Good day, and welcome to the Syndax first quarter 2022 earnings conference call. Today's call is being recorded. At this time, I would like to turn the call over to Maghan Meyers 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 first quarter 2022 financial and operating results. I'm Maghan Meyers with Argot Partners, and with me this afternoon to discuss the results and provide an update on the company's progress are Michael Metzger, Chief Executive Officer, Dr. Briggs Morrison, President and Head of R&D, and Alex Nolte, Chief Accounting Officer. Also joining us on the call today for the question- and- answer session is Dr. Peter Ordentlich, Chief Scientific Officer, and Dr. Anjali Ganguli, Chief Business Officer. This call is being accompanied by a slide deck that has been posted on the company's website. 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 statement 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 factor 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 our views as of today, May 9, 2022 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 Michael Metzger, Chief Executive Officer of Syndax.
Thank you, Maghan Meyers, and thank you to everyone joining us on today's call and webcast. On the heels of a transformational 2021, we're off to a strong start for 2022, and I look forward to sharing with you today our recent progress and several key developments. I'm especially excited to report that Syndax is now on pace to deliver two U.S. applications for potential drug approvals in 2023, a distant and aspirational goal for most biotech companies, and yet a near-term and highly achievable one for Syndax. Despite the challenging market backdrop, we currently find ourselves with a solid balance sheet and the support of a strong pharmaceutical partner to advance the development of one of our lead molecules.
We are well-positioned to expand both of our lead assets into new indications and to build out a commercial organization to support the potential launch of these first and potentially best-in-class products. We also have the flexibility to selectively pursue business development opportunities to augment our pipeline with additional promising molecules to complement the ones we have. The momentum is building at Syndax, and it is indeed a very exciting time for the company. Now turning to slide three, we provide a high-level summary of our current corporate priorities as we strive to realize a future in which people with cancers live longer and better than ever before. Starting with revumenib, our official generic name for SNDX-5613, our highly selective menin inhibitor.
Enrollment in our three pivotal phase II trials in patients with relapsed refractory NPM1 or MLL-r acute leukemia, which we call AUGMENT-101, 2A, 2B, and 2C, remains on track. We're also pleased to announce that we have enrolled our first patients in the BEAT-AML and AUGMENT-102 trials, which represent important expansion opportunities for the franchise in combination with other approved agents and begin to move us into newly diagnosed patients. Beyond acute leukemia, we will be initiating a proof-of-concept trial later this year in colorectal cancer. To our knowledge, represents the first assessment of a menin inhibitor in patients with solid tumors. This is an exciting development, and Briggs will discuss this effort further in a few minutes. Moving to axatilimab, our antibody against CSF1R.
Enrollment is ongoing in our pivotal AGAVE-201 trial in patients with chronic graft-versus-host disease, with top-line data expected in 2023. In addition, we are excited to announce today that we recently received Fast Track designation for axatilimab for the treatment of cGVHD. We are currently making progress working closely with our partner, Incyte, to maximize the value of this important program and expect to begin trials to move axatilimab into earlier lines of cGVHD later this year. Beyond graft-versus-host disease, we remain on track to commence a phase II proof-of-concept trial of axatilimab in idiopathic pulmonary fibrosis or IPF in the fourth quarter of this year. Again, I want to emphasize that we now have two registrational programs ongoing for two first-in-class and potentially best-in-class medicines in two areas of unmet medical need.
With filings for both programs expected in 2023, we are starting to expand the organization to support the potential commercial launch of both molecules in the U.S. Later this year, we expect to hire the company's first chief commercial officer to lead the additional build-out of our commercial organization. Let's now turn to slide four and provide further details on where we are with revumenib. First, we are conducting three single-arm phase II trials that FDA has agreed may each serve as a pivotal trial. Each of these single-arm phase II trials represent an independent path to a separate indication. The AUGMENT-101-2A trial is enrolling patients with relapsed refractory MLLR ALL, 2B is enrolling patients with relapsed refractory MLLR AML, and 2C is enrolling patients with relapsed refractory NPM1 AML.
Each trial is open to patients aged one month or older, and each trial will enroll independent of the other two. We may seek initial regulatory approval for revumenib based on the results of any one of these trials should one trial enroll faster than the others. We may seek initial regulatory approval with any two or three, depending on when they complete enrollment. We are happy to report that additional site initiation and patient accrual across the individual trials is going well, and we are optimistic that we will be able to complete enrollment in at least one of these trials this year. Given our current trajectory and our view of the competitive landscape, we anticipate being the first company to achieve regulatory approval for a menin inhibitor.
Needless to say, we believe being first to market is important and accretive to the long-term value of Syndax. We have agreement with FDA that for each trial, the primary endpoint will be the percentage of patients achieving CR/CRh, with secondary endpoints including durability of CR/CRh response, transfusion independence, overall survival, and safety. Importantly, the trial design allows patients to be treated with revumenib after bone marrow transplant, a design feature that allows us to start to understand the role of revumenib in the post-transplant maintenance setting. We also have agreement with FDA on the statistical design of each trial. Each trial will enroll 64 adult patients and up to 10 pediatric patients.
Beyond the AUGMENT pivotal program in relapsed refractory disease, slide five highlights some of the additional opportunities we are exploring with revumenib, all of which build on the excellent safety and efficacy profile we have seen thus far with revumenib. As I mentioned at the start of today's remarks, we are excited to share that enrollment is now underway in both the BEAT-AML and AUGMENT-102 trials. The phase I BEAT-AML umbrella trial is a collaboration with Leukemia & Lymphoma Society. As part of the collaboration, revumenib, the first menin inhibitor to be included in the trial, will be combined with venetoclax and azacitidine in newly diagnosed AML patients who are unfit for induction chemotherapy. This trial will assess safety as well as initial efficacy, with top-line data expected next year.
We expect a phase II/III trial, which could serve as the basis for a regulatory filing to follow soon after completion of the phase I trial. The middle panel of the slide highlights our AUGMENT-102 trial, which is designed to assess revumenib in combination with standard salvage chemotherapies used for pediatric patients with ALL or AML. I am pleased to report that patients have begun accruing in this trial as well. Both the AUGMENT-102 and BEAT-AML trials are supported by preclinical data, which demonstrate the potential benefit of a menin inhibitor used in combination regimens in these settings, and we are excited to see how these data translate in the clinic. The third panel on the right illustrates the INTERCEPT trial, which is designed to explore the activity of revumenib in patients with AML who have MRD-positive disease.
This trial is being conducted as part of the INTERCEPT master clinical trial being led by the Australasian Leukaemia & Lymphoma Group, and we expect patients to begin enrolling into that trial later this quarter. The INTERCEPT trial is focused on investigating novel therapies to target early relapse in clonal evolution as a preemptive therapy in AML. The trial will enroll patients with measurable residual disease progression following initial treatment, a group of patients at very high risk of relapse that represents an important unmet medical need. A general tenet in cancer treatment is that the earlier you treat the patient's disease, the better patients do and the longer the patients stay on medicine. The INTERCEPT trial is a very creative approach to treating patients early in their disease course.
I'll also note that revumenib is the first menin inhibitor to be included in the INTERCEPT AML master clinical trial. We believe the selection of revumenib for inclusion in two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with revumenib. As we have previously communicated, we are committed to unlocking the full potential of revumenib beyond the relapsed refractory acute leukemia setting. Slide six highlights our goals as a company to be the first to market in the relapsed refractory disease setting. Beyond that, we intend to pursue approval and indication in additional value-enhancing indications in patients with MLLR and NPM1 mutant acute leukemias, including the newly diagnosed and maintenance settings.
As we continue to develop revumenib for use beyond treatment of relapsed refractory patients and into the first-line treatment setting, we see the opportunity to treat up to 12,500 patients identified each year with these two forms of mutant acute leukemia. NPM1 and MLLR represent up to 40% of the overall AML population, which to our knowledge will be the largest subpopulation of AML to be addressed by a new targeted therapy. Our goal is to engage patients early in their treatment journey, get them into remission, and maintain them in that state for months, if not years. That emerging potential for revumenib is why we believe it could be one of the most important new franchises and largest market opportunities in hematology, and certainly worthy of significant investment.
As I mentioned earlier, we are also preparing to start an initial proof-of-concept trial in solid tumors, yet another exciting new area of exploration for revumenib. I will now turn the call over to Briggs, who will walk through the biologic rationale, development strategy, and market opportunity for revumenib in colorectal cancer. Briggs?
Thank you, Michael. Given we have established that the drug is active both in NPM1 and MLLR leukemias and have initiated a series of trials to explore the use of revumenib in earlier lines of leukemia therapy, we believe now is the time to turn our attention to exploring the utility of menin inhibition in diseases beyond leukemia. As we have continued to assess the emerging science across a range of opportunities, we have decided that our initial clinical program outside of leukemia will test the efficacy of revumenib in advanced colorectal cancer. On slide seven, we note that colorectal cancer is the third most frequently diagnosed cancer and is the second leading cause of cancer death in the United States. There remains a significant unmet medical need for patients at all stages of disease, most notably in patients with metastatic disease.
It is well established that the Wnt/beta-catenin pathway is a key driver of essentially all colorectal cancers, with the final common pathway being beta-catenin transcriptional activation of several transforming genes. What has become increasingly clear is that MLL1 is required for beta-catenin to drive transformation in colorectal cancer, and that molecules like revumenib, which disrupt the binding of MLL1 to menin, displace MLL1 from transcriptional start sites and turn off the expression of transforming genes. What is remarkable is that when MLL1 is displaced from the beta-catenin complex, colon cancer cells differentiate into normal colonic cells and lose their ability to proliferate. This differentiation is highly reminiscent of what we see both preclinically and clinically with revumenib driving leukemic cell differentiation. Slide eight is a diagrammatic illustration of what we believe is happening in colorectal cancer cells.
In the panel on the left, MLL1 is a component of the beta catenin transcriptional complex, driving transcription of genes like MYC and cyclins that drive cell division. In the panel on the right, in the presence of revumenib, we see a disruption of the beta catenin complex, which leads to loss of expression and cell differentiation. Given this emerging science, slide nine shows our development strategy for revumenib in colorectal cancer. The initial study will be a signal-seeking trial in patients with refractory colorectal cancer. Given what has been described pre-clinically, we think that we might see tumor responses, actual tumor shrinkage. But given the differentiation that I mentioned earlier, it is also just as likely that we will not see actual responses, but rather will see a lack of progression as the cancer cells differentiate and lose their ability to proliferate.
We have therefore designed the signal-seeking portion of the trial to look for either responses or disease stabilization. Responses are assessed using the well-known RECIST assessments, and disease stabilization is assessed by the disease control rate at six months. That is the percent of patients whose disease has not progressed at six months after starting treatment. I should note that the standard of care in this population of patients provides a very low response rate, about 5%, and the disease control rate at six months is only about 15%. If we start to see responses, we believe there could be a very rapid path to accelerated regulatory approval based upon overall response rate and duration of responses. That is illustrated as one option coming out of our proof of concept trial.
If we don't see a significant response but do see a high rate of stable disease as assessed by the disease control rate, the second option is to proceed to a small randomized trial to confirm the clinical activity using PFS as the primary endpoint. We are currently finalizing the protocol for this trial and expect to start enrolling patients in the fourth quarter of this year, with possible data anticipated by the end of 2023. I want to emphasize that the preclinical science supporting the role of menin MLL1 interaction in beta catenin-driven tumors such as colorectal cancer is quite compelling, and we are eager to translate the science to the clinic. Nonetheless, we are taking a staged approach to studying this in the clinic, starting with what we believe is a modest investment in a signal-seeking trial. Let me now turn the call back over to Michael.
Yeah. Thanks, Briggs. Before we move on, let me further emphasize that seeing disease control rates above standard of care, even seeing a few responses in these metastatic colorectal patients, will indeed be a very exciting result. As you may know, this is an area of high unmet medical need where current therapies are not particularly effective. If we are right and the science translates in the clinic, this discovery would enable Syndax to meaningfully expand the market opportunity for menin inhibition beyond heme malignancies. Let me now turn to axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor. Slide 10 is our pivotal trial for axatilimab in cGVHD. This trial is the axatilimab for graft versus host disease trial called AGAVE-201.
The trial is enrolling patients with cGVHD whose disease has progressed after two prior therapies. Patients must be at least two 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 axatilimab given either every two weeks or every four weeks. The primary endpoint is response rate using the 2014 NIH consensus criteria for cGVHD. Secondary endpoints will include duration of response and validated quality of life assessments using the Lee Symptom Scale. Enrollment to the study is going well, and we are on track to deliver top-line data in the first half of 2023. We're also delighted to announce late last year that we closed our global collaboration with Incyte.
This collaboration brings together two companies with a solid track record of innovation to accelerate and maximize the development of axatilimab. Our phase I, II cGVHD data presented at ASH in December of last year received very positive feedback from the investigator community and further underscores its best-in-class profile. Through our collaboration, Syndax and Incyte will pursue an expanded set of indications in cGVHD and other fibrotic diseases. Together, we plan to assess novel combinations of axatilimab and Incyte's JAK inhibitors with the goal of establishing axatilimab in earlier settings within cGVHD and expanding its market opportunity. As we previously mentioned was our intention, we plan to initiate a robust phase II trial in IPF in the fourth quarter of this year. The first expansion outside of establishing cGVHD is a beachhead into other fibrotic diseases where we believe axatilimab could have a significant impact.
Successful development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support for axatilimab in other fibrotic-driven diseases that Syndax and Incyte could explore over the course of the collaboration. Slide 11 highlights our view of the broad clinical and commercial opportunity for axatilimab. We believe cGVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from cGVHD in the U.S. today. The recent approvals and early successful commercial launches of Incyte's Jakafi and Sanofi's Rezurock have begun to delineate the commercial opportunity in cGVHD. Despite recent advancements in this area, to our knowledge, axatilimab is the only agent in clinical development that specifically targets the monocyte macrophage lineage.
Both Syndax and Incyte believe the data generated to date with axatilimab suggests it has the potential to play an important role in the treatment of cGVHD, both as a monotherapy and given its safety profile in combination with complementary medicines such as Jakafi or other JAK inhibitors within the Incyte portfolio. Through combinations in the frontline setting as well as the opportunity to expand ex U.S., we envision the cGVHD opportunity more than doubling, as shown on this slide. As we move axatilimab into additional indications, starting with IPF, we really see axatilimab contributing materially to the value of our company moving forward. Finally, on slide 12, this summarizes the transactions that led to the acquisition of the menin MLL-r and axatilimab programs.
We believe these transactions underscore our robust capabilities to identify and evaluate high-value differentiated assets, as well as the clinical development expertise to bring these compounds through key value inflection points. We anticipate in 2022 that we'll be able to continue to expand our pipeline through in-licensing of earlier quality differentiated assets. We expect to remain among preferred partners of such transactions. I'm gonna now turn the call over to Alex to review our financial results. Alex?
Thank you, Michael. Let me now take a few minutes to discuss our financial results for the first quarter of 2022. The results of our operations for the first quarter of 2022 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, which was filed today. I would like to point out that our net loss for the quarter was $37.2 million or $0.63 per share, compared to our net loss of $27.7 million or $0.54 per share for the same period last year. This difference is primarily attributed to the increased clinical and CMC activities for both of our programs.
Turning to slide 13, we ended the first quarter with $397.9 million in cash and cash equivalents, and 59 million shares in pre-funded warrants outstanding. Our current cash runway now extends into the second half of 2024 and supports our expanded development and early commercialization plans for both the axatilimab and the menin programs during this period and provides us flexibility for continued business development. Looking ahead, I'd like to provide financial guidance for the second quarter and full year of 2022. For the second quarter of 2022, we expect R&D expense to be $30 million-$35 million and total operating expense to be $38 million-$42 million, including approximately $4 million of non-cash stock compensation expense.
For the full year 2022, we expect R&D expense to be $130 million-$140 million, and total operating expense to be $160 million-$170 million, including approximately $14 million in non-cash stock compensation expense for the full year of 2022.
The increase in R&D and operating expense in 2022 compared to the prior year period is driven by the expansion of both axatilimab and menin into registration trials, expansion into new indications, and initiation of pre-launch commercialization activities. With that, let me now turn the call back over to Michael.
Thank you, Alex. Let me close the call by again emphasizing the tremendous progress we have made as a company. Syndax has always been focused on delivering new medicines that extend and improve the lives of people with cancer and other serious diseases. Today, with two high-value ongoing registration programs, a notable achievement in its own right, we stand on the precipice of realizing this goal. The potential of these programs extends well beyond their initial registration indications, with both offering broad franchise opportunities. We believe revumenib could have utility across a wide range of clinical settings in acute leukemia, as well as potentially in some solid tumors.
Our immediate goal as a company is to be the first to market in relapsed refractory acute leukemia and then drive additional value potential by expanding its use into newly diagnosed and maintenance settings in NPM1 and MLL-r acute leukemias. The same franchise potential holds for axatilimab, where broad opportunity exists both in the various lines of therapy in cGVHD and across a broad range of fibrotic diseases, starting with IPF. Underpinning all of these efforts, we have the balance sheet to aggressively advance our programs through key near-term milestones. Lastly, we remain confident in our ability to identify and bring in novel molecules to deepen our portfolio, particularly in a more challenging market where competition for high-quality assets may be diminished.
We have a proven track record of delivering on this pillar of our corporate strategy, and I believe this is a core strength of our company and management team. We could not accomplish what we have and what we hope to achieve without our 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 the many committed long-term investors who continue to help us in building this great company. With that, I'd like to open the call for questions.
As a reminder, to ask a question, you will need to press star followed by one on your telephone keypad. If your question has been answered or you wish to withdraw your question, press the pound key. Again, that's star one to ask a question. Your first question comes from the line of Madhu Kumar from Goldman Sachs. Your line is now open.
Hey everyone. Thanks for taking our questions. I guess our first one relates to the cadence of recruitment into the phase II arms of the AUGMENT-101 trial. You mentioned that you could either disclose one cohort or several cohorts in the first half of 2023. Given the kind of recruitment cadence you've seen so far, do you expect to report one versus multiple at one go? How are you thinking about that today?
Yeah, Madhu, thanks for the question. Look, I think what we were referring to was actual enrollment in the trial and how the cadence kind of rolls forward from there. As you pointed out, we have three independent trials that are enrolling. We haven't given guidance as to whether one is enrolling more quickly than the other. I think we had said that the AML cohorts would probably finish earlier than the ALL cohorts, but we haven't given any guidance as to whether MLL-r or NPM1 will be first or second. I think the concept of having one or more of the individual trials finish enrollment this year is still operative.
Certainly what follows from that is additional follow-up and a filing or two perhaps in the you know in the 2023 timeframe. We do think that we'll have you know top-line data starting in the first half of 2023.
Okay. One follow-up question. You mentioned that you have agreement with the FDA on a statistical plan for these three AUGMENT-101 cohorts. Can you give us some details about how to think about that in terms of like, is there like an effective CR/CRh rate that needs to be seen? Is there a durability that you're kind of looking at? Like, how should we think about those kind of parameters for evaluating AUGMENT-101 based on your interactions with the regulators so far?
Great. Maybe I'll ask Briggs to address that question.
Yeah, Madhu, for some of your questions, I guess my line is breaking up a little bit, but there is a statistical hypothesis, as you can imagine, that we've agreed to for a sort of lower bound that has to be ruled out. That's the primary endpoint. There is no prespecified requirement for durability. As we talked about with you previously, you know, there's regulatory precedent for both CR/CRh rates and durability from other targeted agents in AML, and that's sort of what we've been thinking about.
Okay, great. Thanks very much, everybody.
Thanks, Madhu.
Next question comes from Phil Nadeau with Cowen and Company. Your line is now open. Phil Nadeau with Cowen and Company, your line is now open.
Operator, maybe we'll put him back in the queue, and we'll circle back.
Phil Nadeau, are you online? Your line is now open.
Hi, can you hear me now?
Yes.
Great. Sorry about that. I don't know what happened there. I guess just to follow up first on Madhu's question. In terms of the durability that you need to file in for approval, one, can you remind us what that is? And then second, what's your data disclosure strategy? Will you wait till you have the full duration and durability that's necessary, or will you give us a preliminary look on the data from AUGMENT-101 before it's fully mature?
Right. Again, I guess maybe I'll ask Briggs to follow up. Thanks for the question, Phil.
Right. Phil, there is no durability that's required for filing. I think if you look at the precedents for some of the other targeted agents, a median duration of response of at least four to six months has been acceptable in the past. I think that's sort of the lower bound of what people would see. As you will recall, the data we showed at ASH, the Kaplan-Meier estimate for durability of response, even at six months, was greater than it was around 70%. If the data for our filing holds up similar to what we presented at ASH, I think we're in very, very good shape from a regulatory point of view.
In terms of data disclosures, again, as Michael pointed out, once a cohort has completed enrollment, the idea is it would, we'll follow the patients from six months from the last patient enrolled, and that would be the data set that we would consider as our filing data set. Obviously, there would be continued follow-up on those patients over time, but the filing data set would be six months after the last patient's enrolled.
That's approximately when we, as investors, should expect to see the data, about six months after you get the last patient for each cohort?
Exactly.
Good. Okay. Second question is on the INTERCEPT trial, how is MRD negativity being assessed for the different genotypes? There is regulatory precedent for MRD negativity for an NPM1 AML patient established by Kronos, but I don't believe the FDA has ever said how you assess MLL-r. MRD negativity for MLL-r. How is the INTERCEPT trial doing that?
Maybe, if Peter is on the line, Peter Ordentlich, maybe you wanna comment on that one.
Hi, this is Peter. For the MLL-r, the MRD is a little tricky, as you note, just because of the individualized nature of the different infusions can occur. I believe it's by flow cytometry, predominantly for the MLL-r patients.
Great. That's very helpful. Last question, we saw that the SAVE trial is on ClinicalTrials.gov now. Can you remind us what the rationale is for looking at combinations with ASTX727? Why choose that as one of the agents that you're first moving into combo studies with?
Yeah. Phil, first of all, it's an investigator-sponsored trial, so that's part of the equation here. Maybe I'll ask Briggs or Peter to comment on the rationale.
Yeah. I'll be happy to. Phil, the logic is the same as VenAza, right? Essentially, the ASTX molecule is essentially an oral Aza. I think the MD Anderson team, as Michael said, it's an investigator-sponsored trial, they were quite interested in being able to potentially develop an all-oral regimen, without having to give parenteral azacitidine. The scientific rationale for the combo is the same as for the VenAza. Why that molecule specifically? I think they're quite interested in an all-oral regimen.
Perfect. Thanks for taking our questions, and congrats on the progress.
Thank you, Phil.
Next question comes from Bert Hazlett with BTIG. Your line is now open.
Thanks. Thank you for taking the questions. I have a couple on SNDX-5613. Revumenib, excuse me. Could you just maybe provide benchmarks? I think you may have done this previously, but for the BEAT-AML trial with regard to frontline VenAza, the combination with frontline VenAza specifically in NPM1 or MLLR patients, what should be the benchmarks we're considering for meaningful activity in that patient group in frontline?
Briggs, you wanna take that one?
Bert, we can send you the VIALE-A trial, which was the VenAza versus Aza first-line trial. The overall response rate, I think if I remember correctly, was sort of in the mid-60%s. The actual CR rate was lower than that. There are some subsequent publications where they break it out by mutational status. But as you can imagine, the number of patients in each one of those is smaller. I think in an early look at the data, looking at an MRD-negative rate more important than looking at the CR or CRi rate. But we'll send you the VIALE-A paper and all the supporting information.
Okay. That's helpful. One kinda strategically, given the effort into solid tumors here with CRC, is this foreshadowing some additional combination therapy or potential combinations, or licensing potential with revumenib and other molecules that focus on the Wnt beta-catenin pathway? Or is this moving into CRC? Or how should we think about what this initial step means strategically for the development of revumenib?
Yeah, thanks for the question, Bert. I'll just say overall strategy here is, we're following. We think we're following good science into a particular form of solid tumor biology. I think that's where we find. We think that this will be something to explore. It is a signal seeking phase I trial, limited investment, as Briggs pointed out in his remarks. Market opportunity is quite significant. There's a lot of unmet medical need in this area of colorectal cancer, and we think the mechanism has very strong rationale. We'll find out essentially if it works.
In terms of a larger strategy in solid tumors, I think we're being, you know, strategic and surgical about how we go into certain other areas outside of hematology and leukemia, I should say. I think this is one such opportunity. There may be others. Again, we're focused, very much focused on the biology at hand and where it takes us, you know, of course, our first focus being very much in the leukemia space. I don't know. Briggs, did you wanna add anything to that?
No, I think that's right. I mean, it's. I wouldn't necessarily think about novel. We wanna just sort of see if this. It does look pretty clinical data in the clinic. Obviously there are additional opportunities if it does work in the beta-catenin pathway beyond colorectal cancer.
Got it. Fair enough. Just one more kind of big picture in this class in general. You're clearly in the lead with a number of these indications and certainly the move into colorectal and the other space. How do you see the competitive landscape evolving in these menin inhibitor space? Thanks.
Yeah. Thanks, Bert. Look, I think you point out what we believe to be true, which is that we're in the lead in terms of developing our drug and becoming the first menin inhibitor approved potentially. That's the thrust of our effort. In terms of looking at other indications, frontline, maintenance, what have you know, those are areas that we'll go into as well. We've talked about it today, we talked about colorectal cancer. There may be other areas to exploit, as Briggs just pointed out, around solid tumors.
You know, essentially, I think we feel like we are, you know, able to leverage our first-mover advantage, exploit the attributes of our agent, which we think are pronounced and we'll have a good opportunity to show that in the market. Others have to put up data and we'll look forward to seeing what they have when they actually, you know, produce the data and present it at conferences.
All right. Thank you.
Thanks, Bert.
Next question comes from the line of Yigal Nochomovitz from Citigroup. Your line is now open.
Hi, team. This is Ashiq Mubarack on for Yigal Nochomovitz. Thanks for taking my questions. A bit of a basic one, but regarding your new pilot study in colorectal cancer, does there need to be an MLL rearrangement to support, I guess, aberrant activation of the Wnt/beta-catenin pathway, or is it all just wild type? Maybe what proportion of the CRC population do you think is addressable-
Yeah.
With menin?
It's more akin to the NPM1 story. It's not. There's not a fusion protein. It's more akin to NPM1, where the NPM1 driven transformation is dependent upon the menin. For beta-catenin, it's similar to
Maybe what proportion do you think is addressable with menin inhibition?
As we've been thinking through this on the beta-catenin pathway in CRC and whether we should be taking a biomarker selected population, but the vast majority of colorectal cancers necessarily have an activation of the beta-catenin pathway. We think it's actually the majority, the vast majority of patients have this pathway activated.
Okay. Maybe one last one for me. How do you expect revumenib to behave in solid tumors versus leukemia? Maybe do you think you would need to dose with a CYP3A4 based on your prior work with in leukemia? Thanks.
Yeah. Want me to take that one, Michael?
Yes, please. Go ahead.
Yeah. The dosing should be the same. Again, you're just blocking the interaction of menin with MLL, just as we do with NPM1, where the dosing is the same. Whether you see responses or whether you see differentiation, as we see in AML, is one that will be very interesting. Preclinically, you actually see a very similar differentiation with AML.
Okay. Maybe the last point on needing a SIP three or four.
No. Again, the just to clarify, it's not that. That you give depends on whether they're also taking a CYP3A4 inhibitor. We think that the exposure response should be the same. Yeah, again, we don't need a CYP3A4 inhibitor. We just need to know what the dose is with or without, and that should be the same in colorectal cancer.
Okay. Sorry, I think the connection isn't great, but I appreciate the answers, Briggs.
Yeah, thanks, Ashiq Mubarack. We can follow up afterwards if need be.
Next question is from Joel Beatty with Baird. Your line is now open.
Hi. Congrats on the progress, and thanks for taking the questions. The first one is on AUGMENT-101, and with a lower bound that has to be ruled out when you submit the data to FDA, do you see any potential for the enrollment size in any of the three arms to change, based on, you know, early data and how it looks?
Yeah. Joel, thank you for the question. Well, as you know, this is a pivotal trial, so we're not looking at the data. I think the concept is that I mentioned in my remarks, 64 patients enrolled in each of the trials, individual trials, and up to 10 pediatric patients. That's sort of the statistics are set around the 64 patients. As of today, we don't see any reason why that would move. That obviously is driven, you know, all the powering is done off of the lower bound. While we haven't disclosed what that is, we feel like it, you know, the statistics hold, and we have agreed with FDA on the design.
In our mind, it does. We don't see any reason why it would change.
Okay, great. Then a question on business development. You know, you've mentioned how that could be a bigger focus for this year. How has the recent biotech downturn affected the outlook for that?
Yeah, thanks for the question, Joel. I think I mentioned that obviously we're in a tough environment, and I don't think many companies are immune to that. But I do think that, you know, our business model is to in-license or acquire other assets. We've generally focused on early stage assets, call it, late stage preclinical through phase I. So these are assets that allow us to do some very good development work, and not spend as much on development at the early stages until we get to a point of value inflection. I think that's the area that we tend to focus on, and I think those are the assets that perhaps are not getting as much attention in the down market.
We continue to be encouraged by some of the things that we're seeing, and we're being very selective on the types of assets and what we could potentially bring into Syndax. In that way, I think we're feeling good about our goals for the future and building our pipeline.
Great. Thank you.
Thanks, Joel.
Thanks, Joel. Final question comes from the line of Peter Lawson with Barclays. Your line is now open.
Great. Thanks for taking my questions. I guess the first one is just around whether we'd see any updated phase I data for the menin inhibitor this year or early next.
Yeah. Thank you, Peter, for the question. I think, you know, in our mind, we're, you know, pretty much focused on enrolling and doing all the work that's required now into phase II to get the drug ultimately approved. That's where our focus is. I guess the only real question, and there are some questions that I'm sure people have, but the question that something we could potentially talk about coming out of the phase I is maybe just an update on the durability of the endpoint of CR/CRh, which we reported on at ASH. As of now, we don't have specific plans to update the market on that, again, because our focus has turned to the phase II.
If that were to change, obviously we'd let people know, and there shouldn't be an expectation necessarily that we would do that. Other than that, I don't think there's much to say about the phase I at any particular time this year. Again, if that were to change, we'll certainly let people know.
Gotcha. Would the durability kind of help with the enrollment for the AUGMENT study in any way, you think, to help investigators get, I guess, greater comfort around the durability of these drugs?
Yeah. Look, thanks for that question, too. I do think that more data helps. Whatever the data is, if it's positive about your program, and people are interested in your program, they tend to notice the you know the data that you put out. Could that help? I would imagine there could be some positive, you know, some benefit to that. I would also offer that physicians are extremely excited today about what we've put out from the phase I, and we did that at ASH, and the follow-through has been tremendous, and our trials are enrolling well. I think we feel very encouraged by the interest of physicians and investigators, and so that's just where we are today.
Additional data never hurts as long as it is supportive of your program.
Good. Thank you. The branch into solid tumor indications. Just curious if we see any preclinical data for CRC or other indications and do you think there's any preclinical evidence that they could work better with the CRC mutations such as the G12C?
Yeah, maybe I'll let Briggs take that question.
Peter Ordentlich, we can send you some, but you know have given us a lot of confidence in this mechanism. Again, as I mentioned earlier, I think combinations with other agents in colorectal cancer think about.
Okay. Perfect. Is there anything coming out from your own work that we could potentially see this year preclinically?
Potentially. Potentially, yes. I wouldn't set an expectation, but the team is, you know, doing some additional work to validate some of the things that we've seen in the literature, so don't know when that will be ready.
Perfect. Thank you so much. Thanks for taking the question.
Thank you, Peter.
This concludes the Q&A portion of the call. I will now turn the call back with Michael Metzger, who will make a few closing remarks.
Great. Thank you, operator, and thank you for joining us on the call this afternoon. We look forward to, I guess, seeing many of you at the upcoming conferences this spring and as well as on any future calls. Again, have a great evening and thanks for joining us. Good night.
This concludes today's conference call. Thank you all for your participation. You