Good day, everyone, and welcome to the Syndax Fourth Quarter and Full Year 2020 Earnings Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Ms. Maghan Meyers of Argot Partners. Please begin.

Welcome, and thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax' fourth quarter 2020 financial and operating results. I'm Maghan Meyers with Argot Partners. And with me this afternoon to discuss the results and provide an update on the Company's progress are Dr. Briggs Morrison, Chief Executive Officer; Daphne Karydas, Chief Financial Officer; also joining us on the call today for the question-and-answer session is Michael Metzger, President and COO; Dr. Michael Meyers, Chief Medical Officer; and Dr. Peter Ordentlich, Chief Scientific Officer.

Thanks very much, Megan, and thank you to everyone for joining us on today's call and 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. 2020 was a transformational year for Syndax. Over the course of the year, we've made great progress in our two clinical stage programs, both of which are on track to be in registrational programs this year. Thanks to the support of our many committed investors, we ended the year well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring target oncology drugs into our pipeline. Let's now turn to Slide 4 and SNDX-5613, our genetically targeted agent for the treatment of leukemia. As we've noted previously, there's extensive validation of both MLL-r and NPM1 mutations as molecular targets in leukemia and well-established diagnostic tests who daily identify patients with these genetic mutations. Premier publications provide a scientific rationale and preclinical validation of our ongoing clinical trial and historic precedents support a rapid regulatory path for such targeted agents in acute leukemias. Slide 5 briefly summarizes the ongoing AUGMENT-101 trial, the first-in-human Phase 1/2 trial in the accelerated understanding of Menin or AUGMENT program. Consistent with what we communicated on our last call, we are on track to present the completed Phase 1 portion of the trial in the near future and to start the Phase 2 expansion cohorts soon thereafter. We have received several questions about the upcoming data disclosure, and so I just want to provide some guidance.

Thank you, Greg. The results of our operations for the fourth quarter of 2020 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 will be available in our fourth quarter and full year report on Form 10-K, which will be filed later this week. I would like to point out that our net loss for the quarter was $20.4 million or $0.44 per share compared to $14 million or $0.44 per share for the same period last year. Turning to Slide 9. We ended the fourth quarter with $293.1 million in cash and cash equivalents, including net proceeds of approximately $135 million from our public offering completed in December of 2020 and 51.4 million shares and prefunded warrants outstanding. This cash balance provides us cash runway well into 2023 and importantly, covers the full development cost of both axatilimab and the 5613 registration ready programs as well as provides us flexibility for continued business development. Looking ahead, I'd like to provide financial guidance for the first quarter and full year of 2021. For the first quarter of 2021, we expect R&D expense to be $25 million to $30 million, and total operating expense to be $30 million to $35 million, including approximately $2 million of non-cash stock compensation.

Thanks very much, Daphne. Let me close the call by again noting that 2020 was a transformational year for our company and we anticipate that 2021 will be no less exciting. We've begun the registrational trial for axatilimab in chronic graft versus host disease and are eager to present our Phase 1 data from the AUGMENT-101 trial in the coming weeks and to start the registrational program for SNDX-5613 shortly thereafter. We are also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indications. We believe that 5613 could have broad utility across a wide range of clinical settings in acute leukemia, and axatilimab could represent a broad franchise opportunity in fibrotic diseases. We are comfortable giving our cash on hand that we have the financial resources to aggressively advance our programs and achieve key upcoming milestones. We also 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 strategy, and I believe this is a core strength of our company. As always, I would 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 would like to thank our committed long-term investors who are helping us to build this great company. With that, I'd like to open the call for questions.

Your first question comes from the line of Philip Nadeau from Cowen & Company. Your line is open.

Congratulations on the progress. And Briggs, there's a few for you, just on some of the parameters you’ve laid out for the data we should expect late this month or next month. In terms of arm A versus arm B, you actually didn't give any color there. Should we have any expectations for relative weighting of those arms?

Phil, thanks for your question. I don't think you've given any guidance on the relative weighting. I think what we anticipate is that we will have a recommended Phase 2 dose for each of the individual arms.

Got it. Okay. And then second, I'm not sure you want to comment on this either. But in the past, you've suggested that MLL-r should be more heavily represented than NPM1 in light of the history of the trial, particularly at some of the heavier enrolling centers. Is that still your expectation? Or could MLL-r and NPM1 be more evenly balanced.

No, that's still our expectation that there'll be more MLL-r, again, just to clarify for people, otherwise known as KMT2A rearrangements, but more of the MLL-r KMT2A than NPM1.

Great. And then just last question on the data. How will you present the safety data? I guess, specifically, will you give us the safety results for all the patients who were enrolled or specifically for the Phase 2 dose?

Both actually. So, we'll present the full safety profile for the entire population that was enrolled and will break out the safety profile for the recommended Phase 2 doses.

Perfect. Then one question for Daphne. Daphne, you mentioned H1 expenses are going to be more heavily weighted than H2. Do you expect Q2 to kind of look similar to Q1? Or is Q1 really going to be the heaviest expense quarter of the year?

Thanks, Phil. So yes, just to clarify, the comment was, we expect the first half expenses to be more heavily weighted than the second half, and we would expect the first two quarters to be similar in cadence.

Perfect. Thanks for taking my question and congrats again on the progress.

Thanks Phil.

Thanks Phil.

Your next question comes from the line of Bert Hazlett from BTIG. Your line is open.

Thanks for the update and taking the question. Could you just describe a little bit more Briggs, please, about -- a little bit more about the Phase 2 expansion part of Augment-101? Do you have any sense for the size and scale of each of the individual arms at this point? Do you have any sense for the potential pace of enrollment or the length of enrollment that, that Phase 2 might take?

Yes. Thanks for the question, Bert. So, the precise size of each of the independent Phase 2 expansion cohortsaxatilimab, again, will be sort of sized on what the sort of null hypothesis is on response rate and what's the alternative. That's still, I think, a final discussion we have to have with FDA. There's sort of a related question of what's the total number of patients that we need from a safety point of view across the three cohorts, including the Phase 1 data. I will emphasize that each of the three are independent, essentially parallel independent Phase 2 cohorts. We could potentially register one or two or all three, but -- and then the second part of your question?

I guess it's dependent upon the first, but the potential length of time enrollment, it might take.

Yes. We haven't given guidance on the timing exactly to your point. Until we know the precise numbers, it's a little hard to give precise definition of timing. What I would say is, thus far, at least the Phase 1 trial has progressed very, very nicely. And so, it's really just a question of knowing how many patients we need, and then we'll give you guidance on how long we think it will take to enroll.

Okay. And then just a more strategic question with regard to the slide that has multiple commercial opportunities in acute leukemia, multiple pathways. How are you thinking strategically about potential expansion here? Is this an in-licensing effort, which you've been successful at previously? Is this corporate collaboration at some point? Just a general framework for how you're thinking about prosecuting these additional efforts?

Yes. So, I think the first part is just to lay out where we believe that the drug can be used. And in some cases, that might entail a combination with established therapies that are generic and available, such as chemotherapy, might require or might be enabled by a corporate partnership with somebody who has a drug that we think makes sense combining. But the strategy is, first, let's lay out where we think the best, where the largest unmet medical need is, where there's a trial that we can get done reasonably quickly, and then decide if there is a corporate partner who would want to work with us on that or is it single agent or is there a combination regimen that we could do ourselves?

Your next question comes from the line of Konstantinos Aprilakis from Stifel. Your line is open.

So, for the sake of clarity on the size of the 5613 update, we're looking forward to later this quarter or early next. Does the 30 patients include the six patients presented last year, should we expect 30 additional patients or 30 total patients? And where do the compassionate use patients fit in?

Yes. Konsti, thanks for your question. So it's -- I said at least 30 patients total, so that includes the six that we presented last year. That's the number of patients from the AUGMENT-101 trial. So that does not include the compassionate use patients, and we're discussing with aton of what's the right -- what's the -- whether we focus completely on the Phase 1 trial or we also present some of the data from the compassionate use patients.

Okay. Perfect. I and then one more quick one. Just you mentioned in your prepared remarks, 5613 combinations at this juncture, if you had to say, what do you think is sort of most promising? It sounds like we're going to get something on that in the near term, but any thoughts at this juncture would be helpful.

Yes. Again, relative to Bert's question, I think that the first order of business, from our point of view is just to lay out where is the right place to further develop the drug and then see if that requires a combination. Clearly, I think if you were going to do first-line with this agent, there's the so-called population of patients who can tolerate intensive chemotherapy. And so, there might be a regimen where you combine with standard upfront chemotherapy. And then there's the population of patients, the so-called unfit, where they don't get chemotherapy, they get other agents. And so, combining the agents in that space makes sense as well, so we're looking at both patients who are candidates for intensive therapy in patients who are not.

All right. Perfect. Congrats on the progress.

Your next question comes from the line of David Lebowitz from Morgan Stanley. Your line is open.

Thank you very much for taking my question. When looking at the 30 patients, we'll be seeing towards the end of this quarter, I know there is going to be a certain number of patients that don't have either the MLL-r or NPM1 as the initial trial did have all-comers with leukemia. And I guess my question is, will there be patients beyond the initial cohort that we saw that were -- did not have mutation? And if so, do you know how many at this point? And can the number of, I guess, non NPM1s and MLL-rs be disclosed at this point? Or I guess, to what extent -- how large is the number of the number should we expect?

Hi, David, thanks for your question. So as you correctly pointed out, when the trial first started, it was an all-comers trial and the data we presented at AACR last year, three of the patients had neither NPM1 nor MLL-r. And the trial as a continued did allow continued enrollment of that population. I think last summer on our August call, we had mentioned that we had refocused the trial to focus only on enrolling NPM1 and MLL-r. So, there will be patients who have neither -- we haven't said specifically how many of those patients they'll be, but there will be some because of that early design of the trial.

Thank you for that. And on the initial description of the call, you were referring to the population as acute leukemias. I know we've seen ALL patients, and we're going to see NPM1 patients. So are we going to also see AML patients in the trial?

Right. So, the -- we will see both ALL and AML. And as you may remember from our AACR presentation, one of the patients had what is known as mixed phenotypic acute leukemia where the leukemia actually has markers consistent with both AML and ALL. So there'll be ALL, AML and at least one mixed phenotypic.

Excellent. And I guess my last question would be. I know that there's a competing Menin inhibitor out there. And would you be able to, I guess, compare and contrast what you know and understand about your molecule with their molecule?

Yes. I mean I don't think -- I'm not quite sure which competitor you're referring to. But it's -- I don't think we're in the position to do a lot of comparing and contrasting the other molecule that's in the clinic. There's actually very little known about the molecule itself. So, I don't think we can say too much about that at this point.

Your next question comes from the line of Justin Walsh was from B. Riley Securities. Your line is open.

Thanks for taking the and congrats on the progress. The cGVHD opportunity is quite intriguing to me. Can you provide any color on how you view that space evolving over the coming years? Specifically, I'm wondering if you think the opportunities growing with the trend towards increased or stem cell transplants or could it be getting crowded with RUX and other drugs going to approval?

Yes. I'd like our Head of New Product Planning take that question.

Thanks, Briggs. Thanks, Justin, for question. Yes. I think there's a lot of change in that space. As you mentioned, there's a couple of new drugs that are under review for the FDA for potential approval. But I think there's two parts to that answer with the advent of new leukemia drugs that are very promising and helping patients get to transplant, there could be an increase in overall number of patients, who unfortunately then develop chronic GVHD as a consequence of that transplant. And there's also, I think a lot of underserved patients that exist today with chronic GVHD, who have been treated with therapies that weren't developed to treat that disease and haven't done as good a job as we think axatilimab could do and maybe perhaps some of the other agents in controlling their disease. So, we think that is really going to be a displacement of some of the non labeled agents used off-label to treat chronic GVHD, and there'll be ways to actually maybe better help these patients, better serve these patients and help them live longer and better with their disease.

Got it. And I have one follow-up I know that we aren't expecting the top line AGAVE-201 data until 2023, but should we see any data readouts before that or anything this year or maybe next year for the earlier trial?

Right. So you may remember, we had started a Phase 2 expansion cohort as part of our Phase 1 trial at 1 mg per kg. And it is -- the team is still allowing that trial to enroll while we get AGAVE up and running. So if a site doesn't yet have AGAVE up and running, but still has patients they want to put on trial, we can put a few more on. And it's not clear yet when we're going to present that data, but there may be data on that updated Phase 2 court at the 1 mg per kg later this year.

Your next question comes from the line of Peter Lawson from Barclays. Your line is open.

Briggs, just on the side effect profile you've seen so far for 5603. Does that preclude or point to any particular combination agent that you'd won in presumably frontline?

Yes. So obviously, we'll present the safety data, I think somebody asked earlier. From what we've seen, it doesn't preclude combining with any of the agents that we would be interested in combining with.

And that applies for both kind of arm A and arm B?

Well, it applies to the so-called chemo eligible patients and the unfit.

Got you. Okay. And then as you move from Phase 1 into Phase 2, do you expect any changes in endpoints? Or how should we think about the, I guess, the inclusion/exclusion and how they potentially change from Phase 1 to Phase 2 or endpoints?

Yes. No, we don't -- again, obviously, the Phase 1 trial, the primary objective, as I alluded to, were PK, safety and defining a recommended Phase 2 dose. The Phase 2 portion, the primary endpoint is a CR rate for efficacy. But the overall inclusion/exclusion don't change. Obviously, the Phase 1 trial has changed over time. We've amended the protocol many times to allow pediatric patients in to focus on NPM1 and MLL-r. So -- but overall, the general population of patients that we're enrolling in terms of relapsed/refractory leukemia doesn't significantly change from Phase 1 to Phase II.

Got you. And then in that kind of third group of patients you mentioned about presenting, so the non MLL-r and the non NPM1 patients. Would you guys expect to see any kind of response in those patients?

Well, I think that's why the FDA asked the companies to enroll a broader population. So, I think their perspective was, we're convinced that your drug potentially could work in NPM1 and MLL-r. There's been extensive preclinical validation. We are convinced that your drug probably would not work in BCR-ABL, but we've always used that as a negative control in our preclinical models. But there are other forms of leukemia that it might be of interest for you to study. So, I think that was why the FDA asked us to enroll an all comers' population.

Okay. And so we could get kind of patient vignettes in that group that could be of interest?

Well, as I said, I think the FDA asked us to enroll a broad population of patients to begin to look at that. It's obviously not a definitive assessment of that population. We focus much more on the MLL-r and NPM1 for the simple reason that we can diagnose those patients today, and it's clear unmet need in a population of patients that from a regulatory point of view, you can identify and you can get an indication for.

There are no further questions at this time. I would now like to turn the call over back to Mr. Briggs Morrison, Chief Executive Officer of Syndax.

Thank you very much, operator. And again, thank you, everybody, for joining us on our call. As I said, I think, 2020 was a transformational year, and we anticipate that 2021 will be no less exciting. And the first piece of news, of course, will be the presentation of our Phase 1 data from the AUGMENT-101 trial. And I think we're really quite excited to present that data and then to take additional questions from everybody, and once you have a chance to see that. So thanks so much for joining the call.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.