Good day and welcome to the Syndax First Quarter 2022 Earnings Conference Call. Today's call is being recorded. At this time I would like to turn the call over to Maghan Meyers of Argot Partners. Please begin.

Thank you, Operator. Welcome and thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax's first quarter 2022 financial and operating results. I'm Megan Meyers with Argot Partners and with me this afternoon to discuss the results and provide an update on the company's progress are Michael Metzger, Chief Executive Officer; Dr. Briggs Morrison, President and Head of R&D; and Alex Nolte, Chief Accounting Officer. Also joining us on the call today for the question-and-answer session is Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer. This call is being accompanied by a slide deck that has been posted on the company's website, so I would ask you to please turn to our forward-looking statements on slide 2. Before we begin, I would like to remind you that any statement 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 our views as of today May 9 2022 only. A replay of this call will be available on the company's website, www.syndax.com following this call. With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Thank you, Megan, and thank you to everyone joining us on today's call and webcast. On the heels of a transformational 2021, we're off to a strong start for 2022 and I look forward to sharing with you today our recent progress and several key developments. I'm especially excited to report that Syndax is now on pace to deliver two US applications for potential drug approvals in 2023, a distant and aspirational goal for most biotech companies and yet a near-term and highly achievable one for Syndax. Despite the challenging market backdrop, we currently find ourselves with a solid balance sheet and the support of a strong pharmaceutical partner to advance the development of one of our lead molecules. We are well-positioned to expand both of our lead assets into new indications and to build out a commercial organization to support the potential launch of these first and potentially best-in-class products. We also have the flexibility to selectively pursue business development opportunities to augment our pipeline with additional promising molecules to complement the ones we have. The momentum is building at Syndax and it is indeed a very exciting time for the company. Now turning to slide 3. We provide a high-level summary of our current corporate priorities as we strive to realize the future in which people with cancer live longer and better than ever before. Starting with Revumenib, our official generic name for SNDX-5613, our highly selective menin inhibitor. Enrollment in our three pivotal Phase 2 trials in patients with relapsed/refractory NPM1 or MLR acute leukemia, which we call AUGMENT-101, 2A, 2B and 2C remain on track. We're also pleased to announce that we have enrolled our first patients in the BEAT-AML and AUGMENT-102 trials, which represent important expansion opportunities for the franchise in combination with other approved…

Thanks very much, Michael. Look given that we've already established that our drug is active both in NPM1 and MLLr leukemias and have initiated a series of trials to explore the use of Revumenib in earlier lines of leukemia therapy we believe now is the time to turn our attention to exploring the utility of menin inhibition in diseases beyond leukemia. As we have continued to assess the emerging science across a range of opportunities, we've decided that our initial clinical program help advanced colorectal cancer. On Slide 7, we note that colorectal cancer is the third most frequently diagnosed cancer and is the second leading cause of cancer death in the US. With it's significant unmet medical need most notably in patients with metastatic disease. It's well established that the β-catenin pathway is a key driver of essentially all final common pathway being β-catenin transcriptional activation of several transforming genes. What has become increasingly clear is is required for β-catenin for cancer and that molecules like Revumenib which disrupt the binding of MLL1 to menin displace MLL1 from transcriptional start sites forming genes. What's really quite remarkable is that when MLL1 is displaced from the β-catenin complex, the colon cancer cells differentiate into normal colonic cells and lose their ability to proliferate. This differentiation is highly reminiscent of what we see both preclinically and clinically with revenue and differentiation. Solid is a diagrammatic illustration of what we believe is happening in colorectal cancer cells. And the panel on the left MLL1 is a component of the β-catenin of genes like MYC and cyclin that drive cell division. And the panel on the right in the presence of Revumenib, we see a disruption of the β-catenin loss of expression and cell differentiation. Living this emerging science, Slide 9 shows our…

Yes. Thanks, Briggs. Before we move on, let me further emphasize that seeing disease control rates above standard of care, even seeing a few responses in these metastatic colorectal patients will indeed be a very exciting result. As you may know, this is an area of high unmet medical need, where current therapies are not particularly effective. If we are right and the science translates in the clinic, this discovery would enable Syndax to meaningfully expand the market opportunity for menin inhibition beyond heme malignancies. Let me now turn to axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF-1 receptor. Slide 10 is our pivotal trial for axatilimab in cGVHD. This trial is the axatilimab for graft versus host disease trial called AGAVE-201. The trial is enrolling patients with cGVHD, whose disease has progressed after two prior therapies. Patients must be at least two years of age and have met overall entry criteria. This is a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axatilimab given every two -- either every two weeks or every four weeks. The primary endpoint is response rate using the 2014 NIH consensus criteria for cGVHD. Secondary endpoints will include duration of response and validated quality of life assessments, using the Lee Symptom Scale. Enrollment to the study is going well and we are on track to deliver top line data in the first half of 2023. We're also delighted to announce late last year that we closed our global collaboration with Incyte. This collaboration brings together two companies with a solid track record of innovation to accelerate and maximize the development of axatilimab. Our Phase 1/2 cGVHD data presented at ASH in December of last year received very positive feedback…

Thank you, Michael. Let me now take a few minutes to discuss our financial results for the first quarter of 2022. The results of our operations for the first quarter of 2022 and the comparison to the prior 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 which was filed today. I would like to point out that our net loss for the quarter was $37.2 million or $0.63 per share, compared to our net loss of $27.7 million or $0.54 per share for the same period last year. This difference is primarily attributed to the increased clinical CRC activities for both of our programs. Turning to slide 13, we ended the first quarter with $397.9 million in cash and cash equivalents and 59 million shares and prefunded warrants outstanding. Our current cash runway now extends into the second half of 2024 and supports our expanded development and early commercialization plans for both the axatilimab and the menin programs during this period and provides us flexibility for continued business development. Looking ahead, I'd like to provide financial guidance for the second quarter and full year of 2022. For the second quarter of 2022, we expect R&D expense to be $30 million to $35 million and total operating expense to be $38 million to $42 million including approximately $4 million of non-cash stock compensation expense. For the full year 2022, we expect R&D expense to be $130 million to $140 million and total operating expense to be $160 million to $170 million, including approximately $40 million in non-cash stock compensation expense for the full year of 2022. The increase in R&D and operating expense in 2022, compared to the prior year period is driven by the expansion of both axatilimab and menin into registration trials, expansion into new indications and initiation of pre-launch commercialization activities. With that let me now turn the call back over to Michael.

Thank you, Alex. Let me close the call by again emphasizing the tremendous progress we have made as a company. Syndax has always been focused on delivering new medicines that extend and improve the lives of people with cancer and other serious diseases. And today with two high-value ongoing registration programs, a notable achievement in its own right, we stand on the precipice of realizing this goal. And the potential of these programs extends well beyond their initial registration indications with both offering broad franchise opportunities. We believe Revumenib could have utility across a wide range of clinical settings in acute leukemia as well as potentially in some solid tumors. Our immediate goal as a company is to be the first to market in relapsed refractory acute leukemia and then drive additional value potential by expanding its use into newly diagnosed and maintenance settings in NPM1 and MLLR acute leukemias. The same franchise potential holds for axatilimab, where broad opportunity exists both in the various lines of therapy in cGVHD and across a broad range of fibrotic diseases starting with IPF. Underpinning all of these efforts, we have the balance sheet to aggressively advance our programs through key near-term milestones. And lastly, we remain confident in our ability to identify and bring in novel molecules to deepen our portfolio, particularly in a more challenging market where competition for high-quality assets may be diminished. 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 and management team. We could not accomplish what we have and what we hope to achieve without our 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 would like to thank the many committed long-term investors who continue to help us in building this great company. And with that, I'd like to open the call for questions.

Your first question comes from the line of Madhu Kumar from Goldman Sachs. Your line is now open.

Hey everyone. Thanks for taking our questions. I guess our first one relates to the cadence of recruitment into the Phase 2 arms of the AUGMENT-101 trial. So, you mentioned that you could either disclose one cohort or several cohorts in the first half of 2023. Given the kind of recruiting cadence you've seen so far, do you expect to report one versus multiple and one go? How are you thinking about that today?

Yes, Madhu thanks for the question. Look I think what we were referring to was actual enrollment in the trial and how the cadence kind of rolls forward from there. So, we have three independent -- as you pointed out, we have three independent trials that are enrolling. We haven't given guidance as to whether one is enrolling more quickly than the other. I think we had said that the AML cohorts would probably finish earlier than the ALL cohorts, but we haven't given any guidance as to whether MLLR or NPM1 will be first or second. And so I think the concept of having one or more of the individual trials finish enrollment this year is still operative. And certainly what follows from that is additional follow-up and a filing or to perhaps in the 2023 timeframe. But we do think that we'll have top line data starting in the first half of 2023.

Okay. And one follow-up question. You mentioned that you have agreement with the FDA on a statistical plan for these three AUGMENT-101 goers. Can you give us some details on how to think about that in terms of like is there like an effective CR/CRA trade that needs to be seen? Is there a durability that you're kind of looking at? Like how should we think about those kind of parameters for evaluating AUGMENT-101 base and your interactions with the regulators so far?

Great. Maybe I'll ask Briggs to address that question.

Yes. So we do for some of the apologies I guess my line is breaking up a little bit. But there is a statistical hypothesis as you can imagine that we've agreed to for sort of a lower bound that has to be ruled out. That's the primary end point. There is no prespecified requirement for durability as you talked about with you previously there's regulatory precedent for both CR/CRH rates and durability from other targeted agents in AML and that's sort of what we've been thinking about.

Okay. Great. Thanks very much everybody.

Thanks, Madhu

Next question comes from Phil Nadeau with Cowen & Company. Your line is now open.

Can you hear me now?

Yes.

Phil Nadeau with Cowen and Company, your line is now open.

Operator, maybe we will put him back in the question and we will circle back.

Phil Nadeau, are you online? Your line is now open.

Hi. Can you hear me how?

Yes.

Great. Sorry about that. I don't know a happen there. So I guess, just a follow-up first on Madhu's question. In terms of the durability that you need to file in for approval one can you remind us what that is? And then second, what's your data disclosure strategy? Will you wait until you have the full duration of durability that's necessary or will you give us a preliminary look on the data from AUGMENT-101 before it's fully mature?

Right. Again I guess maybe I'll ask Briggs to follow-up. Thanks for the question, Phil.

Right. So far there is no durability that's required for filing. I think if you look at the precedence for some of the other targeted agents a median duration of response of at least four months to six months has been acceptable in the past. So I think that's sort of the lower bound of what people would see. As you will recall the data we showed at ASH the Kaplan-Meier estimate for durability of response even at six months was greater than it was around 70%. So if the data for our filing holds up similar to what we presented at ASH I think we're in very, very good shape from a regulatory point of view. In terms of data disclosures again as Michael pointed out once a cohort has completed enrollment the idea is it would will follow the patients from six months from the last patient enrolled. And that would be the data set that we would consider as our filing data set. Obviously there would be continued follow-up on those patients over time but the filing data set would be six months after the last patient is enrolled.

And so that's approximately when we -- as investors should expect to see the data about six months after you get the last patient for each cohort?

Exactly.

Got it. Okay. And then second question is on the INTERCEPT trial. How is MRD negativity being assessed for the different genotypes? There is regulatory precedent for MRD negativity for NPM1/AML patient established by Crohn . But I believe the FDA has ever said what -- how you assess MLR, sorry, MRD negativity for MLLR. How is the INTERCEPT trial doing that?

So maybe if Peter is on the line, Peter Ordentlich, maybe you want to comment on that one.

Hi. This is Peter. For the MLR the MRD is a little tricky as you note just because of the dried nature of the different infusion can occur. I believe biclocytometry predominantly for the MLR patients.

Great. That's very helpful. And then last question. We saw that the SAVE trial is on clinicaltrials.gov now. Can you remind us what the rationale is for looking at combinations with ASTX727? Why choose that as one of the agents that you're first moving into combo studies with?

Yes Phil, first of all it's an investigator-sponsored trial. So that's part of the equation here. But maybe I'll ask Briggs or Peter to comment on the rationale.

Yes, I'll be happy to. So Phil, the logic is the same as Ven/Aza, right? Essentially the SX molecule is essentially an oral as. So I think the MD Anderson team, as Michael said, it's an investigator-sponsored trial they were quite interested in being able to potentially develop an oral regimen we're not having to give parenteral azacitidine. So the scientific rationale for the combo is the same as for the Ven/Aza. Why that molecule, specifically I think they're quite interested in an all-oral regimen.

Perfect. Thanks for taking our questions and congrats on your progress.

Thank you, Phil

Next question comes from Bert Hazlett with BTIG. Your line is now open.

Thanks. Thank you for taking the questions. I have a couple on 5613. Forgive me for not Revumenib. Could you just maybe provide benchmarks. I think you may have done this previously but for the BEAT-AML trial with regard to frontline Ven/Aza, the combination with frontline Ven/Aza, specifically in NPM1 or MLLr patients, what should be the benchmarks we're considering for meaningful activity in that patient group in front line?

Briggs, do you want to take that one?

Yes. So Bert, we can send you the Viale-A trial, which was the Ven/Aza versus AZA first-line trial. The overall response rate, I think if I remember correctly it was sort of in the mid-60s, the CR , the actual CR rate was lower than that. There are some subsequent publications where they break it out by mutational status. But as you can imagine the number of patients in each one of those is smaller. So I think in an early look at the data looking at an MRD negative rate -- than the looking at the for -- CR/CRI rate but we'll send you the Viale-A paper and all supporting information.

Okay. That's helpful. Then one kind of strategically, given the effort into – into solid tumors here with CRC. Is this foreshadowing some additional combination therapy or potential combinations or licensing potential with Revumenib and other molecules that focus on the Wnt/b-catenin pathway or is this moving into CRC, or how should we think about what this initial step means strategically for the development of Revumenib?

Yes. Thanks for the question, Bert. I'll just say, overall strategy here is we're following -- we think we're following good science into a particular form of solid tumor biology. And I think that’s where we find -- we think that this will be something to explore. It is a signal-seeking Phase I trial limited investment as Briggs pointed out in his remarks. So market opportunity is quite significant. There's a lot of unmet medical need in this area of colorectal cancer. And we think the mechanism has very strong rationale. We'll find out essentially if it works. But in terms of a larger strategy in solid tumors, I think we're being strategic and surgical about how we go into certain other areas outside of hematology and leukemia I should say. So I think, this is a -- this is one such opportunity. There may be others. But again, we're focused -- very much focused on the biology at hand and where it takes us with of course our first focus being very much in the leukemia space. I don't know Briggs do you want to add anything to that?

No, no I think that's right. I mean it's -- I wouldn't necessarily think about novel, we want to just sort of see is this -- it does the preclinical data or the clinic -- obviously is there are additional opportunities if it does work and it’d be b-catenin pathway beyond colorectal cancer.

Got it. Fair enough. And then just one more kind of big picture in this class in general. How do you see -- you're clearly in the lead with a number of these indications and certainly to move into colorectal and the other space, how do you see the competitive landscape evolving these men interaction inhibitor space? Thanks.

Yes. Thanks, Bert. Look, I think you pointed to us, you point out, what we believe to be true which is that we're in the lead in terms of developing our drug and becoming the first menin inhibitor approved potentially. And that's our -- that's the thrust of our effort. And in terms of looking at other indications, frontline maintenance, what have you that's -- those are areas that we'll go into as well. And then, we've talked about today, we talked about colorectal cancer. There may be other areas to exploit as Briggs just pointed out around in solid tumors. But essentially, I think we feel like we are able to leverage our first-mover advantage exploit the attributes of our agent, which we think are pronounced and we'll have a good opportunity to show that in the market. Others have to put up data and we'll look forward to seeing what they have, when they actually produce the data and present at the conference.

All right. Thank you.

Thanks, Bert.

Next question comes from the line of Yigal Nochomovitz from Citigroup. Your line is now open.

Hi team, this is Ashiq Mubarack on for Yigal. Thanks for taking my questions. A bit of a basic one. But regarding your new plant study in colorectal cancer, does there need to be an MLL rearrangement to support I guess aberrant activation of the wind beta-catenin pathway or is it all just wild type? And maybe what proportion of the CRC population do you think is addressable with menin?

Yes, yes it's more akin to the NPM1 story. It's not -- there's not a fusion protein. It's more attend NPM1 where the NPM1 driven transformation is dependent upon the -- for beta-catenin similar to.

Okay. And maybe what proportion, do you think is addressable with menin inhibition?

All right. So if you look at -- actually we -- as we've been thinking through the beta-catenin pathway in CRC and whether we should be taking a biomarker selected population, but the vast majority of colorectal cancers have -- either have an activation necessarily but has an activation of the beta continue to pathway. So we think it's actually the majority -- the vast majority of patients have this pathway activated.

Okay. And maybe one last one for me. How do you expect Revumenib to behave in solid tumors versus leukemia? And maybe do you think you would need to dose with the CYP3A4 based on your prior work within leukemia? Thanks.

Yeah. So the dosing should be a -- do you want me to take that, Michael?

Yeah, please. Go ahead.

Yeah. So the dosing should be the same. Again you're just blocking the interaction of menin with MLL just as we do with NPM1 where the dosing is the same -- the dose how whether you see responses or whether you see differentiation as we see in AML is one that will be very interesting, pre-clinically you actually see a very similar differentiation with AML.

Okay. And maybe the last point on leaving us at CYP3A4?

No again -- so just to clarify it's not that that -- depend on whether they're also taking a CYP3A4 inhibitor. So we think that that the exposure response should be the same in -- so again we don't need a CYP3A4 inhibitor. We just need to know what the dose is with or without. And that should be the same in colorectal cancer.

Okay. Sorry, I think the connection is incorrect. But I appreciate the answers.

Yeah. Thanks, Ashiq. We can follow-up afterwards maybe.

Next question is from Joel Beaty with Baird. Your line is now open.

Hi, congrats on the progress, and thanks for taking the questions. The first one is on AUGMENT-101. And with a lower bound that has to be rolled out when you submit the data with FDA. Do you see any potential for the enrollment size in any of the three arms to change based on early data and how it looks?

Yeah, Joel, thank you for the question. Well, as you know it's a pivotal trial. So we're not looking at the data. I think the concept is that we have -- and I think we -- I mentioned in my remarks 64 patients enrolled in each of the trials, individual trials and up to 10 pediatric patients. So that's the statistics are set around the 64 patients. And as of today there's no -- we don't see any reason why that would move. And that obviously is driven -- all the powering is done off of the lower bound. So while we haven't disclosed what that is we feel like the statistics hold and we have agreed with FDA on the design. So in our mind that we don't see any reason why it would change.

Okay, great. And then a question on business development. You mentioned how there could be a bigger focus for this year. How does the recent biotech downturn affected the outlook for that?

Yeah. Thanks for the question, Joel. Yeah, I think I mentioned that, obviously we're in a tough environment. And I don't think many companies are immune to that. But I do think that our business model is to in-license or acquire other assets. We've generally focused on early-stage assets call it lead stage preclinical through Phase 1. So these are assets that allow us to do some very good development work and not spend as much on development at the early stages until we get to a point of value inflection. And so, I think that's the area that we tend to focus on. And I think those are the assets that perhaps are not getting as much attention in the down market. And so, we continue to be encouraged by some of the things that we're seeing and we're being very selective on the types of assets and what we could potentially bring into Syndax. And so it's -- in that way, I think we're feeling good about our goals for the future and building our pipeline.

Great. Thank you.

Thanks, Joel.

Final question comes from the line of Peter Lawson with Barclays. Your line is now.

Great. Thanks for taking my question. I guess the first one is just around whether we'd see any updated Phase 1 data for the menin inhibitor this year or early next?

Yes. Thank you Peter for the question. I think in our mind, we're pretty much focused on enrolling and doing all the work that's required, now in the Phase 2 to get the drug ultimately approved. And so, that's where our focus is. I guess the only real question, and there are some questions that I'm sure people have but the question that is something we could potentially talk about coming out of the Phase 1 is maybe just an update on the durability of the endpoint of CRC/CH, which we reported on at ASH. As of now, we don't have specific plans to update the market on that, again, because our focus has turned to the Phase 2. But if that were to change obviously, we'd let people know and there shouldn't be any expectation necessarily that we would do that. So, other than that, I don't think there's much to say about the Phase 1 in any particular time this year. But again, if that were to change, we'll certainly let people know.

Got you. Would that durability kind of help with the enrollment for the AUGMENT study in any way you think to help investigators get, I guess, greater comfort around the durability of these drugs?

Yes. Look, thanks for that question too. I do think that more data helps. Whatever the data is, if it's positive about your program and people are interested in your program, they tend to notice the data that you put out. And so could that help? I would imagine there could be some positive -- some benefit to that. I would also offer that physicians are extremely excited today about what we've put out from the Phase 1 and we did that at ASH and the follow-through has been tremendous and our trials are enrolling well. So I think we feel very encouraged by the interest of physicians and investigators. And so that's just where we are today, but additional data never hurts as long as it is supportive of your program.

Got you. Thank you. And then the branch into solid tumor indications, just curious if we see any preclinical data for COC or other indications? And do you think there's any preclinical evidence that they could work better with the CRC mutations such as the G12C?

Yes. Maybe I'll let Briggs take that question.

Yes. So Peter we can send you come out, but have given us a lot of confidence in this mechanism. Again, as I mentioned earlier I think combinations with other agents in colorectal think about. But, yes.

Okay. Perfect. But is there anything coming out from your own work that we could potentially see this year pre-clinically?

Potentially? Potentially, yes. I wouldn't set an expectation, but the team is doing some additional work to validate some of the things that we've seen in the literature. So I don't know when that will be ready.

Perfect. Thank you so much. Thanks for taking the question.

Thank you, Peter.

This concludes the Q&A portion of the call. I will now turn the call back with Michael Metzger who will make a few closing remarks.

Great. Thank you operator. And thank you for joining us on the call this afternoon. We look forward to I guess see many of you at the upcoming conferences this spring and as well as on any future calls. Again, have a great evening and thanks for joining us. Good night.

This concludes today's conference call. Thank you all for your participation. You may now disconnect.