the Beat AML team is because this trial is already up and the sites are all up and the Beat AML team is sort of ready to go, we will let them run the trial. They've proven that they can do this quite efficiently and effectively, we think the trial actually will start faster because they already have all their sites opened. This is just another arm added into the trial, and we've worked closely with them on data disclosures. I think they are as excited to present data as we are.

And our next question comes from David Lebowitz of Morgan Stanley.

When you look at the menin data to date thus far, could you, I guess, elaborate on the efficacy across the doses and how that plays into the ultimate dose selection?

Yes. So again, David, the dose selection -- the recommended Phase II dose selection is not based on efficacy. The dose selection is based upon safety, tolerability and PK. What we have said previously is that when we were looking at the 113 Arm B, 226 Arm A, the efficacy in that population is roughly the same as it is in the overall population, which is really the way that we presented the data. And obviously, we'll have a lot more to say about efficacy by dose, by arm and by mutational status at the end of the year at a medical conference. And as I said in my prepared remarks, we'll also -- we're excited to be able to show the initial durability of the CR/CRh responses as well.

And with respect to the QT elongation, I guess you spoke about how practices were handling, I guess, the newer patients on the different doses differently. Is there any way you could elaborate on how that changed and why those 2 doses seem to have no QT elongation, whereas lower doses did in the prior release?

Yes. So again, if you look at 113 Arm B and the 226 Arm A, there was 1 DLT in each of those. And again, in Arm B, relatively large number of patients. As I said, with the helping sites to make sure that they're adequately or supplementing electrolyte seems to be helping on those intermediate doses, but we'll sort of see how that plays out as we enroll more patients. I think what we had said at the last -- when we presented the data in April is that at the recommended Phase II dose, we were seeing somewhere around 8% or 9% Grade 3 QTc prolongation. It's possible with this closer interaction with the sites and people getting more comfortable with what needs to be done that, that rate could come down as we enroll more patients.

I'm showing no further questions at this time. I'd like to turn the call back over to Dr. Morrison for any closing remarks.

Thanks so much, operator, and thanks, everybody, for joining us on the call. Again, we think it was a very productive quarter. We're excited about the data that we'll be updating at the end of the year at a medical conference, and we're excited to be able to start our first first-line trial. And as Daphne pointed out, I think we're well financed to be able to get through a lot of this work. So thank you all for your attention and your questions. If there's anything else we can do, please get in touch with us.

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may all disconnect. Have a great day.