Syndax Pharmaceuticals, Inc. (NASDAQ:SNDX) Q2 2022 Earnings Conference Call August 8, 2022 4:30 PM ET
Company Participants
Sharon Klahre – Head, Investor Relations
Michael Metzger – Chief Executive Officer
Briggs Morrison – President and Head, R&D
Keith Goldan – Chief Financial Officer
Anjali Ganguli – Chief Business Officer
Conference Call Participants
Phil Nadeau – Cowen & Company
Kalpit Patel – B. Riley Securities
Ashiq Mubarack – Citi
Joel Beatty – Baird
Peter Lawson – Barclays
Operator
Good day everyone and welcome to the Syndax Second Quarter 2022 Earnings Conference Call. Today’s call is being recorded.
At this time, I would like to turn the call over to Sharon Klahre Head of Investor Relations at Syndax Pharmaceuticals.
Sharon Klahre
Great. Thank you operator. Welcome and thank you all for joining us today for a review of Syndax’s second quarter 2022 financial and operating results. I’m Sharon Klahre and with me this afternoon to provide you an update on the company’s progress and to discuss financial results are Michael Metzger, Chief Executive Officer; Dr. Briggs Morrison, President and Head of R&D; and Keith Goldan Chief Financial Officer. Also joining us on the call for the question-and-answer session is Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer.
This call is accompanied by a slide deck that has been posted on the Investors page of the company’s website. You can now turn to our forward-looking statements on slide two.
Before we begin, I’d like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these statements as a result of various important factors including those discussed in the risk factors section in the company’s most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today August 8, 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. Michael?
Michael Metzger
Thank you, Sharon and thank you to everyone joining us on today’s webcast. I also want to introduce Keith Goldan, our Chief Financial Officer who joined us in June. Keith has over 20 years of experience as a CFO in our business and we look forward to his valuable contributions in the years ahead as a key member of our team. You will hear from Keith during the financial portion of this call.
We’ve made significant progress advancing our pipeline in the second quarter and I look forward to sharing the details from the quarter and what lies ahead for Syndax. I believe we are in a great position to deliver on the strategic goals and milestones that I set out at the beginning of the year including delivering pivotal data from both the revumenib and axatilimab clinical programs beginning in the first half of 2023 and continuing the expansion of both molecules into earlier treatment settings and new indications.
Our clinical efforts are supported by a strong balance sheet that enables us to aggressively advance our programs through our key near-term milestones as well as by a strong partner that will help us successfully advance one of our lead molecules.
We have designed a broad development plan for both revumenib and axatilimab that is focused on fully realizing the value of each drug candidate given their compelling clinical profiles. We expect regulatory filings for both programs in 2023 and are laying the groundwork to support a strong launch of these first and potentially best-in-class products. We are excited about the opportunities and important milestones ahead.
Turning to slide three, we provide a high-level summary of our current corporate priorities. Starting with revumenib, previously referred to as SNDX-5613, our highly selective menin inhibitor.
Our pivotal Phase II AUGMENT-101 trial evaluating revumenib in patients with relapsed/refractory NPM1 mutant or MLLr acute leukemia is enrolling well and we continue to expect data from one of the three cohorts, beginning in the first half of 2023. Data from the Phase 1 portion of this trial, continues to mature and we are looking forward to announcing updated data in the fourth quarter of this year.
Beyond the AUGMENT-101 trial in relapsed/refractory disease, Revumenib is the focus of several ongoing and planned trials that present important expansion opportunities. The ongoing BEAT-AML and AUGMENT-102 trials, will provide data on safety and initial efficacy of revumenib in combination with approved agents.
Additionally, we expect the Australasian leukemia and lymphoma group to initiate the INTERCEPT trial in the fourth quarter of 2022. This trial explores the activity of Revumenib in patients with AML, who have MRD-positive disease. Beyond acute leukemia, we have also identified solid tumor indications, that could benefit from revumenib and we are preparing to initiate a proof-of-concept trial in colorectal cancer in the fourth quarter of this year.
Moving to axatilimab our antibody against CSF-1R. Our pivotal Phase 2 AGAVE-201 trial evaluating axatilimab in patients with chronic graft versus host disease or cGVHD, is enrolling well and we continue to expect data in the first half of 2023. We are actively working with our partner Incyte, to maximize the value of the axatilimab program and this includes planning additional trials of axatilimab earlier — in earlier lines of cGVHD.
We anticipate that Incyte will initiate a trial of axatilimab in combination with Jakafi in the fourth quarter of this year. Beyond cGVHD, we expect to begin a Phase 2 trial of axatilimab in idiopathic pulmonary fibrosis or IPF in the fourth quarter of this year.
Briggs will speak to our strategy in IPF including the trial design, later in his remarks. We also continue to assess business development opportunities to complement our existing pipeline. While our bar is high in-licensing drug candidates, given the strength of our pipeline, we continue to evaluate potential opportunities to in-license earlier-stage, targeted oncology compounds that we believe could become high-value differentiated assets.
Let’s now turn to Slide 4m and I’ll provide further details on the revumenib program. First, we are conducting three single-arm Phase 2 trials that FDA has agreed, may each serve as a pivotal trial. Each of these single-arm Phase 2 trials represent, an independent path to a separate indication and will serve as the basis for a full regulatory filing in the US. The AUGMENT-101 2a trial is enrolling patients with relapsed/refractory MLLr/ALL. 2b is enrolling patients with relapsed/refractory MLR AML. And 2c is enrolling patients with relapsed/refractory NPM1 mutant AML.
Each trial is open to patients aged one month or older, and each trial will enroll independent of the other two. 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 approximately 64 adult patients and up to 10 pediatric patients.
Patient accrual across the individual trials is going well and we remain optimistic that we can complete enrollment in one of these trials this year. As we look at the competitive landscape and engage with experts in the field, we believe revumenib’s compelling clinical profile as demonstrated in the robust Phase 1 experience in 59 patients that we presented at ASH in 2001, positions revumenib to not only be the first-in-class but also at potentially best-in-class treatment.
Importantly, we have decided to provide updated data from the Phase 1 portion of the AUGMENT-101 trial in the fourth quarter. We are seeing improvements in key metrics of the data since last year’s ASH presentation and we believe this update will further strengthen our leadership position and confidence in the outcome of the pivotal trial.
Beyond the AUGMENT-101 pivotal program in relapsed/refractory disease, slide 5 highlights some of the additional opportunities that we are exploring with revumenib, all of which build on revumenib’s excellent safety and efficacy profile that lends well to the treatment across all settings and in combination with currently approved agents.
The Phase 1b AML umbrella trial is currently enrolling patients. As part of our collaboration with the Leukemia and Lymphoma Society, revumenib the first menin inhibitor to be included in this trial is being combined with venetoclax and asocitidine in newly diagnosed AML patients who are unfit for induction chemotherapy. This trial will assess safety as well as initial efficacy. We expect initial data from this trial to be available in 2023. Longer term, we expect that positive BEAT AML trial results would lead to a Phase 2/3 trial, which could serve as the basis for a regulatory filing.
Our other combination trial that is currently enrolling patients, the AUGMENT-102 trial is designed to assess revumenib combination with standard salvage chemotherapies for patients with acute leukemias. 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 knee settings. Further, revumenib is suitable for combination — for use in combination based on its safety profile as seen in the Phase I portion of the AUGMENT-101 trial.
The INTERCEPT trial is focused on investigating novel therapies to target early relapse and clonal evolution as a preemptive therapy in AML and is being conducted as part of the INTERCEPT MASTER clinical trial led by the Australasian, Leukemia and Lymphoma Group. The trial is designed to explore the activity of revumenib as monotherapy in patients with AML who have MRD-positive disease following initial treatment, a group of patients at very high risk of relapse. Of note is that revumenib is the first men inhibitor to be included in the INTERCEPT, AML MASTER clinical trial. The INTERCEPT trial is a very creative approach to treating patients early in their disease course, which is important because the general tenant in oncology is that the earlier you treat the patient’s disease, the better patients do and the longer patients stay on medicine. We currently expect the Australasian, Leukemia and Lymphoma Group to initiate dosing in the fourth quarter of this year.
Turning now to slide 6. Our goal is to unlock the full potential of revumenib beyond the relapsed/refractory acute leukemia setting. In acute leukemia, we plan to engage patients early in their treatment journey get them into remission and hopefully maintain them in that state for months if not years. With these expansion opportunities, we see the potential to address upwards of 12,000 NPM1 mutant and MLLr acute leukemia patients across various settings. These two forms of acute leukemia together 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.
Beyond the acute leukemia opportunity, we believe there is significant value in expanding to solid tumors where revumenib could address areas of unmet need. As we mentioned on our first quarter call, we plan to start an initial proof-of-concept clinical trial in colorectal cancer in the fourth quarter of this year.
The Phase 1 trial is designed as a signal-seeking trial in 20 to 30 patients with refractory colorectal cancer to look for responses or disease stabilization. We are excited about this opportunity given the compelling preclinical signs supporting the role of menin-MLL1 interaction in beta-catenin driven tumors such as colorectal cancer. We anticipate that revumenib could be one of the most important new franchises in hematology along with the added potential in solid tumors. We are laying the groundwork for potential launches so that we are well prepared to get medicine quickly to physicians and the patients they treat and take advantage of our leading position. We are educating and building mind share with oncologists as they utilize and gain comfort with the drug while it’s in clinical trials.
Let me now turn back to axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF-1 receptor. Slide 7 outlines our pivotal AGAVE-201 trial evaluating axatilimab in patients with cGVHD. The trial is enrolling patients 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 210 patients will be randomized to one of three treatment groups each investigating a distinct dose of axatilimab given every two weeks or every four weeks.
The primary endpoint is overall response rate using the 2014 NIH consensus criteria for cGVHD, while secondary endpoints include duration of response and validated quality-of-life assessments using the lease symptom scale. Enrollment to the study is going well and we are on track to complete enrollment by the end of this year and deliver top line data in the first half of 2023. This trial is supported by positive Phase 1/2 data in 40 cGVHD patients we presented at ASH in 2021, where the overall response rate was 68% and the median time on treatment was over six months.
Along with an excellent safety profile, these results were well received among thought leaders who recognized axatilimab, as having a clinical profile that would be beneficial in the treatment of these heavily pretreated patients. In collaboration with our partner Incyte, we are eager to expand the axatilimab program to include combination therapy as well as to assess its use in other fibrotic diseases including IPF. The collaboration has brought together two companies with solid track records of innovation and we are benefiting from Incyte’s expertise in cGVHD.
We are currently planning to assess a novel combination of axatilimab at Jakafi with the goal of establishing axatilimab in earlier settings within cGVHD and expanding its market opportunity. We anticipate this combination trial could begin in the fourth quarter of 2022. As we previously mentioned was our intention, we plan to initiate a robust Phase 2 trial in IPF in the fourth quarter of this year. IPF is the first expansion opportunity that we have committed to pursuing beyond cGVHD and we believe axatilimab could have a significant impact in this disease.
I will now ask Briggs to walk through the biologic rationale, development strategy and market opportunity for axatilimab and IPF. Briggs?
Briggs Morrison
Thanks very much Michael. Turning to Slide 8. Axatilimab you may recall is an IgG4 monoclonal antibody that binds to the CSF-1 receptor and blocks the interaction with its two ligands CSF-1 and IL-34 thereby decreasing the proliferation and function of CSF-1R-dependent monocytes macrophages.
Preclinical data has indicated that bone marrow-derived monocytes, which are dependent on CSF-1 could mediate the inflammatory and fibrotic components of a number of diseases. As I’ve noted before, our work with experts in the field of fibrotic diseases points to a strong consensus that the scientific basis for the efficacy of axatilimab in chronic graft versus host disease is likely to extend to a wide variety of other fibrotic diseases, including IPF.
We’ve established that axatilimab is active in chronic graft versus host disease and we’re excited about the opportunity to expand axatilimab into other fibrotic diseases where the monocyte macrophage lineage plays a key role. And today we’ll focus on our development on IPF.
So IPF is a chronic fibrosing lung disease for which there are currently very limited treatment options. Only two drugs have been approved and both have only been shown to slow, but not stop or reverse disease progression. The only opportunity for a cure is a lung transplant, which is limited to less than 5% of patients.
With the estimated US prevalence of IPF growing to over 180,000 by 2026, we think there is an increasing need for new and safe effective medications. There are several reasons why we are excited to pursue our product disease outside of cGVHD and why we have confidence that axatilimab can have a meaningful benefit in IPF. There is a wealth of emerging preclinical and clinical data indicating that the CSF-1 signaling pathway appears to play a significant role in the development of pulmonary fibrosis and there’s a growing understanding of the important role that macrophages play as a master regulator of the fibrotic process.
Preclinical data, which I’ll review in a minute, supports our planned clinical program. Perhaps the greatest relevance is the data we’ve generated in patients with pulmonary manifestations of chronic graft versus host disease where we have observed clinically important improvements in lung function. For example, within our Phase 1/2 data that we presented at ASH in 2021 in heavily pretreated patients, we saw lung-specific response rate in five of 15 patients. Furthermore, axatilimab has shown good safety and tolerability profile in this Phase 1/2 trial at the doses that we’ve identified to use in our IPF trial.
Slide 9 briefly summarizes some of the data that supports our entry into this proof-of-concept trial. In the panel on the left, we show data from an experiment in which bleomycin is instilled in lungs of mice, which is known to induce pulmonary fibrosis. In this case bleomycin was instilled. And nine days later the animals were treated with an anti-CSF-1R antibody or a saline control. The histologic section on the top left shows a normal lung with extensive white airspace. Conversely, the bleomycin lung has extensive fibrosis the dark colored material in the slide.
Strikingly the lung treated with bleomycin and then therapeutically treated with an anti-CSF-1R antibody on day nine has significantly less fibrosis and markedly preserved white air space. Semi-quantitative analysis of these histologic section heal what’s known as an Ashcroft score. And you can see a statistically improved Ashcroft score in the bar graph on the bottom left with the administration of the anti-CSF-1R antibody.
In the panel on the right, we show data from COMET investigators. COMET is a trial that aims to correlate outcomes with biochemical markers to estimate time to progression in IPF.
The patients were assessed at baseline and then followed overtime and the primary endpoint of the trial was progression-free survival as determined by the time until any one of the following: death, acute exacerbation of IPF, lung transplant or a decrease of 10% in FEC or 15% in DLCO. The investigators conducted a screen from biomarkers that would predict IPF progression.
The data in the figure on the right shows that patients who have high levels of specific monocytes have a much worse prognosis than patients without these high levels of these monocytes. In the table below the graph as a reminder that axatilimab has been shown to specifically deplete the non-classical and intermediate monocytes the cell type that’s correlated with more rapid disease progression in IPF.
As we review this data with experts, they are particularly excited about the prospect of axatilimab not simply targeting a specific pathway, but instead targeting and depleting a specific inflammatory cell thus leaving very little room for redundancy or resistant mechanisms.
On slide 10, we’ve laid out the design of our Phase 2b trial in IPF. This is a multinational trial that will enroll 170 patients with IPF randomized 1:1 to receive 75 milligrams of axatilimab every two weeks or placebo over a 52-week double-blind treatment period.
We’ve leveraged the data from the ongoing chronic graft versus host disease program to select an optimal dose that we believe is well suited to the IPF patients considering an expectation that approximately 80% will be on background medications.
In order to maximize the probability of success in the trial, we’ve worked with experts to design a study that essentially mirrors a pivotal Phase 3 trial. Primary endpoint will measure change from baseline and which is a current registrational endpoint in IPF.
These secondary endpoints include disease progression, St. George’s Respiratory Questionnaire, which is a quality of life instrument designed for patients with obstructive airway disease, the six-minute walk test and diffusing capacity for carbon monoxide. We anticipate enrollment in the IPF trial to initiate in the fourth quarter of this year. And if successful we believe this trial along with perhaps one additional Phase 3 trial could potentially form the basis for FDA approval in IPF.
Let me now turn the call back over to Michael.
Michael Metzger
Great. Thank you, Briggs. I’d like to highlight that successful development in IPF would allow us to unlock a very important indication of considerable value. Thus we’re very eager to get this trial up and running and anticipate doing so in the fourth quarter of this year.
Slide 11 highlights the broad clinical and commercial opportunity for axatilimab. We believe cGVHD represents a high unmet medical need and an important commercial opportunity with approximately 14000 patients suffering from cGvHD in the US.
Successful commercial launches of Incyte, JAKAFI and Sanofi’s resurrect are encouraging both posting meaningful early revenues that begin to speak to 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.
We and Incyte believe that data generated to-date with axatilamab and 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. Through combinations in the frontline setting as well as the opportunity to expand to ex-US markets we envision the cGVHD opportunity more than doubling as shown on this slide.
I’ll now turn the call over to Keith to review our financial results.
Keith Goldan
Thank you, Michael. Let me now take a few minutes to discuss our financial results for the second quarter of 2022.
Turning to slide 12. The results of our operations for the second quarter of 2022 and the comparison to the prior year’s quarter are included in our press release, so I won’t repeat them in these remarks. Additional financial details are available in our second quarter report, which was filed earlier today on Form 10-Q.
I would like to point out that our net loss for the quarter was $37.6 million, or $0.62 per share compared to a net loss of $22.9 million or $0.44 per share for the same period last year. This difference is primarily attributed to an increase in research and development expense, driven by the expansion of both revumenib and axatilimab into registration trials, expansion into new potential indications and increased manufacturing activities.
We ended the second quarter with $378.9 million in cash equivalents and marketable securities, and 60.4 million shares and prefunded warrants outstanding, and we continue to forecast the cash runway into the second half of 2024.
Our current cash on hand, supports our development and pre-commercialization plans for both the revumenib and axatilimab programs, during this period and it provides us flexibility should we decide to engage in business development.
Looking ahead, I’d like to provide financial guidance for the third quarter and full year of 2022. For the third quarter of 2022, we expect R&D expense to be $25 million to $30 million, and total operating expense to be $35 million to $40 million.
For the full year 2022, consistent with previous guidance, we expect R&D expense to be $130 million to $140 million and total operating expense to be $160 million to $170 million, including approximately $15 million of non-cash stock compensation expense.
With that, let me now turn the call back over to Michael.
Michael Metzger
Thank you Keith. As you can see, we continue to make significant progress executing against the ambitious goals and milestones that we set forth in the beginning of this year. Syndax has always been focused on delivering new medicines that extend and improve the lives of people with cancer. And today, with two 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 that we believe are achievable given their compelling clinical profiles.
We believe revumanib could have utility across a wide range of clinical settings in acute leukemia as well as potentially in 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 mutant and MLLr acute leukemias.
The same franchise potential holds for axatilamab, where broad opportunity exists both in various lines of therapy in cGVHD and across a broad range of fibrotic diseases starting with IPF. We are in a strong financial position with a balance sheet that allows us to deliver on key near-term milestones. We remain confident in our ability to identify and bring in novel molecules to deepen our portfolio. 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.
Lastly, we are thankful to our Syndax team, collaborators and most importantly the patients, trial sites and investigators involved with our clinical programs for helping us to execute on our mission of realizing a future in which people with cancer live longer and better than ever before.
Further, thank you, to our committed long-term investors, who share in our vision and support us in building Syndax. With that, I’d like to open the call for questions.
Question-and-Answer Session
Operator
[Operator Instructions] We’ll take our first question from Madhu Kumar with Goldman Sachs. Please go ahead.
Unidentified Analyst
Hi. This is Ammar [ph] on for Madhu. So for our first question you’d like to know what should we be looking for in the updated AUGMENT-101 data in 4Q? What will be the focus durability of response or other disease features?
And then second question, how many of the three cohorts from the Phase 2 revumenib of cohort will be expected to complete enrollment by year-end? And should we expect the NDA to wait for what’s for cohorts?
Michael Metzger
Great. Thank you, Ammar. So let me take your first question related to the update at the end of the year for revumenib. I think the plan — and we talked about this as a possibility. The plan is to update the data set at an opportunity in the fourth quarter.
We had presented a fulsome data set, as you know as of ASH at last year’s meeting. The plan is to present a comprehensive update and similar detail as to what was presented at that meeting.
So we’re not going to comment specifically on the data what will be shown, but I think you should assume that it will be a similar level of detail in that presentation as well. And then, in terms of your second question, remind me — sorry, just remind me that question.
Unidentified Analyst
Yes. How many of the three cohorts from the Phase 2 revenue Revumenib were? What should we expect to be complete enrollment by year-end? And then, should we expect the NDA to wait for cohorts?
Michael Metzger
Right. So the guidance that we’ve given is that we’ll have at least — we’ll have one cohort we hope to have at the end of the year — by the end of the year enrolled and that, we will not necessarily wait to file to get all three cohorts together
But we’ll — as soon as we have the data together for one cohort, at least one cohort, we’ll look to file that to the FDA. So it could be — it could mean an ongoing submission of data for additional cohorts beyond the initial.
Unidentified Analyst
Great. Thanks for taking my questions.
Michael Metzger
Thank you.
Operator
And we’ll move next to Phil Nadeau with Cowen & Company. Please go ahead.
Phil Nadeau
Good afternoon. Thanks for taking my questions. First a follow-on to the last question. In the prepared remarks, there was an intriguing teaser saying that some of the measures that were disclosed at ASH last year have improved over time. We’re curious whether you’d be willing to disclose which of those measures did improve today.
Michael Metzger
Yes. So thanks for the question, Phil. No, we’re not going to get into the detail there. I think, there are lots of detail that was provided in the ASH presentation last year, some of it may be are a bit more important to certain investors and others than not.
But I’d say that it will be a comprehensive update and we’re looking forward to presenting all the detail, which should, I think, further strengthen our position and build confidence in the outcome of the pivotal trials as well.
Phil Nadeau
That’s understandable. A couple of questions on the earlier-stage pipeline. In terms of colorectal cancer, what level of response would you need to see from revumenib to move forward in that indication?
Michael Metzger
Yes. Thanks for the question again. Maybe I’ll ask Briggs to address that please.
Briggs Morrison
Right. So, Phil, you may remember we set the trial up as a — we could win on one of — either a response rate or disease control rate. And as you may recall, the standard of care for this refractory population of patients has a very low less than 5% response rate. So I don’t want to go into all the details of the statistics.
But if the lower bound exceeds that historical 5% then that would be intriguing to us. And then, the disease control rate, again, for standard of care at six months is probably no greater than 15%. So if we saw a disease control rate exceeding that that would also capture our attention. And I think what we’ve outlined is that, if we were to see responses, we could potentially advance more rapidly given that the drug is giving responses.
If we saw a disease control rate our — the protocol is set up to immediately go into a small randomized Phase II to try to confirm that, because I think a single-arm disease control rate is a little more challenging to interpret, could get us excited to do the randomized portion. So that’s the way the trial is set up.
Phil Nadeau
That’s very helpful. And then last question kind of a similar question on IPF. What FVC change is the trial powered to detect, if you want to…
Briggs Morrison
I don’t — yes. No I don’t think we’re at liberty to talk about that. I mean, I think what we looked at the regulatory precedence for the other two drugs that are approved and try to power for a degree of — a change from baseline in FVC, that would be clinically meaningful.
Phil Nadeau
Got it. Thanks for taking my questions and congrats on the progress.
Briggs Morrison
Thank you, Phil.
Operator
And we’ll move next to Kalpit Patel with B. Riley Securities. Please go ahead.
Kalpit Patel
Yes. Hey, good afternoon and thanks for taking the question. For revumenib you have ongoing efforts to explore the drug in an earlier line setting. I guess, how are you thinking about your strategy for advancing the drug with the seven plus three combo in AML? Would that be a potential future development opportunity?
Michael Metzger
Yes. Thanks for the question. I’d say absolutely. I think there are a number of combinations that we’re looking at. And as you’re pointing out seven plus three is the fit population. And certainly our drug could be used in that setting. We’re looking at designing trials to address that as well. So that’s in the planning process.
Kalpit Patel
Okay. And then, diving a little more into the planned updated Phase I data from AUGMENT-101. I’m not sure if you’ll comment, but should we expect maybe a breakdown of CR/CRh rates based on the dose and on the underlying patient characteristics, for example, which patients progressed on venetoclax and then received a CR or CRH.
Michael Metzger
Yes. Thanks for the question. I think you should expect to see a similar level of detail as to what we provided at ASH in 2021. Whether or not we’re going to provide further breakdown on any subsets and things of that nature, you just have to wait to see for the update in the fourth quarter.
Kalpit Patel
Okay. And then one last question for the cGVHD trial with Jakafi, is there going to be a comparator arm, or has that not been decided for this trial?
Michael Metzger
Yes. I mean we’re — again, we haven’t disclosed the details of that trial as of yet. But stay tuned that will be forthcoming.
Kalpit Patel
Okay, fantastic. Thank you very much for taking the question.
Michael Metzger
Thank you.
Operator
And we’ll move next to Yigal Nochomovitz with Citi. Please go ahead.
Ashiq Mubarack
Hi, team. This is Ashiq Mubarack on for Yigal. Thanks for taking my questions. I just had a couple on the competitive landscape, the menin competitive landscape. How are you thinking about data from one of your key competitors with the menin inhibitor, which is expected later this year?
And ultimately, do you think the NPM1 and MLLR leukemia spaces, specifically related to menin, is a winner-take-all situation, or do you think it’s a little more nuanced than that? And maybe how are you thinking about the first-mover advantage part and stickiness with prescribers and so on? Thanks.
Michael Metzger
Yes. Thanks Ashiq. I think look I think first-to-market advantage is important. We feel very good about our current position. We presented a lot of data at ASH last year. And I think the clinical profile is quite compelling, as I think you’d agree. And so I think it positions us very nicely, and we’ll have an update at the end of this year. We’re enrolling our trials very well and I think we’ll have — a position to have one enrolled this year and then data next year. So I think we’re well set up for success.
And then in terms of NPM1, MLLr winner-take-all, that’s a tough one to comment on. I think we have what we think is a very compelling compound an opportunity for us to exploit. And we’ll do that to the greatest extent we can, whether or not there are other competitors in the space time will tell. As of now, we’re really the only ones to present any meaningful data. So I think we’ll have to see. But we like our position. We like our chances and I think we’re well positioned to do that.
Ashiq Mubarack
Okay, great. And then maybe if I can ask one more on the competitive space. What are your thoughts generally on the strategy of covalent menin inhibition? Please correct me if I’m wrong but my understanding is that menin inhibition results in the menin protein turning over pretty rapidly. So, I’m just wondering if you think there is even an advantage to a covalent inhibition or even a longer half-life. Thanks.
Michael Metzger
Yes. No, thanks for the question, Ashiq. So, maybe I’ll ask Briggs to comment on that as well.
Briggs Morrison
Yes. No, I think you captured it correctly the protein does turn over, so you’re going to need drug on board to inhibit newly synthesized protein. And again, I think our view is we can safely and adequately completely cover the target. We’ve shown IC90s a trough — I mean exposures to trough that exceed the IC90. So, it’s not clear to us what covalent will do that would exceed what we can do already with our molecule.
Ashiq Mubarack
Okay, great. Thank you so much for all the color.
Michael Metzger
Thanks, Ashiq.
Operator
And we’ll go next to Joel Beatty with Baird. Please go ahead.
Joel Beatty
Hi, thanks for taking the question. The first one is on revumanib and the opportunity in the first-line unfit patients. The slides show a pretty large opportunity in increasing number of eligible patients. Could you describe the characteristics of the unfit patients that could make them a good market – a good target for revumenib? And then the second question is on IPF. Based on the preclinical data you’ve had so far many hypotheses on how the drug could work on top of one of the two approved drugs versus as a monotherapy.
Michael Metzger
Yes. Great. Thank you Joel for the questions. Maybe I’ll ask our Chief Business Officer, Anjali Ganguli to address the first related to market opportunity in the unfit patient population for revumenib?
Anjali Ganguli
Sure. Thanks Michael. Yes in the front line as you commented there are the two populations and I think there’s an understanding that they’re almost evenly split maybe a slight advantage to the fit population and the unfit is treated more and more with Ven/Aza. And I think our combination in the AML could allow us to justify moving forward into a Phase III to get a label in that population.
Those patients could potentially see long duration of treatment with the revumenib in that setting as we’ve seen patients tolerate the drug really well. And so it would be close to a year of therapy I think on average the then estimate is over 11 months. And so the – if you imagine 20,000 to 21,000 patients a year with incident and AML 50% in the unfit and then 12 months duration for the population that we’re targeting. That could be up to 40% of AML.
So it starts to be a pretty sizable opportunity. And then the fit it really depends on an howling keep them on therapy beyond induction consolidation but we are seeing treatments – like with [indiscernible] trial where they’re seeing patients being treated up to three years. So that could also get to a very large population.
Michael Metzger
Great. Thanks, Anjali. And maybe Briggs can I ask you to weigh in on the IPF question please?
Briggs Morrison
Yes. Sure. Thanks so much Joel. So again what I noted in our comments and it’s very similar to the observations we’ve made in cGVHD, the only mechanism that is actually depleting what are potentially the driver cells for the fibrosis which are these pro-inflammatory macrophages. So that pirfenidone and entetinib work sort of downstream on a specific pathway that are believed to be involved at the fibro brass level of laying down collagen. This is acting more proximal and completely takes out these inflammatory monocytes and macrophages which probably best we can tell from the preclinical work, impacts a much broader set of processes than just the pathways that are impacted by the two approved drugs. And that’s why we’re continuing — we’re doing the trial as an addition to those two approved drugs to test that hypothesis.
Joel Beaty
Great. Thank you.
Briggs Morrison
Thank you, Joel.
Operator
We’ll take our last question from Peter Lawson with Barclays. Please go ahead.
Peter Lawson
Thanks for taking the question. Just Mike on the improvement in key metrics, should we assume that that’s around efficacy that you’re seeing?
Mike Metzger
Yes. No thanks for the question, Peter. I think we’re pointing out that we’ve seen the dataset improve. And obviously key metrics are things that you’re — I would say you’re most paying attention to. And so, among others. And so, we’re excited to present the data in the fourth quarter. And probably not going to say any more than that at this point but you’ll have to just tune in in the fourth quarter.
Peter Lawson
Got you. Appreciate that. Thank you. And then the first time that we you think we could see combination data for the menin inhibitor. When do you think that could happen?
Mike Metzger
Yes. Thanks Peter. So, as I mentioned in my remarks we have two combination trials ongoing AUGMENT-102 and the BEAT-AML trial. I think we expect data to start to accumulate in 2023 and that will most likely come from the BEAT-AML trial first. And so, we don’t have specific timing for that just yet, but we’ll update as we get a little bit closer how that’s materialized.
Peter Lawson
Got you. Thank you. And I guess just the final question. The decision to have that year-end data was that driven by the improvement in the key metrics that you were seeing?
Mike Metzger
Look I think we had said early on and repeatedly was that, our focus has been to enroll our trials and really operationally to get done, what we needed to get done. And if we had the opportunity to update the data set sometime in the end of the year that we may choose to do that. I think, we are encouraged — quite encouraged by what we’re seeing. And it really gives us the opportunity more so to engage with physicians at ASH. We plan to have a presence there. And so, this is a really I think a really good way to get in front of physicians and have them relate to what we’re doing in AML. So, I think that’s — those are some of the factors, but we are quite excited about the data and what we can — what we’ll be able to say at the end of the year.
Peter Lawson
And just finally just since I’ve got kind of the last sort of questions, business development, just your thoughts around kind of assets, asset pricing and potential size that you’re kind of potentially looking at?
Michael Metzger
Yes. As you know Peter, we’re completely focused on building value for Syndax shareholders and building this portfolio is part of that strategy. Business development has always been a part of what we do. We have a high bar as I’ve said many, many times to bring in high-quality assets. They’re hard, hard to find. And we tend to focus on the earlier-stage assets, because I think that we have the opportunity to bring I think differentiated assets in Syndax at that stage and really exploit the expertise we have to develop them. So that is our focus on business development. It’s earlier-stage assets, targeted oncology and that has continued to be the case for quite some time. And hopefully, we can add to the portfolio in the future. That’s the general strategy we have.
Peter Lawson
Great. Thanks so much.
Michael Metzger
Thank you.
Operator
At this time, there are no more questions from the audience. I will now hand it back to the Syndax team.
Michael Metzger
Great. Thank you, operator, and thank you all for joining us on the call today. We look forward to seeing many of you this week at the industry conferences and I wish you all a great end to the summer and a very pleasant evening. Thank you again.
Operator
This does conclude today’s program. Thank you for your participation. You may disconnect at any time. Have a wonderful afternoon.
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