Syndax Pharmaceuticals - Earnings Call - Q4 2020

Transcript

Speaker 0

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

Speaker 1

Welcome, and thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax's fourth quarter twenty twenty financial and operating results. I'm Megan Myers with Argo Partners, and with me this afternoon to discuss the results and provide an update on the company's progress are doctor Briggs Moriksen, chief executive officer Daphne Corvitas, chief financial officer. Also joining us on the call today for the question and answer session is Michael Metzger, president and COO, doctor Michael Myers, chief medical officer, and doctor Peter Ordendlik, chief scientific officer. This call is being accompanied by a slide deck that has been posted to the company's website, so I would ask you to please turn to our forward looking statements on slide two. 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 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, 03/08/2021 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 Doctor. Briggs Marsden, Chief Executive Officer of Syndex.

Speaker 2

Thanks very much Megan and thank you to everyone for joining us on today's call and 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. 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 four and SNDX-five 613, our genetically targeted agent for the treatment of leukemia. As we've noted previously, there's extensive validation of both MLLr and NPM1 mutations as molecular targets in leukemia. And well established diagnostic tests routinely identify patients with these genetic mutations. Premier publications provide the scientific rationale and preclinical validation of our ongoing clinical trial. And historic precedent support a rapid regulatory path for such targeted agents in acute leukemias.

Slide five briefly summarizes the ongoing AUGMENT-one 101 trial, the first in human Phase onetwo 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 one portion of the trial in the near future and to start the Phase II expansion cohorts soon thereafter. We have received several questions about the upcoming data disclosure, and so I just want to provide some guidance. Our intent is to present the completed Phase I trial. The primary objectives of Phase I are to determine the safety, tolerability, the maximum tolerated dose, and the recommended phase two dose of SNDX-five thousand six hundred thirteen in patients with relapsed or refractory acute leukemia.

We anticipate addressing these primary objectives in our data presentation. We will also have characterized the PK parameters of 5,613. We anticipate having data for at least thirty patients with relapsed refractory leukemia. There will be patients whose leukemia has an MLL r rearrangement. There will be patients whose leukemia has an NPM1c mutation, and there will be patients whose leukemia has neither of these genetic lesions.

Although clinical efficacy is not objective of the phase one trial, we anticipate summarizing the efficacy that has been observed. We anticipate that the data will be presented by the principal investigator of the AUGMENT-one 101 trial, Doctor. Eitan Stein from the Memorial Sloan Kettering Cancer Institute, an extremely well respected international expert in the field of adult leukemias who has extensive experience developing novel targeted agents. Doctor. Stein's presentation will be similar in content to a typical presentation scientific congress such as ASH and there'll be opportunities for Q and A.

We are working with Doctor. Stein to find a suitable date, but anticipate securing a date prior to the April. We have of course been busy preparing for the Phase II portion of the trial, which will enroll three distinct expansion cohorts, each of which consists of a specific genetically defined relapsed or refractory acute leukemia, and which is on track to initiate over the next couple of months. The three cohorts will include patients with MLLr acute lymphoid leukemia, ALL, patients with MLLr acute myeloid leukemia, AML, and patients with NPM1 mutant AML. The phase two portion will further characterize the safety of 5,613 and will provide a robust 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 the results are positive, this Phase II portion of AUGMENT-one 101 could potentially support a regulatory filing given existing regulatory precedents. Over the last period we've also been conducting extensive research into the broad landscape of clinical opportunities for 5613 beyond the initial approval in relapsed refractory acute leukemias as illustrated on slide six. While we are not in a position today to lay out the specific next steps in building out the '5 thousand six hundred thirteen franchise, I can say that we are using this ongoing analysis to inform specific combination regimens that we anticipate starting the study later this year. Several investigators and leading companies have already reached out to us with novel exciting ideas for future development of SNDX-five thousand six hundred thirteen, and we are evaluating those opportunities.

Let me now turn to slide seven, and axitelimab, formerly known as SNDX-six thousand three hundred fifty two, a potentially best in class monoclonal antibody therapy targeting the CSF-one receptor. As you know, we recently presented our Phase I chronic graft versus host disease data at ASH and have initiated our pivotal trial for axitelimab in chronic graft versus host disease. This trial is the axatilamab for graft versus host disease trial called AGAVEY-two zero one, and is outlined on this slide. 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 axitelimab given either every two weeks or every four weeks. The primary endpoint is overall response rate using the twenty fourteen NIH consensus criteria for chronic graft versus host disease. Secondary endpoints will include duration of response and validated quality of life assessments using the Lee Symptom Scale. Enrollment to the study is underway, and we are on to deliver top line data in 2023. We believe that chronic graft versus host disease represents a high unmet medical need and an important commercial opportunity with approximately fourteen thousand patients suffering from chronic graft versus host disease in The US today.

With the recent positive pivotal results from both Incyte's Jakafi and Kadmin's KD025, we may soon see regulatory approvals and 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 state 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, potentially 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 axitelimab 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 the axitelimab 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 eight summarizes the transactions that led to the acquisition of the Menin MLLr and axitelimab 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 skills to evaluate and identify high quality assets and the clinical development experience to bring these compounds through valuable inflection points. We expect to remain among preferred partners for such transactions. I'll now turn the call over to Daphne to review our financial results.

Daphne?

Speaker 0

Thank

Speaker 3

you, Briggs. The results of our operations for the fourth quarter of twenty twenty 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 ks, which will be filed later this week. I would like to point out that our net loss for the quarter was $20,400,000 or $0.44 per share compared to $14,000,000 or $0.44 per share for the same period last year. Turning to Slide nine, we ended the fourth quarter with $293,100,000 in cash and cash equivalents, including net proceeds of approximately $135,000,000 from our public offering completed in December 2020 and 51,400,000.0 shares and pre funded warrants outstanding.

This cash balance provides us cash runway well into 2023 and importantly covers the full development costs of both axatilamab and the 5,613 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 2021, we expect R and D expense to be $25,000,000 to $30,000,000 and total operating expense to be 30,000,000 to $35,000,000 including approximately $2,000,000 of non cash stock compensation. For the full year of 2021, we expect R and D expense to be 90,000,000 to $100,000,000 and total operating expense to be $110,000,000 to $120,000,000 including approximately $2,000,000 of non cash stock compensation expense per quarter. We expect first half expenses to be more heavily weighted than the second half due primarily to the ramp up in CMC activities for both programs during the first two quarters of the year.

With that, I would now like to turn the call back over to Briggs.

Speaker 2

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 axatilamab in chronic graft versus host disease and are eager to present our Phase I data from the AUGMENT-one 101 trial in the coming weeks and to start the registrational program for SNDX-five thousand six hundred thirteen shortly thereafter. We are also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indications.

We believe that five thousand six hundred thirteen could have broad utility across a wide range of clinical settings in acute leukemia. And axitelimab could represent a broad franchise opportunity in fibrotic disease. We are comfortable given our cash on hand that we have the financial resources to aggressively advance our programs and achieve key upcoming milestones. We 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.

Speaker 0

Your first question comes from the line of Phil Nadeau from Cowen and Company. Your line is open.

Speaker 4

Good afternoon. Congratulations on the progress and thanks for taking my questions. Briggs, a few for you just on some of the parameters you 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?

Speaker 2

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

Speaker 4

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 MLLr could 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 MLLr and NPM1 be more evenly balanced?

Speaker 2

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

Speaker 4

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 two dose?

Speaker 2

Both actually. So we'll present the full safety profile for the entire population that was enrolled. And we'll break out the safety profile for the recommended Phase two dose.

Speaker 4

Perfect. And one question for Daphne. Daphne, you mentioned H1 expenses are going to be heavily 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?

Speaker 3

Thanks, Bill. 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.

Speaker 4

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

Speaker 2

Thanks, Phil.

Speaker 3

Thanks, Phil.

Speaker 0

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

Speaker 5

Thanks. Thank you 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 II expansion part of AUGMENT-one 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 Phase II might take?

Speaker 2

Yeah, thanks for the question Bert. So the precise size of each of the independent Phase II expansion cohorts, 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, you know, what's the total number of patients that we need from a safety point of view across the three cohorts, including the Phase I data. I will emphasize that each of the three are independent, essentially parallel independent Phase II cohorts.

We could potentially register one or two or all three. Then the second part of your question?

Speaker 5

I I guess it's dependent upon the first, but but the the potential

Speaker 2

Oh, the time.

Speaker 5

Length of time enrollment might take.

Speaker 2

Yeah. We haven't we haven't given guidance on the timing because exactly to your point, until we know the precise numbers, it's a little hard to give precise, definition of timing. What would say is thus far at least the phase one trial has progressed very, very nicely. And so, you know, 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'll take to enroll.

Speaker 5

Okay, thank you. And then just a more strategic question with regard to the slide that says 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 general framework for how you're thinking about prosecuting these additional efforts.

Speaker 2

Yeah, 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 can sort of do ourselves?

Speaker 5

Okay. Thank you for that. That's all I had. Thanks.

Speaker 0

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

Speaker 6

Hey, Good afternoon, guys. Thanks for taking my question. So for the 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? Meaning, should we expect 30 additional patients or 30 total patients?

And where do the compassionate use patients fit in?

Speaker 2

Yeah, hi, Tatsi. Thanks for your question. So I said at least 30 patients total. So that includes the six that were presented last year. That's a number of patients from the AUGMENT-one 101 trial.

So that does not include the compassionate use patients. And we're discussing with Eitan of what's the whether we focus completely on the Phase I trial or we also present some of the data from the compassionate use patients.

Speaker 6

Okay, perfect. Thanks for that clarification. And then one more quick one. Just you mentioned in your prepared remarks 5,613 combinations, you know, at this juncture, if you had to say, what do you think is sort of most promising? It sounds like we're going get something on that in the near term, but any thoughts at this juncture would be helpful.

Speaker 2

Yeah, again, to Bert's question, I think that the first order of business from our point of view is just to lay out where's the right place to further develop the drug. And then see if that requires a combination. Clearly I think if you were gonna 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 with agents in that space makes sense as well. So we're looking at both the patients who are candidates for intensive therapy and patients who are not.

Speaker 6

All right, perfect. Thank you. Congrats on the progress.

Speaker 0

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

Speaker 7

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's going to be a certain number of patients that don't have either the MLLr or NTM1 as the initial trial that have all comers with leukemia. And I guess my question is, 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 they can the number of, I guess, non NPM1s and MLRs be disclosed at this point?

Or I guess, to what extent how large is the number the number should we expect?

Speaker 2

Yes. 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 MLLr.

And the trial, as it 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 MLLr. 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.

Speaker 7

Thank you for that. And on the initial description of the call, were referring to the population as leukemias. I know we've seen ALL patients and we're going to see MPM1 patients. Are we going to also see AML patients in the trial?

Speaker 2

Right. So 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.

Speaker 7

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?

Speaker 2

Yeah. I mean, I don't think I'm not quite sure which competitor you're referring to. But 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, you know, I don't think we can say too much about that at this point.

Speaker 7

Thanks for taking my question.

Speaker 0

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

Speaker 8

Hi. Thanks for taking the question and congrats on the progress. The, 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 opportunity is growing with the trend towards increased number of stem cell transplants?

Or could it be getting crowded with rux and other drugs going to approval?

Speaker 2

Yes. I'd like, our, Head of New Product Planning, Angelique Angouli, to take that question.

Speaker 9

Thanks, Frank. Thanks, Justin, for the question. Yeah. You know, I think there's there's a lot of change in that space. As you mentioned, there's a couple new drugs that are under review for the FDA for potential approval.

But, you know, I think there's 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 there's also, I think, a lot of un underserved patients that exist today with chronic GVHD who have been treated with, therapies that weren't developed to treat that disease and and haven't done as good a job as as we think axatilamab could do and maybe perhaps some of the other agents in controlling their disease. So we think that it's really gonna be a displacement of some of the, you know, nonlabeled agents, the 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 and help them, live longer and and better with their disease.

Speaker 8

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

Speaker 2

Right. So you may remember, we, had, started a Phase II expansion cohort, as part of our Phase I trial at one mg per kg. And the team is still allowing that trial to enroll while we get AGAWE up and running. So if a site doesn't yet have AGAWE 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 gonna present that data, but there may be data on that updated phase two cohort at the one mg per kg later this year.

Speaker 8

Perfect. Thank you. That's all for me.

Speaker 0

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

Speaker 10

Hey, thanks for taking my question. Thanks for the update. Briggs, just on the side effect profile you've seen so far for 05/2013, does that preclude or point to any particular combination agent that you'd want in presumably frontline?

Speaker 2

Yes. So obviously we'll present the safety data I think as 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.

Speaker 10

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

Speaker 2

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

Speaker 10

Good. Okay. And then as you move from Phase one to Phase two do you expect any changes in endpoints? Or how should we think about the I guess the inclusionexclusion and how that could potentially change from Phase I to Phase II endpoints?

Speaker 2

Yeah, no, we don't, you know, again, obviously the Phase I trial, the primary objectives as I alluded to were, PK safety, and defining a recommended Phase II dose. The Phase II portion, the primary endpoint is a CR rate for efficacy. But the overall inclusionexclusion don't change. Obviously the Phase I trial has changed over time. We've amended the protocol many times to, you know, allow pediatric patients in to focus on NPM1 and MLR.

But overall the general population of patients that we're enrolling in terms of relapsedrefractory leukemia doesn't significantly change from Phase I to Phase II.

Speaker 10

Got you. Thank you. And then in that kind of, third group of patients you mentioned about presenting so the non MLR and the non NPM1 patients, would you expect to see any kind of response in those patients?

Speaker 2

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 MLLr. There's been extensive preclinical validation. We're convinced that your drug probably would not work in BCR ABL. We've always used that as a negative control in our preclinical models.

But there are other forms of leukemia that we, you know, 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.

Speaker 10

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

Speaker 2

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. You know, we focus much more on the MLLr 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.

Speaker 10

Got you. Okay. Thanks so much. Thanks to the answers.

Speaker 0

Once again, to ask a question, you will need to press star then the number one on your touch tone telephone. Again, that's star then the number one on your touch tone telephone. Once again, to ask a question, that's star then the number one on your touch tone telephone. 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.

Speaker 2

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 I data from the AUGMENT-one 101 trial. And I think we're really quite excited to present that data and then to take additional questions from everybody once you have a chance to see that.

So thanks so much for joining the call.

Speaker 0

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