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 a review of Syndax's Q3 2020 financial results. With me this afternoon to discuss the results and provide an update on the company's progress are Doctor. Briggs Morrison, Chief Executive Officer and Daphne Kiritis, 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 Doctor.
Michael Myers, Chief Medical Officer and Doctor. 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 reports 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, www.syndex.com, following the call. So with that, I'm pleased to turn the call over to Doctor. Briggs Morrison, Chief Executive Officer of Syndax.
Thank you very much, Melissa, and thank you to everyone who's joining us on today's call and the webcast. The Q3 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 2 exciting and promising programs, while we also continue to look for additional oncology pipeline opportunities. Let's now turn to Slide 4 and SNDX-five thousand six hundred and thirteen, 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 5 briefly summarizes the ongoing AUGMENT-one hundred and one trial, the first in human Phase III 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've been busy over the last quarter preparing for the Phase 2 portion of the trial, which will enroll 3 distinct expansion cohorts, each of which consists of a specific genetically defined relapse or refractory acute leukemia and which is on track to initiate early next year.
The 3 cohorts will include patients with MLLr acute lymphoid leukemia, or ALL patients with MLLr acute myeloid leukemia or AML and patients with NPM1 mutant AML. The Phase 2 portion will further characterize the safety of SNDX-five thousand six hundred and thirteen 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, as Phase II portion of AUGMENT-one hundred and one 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-five thousand six hundred and thirteen beyond the initial approval in relapsedrefractory 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-five thousand six hundred and thirteen 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-five thousand six hundred and thirteen. Let me now turn to Slide 7 and axotilumab, formerly known as SNDX-six thousand three hundred and fifty two, our potentially best in class monoclonal antibody therapy targeting CSF1 receptor. As you know, we've been conducting a Phase III trial with acratelimab 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 are enrolled in the Phase 1 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 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 axitilomab in chronic graft versus host disease. This trial is the axitilomab for a chronic graft versus host disease trial called AGAVE-two zero one and is outlined on Slide 8.
The trial will enroll patients with chronic graft versus host disease whose disease has progressed after 2 prior therapies. Patients must be at least 6 years of age and have met overall entry criteria. This is a pivotal, dose ranging trial in which patients will be randomized to 1 of 3 treatment groups, each investigating a distinct dose of axitolomib even either every 2 weeks or every 4 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 Cadman's KD-twenty five, 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, axotilumab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. We believe the data generated to date with axotilomab 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 axotilumab 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 axitilomab franchise beyond chronic graft versus host disease and take advantage of what we believe are significant set of opportunities that could materially enhance shareholder value. Finally, Slide 9 summarizes the transactions that led to the acquisition of the Menin MLR and axotilumab 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 of such transactions. I'll now turn the call over to Daphne to review our financial results.
Thank you, Briggs. The results of our operations for the Q3 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 Q3 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 $20,400,000 or $0.46 per share compared to $12,800,000 or $0.41 per share for the same period last year. Turning to Slide 10.
We ended the Q3 with $170,200,000 in cash and cash equivalents and 44,400,000 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 $40,000,000 to $45,000,000 including approximately $2,000,000 of non cash stock compensation expense per quarter and $4,000,000 in milestone payments to UCB based on achievement of positive milestones associated with axitilomab. For the Q4 of 2020, R and D expenses are expected to increase as our development activities for both SNDX-five thousand six hundred and thirteen and axitilomab continue to ramp up heading into registration ready trials for both programs. 4th quarter G and A expenses are expected to remain at 3rd quarter levels.
For the 4th quarter, we expect R and expenses to be between $15,000,000 to $20,000,000 and total operating expenses to be between $20,000,000 to $25,000,000 Given our cash operating expense guidance for the Q4 of 2020, we continue to expect to end the year with approximately $145,000,000 of cash, which gives us cash runway into 2022 to meet our key development milestones. I would like to now turn the call back over to Brig.
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 1 aspatilumab data at ASH in December of this year, followed soon thereafter by the Phase 1 data on SNDX-five thousand six hundred and thirteen in early 2021. We currently anticipate having both programs in Phase II early next year.
AGAVE-two zero one is a pivotal trial for axitilomab, It's possible that the Phase 2 portion of AUGMENT-one hundred and one could also be registrational for SNDX-five thousand six hundred and thirteen. So by early next year, we could have 2 registrational programs ongoing. We are also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indications. We believe across a wide range of clinical settings in acute leukemia and axitilumab 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.
Thank you. Your first question comes from the line of Phil Nadeau with Cowen and Company.
Good afternoon. Thanks for taking my questions and congrats on the progress. Just a few on the meninib program. I guess first for the Phase 2, 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?
Hi, Phil. Thanks for your question. So what I would say is there's regulatory precedent. If you look at, for example, the IDH inhibitors that were approved as monotherapy based upon single arm trials. And I think in those cases, the CR rate was somewhere in the mid-20s with a durability of response, median durability of response somewhere around 8 months.
So I think something in that ballpark, that the regulatory precedent would suggest could be an acceptable package to submit to FDA. The exact number of patients is still to be determined.
Perfect. That's helpful. 2nd, I'm sure you're getting this question all the time. We are too curious going to 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 MLLr 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 registration program.
Perfect. And last question for me is on axetilumab. You mentioned that as we look at the abstracts, we should look at the patient demographics. Can you give us some sense of what the historical response rates would be in GVHD given or in light of the patient demographics in your study? What would be kind of the relevant compare?
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 cadmium 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 CAT data, some of those patients had received ibrutinib or RUC, 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.
Perfect. Thanks for taking my questions, and we look forward to the abstracts on Friday.
Your next question comes from the line of Bert Hazlett with BTIG.
Yes, thank you. Congratulations on the progress as well. And I'll just follow on there with regard to axotilumab. 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 2 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 axotilimab 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, axitelimab 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 hit 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 trying to think about.
So the initial potentially pivotal portion will be in this in the refractory population and then you look to move it kind of more frontline over time in combination with others?
Exactly. That's a fair summary.
Thank you. And then just with regard to 5,613, 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 outcome 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-one hundred and one is open at this point to patients basically a month of age or older. And the Phase 2 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 relapsedrefractory population, we will study a broad age group. I do believe that, as I mentioned 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.
Thank you. And then just one more for me. Just on that point and the potential combination regimens with 5,613, Is this something where thinking about the strategy of 5,613 more broadly and the strategy of Syndax, is this something where you're just looking to engage in potential combinations with 5,613? Or is this a licensing strategy in AML or blood based tumors more broadly? Just how do we think about that from a strategic standpoint for Syndax?
Yes. I'll ask that Michael Messer take that question.
Sure, Bert. 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 need perspective. And those may be trials that we do on our own. They 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.
Your next question comes from the line of Joel Beatty with Citi.
Hi, guys. This is Sean Egan calling in for Joel. The first one on ecotilumab. 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 Catamount had a lower bound of 30% response rate.
What does it look like for you guys?
We haven't disclosed what the stats are on the program. But yes, there is an implied lower bound in the number of patients that are being enrolled.
Great. And then for 5,613, 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 clinicaldrawal.gov, these are relapsedrefractory patients. That's the population that's being studied in Phase 1 and that's the population that we anticipate studying in Phase 2.
Great. And I noticed you guys gave a little bit more color on kind of moving axitilomab 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 scuttlemo will kind of move out first?
Michael Mextor, do you want to take that question?
Sure. So look,
I think we see the axitelimab franchise as being very significant. And 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.
Great. Thank you so much for answering my questions.
Your next question comes from the line of Madhu Kumar with Baird.
Hey, thanks for taking our questions. So first one relates to the 3 reasons of 3,613. How do you think about the potential of this drug being used as a bridge to transplant or is it kind of post transplant maintenance studies in various leukemias?
Hi, Madhu. Thanks for your question. So first off, I would say, in our ongoing trial and as we go into Phase if a patient has relapsedrefractory leukemia and goes into a complete response and is eligible for transplant, it's not it is perfectly acceptable and probably should be anticipated that many of the investigators will want to take their patients to transplant. They tend not to take a patient to transplant unless they can get them into remission. So 5,613 can get them into remission.
There will be some patients who go on to transplant from there if they're transplant eligible. The question of do you continue 5,613 after the transplant in a maintenance type of way is an important question that we're thinking about and thinking about designs that could address that.
Okay. And then one other question we've gotten a lot since April was April, the observations of QT prolongation in 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 and be, relapse the impact of leukemia?
Yes. Again, I think the physicians that we've spoken to are quite used to seeing drugs that cause minor abnormalities and QT prolongation. It's they are very comfortable monitoring for this. If there's a dose adjustment that needs to be made, should there be a prolonged QT prolongation, they're comfortable with that. So it's I think the AML docs that we have spoken to, particularly in the relapsedrefractory population, if you've got a drug that is getting patients into remission, they really don't see this as a significant barrier to using the drug.
Sure. 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 unmarketed development of things like axotilumab? Like how do you strike that
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.
All right. Excellent. Thank you so much.
Your next question comes from the line of Peter Lawson with Barclays.
Hey, thanks. Thanks for taking the question and congratulations on the oral presentation of axitilomab. 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 in prior therapies?
Yes, Peter. So the abstract comes out on Thursday. And as I said in my prepared comments, again, it's 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. Thank you. 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. As I said, I think that it's the only drug in development that specifically targets the monocyte macrophase lineage. And so I think it and again, you'll get a sense I think you'll get a sense you probably already have a sense from data we've released from some of our other trials of axotilomab. So that's a well tolerated agent. So I think that the initial path really to get the drug approved in these patients who have probably failed all other therapies.
And then as an earlier question alluded to, think about ways of moving it into earlier lines of therapy, again, potentially in combination with other agents that work through complementary mechanisms.
Great. Thank you. And then just on the MEDIN 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 enrollment is going within the various arms, the CYP3A4alpha with and without kind of thing?
And also you've seen in PM1 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 expand backfill cohorts where we had cleared safety and seen efficacy. And that was in large part driven by the investigators who were 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 of that will be presented when we present the completed Phase I trial.
Okay. Thanks so much. I'll get back to the queue.
And there are no further questions at this time. So I would like to turn the call over to Doctor. 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 2 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.