Ladies and gentlemen, thank you for standing by and welcome to the Syndax First Quarter 2021 Earnings Conference Call. At this time all participants are in a listen-only mode. After the speaker’s presentation, there will be a question-and-answer session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Melissa Forst with Argot Partners. Please begin.

Thank you. 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 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; Daphne Karydas, Chief Financial Officer; also joining us on the call today for the question-and-answer session will be Michael Metzger, President and COO; 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 our 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. These include those discussed in the Risk Factors section on 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 11, 2021 only. A replay of this call will be available on the Company's website following the conclusion of the call. And with that, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer of Syndax.

Great. Thank you so much Melissa and thank you to everyone for joining us on today’s call, and the webcast. Slide three 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've continued to make great progress in both our clinical programs during the first quarter of this year. We reported the initial data from the Phase 1 trial of SNDX-5613, our selective menin inhibitor, and are on track to begin potential registration cohorts in that program shortly. In addition, we have completed enrollment of 23 chronic graft versus host disease patients on axatilimab at 1 mg per kilogram in our Phase 2 of expansion cohort. And enrollment is on-going in our pivotal AGAVE 201 trial. We therefore remain on track to have two registrational programs on-going this year for two, first-in-class and potentially best-in-class medicines for two 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.

Thank you, Brigg. The results of our operations for the first 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-10Q which was filed earlier today. I would like to point out that our net loss for the quarter was $27.7 million, or $0.54 per share, compared to $19.1 million, or $0.56 per share for the same period last year. Turning to slide 12, we ended the first quarter with $271.3 million in cash and cash equivalents and 51.6 million shares and pre funded warrants outstanding. This cash balance provides us cash runway into 2023 and importantly, covers the development costs of both the axatilimab and the menin registrational programs to their first approval, as well as provides us the flexibility for continued business development. Looking ahead, I'd like to provide financial guidance for the second quarter of 2021. For the second quarter, we expect R&D expense to be between $30 million and $35 million and total operating expense to be between $35million and $40 million including approximately $2.5 million of non-cash stock compensation expense. Full year 2021 guidance remains unchanged. And we continue to expect R&D expense to be between $90 million and $100 million and total operating expense to be between $110 million and $120 million, including approximately $2.5 million of non-cash stock comp expense per quarter. We continue to expect first half expenses to be more heavily weighted than the second half, due primarily to the ramp up and CMC activities for both programs in the first half of the year. With that I would like to now turn the call back over to Briggs.

Thanks so much Daphne. Let me close the call by again noting that we have begun the registration the trial for axatilimab in chronic graft versus host disease and on track to start the registrational program for 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 we consider having two on-going registration programs as a major achievement. We're also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indications. We believe 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 given our cash on hand and 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 strategy, and I believe it 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, the trial sites and the investigators involved with our clinical programs. In addition, I'd 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.

Our first question comes from Philip Nadeau with Cowen & Company. You may proceed with your question.

Definitely. Thanks for taking our questions and congratulations on the progress. First, a clarifying question on that the data that you released tonight in terms of the NPM1 patients and the 29% overall response rate. Have you disclosed whether the two responders have had complete hematologic recovery?

So so one of the two NPM1 patients is the vignette that I covered today, and was one of the three vignettes that Eytan covered. So that patient clearly had initially a CRi, and then had full hematologic recovery, went on to a bone marrow transplant. We have not given any further information on the second patient who had a complete response.

Got it? Okay. Second question is in regards to the Phase 2 dose. Many people have noted that recently another cohort was added to the dose escalation study looking at cobicistat boosting. Can you talk about the goals for that cohort and how that plays into your decision on which dose to move into the pivotal study?

Yes, thanks for the question. So the cobicistat arm is really an exploratory arm to look at the effect of cobicistat on the PK 5613. It has nothing to do with the doses that we will take into Phase 2. We're not waiting for the data from the cobicistat arm to start Phase 2. So Phase 2 is the data set that we presented at our data disclosure. So the 226 in Arm A and the 113 in Arm B. Cobicistat is an exploratory sort of Lifecycle Management study just to look at the PK effect of cobicistat on the PK and 5613.

Perfect. Last question from us. I was curious if you'd be willing to address it, I guess the biggest perspective we got after the initial dose was people who were worried that the therapeutic window 5613 was a bit too narrow that if could push the dose just a little bit harder, maybe the efficacy would improve a bit. But they perhaps are somewhat limited by QTc prolongation at higher doses. What's your perspective on that that argument? How valid is it? And what gives you confidence that, that you're maximizing efficacy at the doses that are acceptably safe?

Yes, so as we indicated in the presentation, we had pre specified criteria for our recommended Phase 2 dose, including exposures that we thought were required for efficacy. We've been able to meet those criteria at the recommended Phase 2 dose, the response rates at the recommended Phase 2 dose are generally the same as what we see in the overall population, which again, is not all that surprising, since many of the patients, in fact were treated at the recommended Phase 2 dose. Again, the vignette, I just presented today is the patient treated at the recommended Phase 2 dose had NPM1 disease, a rapid CRi, that then progress to full count recovery. So we feel very comfortable that the dose that we're picking for our recommended Phase 2 dose meets our criteria, and that we're not leaving any efficacy on the table by not going higher.

That's very helpful. Thanks for taking our questions.

Thank you. Next question comes from Bert Hazlett with BTIG. You may proceed with your question.

Yes, I think you just answered it. Thank you for taking the question. And congratulations on the progress. I think you just answered it, but maybe just asked slightly differently. So what then are the specific goals of the interim cohort? The interim dose cohort? And is that a gating item to moving forward into the potential pivotal start of 5613?

Yes, thanks for the question Bert. So, as I said to Phil, we're very comfortable with the dose, the 326 Arm A, 113 Afm B, as recommended Phase 2 dose. The investigators and our clinical team wanted to study that intermediate dose to see if in fact, there was a dose in between the doses we studied that could also meet our criteria. If those intermediate doses do meet our criteria, all of our criteria, they could be the doses that we take into Phase 2. If they don't fit, it's not a problem. So those are gating. We do want to wait to get the answer to that question before we start the Phase 2 trial. And again, we feel like we're on track to have that by the end of the quarter.

Okay, that's it for me. Thank you.

Thank you. Our next question comes from Colleen Kusy with Baird. You may proceed with your question.

Hi, good afternoon. Thanks for taking our questions and congrats on the progress. For the for the clear -- thanks for the clarity on the NPM1 patients. I know you noticed the two of them to come to infections. Did you see any of those and the MLR patients enrolled in this study?

I don't remember off the top my head. I think there was one MLR patient. Maybe Michael Myers, you can answer that question. It was one MLR patient who didn't make it through because of an early infection, Michael.

Yes, Briggs, thank you for that. Colleen. Yes, we have seen MLL-r patients be to have infections, it is an expected complication of AML, especially in patients who have active disease whose counts are not sufficient to protect them from specifically bacterial infections. So as Eytan Stein said in the presentation, infectious combinations of AML are expected and not at all unusual.

That's helpful. Thank you. And what, what is the protocol for stem cell transplants in this study? And will there be any changes for the Phase 2?

While there isn’t a protocol for stem cell transplant in this study. The standard-of-care for the treatment of acute leukemias if you can get a patient into a complete response, and particularly if you can get a patient into an MRD, negative complete response. And the patient is otherwise eligible for transplant, meaning they have identified an adequate donor, their other general medical conditions are stable, then the patient goes to transplant. So it's the investigator and the treating physician’s decision about whether they want to take them to transplant. But what they're hoping for is that they can get the patient into an MRD, negative complete response. And if so, then they will work to take the patient to transplant. It's not formally part of our Phase 1 study, but it is obviously a very good result for the patients who are able to go to transplant.

That's great. Thanks. And then for the updated data today is, can you confirm where those centrally reviewed or how were those reviewed?

They're reported to us by the -- they are scans that you centrally review as you do for solid tumors. So the information is communicated to us by the investigator and then Michael and his team review the information to confirm it.

Okay. That's helpful. Thank you.

Thank you. Our next question comes from Peter Lawson with Barclays. You may proceed with your question.

Congrats on the progress and the update. For 5613, is there any way of breaking out the CR, CR rate for the I guess the 113 milligram go forward dose?

Yes, Peter. I think they're -- they will, we're looking for opportunities to present the data at Scientific Congresses will break out everything by dose and arm. So I think you're going to look forward to that added up updated scientific presentation.

It, could you disclose if it's above or below the overall CR/CRh rate?

So as I said before, if you look at any of the parameters that we've looked, we've reported on overall response rate through our CRh responses and NPM1, responses at MLL-r at the recommended Phase 2 dose, those responses are generally consistent with what reported for the overall population.

Got you. Thank you. And then just on the additional arm that was added, just if I could circle back on that, would that be something you'd want to file on with the 634 kind of on board? Just trying to work through that if that's something that gets reported out in two years’ time, or it's something you kind of have to perhaps use as a go-forward strategy?

Right. So as I indicated, I think in sales questions, it's not a gating item for Phase 2, we will proceed with the doses that we've been talking about for Phase 2, this is really an exploratory arm part of exploratory arm as part of our sort of Lifecycle Management. We are thinking down the road to the point where we get patients in remission, who then perhaps in a maintenance point of view, if we can have greater exposure for any given dose, that obviously decreases the cost of goods. But it's really more of a downstream lifecycle. The head, we're thinking about long term chronic therapy, and it really doesn't play a role in the on-going phase, Phase 1 to Phase 2 transition.

Got you. Thank you that that's really helpful. So it could be in that maintenance setting where you kind of extend the drug into post therapy.

Exactly.

Perfect. Thanks so much.

Thank you. Our next question comes from Justin Walsh with B. Riley Securities. You may proceed with your question.

Thanks for taking the question. A couple of months ago, a competitor announced that it's using MRD negative CR as a primary endpoint for its drug and newly diagnosed NPM1. mutant AML. First, do you have any comments on how this endpoint is different and may or may not impact your thinking for the regulatory strategy for SNDX-5613? And second, how do you see the targeted NPM1 mutant AML landscape evolving with a potential for multiple therapies available for the population?

I guess thanks so much for your question. So the first has to do with MRD negativity as an as an endpoint. You know, we give a lot of credit to our competitor who has brought that forward and apparently gotten FDA endorsement, to use that as a, a endpoint for accelerated approval in a randomized trial. To our knowledge, that that has an endpoint in a single arm trial in a relapsed refractory population is not something the agency has been open to date, obviously, something for further, further regulatory discussions. So I think that that is a -- is probably not something we're going to be able to discuss with the FDA, but we're not counting on that being an endpoint for our relapsed refractory population. But similar to what they've described, we do think that could be an endpoint in a, let's say, a first line trial where you use that as your accelerated approval endpoint. I think your second question about the landscape for NPM1 disease. I think there's, obviously we believe that the Menin inhibition pathway dependent inhibitors are going to be very important agents for those patients, whether there'll be other agents that that work for those patients as well, time will tell.

Got it? And I've one more question. You've mentioned the potential approvals in cGVHD. I was wondering if you can provide some additional color and your thoughts on the landscape there. Do you anticipate that most of the cGVHD patients who end up cycling through all of the available drugs or do you think that they'll remain on one drug for a long period of time, and there'll be a lot of competition in the first and second line on that front?

Yes, it's a good question. The, I think the landscape and chronograph was associated with is its infancy is sort of evolving. We, we haven't really had, approved drugs. There's not a defined treatment pathway for patients if you are on this one, and that one. We also think that different agents may have let’s a better efficacy for different manifestations of the disease. So I think it's something that we'll sort of see how that evolves. But, I think we're quite excited to have an agent that shows broad activity against many manifestations of the disease. And of course, is the only one that's targeting macrophages. I think the other part to your question about how this landscape will evolve is, are there rational combinations that perhaps even earlier in the treatment course you could have a more profound effect on the patient's disease?

Got it. Thanks for taking the questions.

Thank you. Our next question comes from David Lebowitz with Morgan Stanley. You may proceed with your question.

Well, thank you very much for taking my question. Understanding that the numbers are somewhat limited at this point, is there any qualitative insight you can give us as to the effect of 5613 on ALL patients in the study?

Yes, I think, David, you're right that numbers are on the small side, most of the patients with MLL-r that have come in have been AML patients. Again, one of the vignettes that Eytan reviewed at the date of closure was a patient with what we call mixed phenotypic, acute leukemia. Many people bucket that in, in the ALL bucket, but the for the numbers are small. I guess I'd say pure question qualitatively, it looks the same in ALL as it does in AML. But the numbers are small.

Fair enough. And as far as the NPM1 patients, I guess, how does that 29% response rate look, vis-à-vis the response rate for the current standards and the similar treatment population?

Yes, so again, for relapsed refractory acute leukemia. In for both NPM1, and MLL-r there really aren't good therapies for these patients. So today, if they're truly relapse refractory it with either of those mutation is they're generally being treated with chemotherapy. And there's not a lot of really solid data on the response rate in it for those specific lesions. But overall, if you look into relapsed refractory population, you'll see a response rate, again, a CR rate for chemotherapy, probably no higher than 10%. So, we think that what we're seeing both in NPM1, and in MLL-r, again, with a safe oral agent, is probably quite an excess of what you would anticipate with get another round of toxic chemotherapy.

Thanks for taking my question.

Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back over to Dr. Morrison for any further remarks.

Great, thanks very much operator. Thanks, everybody, for joining us on the call today. Again, I think we remain really quite excited about what we're seeing both with 5613 and with axatilimab, and we look forward to presenting additional data in the future. Thank you for joining.

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