Good day, everyone, and welcome to the Syndax Third Quarter 2020 Earnings Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Melissa Forst 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 review of Syndax' third quarter 2020 financial 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 today for the question-and-answer session will be 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 would ask you to please turn to 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, November 2, 2020, only. A replay of this call will be available on the company's website following the call.

Thank you very much, Melissa, and thank you to everyone who's joining us on today's call and the webcast. The third quarter has been quite busy for us here at Syndax. So let's just jump right in. 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 are intensely focused on our two exciting and promising programs while we also continue to look for additional oncology pipeline opportunities. 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 routinely 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 I/II trial in the accelerated understanding of Menin, or AUGMENT program. Consistent with what we communicated on our last call, we anticipate presenting the completed Phase I portion of the trial in early 2021. We have been busy over the last quarter preparing for the Phase II portion of the trial, which will enroll three distinct expansion cohorts, each consisting of a specific genetically defined relapsed or refractory acute leukemia. The three cohorts will include patients with MLL-r acute lymphoid leukemia or ALL; patients with MLL-r acute myeloid leukemia or AML; and patients with NPM1 mutant AML. The Phase II portion will further characterize the safety of SNDX-5613 and will provide an initial estimate of the complete response rate as the primary measure of therapeutic benefit. 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 if results are positive, this Phase II portion of AUGMENT-101 could potentially support a regulatory filing, giving existing regulatory precedence. Over the last period, we've also been conducting extensive research into the broad landscape of clinical opportunities for SNDX-5613 beyond the initial approval in relapsed/refractory acute leukemias as illustrated on Slide 6. While we are not in a position today to lay out the specific next steps in building out the SNDX-5613 franchise, I can say that we are using this ongoing analysis to inform specific combination regimens that we anticipate starting to study in the near future. Several investigators have already reached out to us with novel exciting ideas for the future development of SNDX-5613. Let me now turn to Slide 7 and axatilamab, formerly known as SNDX-6352, our potentially best-in-class monoclonal antibody therapy targeting the CSF-1 receptor. As you know, we've been conducting a Phase I/II trial with axatilamab in chronic graft versus host disease, and we are pleased to announce that the organizing committee of this year's ASH has selected our abstract for oral presentation, which will be on December 6. The abstract itself includes 12 patients and will publish this Thursday, November 5. The data in the abstract was current as of the abstract submission date back in August, with a data cutoff date in July, and we anticipate that the oral presentation will have a larger data set of about 15 patients who enrolled in the Phase I portion of the trial. We are not able at this time to comment on the actual data in the abstract, given that it is currently embargoed, and yet we would encourage investors to pay attention to the patient demographics, especially the number and type of prior therapies the patients had before they went on to our trial; the response rate; the tolerability profile; and the clinical efficacy in hard-to-treat organs. Our team has completed the end of Phase I regulatory discussions with the FDA, and we're pleased to announce that we have agreed on a pivotal trial for axatilamab in chronic graft versus host disease. This trial is the axatilamab for chronic graft versus host disease trial called AGAVE-201 and is outlined on Slide 8. The trial will enroll patients with chronic graft versus host disease, whose disease has progressed after two prior therapies. Patients must be at least six 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 axatilamab given either every two weeks or every four 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. We anticipate beginning enrollment this year with top-line data likely available in 2023. We believe that chronic graft versus host disease 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 recent positive pivotal results from both Incyte's Jakafi and Kadmon's KD025, we may soon see commercial launches that will begin to delineate the commercial opportunity in chronic graft versus host disease. Despite recent advances in this area, to our knowledge, axatilamab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. We believe the data generated to date with axatilamab 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 found a strong consensus that the scientific rationale for the efficacy of axatilamab in chronic graft versus host disease firmly supports its potential in a wide variety of fibrotic diseases such as idiopathic pulmonary fibrosis and scleroderma. We are actively evaluating options by which to build out the axatilamab franchise beyond chronic graft versus host disease and take advantage of what we believe are a significant set of opportunities that could materially enhance shareholder value. Finally, Slide 9 summarizes the transactions that led to the acquisition of the Menin-MLL-r and axatilamab programs. We believe that we will be able to continue to expand our pipeline through the acquisition or in-licensing of quality differentiated assets. We believe that we have the necessary skill to evaluate and identify high-quality assets and the clinical development experience to bring those compounds to valuable inflection points. We expect to remain among the preferred partners for such transactions.

Thank you, Briggs. The results of our operations for the third 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 third quarter report on Form 10-Q, which will be filed later this week. I would like to point out that our operating loss for the quarter was $20.4 million or $0.46 per share compared to $12.8 million or $0.41 per share for the same period last year. Turning to Slide 10. We ended the third quarter with $170.2 million in cash and cash equivalents and 44.4 million shares and prefunded warrants outstanding. Looking ahead, I'd like to provide financial guidance for the remainder of the year. Our second half operating expense guidance remains unchanged at $40 million to $45 million, including approximately $2 million of noncash stock compensation expense per quarter and $4 million in milestone payments to UCB based on achievement of positive milestones associated with axatilamab. For the fourth quarter of 2020, R&D expenses are expected to increase as our development activities for both SNDX-5613 and axatilamab continue to ramp up heading into registration-ready trials for both programs. Fourth quarter G&A expenses are expected to remain at third quarter levels. For the fourth quarter, we expect R&D expenses to be between $15 million to $20 million and total operating expenses to be between $20 million to $25 million. Given our cash operating expense guidance for the fourth quarter of 2020, we continue to expect to end the year with approximately $145 million of cash, which gives us cash runway into 2022 to meet our key development milestones.

Great. Thanks so much, Daphne. As I hope you have appreciated from my prepared remarks, we are increasingly excited about both of our clinical programs. We look forward to the oral presentation of the Phase I axatilamab data at ASH in December of this year, followed soon thereafter by the Phase I data on SNDX-5613 in early 2021. We currently anticipate having both programs in Phase II early next year. AGAVE-201 is a pivotal trial for axatilamab, and it's possible that the Phase II portion of AUGMENT-101 could also be registrational for SNDX-5613. So by early next year, we could have two registrational programs ongoing. We are also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indications. We believe SNDX-5613 could have broad utility across a wide range of clinical settings in acute leukemia, and axatilamab could represent a broad franchise opportunity in fibrotic diseases. We are comfortable that given 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 Phil Nadeau with Cowen & Company.

Congrats on the progress. Just a few on the Menin program. I guess, first, for the Phase II. In order to support a filing, do you have a sense from your FDA conversations what the CR rate would need to be? How durable the responses would have to be? And how many patients would be required in the initial analysis?

Phil, thank you for your question. I would say there is regulatory precedent; for example, the IDH inhibitors were approved as monotherapy based on single-arm trials. In those cases, the complete response rate was around the mid-20s, with a median durability of response of approximately 8 months. Therefore, something in that range could be an acceptable submission package to the FDA, though the exact number of patients is still to be determined.

Perfect. That's helpful. Second, I'm sure you're getting this question all the time. We are too curious about obviously have data at ASH with something coming on the abstracts this week. Investors are curious what implications that data could have for Syndax. I'm curious, from your opinion, what will you be evaluating in that data? And any pointers for us as we look through and we try to interpret the impact on Syndax?

Yes. Look, I think that when we presented data at AACR validating that this mechanism can work for MLL-r leukemias, both companies benefited from that. Should they present data on NPM1 leukemias that validate that this mechanism can work there, I think both companies would benefit from that. But to be honest, I think our focus right now, as I said in my prepared remarks, we're trying to get our sites open for Phase II and getting ready to start that Phase II trial. So we're interested in what our competitor has, but our key focus is really trying to deliver our molecule through its potentially registrational program.

Perfect. My last question is about axatilamab. You mentioned that we should consider the patient demographics when looking at the abstracts. Can you provide some insight into the historical response rates for GVHD, considering the patient demographics in your study? What would be a relevant comparison?

Yes, it's actually hard to have a relative comparator because the patients that we've enrolled are very heavily pretreated. You may remember that the vast majority of them have received ibrutinib, many of them have received ruxolitinib, and many have received the Academy compound. So this is a very refractory population of patients. So there's not really a precedent I would say, if you go up in earlier lines of therapy, the data, some of those patients had received ibrutinib or RUX, some had not. I think given that picture, I think anything above a 50% response rate in this heavily refractory population, we would be quite excited with. And I think the other thing to look at is not just the overall response rate, but the specific organs because there are some organs that have been harder to treat than others in GVHD.

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

Congratulations on the progress as well. And I'll just follow on there with regard to axatilamab. Is the development of the molecule then set towards the refractory setting? And if it is initially, do you plan to potentially move it forward to more frontline settings? Just a little bit more color just given the data we're about to see and your thoughts on the overall development scheme for the program.

Yes. Thanks for the question, Bert. So we do believe, as I pointed out in the pivotal trial, these will be patients who have failed at least two prior therapies. So it is a refractory population. Again, as I pointed out in my prepared remarks, I think that the emerging safety profile for axatilamab makes it quite amenable to combine with other agents. So we can certainly foresee future development where the drug gets moved up into earlier lines, potentially in combination with other mechanisms. Remember, axatilamab is really the only agent in development for GVHD that is specifically focused on the monocyte macrophage lineage. Some of the other agents that are around work on T cells or B cells. And it may well be that a combination of a drug that hits its T cells and a drug that hits macrophages or monocytes is the right combination. And I think because of the tolerability profile, I think those types of combinations are things that we're starting to think about.

So the initial potentially pivotal portion would be in the refractory population, and then you would aim to move it more to the front line over time in combination with other treatments.

Exactly. That's a fair summary.

Okay. And then just with regard to 5613, thank you for the comments there as well. Is there an ability to have a rapid development course in the pediatric group specifically? There's obviously some urgency to move it into pediatric patients at effective dosing levels that we heard from the pediatric ad com earlier this year. Is there a separate course to be pursued there? Or is that just something that will be wrapped in the overall development program?

So the ongoing trial, AUGMENT-101, is open at this point to patients basically a month of age or older. And the Phase II portion, if that Phase II portion were registrational, that will be open to pediatrics as well as adults. So the initial, if you will, monotherapy relapsed/refractory population, we will study a broad age group. I do believe that, as I said in my prepared remarks, there are combinations both in kids and adults that we're looking at to bring a fuller picture to the power of the molecule, but the single-agent trial is open to both pediatrics and adults.

Okay. And then just one more question from me. Regarding the potential combination regimens with 5613, are you primarily focused on exploring combinations with 5613, or is there a broader licensing strategy for AML or blood-based tumors? How should we view this strategically for Syndax?

Yes. I'll ask that Michael Metzger to take that question.

Sure, Briggs. Thanks for the question. So I think we think about this as an indication-by-indication strategy build out. And so I think we're evaluating all the opportunities from a commercial perspective, the unmet needs perspective, and those may be trials that we do on our own. It may be trials that we do in collaboration through clinical collaboration, or more broadly, there may be something more strategic than that at some time in the future. So we're looking at all those opportunities and what's the best way to advance the molecule.

Congratulations on the progress.

Your next question comes from the line of Joel Beatty with Citi.

This is Shawn Egan calling in for Joel. The first one on axatilamab. When you guys had your end of Phase I meeting with the FDA, was there any kind of agreement on the threshold for success? I know Kadmon had a lower bound of 30% response rate. What does it look like for you guys?

We haven't disclosed the statistics on the program. However, there is an implied lower bound in the number of patients being enrolled.

Great. And then for 5613, the Phase II monotherapy, potentially registrational trial in the broad age group. Will that be in the relapsed/refractory setting? Or could you give a little bit more color on the inclusion criteria there?

Right. So I think we'll say more about that once we have full FDA agreement that it is registrational. But the way the trial is set up now, and you can see on ClinicalTrials.gov, these are relapsed/refractory patients. That's the population that's being studied in Phase I, and that's the population that we anticipate studying in Phase II.

Great. And I notice you guys gave a little bit more color on kind of moving axatilamab into some additional indications. Maybe could you talk about how quickly we could expect that to happen? And any kind of priority on whether IPF or scleroderma will kind of move ahead first?

Michael Metzger, do you want to take that question?

Sure. Look, I think we see the axatilamab franchise as being very significant. I'll also say we're fully committed to unlocking value for the program and building shareholder value around it. I think there are many opportunities by which to do that. And so really, we're just looking at all the different options, currently exploring all the options to build value. That's essentially where we are now.

Your next question comes from the line of Madhu Kumar with Baird.

First one relates to the 5613. How do I think about the potential of this drug being used as a bridge to transplant or in the kind of post-transplant maintenance studies in various leukemias?

Thank you for your question, Madhu. To start, during our ongoing trial as we advance to Phase II, if a patient with relapsed or refractory leukemia achieves a complete response and qualifies for a transplant, it is completely reasonable, and likely expected, that many of the investigators will pursue transplant for their patients. Typically, they will not consider transplant unless the patient is in remission. Therefore, if 5613 helps them achieve remission, some patients may proceed to transplant if they are eligible. We are actively considering whether to continue 5613 as a maintenance treatment after the transplant, which is an important aspect we are evaluating and thinking about potential study designs for.

Okay. And then one other question we've gotten a lot since April was the observations of QT prolongation in kind of the early phases of the dose escalation. So obviously, you can't get into anything that's happened further on the line, but what has been the response from physicians about thinking about the QT events you've seen so far, and how they would manage it on the relapsing effect of leukemias?

Yes, the physicians we've talked to are quite accustomed to observing drugs that cause minor abnormalities and QT prolongation. They feel confident in monitoring this and making any necessary dose adjustments if prolonged QT occurs. The AML doctors we've consulted, especially in the relapsed refractory population, view a drug that successfully brings patients into remission as a positive development and do not see QT prolongation as a major obstacle to its use.

One last question. Bigger-picture question on strategy and kind of capital deployment. How do you balance the capital deployment to find new assets versus the fully unlocked development of things like axatilamab? Like how do you strike that balance?

I don't know if Daphne, maybe you want to take that question?

Yes. Thank you for the question. We look at all of the opportunities and think about, as Michael mentioned earlier, maximizing shareholder value. And as we move forward, our priorities are certainly to meet important milestones on the current programs and continually evaluate and look at the opportunities with respect to IRR and NPV values of internal versus external opportunities and always looking to be very efficient and thoughtful about how we deploy that capital. But it's a constant evaluation process.

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

Congratulations on the oral presentation of axatilamab. I guess, firstly, the ASH abstract that we see, is that going to be data-rich in terms of trying to understand response rates and tolerability and prior therapies?

Yes, Peter. So the abstract comes out on Thursday. And as I said in my prepared comments, again, the data was as of July. So there's 12 patients, but there's information there on prior therapies, on response rates and on organ-specific response rate.

Great. And then where do you see it fitting into the emerging treatment paradigm just with a couple of new drugs in that space over the next couple of years?

Yes, I believe this is the only medication in development that specifically targets the monocyte macrophage lineage. From the data we've shared about some of our other trials on axatilamab, you might already have a sense of its potential. It’s a well-tolerated agent, and I see the initial goal as obtaining approval for use in patients who have likely exhausted other treatment options. Furthermore, as was mentioned in an earlier question, we will explore opportunities to introduce it in earlier treatment lines, possibly in combination with other agents that operate through complementary mechanisms.

Great. And then just on the Menin program, so early 2021 for data. Is that going to be at a medical conference? Or is that going to be press released? And then just how enrollments going within the various arms, the 6384 alpha with and without kind of thing and also you've seen NPM1 patients?

So the enrollment continues to go very well. I think we mentioned on our last call that one of the changes we made to the trial was to be able to backfill cohorts where we had cleared safety and seen efficacy. And that was, in large part, driven by the investigators who are asking for more slots to put patients onto the trial, given what they're seeing. So enrollment continues to go very well. We haven't given any more information about where we are on the two arms or the types of patients. All that will be presented when we present the completed Phase I trial.

And there are no further questions at this time. So I would like to turn the call over to Dr. Morrison.

Well, first, let me thank everybody for joining us on the webcast and on the call and for your continued interest in Syndax. As I said in my prepared remarks, it's an incredibly exciting time for us here at the company. It's quite possible that by early next year, we will have two programs in pivotal registration trials, and that's really super exciting. So I don't want to hold people from getting their rest before they have to go vote tomorrow, but thanks so much for your attention and your time.

Ladies and gentlemen, thank you for your participation. This concludes today's conference call, and you may now disconnect.