Syndax Pharmaceuticals Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
November 2, 2023

Key Takeaways

  • AGAVE-201 pivotal trial of axitilomab showed a 74% ORR in heavily pretreated chronic GvHD patients with durable responses and low discontinuation, supporting a BLA filing by year-end.
  • AUGMENT-101 pivotal data for revumenib in relapsed/refractory KMT2A acute leukemia reported a 63% ORR and enabled many patients to proceed to transplant, underpinning an NDA under the FDA’s RTOR program.
  • Phase 1 expansion in NPM1-mutated AML showed a 50% ORR, 36% CR/CRh and 100% MRD negativity with durable remissions up to 30 months, bolstering a potential first-in-class approval path in 2025.
  • Net loss widened to $51.1 M ($0.73/share) vs. $35.4 M last year due to higher R&D, clinical and SG&A expenses, and geopolitical events in Israel may delay NPM1 pivotal trial enrollment into early Q2 2024.
  • $379 M cash runway as of September 30, 2023 provides funding into H2 2025 to support planned commercial launches of axitilomab and revumenib and further clinical expansion.
AI Generated. May Contain Errors.
Earnings Conference Call
Syndax Pharmaceuticals Q3 2023
00:00 / 00:00

There are 8 speakers on the call.

Operator

Good day, everyone, and welcome to the Syndax Third Quarter 2023 Earnings Conference Call. Today's call is being recorded. At this time, I'd like to turn the call over to Sharon Clary, Head of Investor Relations at Syndax Pharmaceuticals.

Speaker 1

Thank you, operator. Welcome and thank you all for joining us today for a review of Syndax's Q3 2023 financial and operating results. I'm Sharon Clary. With me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer Doctor. Neil Gallagher, President and Head of R and D and Keith Goldin, Chief Financial Officer.

Speaker 1

Also joining us on the call today for the question and answer session are Doctor. Peter Ordenlich, Chief Scientific Officer and Doctor. Angeli Ganguly, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the Investor page of the company's website. You can now turn to our forward looking statements on Slide 2.

Speaker 1

Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered These forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ 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 made represent our views as of today, November 2, 2023 only. A replay of this call will be available on the company's website, www.syntax.com, following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Speaker 2

Thank you, Sharon, and thank you to everyone joining us on the webcast. This continues to be an exciting year for Syndax and I look forward to sharing a number of updates with you on the significant progress Throughout the Q3, we delivered on key pipeline milestones that are highlighted on Slide 3, including reporting positive Top line AGAVE-two zero one pivotal data of axitilomab for the treatment of chronic graft versus host disease. We also reported positive top line pivotal AUGMENT-one hundred and one data for revumentiv in adult and pediatric patients with relapsedrefractory KMT2A rearranged acute Together these results put us on a clear path to becoming a commercial stage biopharmaceutical company in 2024 with 2 potentially first and best in class products. We are also happy to provide data today from additional relapsed or refractory NPM1 patients That we're enrolled in the final stages of the Phase 1 portion of the AUGMENT-one hundred and one trial. Neil will walk us through the data a little later in this call, But in summary, we are encouraged by the 36% CRCRH rate and deeper responses that we are seeing in the NPM1 population.

Speaker 2

Responses elicited by revumentib in the MPM-one population are durable with some patients in remission beyond 22 months, Further supporting the rationale that revumentiv can provide a meaningful benefit to MPM-one patients and emphasizing its blockbuster commercial We continue our positive momentum heading into the end of 2023 With a primary focus on completing 2 potential regulatory filings by year end and launching both drugs in 2024. This will put Syndax in a very unique position to create value as a SMIDCAT Biotech company. We will have a significant presence At the American Society of Hematology ASH Annual Meeting, including at our planned investor event and expect to provide several Data updates on both these programs at that time. I am pleased to share that as of a few days ago, We initiated the NDA submission of revimenev for KMT2A acute leukemia under the FDA's real time oncology review program or RTOR. We view RTOR as a significant benefit for the revumentiv program.

Speaker 2

It complements our BTD and fast track status for KMT2A and provides a more efficient review process to ensure that revimenev is available to patients as early as possible. Under our tour, the sponsor has consistent engagement with the FDA throughout the submission process. Drugs are accepted for review into this program Need to meet specific eligibility criteria, the most important of which is the likelihood of demonstrating substantial improvement over available therapy. In accordance with FDA guidance for AML and in line with the approvals of other AML agents in the relapsed refractory setting, We anticipate rivimeneb would be granted full approval based on the results of AUGMENT-one hundred and one. With our partner Incyte, we also remain on track As you saw from our press release earlier today, Data from both the AGAVE-two zero one and AUGMENT-one hundred and one pivotal trials, including post transplant maintenance data Along with revumentib combination data from the SAGE trial will be presented at the ASH meeting in December.

Speaker 2

Beyond the Congress Presentations. We will also have the opportunity to share additional data from ongoing Revimedib combination trials at our ASH Investor event, which will further reinforce Revimed's compelling clinical profile and meaningfully add to its value proposition. We are well funded with $379,000,000 in cash as of September 30. Our current balance sheet not only supports our planned commercial launches And the trials that we have outlined also allows us to expand beyond our core registration indications and pursue select business development opportunities. Now let's dive into revimenop, our highly selected menin inhibitor.

Speaker 2

I'll ask Neil to provide a recap of the results from the AUGMENT-one hundred and one pivotal trial, Speak to the ASH abstracts and review the data from the MPM-one patients in the Phase 1 portion of the AUGNET-one hundred and one trial. Neil? Thank you, Michael.

Speaker 3

I will now review the OGNET-one hundred and one pivotal data in relapsed or refractory KMT2A acute leukemia beginning on Slide 4. As previously reported, the independent data monitoring committee reviewed the data and recommended that trials stop early for efficacy in accordance with a predefined interim analysis. We are very pleased with the robustness of the data that we reported. Almost 2 thirds of these heavily pretreated patients Achieved clinically significant responses, enabling many to receive potentially curative transplant. Importantly, a proportion All responders in the trial were started on revumeneb in the post transplant maintenance setting.

Speaker 3

The desire for physicians to restart revumeneb as post transplant maintenance speaks to its efficacy and tolerability And their belief that it may offer a better outcome for their KM220 acute leukemia patients. Importantly, the ability of these heavily pretreated patients to both respond to And tolerate reviemanov therapy also underscores its potential to be adopted into frontline combinations. Turning to Slide 5, The majority of patients in the efficacy evaluable population, which include adult and pediatric AML and ALL patients achieved clinically significant responses to treatment with High overall response rate of 63%. The CRCRH rate in this population was 23%. The response rates observed in KMT2A AML Specifically, we are consistent with those in the overall efficacy of valuable population with 65% achieving a response and 24.5% achieving CR or CRH.

Speaker 3

The MRD negative rate among CRC or H responders was also impressive at 70%. At the time of the data cutoff, the median duration of CRC or H response 6.4 months across both the efficacy of Valuable and AML populations with 46% or 6 patients remaining in response. Of note, this is a Kaplan Meier estimate and the data will continue to mature over time. Therefore, the median DOR may 63%, but 39% of responding patients proceeded to bone marrow transplant, which is notably higher than historical benchmark in this population of less than 5%. Eighty patients were transplanted prior to achieving CR CRH at the discretion of the attending physician.

Speaker 3

Clearly, if physicians had decided to wait a little longer prior to transplant, Then more of these patients could have achieved a best response CR CRH. For example, if all 8 of these patients had achieved CR CRH, then the rate would have been 37%. 71% of these patients, 10 of 14, either restarted revumeneb or were eligible to restart as maintenance therapy. At the time of data cut off, some patients were treated in the maintenance portion for as long as 8 months and several are continuing on therapy, which we believe speaks to revu menim's compelling overall clinical profile and the potential for long term maintenance in this setting. The ability of revumentib to rapidly induce blast free responses in heavily pretreated patients, thereby enabling them to undergo potentially curative bone marrow transplant Followed by post transplant maintenance represents a potential paradigm shift in the standard of care in this setting.

Speaker 3

We have a presentation at the ASH meeting That will highlight revumeneb for post transplant maintenance, including patients on therapy in remission beyond 18 months. The data from AUGMENT-one hundred and one indicate that revumenab is well tolerated and the safety profile is consistent with what was previously reported. We believe that the emerging benefit risk profile of revimeneb supports its use not only as a monotherapy in the relapsed refractory setting Before and after transplant, but also its potential use in combination with frontline standards of care for which initial data are forthcoming will be forthcoming later this year. Turning to Slide 7. Today, we announced encouraging data from 3 additional patients with MPM-one mutated relapsed or refractory AML Included in the Phase 1 portion of the AUGMENT-one hundred and one trial for a total of 14 NPM1 patients treated at doses meeting the RP2D criteria.

Speaker 3

These patients are enrolled in Phase 1 to complete the pharmacokinetic characterization of revivimene. Among these 14 patients, 7 achieved a response to treatment for A 50% overall response rate, 5 of 14 achieved a CR or CRH rate of 36% And 100% of the CRH responders were MRD negative. On Slide 8, you may see that these responses Are durable with 4 of 5 of the patients remaining in response, 3 already beyond 6 months, 1 beyond 22 months And one over 30 months at the time of the analysis. Revimeniv also enabled 43% of NPM1 responders to proceed to transplant. 1 of the patients who proceeded to transplant have been enrolled following the AUGMENT-one hundred and one protocol update, which allowed patients to restart reviomedov post transplant.

Speaker 3

This patient remains on revuimenev maintenance at the time of the analysis. Similar to the Phase 2 results observed with KvT2A population, revuimenev was well tolerated Patients with relapsedrefractory MPM1 AML. There were no Grade 4 or 5 QT prolongations, no patients experienced more than Grade 2 differentiation syndrome And no patients discontinued due to treatment related adverse events. As Michael said earlier, these data continue to support our conviction The revumentib will be an important treatment for MPM-one AML as well as for KM-two twenty eight acute leukemias and we expect that MPM-one pivotal trial results will be consistent with the data generated to date and highly supportive of a first to market approval. The pivotal cohort of the UGGM-one hundred and one trial continues to enroll relapsed The trial is designed to enroll 64 patients and up to 20 pediatric patients.

Speaker 3

While the Trial continues to recruit well in the U. S. And internationally. We now forecast completion of enrollment in the late Q1 or early Q2 next year Due to a few high enrolling sites in Europe coming online later than we expected in the Q3, coupled with the recent events in Israel where we have a High concentration of sites. I would note that Israel accounts for 16% of our enrolling sites and historically these have been very high enrolling.

Speaker 3

We are now looking forward looking to make up for any potential shortfall at our sites, but it's difficult for us to predict the impact that the evolving geopolitical Nonetheless, we expect to be in a position to report data in the Q4 of 2024 and importantly continue to look forward So a potential approval in 2025 based on an sNDA filing following Ravi Menon's anticipated initial approval in KMT2A. Turning to Slide 9. In addition to sharing the AUGMENT-one hundred and one pivotal data at ASH, we look forward to Doctor. Gutz Ise highlighting his SAVE trial results And an oral presentation on Saturday morning during the meeting. This is an investigator sponsored Phase Ib trial conducted by Doctor.

Speaker 3

Issa at the MD Anderson Cancer Center, Evaluating an all oral combination of reviumenib with venetoclax and a fixed dose combination of decitabine and cetoziridine in children and adults With relapsed refractory AML or mixed phenotype acute leukemias. At the time of the data cut off, the trial was enrolling at the current monotherapy RP2D of 100 and 3 milligrams every 12 hours with a strong CYP3A4 inhibitor. In total, 8 patients with either NPM1, KM220A or not 98 mutations were enrolled in the trial, having received 2,500,000 prior lines of therapy. Approximately 2 thirds of patients received prior venetoclax. All patients on a strong CYP3A4 inhibitor were on a strong CYP3A4 inhibitor and were therefore treated with rivimumab and either 113 milligrams Q12 early or 160 milligrams 63 milligrams Q12 early.

Speaker 3

7 of 8 patients were evaluable for response. All 7, 100 percent achieved a response. 6 of 7 achieved a CRC and 2 of 7, 28% achieved a CRH. Importantly, responses were observed across relapsed or 3 NPM1, KIN2A or UP98 acute leukemia patients. 3 patients transitioned to hematopoietic stem cell transplantation following response And 2, continue in remission and have started maintenance as of the data cutoff.

Speaker 3

We are highly encouraged by the combinability of revumental with venetoclax And the hypomethylating agent in this trial, this combination was well tolerated at active doses, including the current monotherapy RP2D. I'll now turn the call back to Michael.

Speaker 2

Thank you, Neil. Turning to Slide 10, we believe that revumetiv could form the backbone of We have expanded our clinical strategy beyond the relapsed or refractory setting into earlier settings and post transplant maintenance, including combinations with approved therapies. In an attempt to accelerate the generation of evidence of clinical benefits seen with reviveniv across various settings of KMT2A and NPM1 acute leukemias, We are collaborating with cooperative groups and leading investigators in addition to the clinical trials that Syndax is conducting. In addition to the SAGE trial that As Neil described earlier, we plan to present initial data from the BEAT AML and AUGMENT-one hundred and two trials in the Q4 at our planned investor event at ASH. The Phase 1 BEAT AML trial is part of our collaboration with Leukemia and Lymphoma Society and revumentiv is being combined with venetoclax and azacitidine to of the trial to confirm the RP2D for this combination and we continue to expect to share data on safety and efficacy from the trial at our ASH investor event.

Speaker 2

The AUGMENT-one hundred and two trial is designed to assess the safety of revumentiv in combination with standard salvage chemotherapies For patients with relapse or refractory acute leukemias, we anticipate presenting an update on the initial safety and potential RP2D from the trial at our ASH We look forward to initiating a trial of revumentib in combination with standard of care intensive chemotherapy known as 7+ 3 in newly diagnosed patients with acute leukemia in late 2023 or early 2024. This trial will also include an option for maintenance with revumentib Monotherapy. Beyond the acute leukemia trials we've laid out here, we are rolling a proof of concept Signal seeking Phase 1 clinical trial in metastatic colorectal cancer based on compelling preclinical science supporting the role of the men and KMT2A interaction in beta as encouraging as it's difficult to treat patient population with the monotherapy and we expect to follow these patients to gather sufficient efficacy into 2024. We anticipate being able to provide an update on the progress of the dose escalation phase of the trial in the Q1 of 2024. Now to Slide 11.

Speaker 2

KMT2A and MPM1 acute leukemias represent up to 40% of AML patients and there are no FDA approved targeted therapies for this Population, including the expansion opportunities, there is the potential to address upwards of 12,000 NPM1 mutant And KMT2A rearranged acute leukemia patients across various settings. We are committed to bringing these encouraging clinical benefits to even more patients And this remains an area with significant unmet need. We believe that relapse or refractory KMT2A acute leukemias alone represent A $650,000,000 to $750,000,000 market opportunity in the U. S. Based on the estimated patient population, duration of treatment and current pricing assumptions.

Speaker 2

KMT2A rearrangements represent approximately 10% of AML and ALL, which translates into an incidence of approximately 2,600 KMT2A Rearranged acute leukemia patients, a very high percentage of whom are refractory to frontline standard of care treatments. Based on the enthusiasm we are hearing from physicians and the potential to shift the treatment paradigm in KMT2A to incorporate maintenance treatment post transplant, We believe the median duration of therapy across the treatment population would be approximately 9 months and we believe the data generated in AUGMENT-one hundred and one Support pricing competitive with or above other targeted therapies in AML such as FLT3 or IDH inhibitors. With no treatment options approved for these patients and no near term competition, revumentum could easily become the treatment of choice for all We expect that our first mover advantage and experienced physicians will gain treating their patients with revimetim could extend meaningfully beyond KMT2A and allow us to build a formidable franchise in the next few years. Supported by the compelling NPM1 data we presented today, We believe revumentib will also provide meaningful benefit in relapsed or refractory NPM1 patients. Our market research suggests that if approved, Oncologists are likely to reach for revumentiv as either their second or third line agent of choice for patients with MPM-one mutant AML.

Speaker 2

We estimate that this population will be slightly larger than relapsedrefractory KMT2A acute leukemia population. And based on our Phase 1 results, We also believe overall efficacy and treatment duration will be consistent between the KMT2A and NPM1 populations. Having first mover access to 2 distinct market segments in acute leukemias, KMT2A and NPM1 creates a total accessible population of 5000 to 6000 patients In the relapsed refractory setting and an addressable market opportunity of approximately $1,000,000,000 to $1,500,000,000 for revumentum in the U. S. Alone.

Speaker 2

We anticipate that revimeta will begin to carve out a dominant share of the relapsed and refractory NPM1 market starting in 2025. Now let's dive into axitilumab, our monoclonal antibody targeting the CSF1 receptor beginning on Slide 12. In collaboration with Incyte, we shared positive results from the global pivotal AGAVE-two zero one trial evaluating the efficacy, safety and tolerability Of axitilumab in 241 patients with active chronic GvHD whose disease had progressed after at least 2 prior therapies. As a reminder, the trial met its primary endpoint of overall response rate by cycle 7 day 1 using the 2014 NIH consensus criteria The overall response rate or ORR was 74% At a dose of 0.3 milligrams per kilogram administered every 2 weeks. The responses were durable with a median duration of response not yet reached at the time of data cutoff And 60% of responders were still responding at 1 year.

Speaker 2

Axotilumab was well tolerated in the trial with a low 6% rate of discontinuations And the most common adverse events were consistent with the on target effects that were observed in prior trials. I want to remind you that robust efficacy was observed Despite the patients being very advanced and heavily pretreated, as an example, I would highlight that there are meaningful differences in patient populations between the 2 or more prior lines of therapy. Notably, patients in the AUGOV-two zero one trial had a longer median time since diagnosis, More severe chronic GVHD and had received more prior lines of therapy, including a greater number of patients have received Jakafi Then patients included in the Resirock trial. We believe these points of differentiation underscore just how impressive the AGAVE-two zero one trial results And point to the significant value axitilomab could bring to patients if approved. These results not only Support the promise of axotilumab safety and efficacy profile, but reinforce potential as a first and best in class CSF1R monoclonal antibody in chronic GvHD.

Speaker 2

Axotilumab is the 1st investigational chronic GVHD treatment to target inflammation and fibrosis through the inhibition of disease associated macrophages And the AGAVE-two zero one data demonstrates the potentially pronounced impact this mechanism alone or in combination with standard of care therapies Already available for the management of this disease may have on patients suffering from chronic graft versus host disease. In collaboration with Incyte, we intend to file a BLA by year end 2023. Additionally, we look forward to showcasing the full results during the plenary session at ASH. Turning to Slide 13, approximately 14,000 U. S.

Speaker 2

Patients suffer from chronic graft versus host disease, 50% of whom require treatment beyond second line due to disease progression, inadequate response or disease manifestations that aren't wholly addressed with Unfortunately, there are no cures for this advanced population of chronic GvHD patients. Patients are initially treated with Corticosteroids and then cycled through a variety of additional therapies. While patients may be treated with several of the approved therapies, The order in which they are used may depend on the physician's experience with how a given agent may address specific manifestations of the disease. Jakafi and Resirock have had successful commercial launches, which speaks to the unmet need in chronic GvHD that translates to a substantial commercial opportunity. It is our conviction that axotilumab could provide an effective differentiated practice changing intervention for this underserved population.

Speaker 2

Axotilumab suppresses monocyte derived macrophage activation and proliferation, which may provide more comprehensive control of the disease than currently approved therapies. This is a key differentiator and also supports moving axitilumab earlier in the treatment paradigm to potentially prevent organ damage before it occurs. Because axotilumab is an antibody, drug drug interactions are expected to be minimal and axotilumab's unique mechanism of action may offer the benefit of being an A deal combination partner with standard of care therapy is currently used for the treatment of chronic GVHD. The opportunity to expand to ex U. S.

Speaker 2

Markets And additional high value indications as well as combinations in earlier settings in chronic GVHD, both in adults and pediatrics Could build significant additional value for axitilumab. We are looking forward to the initiation of additional trials of axitilumab, including a 26 We randomized placebo controlled Phase 2 trial in 135 idiopathic pulmonary fibrosis patients expected to begin by year end As well as a combination trial to be conducted by Incyte in chronic GvHD patients with Jakafi in mid-twenty 24. I will now turn the call over to Keith to review our financial results. Keith?

Speaker 3

Thank you, Michael. Let me take a few minutes To discuss our financial results for the quarter ended September 30, 2023. Turning to Slide 14. The results of our operations for the Q3 of 2023 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 Q3 2023 report, which was filed earlier today on Form 10 Q.

Speaker 3

I'd like to point out that our net loss for the Q3 was $51,100,000 or $0.73 per share compared to a net loss of $35,400,000 or $0.58 per share for the comparable period last year. The difference in our net loss was driven largely by an increase in employee related expenses and professional fees within both SG and A and R and D, combined with increased clinical and manufacturing expenses. We ended the 3rd quarter with $379,300,000 in cash, Equivalents and short and long term investments and 69,900,000 shares and prefunded warrants outstanding. Our balance sheet is expected to provide runway into the second half of twenty twenty five, which allows us to appropriately invest Looking ahead, I'd like to provide financial guidance for the rest of this year. For the full year of 2023, The company expects research and development expenses to be $160,000,000 to $165,000,000 and total operating expenses to be $225,000,000 to $230,000,000 both of which are inclusive of approximately $30,000,000 of non cash Stock compensation expense.

Speaker 3

Note that this is a reduction from our prior guidance of $160,000,000 to $175,000,000 for R and D expense and $225,000,000 to $240,000,000 for total operating expenses. With that, let me now turn the call back over to Michael.

Speaker 2

Thank you, Keith. Before we open the call for questions, I'd like to provide a summary of what was presented today. In the near term, we remain laser focused on delivering quality data readouts, including the full AUGMENT-one hundred and one and AUGAV-two zero one data sets, As well as data from several other combination trials at the ASH Annual Meeting and our planned investor event by year end. We are excited to provide positive final Phase 1 results for revumentiv treatment in relapsedrefractory NPM1 patients, Further demonstrating its best in class profile in another important indication with high unmet medical need. Pivotal data from these trials will serve as the basis For revimeneb and an Incyte initiated BLA submission in chronic GvHD for axotilumab by year end 2023.

Speaker 2

Both revimenop and axitilumab have significant market opportunities with the potential to gain quickly gain considerable market share and have a meaningful The impact on the lives of underserved patients in each setting. In addition, we continue to explore ways to capture the maximum value of our current pipeline By expanding into opportunities beyond the initial registration indications and in doing so aim to bring the encouraging clinical benefits of our lead candidates to even more patients in need. It has been a transformational year for Syndax and we expect to maintain this momentum in the coming months With a number of upcoming value generating milestones that are laid out on Slide 15, I remain confident that we have the resources and expertise To execute on our goals and the strategic long term vision that will enable our successful transition into a commercial stage biopharmaceutical organization. As always, I would like to extend my gratitude to the Syndax team, collaborators and most importantly, the patients, trial sites and investigators involved with our clinical programs. Through your integral work, we are advancing our mission of realizing a future with which people with cancer live longer and better than ever before.

Speaker 2

I'd also like to thank our committed long term investors who continue to share in our vision and support us in building Syndax. With that, I would like to open the call for questions.

Operator

Our first question is from Brett Canino at Stifel. Your line is now open. Please ask your question.

Speaker 4

Hi, and thank you for the questions. Looking forward to Ash. I have a 2 parter on the SAVE trial, actually, the all oral triplet where you had the abstract. Yes. First, when you speak to AML physicians, do you get the sense they're looking to use off label combinations in the relapsed refractory setting?

Speaker 4

Because if we on the street that are anchored to your monotherapy data, I guess what might that then mean about the ultimate Tuning in this treatment line in relapsed refractory as we think about efficacy, percent of transplant, maintenance, etcetera? And then I have a follow-up.

Speaker 2

Brad, thanks for the question. I'm going to ask Neil to make a comment.

Speaker 3

Yes. Look, thanks for the question. Obviously, this is a preliminary dose ranging and there's more work to be done. We see the value in the data that Doctor. Issa is generating in a couple of different ways.

Speaker 3

So, first of all, the demonstration of the combinability of revumana with venetoclax And the study is ongoing with revimeta being administered at full dose In CL1, as is mentioned in the abstract. The other thing to bear in mind is that historically, if you look at this population, They're quite heavily pretreated. Most of them have actually failed venetoclax, nihympethylating agent. And One would expect the response rate therefore to venetoclax plus an HMA to be quite low, actually probably less 10% and here we're seeing much, much higher response rates than a 28% CRCRAH rate. So, this is actually incremental progress, Albeit based on early data, incremental progress for those patients.

Speaker 4

Great. And then Yes. On the safety for the regimen, I guess, is this higher and more prolonged myelosuppression than would be expected from the components? And how are you thinking about this too as we think about the frontline Venase combo that might be a different patient population in terms of Yes. How myelosuppression might affect them?

Speaker 4

Thank you.

Speaker 3

Yes. Thanks for the question. Just continuing on. So, Well, as the authors themselves conclude, the safety profile is what you would expect from Van and the hypomethylating agent. So, there's The triplet, if you can call it a triplet, appears to be extremely well tolerated, right, for I'm going to have a pre treated patients.

Speaker 3

And I just going to your point about what does this mean as we advance the Combinations in earlier stage patients, I think it signals good things, right, because if heavily pretreated patients can actually Tolerate the combination, then it is highly likely that less heavily pretreated patients will also tolerate the combination well. So, we are encouraged. As I mentioned during my prepared remarks, we're overall, when we look at the data That are evolving some of the data that we've presented today. We're highly encouraged for the opportunity to advance, radiumatinib into earlier stage combination therapies.

Speaker 2

Thanks, Brent.

Operator

Great. Our next question is from Anupam Rama at JPMorgan. Your line is open. Please ask your question.

Speaker 4

Hi, this is actually Malcolm Kuno on for Anupam. Thank you for taking the question. What additional data are you planning to present at ASH on AUGMENT-one hundred and one KMT2A Versus what we already know from the top line data? Thank you.

Speaker 2

Yes, Malcolm, thank you for the question. So as we had previously said, I think we said in the remarks, obviously, we've presented top line In recent days and we'll be at ASH, we have an abstract that was that came out today that explains that we'll have a presentation at ASH At our investor event, I think it could be the data that's been top lined is the data cut, but we'll have additional analyses that I think going to more specific detail around that particular data cut, whether it's And then not to speculate specifically around what we're going to present, but I think there are some important analyses that will allow people to get a even deeper feel for what we presented previously. So stay tuned, but we'll have obviously more data at ASH and then again, at our Investor Day.

Speaker 3

Excellent. Thank you.

Operator

Our next question is from Chris Shibutani at Goldman Sachs. Your line is open. Please ask your question.

Speaker 4

Hi, good afternoon. Thank you so This is Charlie on for Chris. Just to kind of follow-up on the last question, wondering if you have the same data cut for the AUGMENT-one hundred and one presentation at ASH. So it sounds like we're going to assume the same 57 patients that we had for the top line results. Just wondering with the rolling submission with the FDA currently, Are they going to be looking for those additional 37 patients that are after that data cut?

Speaker 4

Thank you.

Speaker 2

Yes, Charlie, thank you. You're correct. It is the same data cut at ASH. I mean, we're very focused now on getting our NDA filed. And as you noted, under Arthur, we have a Pretty rigorous and short timeline to complete the filing by year end.

Speaker 2

So, it is a rolling submission. The agency has very specifically agreed to our data plan, which is, again, efficacy on the 57 patients With safety on the overall 94, which we outlined when we top line the data and confirmed through our meeting at our beginning our ROTOR process. So the data will be they see all the data, but there's no new data cut Require from an advocacy standpoint and the safety obviously will be submitted as such. So that's the way to look at it.

Speaker 4

Okay, great. Thank you so much.

Speaker 2

Thank you.

Operator

Our next question is from Yigal Nochomovitz. Please unmute yourself and ask your question.

Speaker 4

Hi, team. This is Asha Gubarak on for Yigal. Thanks for taking my questions. I just had one on the post transplant setting data you shared. It seems like you're getting some very long durability In terms of patients staying on drug for long periods

Speaker 2

of time post transplant, which is great. I guess how

Speaker 4

are you thinking about the commercial opportunity sort of on average in

Speaker 2

I'm going to turn it over to Angeline to answer that, please.

Speaker 1

Hi, Ashit. Thank you so much for that question. So we've been thinking about And speaking to a number of physicians about how they want to use revimenev based on the data we're generating, And they see that there's an opportunity to treat patients in the post transplant maintenance setting. The drug is able to get patients to deep durable responses. And they see No downside for continuing the monotherapy after transplant.

Speaker 1

And the goal, I think, would be to keep them on as long as Possible, but the standard today is assumed to be close to 2 years. Obviously, not every patient will achieve that and not every patient I was able to successfully receive a transplant. So, we estimate That conservatively that, duration on average will be close to 18 months.

Speaker 4

Okay. That's very helpful. I guess a conceptual question on the same topic. What's the decision making for the physician behind choosing the end to end Treatment in the post transplant setting, is it disease progression or is there a point at which they kind of determine the benefit maybe Lowering over time. Yes.

Speaker 4

I would say the risk of disease progression. Thanks.

Speaker 2

Yes. Good question. So Neil, why

Speaker 4

don't you comment on that?

Speaker 3

Yes. Thanks for the question. As you noted, we're seeing patients actually remaining on the drug for very protracted periods of time. And that says to us that it speaks to the tolerability profile of the drug, which It's consistently been very good. The feedback, we've obviously talked to investigators and other physicians about this, and They are very keen when we speak with them.

Speaker 3

First of all, they wanted this option. Just to remind you, they wanted this option in the study. It wasn't there in the earlier part of the study and we included it in 2, at the request of the investigators. So that's one point. The other point is, as we talk to them now, They see themselves keeping patients on for protracted periods of time, right.

Speaker 3

So they talk about 2 years, right, for instance. But in fact, there's evidence to suggest that patients could stay on longer than that as well. So I don't I think as long as patients and remember that these patients are extremely high risk, very heavily pretreated. The KM2a cohort That we've presented, that we reiterated today, very heavily pretreated and, therefore, there's no the way the physicians are looking at it is why take the risk the patients are The drug is getting the patients into response, getting the patients to transplant, well tolerated and therefore the patients can go back on it after transplant. Why not just keep the patients on the drug?

Speaker 3

That's the feedback that we're getting.

Speaker 4

Got it. Very helpful. Thanks very much.

Speaker 2

You're welcome. Thank you.

Operator

Our next question is from Phil Nadeau at TD Cowen. Your line is open. Please ask your question.

Speaker 5

Good afternoon. A couple of questions from us. First, congrats on the 36% CR CRH rate with the 3 additional patients. In terms of the pivotal trial NPM1 for revimendib, can you discuss in a bit more detail what's the implications of the 16% of enrollment coming Out of Israel, is it that there's a chance that those patients will be lost to follow-up or the data will be lost? How does that impact the timelines and The number of patients that you need to enroll?

Speaker 2

Yes. Thanks for the question, Phil. Look, I think It's an unfortunate set of events going there. Our trial sites are still up and running. In Israel, Data is centralized, so we have obviously good control over the data, not the issue.

Speaker 2

The implications We think are hard a little bit hard to predict, but we have a lot of other sites that we're doing quite well with enrollment elsewhere. And so I think that's something we feel very confident we can pick up and complete the trial by the end of the Q1 or very early in the Q2. So It's something that's a little bit unfortunate, but these as I said or as Anil said in the remarks, These are typically high enrolling sites and it was just a little bit unfortunate, but we feel very confident that we'll be able to get it done on time.

Speaker 5

Got it. That's helpful. And then a follow-up question on the SAFE trial. I believe the abstract said that enrollment continued in SAFE and additional Or updated data will be presented at the meeting. What can we expect in terms of patients at dose level 1 At ASH, I think there were 2 in the abstract.

Speaker 5

Would there be another 4 DASH? Or could dose level 1 enroll beyond the 6 that were enrolled at dose level 0?

Speaker 2

Yes, Phil, thanks for the question. It's a little bit hard to answer at this point. I think they're continuing to Enroll at that dose level, as you know, there are only a few that were enrolled so far. The results have been quite strong and striking. So they're looking forward to expand that to additional patients and that will be obviously presented at ASH In the presentation, but I can't give you specific numbers on how many patients will be expanded to.

Speaker 2

I just don't have that detail.

Speaker 5

Fair enough. Thanks for taking our questions.

Speaker 2

Yes. Thank you so much.

Operator

Our next question is from Jason Simonsky at Bank of America. Your line is open. Please ask your

Speaker 1

Hi. This is Alex Hammond on for Jason Zemansky. Thank you for taking my question. What sort of data do you think is necessary before the community can start to feel

Speaker 2

Thanks for the question. Well, look, I think the data that we generated to date, both as a monotherapy and now In NPM1 and for KMT2A really is a good source of or I should say, it underpins well what We would expect to see a contribution of components, right, when you think about combining drugs such as with FINESA and with chemotherapy. So we feel very confident that we have best in class monotherapy data and that's a good starting point. With combinations, first things first, and Neil may comment Extremely important and the SAVE information, the SAVE trial information that came out today really supports that. We'll have data at ASH For the beta AML trial, which is frontline patients, the SAVE trial were that's in relapsed refractory patients, but beta AML is in Newly diagnosed patients and the opportunity to not only safely dose patients, but dose them at the full monotherapy dose As well as drive response rates as you'd hope to be as good or better than what they see in the doublet, That's what we're looking for.

Speaker 2

And I would also say MRD negativity is a big driver of physician choice And how they think about treating their patients. We've been able to show deep durable responses signaled by MRD negativity and that's Something we'll look at in these combinations as well where patients are not necessarily getting to full MRD negative status. So There is those are the types of things that we'll look for and we expect to have meaningful data for the end of the year to kind of elucidate all that.

Operator

Our next question is from Peter Lawson at Barclays.

Speaker 6

Do you have enough data now to file for a breakthrough designation? And do we get an update this data at the Investor Day? And then Are patients going on to transplant and could that cause a downdraft in the CR, CRH

Speaker 2

So I think you had a couple of different questions here. One was taking it from in reverse order here. Could patients go on to do we see patients go to transplant? I think the answer the MPM-one patient, think the answer is obviously yes. You see that in the swimmer's lane that we have on our slides as well as We mentioned in the remarks, so patients are going to transplant, 3 of the patients of the 14 went to transplant and many of them are staying On treatment for and also in remission.

Speaker 2

So, I think that is an important fact pattern. Also important to note are what we saw in the Phase 1 sorry, the pivotal trial for KMT2A, we And Neil mentioned in his remarks, the number of patients who didn't reach complete count recovery, so didn't Reached CRCRA's best response and we're taking to transplant very quickly. That actually ended up penalizing us a bit On the CRCRA trait, as Dale remarked, it could have been as high as 37% if all those patients had converted and maybe didn't go to transplant as quickly. What we're seeing with NPM1 is the treatment course is a little bit slower in terms of taking patients to transplant. So these patients are also not necessarily as fit as what you'd see with KMT2A, younger patients.

Speaker 2

So we're actually not Seeing if you look at the data, we're not seeing patients at CRP or incomplete hematological recovery points. And so what you're seeing is all of our patients are CR, CRH and MRD negative and some of them are going to transplant. So it just tells you the time course Probably has an impact in terms of reaching your full potential for CRH as an MPL1 patient. So we don't think Actually, that's going to meaningfully impactful in the Phase 2. In fact, we see it as the opposite.

Speaker 2

We see that CRC range could actually be more reminiscent of what we're seeing now, which is in the mid-30s or higher on NPM1. We'll have to see what the data bears out, but we don't think that same treatment paradigm in terms of the speed at which physicians take their patients to transplant It's going to penalize in the same way it did for us on the CRC00H and KMT2A. We will have an update. This is the data. We may have some more to say at our investor event on MPM-one, but this is the data that we have in hand.

Speaker 2

And so we wanted to get it Obviously, out to you today, but we haven't really bottomed out on what else we would analyze for our R and For our Investor Day for in and around ASH. And maybe there was another question on it. Yes, for sure. For sure, right.

Speaker 4

Exactly.

Speaker 2

Right, Peter. Thank you. So look, I think we've said in the past, you need approximately 20 to 30 patients at the RP2D to File for breakthrough therapy designation. As you see here, this is 14 patients at the RP2D. So, right now, we don't expect that we would be able to Make that application.

Speaker 2

Obviously, that's something that's open to us at some point in time relative to our pivotal data, which is obviously coming. So, That's it. Thank you. Perfect. Thanks so much.

Speaker 2

Thanks, Peter.

Operator

Our next question is from Michael Schmidt at Guggenheim. Your line is open. Please ask your questions.

Speaker 4

Hey, guys. Good afternoon. Thanks for taking my questions. In the NPM1 cohort, How many patients had overlapping co mutations, other genetic alterations and potentially have had Received other target agents prior to receiving remimeneb? And how do you expect that dynamic to play out in the pivotal cohort and ultimately on the market?

Speaker 2

Yes, Michael, thanks for the question. So we didn't break out that data in the Swimmers Lane, but I'll tell you, as you noticed in the we did say that a lot of obviously a lot of prior therapy for these patients. In terms of co mutations, I think the vast majority, if not all, were co mutated. So there were obviously, there's variations on the theme of what we saw, but We didn't break that out, but I think suffice to say, we had most patients were co mutated. Yes, and it's obviously representative Of what you would think?

Speaker 4

Okay. And in order to how does that affect Potential sequencing of therapies, should the data be replicated in your pivotal study, if approved in your opinion?

Speaker 2

Yes, I think what you're getting at is whether or not physicians will look at targeting these specific mutations For treatment and obviously the paradigm for NPM1 at least in the unfit population Where the 5th population, they get chemo or they get VENASA upfront and then physicians look to target their mutations with either FLT3 or an IDH inhibitor. And we do expect that if these patients have those co mutations, that's what's going to happen in the real world and in our trial as well. So What ends up resulting and I think the remarks that I made suggest this that physicians will be reaching for 2nd or third line Reviveniv, after they've taken action against obviously frontline and then after they're going after their targeted mutation to the extent they have one. So I think the data that we presented today shows that, right? It shows that patients do extremely well, Treated in, call it, the 3rd line, 4th line setting on our drug.

Speaker 2

And as they Progress and get into very, very late lines of therapy, which we've had some patients also like that, they don't do as well. I think the targeting of these mutations will likely come before revenue. Thanks so much. Thank you. Our next

Operator

question is from Kalpit Patel at B. Riley. Your line is open. Please ask your question.

Speaker 4

Yes. Hey, good afternoon and congrats on all the updates today. Maybe a couple more questions related to the Made a good use of revimed. Now that you have all the post transplant data here, How are you seeing the median duration of treatment for revumentib between the KMT2A populations and the NPM1 populations, do you expect them to be very similar to each other?

Speaker 2

Yes. Jalpa, thank you for the question. I think, yes, I think we do think it's going to be very similar. It's interesting how the data converges a bit, right? So you have Patients in the KMT2A population that a great percentage go get a high overall response rate, Get taken to transplant and put back on drug and stay on drug and do very, very well.

Speaker 2

The speed at which they get a best response first and best response and then move to transplant It is noteworthy in KMT2A. It's a beat slower with MPM-one, which probably allows their accounts to recover, As I mentioned earlier, but the paradigm is seems to be similar, right, at least in relapsed refractory disease Where physicians are interested in putting them back on once you get to a CR, you take them to transplant and you put them back on drug. I think that's also new and it's a new paradigm, but it's actually a very positive Back pattern for the drug in terms of the ability to treat patients for a long time and keep them in remission. So we're actually very encouraged by what we're seeing, Both by from the efficacy standpoint and the tolerability and safety standpoint to allow this to be the new paradigm. So It's quite interesting how it's turned out to be pretty similar.

Speaker 2

Okay. And It's nice to see

Speaker 4

the additional responses in the NPM1 patient population. I'm just curious if you have any more NPM1 patients For that, I believe, July cutoff in

Speaker 2

that date in that Phase 1? Yes. Thanks for the follow-up. We do not. That is it.

Speaker 2

We are this is final data in terms of patients, that's all we have. We were looking to complete the pharmacokinetic work In the Phase 1, and we had talked about that in the past, and this was these are the remaining patients to accomplish that. Okay, perfect. Thank you. Thank you.

Operator

Our next question is from Justin Villein at BTIG. Your line is open. Please ask your question.

Speaker 4

Hi, thanks for taking the question and congrats on the progress here. Maybe a question just on the SAVE AML study. I think the abstract showed there wasn't much differentiation syndrome in here. Can you comment on whether you'd expect Differentiation syndrome to be reduced in the combination setting moving forward? Thank you.

Speaker 3

Yes. Thanks, Justin. The answer is yes. I mean, the data as we've discussed the data are highly encouraging. I think that Clearly, the combination with venazar of reviomedib with Winzen, a hydromethylating agent is extremely well tolerated.

Speaker 3

So, there's no reason to Expect that we would see a different pattern as we advance, for instance, as we advance combinations of then hypomethylating agent into earlier lines So, I think it's both expected and gratifying to see.

Speaker 4

Great. Thanks. And congrats again on the plenary for axotilumab. Anything additional we should look out for at ASH Beyond what we saw at the top line?

Speaker 2

Justin, I think, yes, thank you. We obviously have the plenary for axotilinab, which is Very exciting. I think we have 5 abstracts out today, so a lot of information saved As we talked about, but also some of the combinations and so we yes, just a lot of Interesting information coming your way and obviously we'll have lots to say at our event at ASH as well. So, looking forward to seeing everybody there.

Speaker 4

Great. Thanks for taking the questions.

Speaker 2

Thank you.

Operator

Our next question is from George Farmer at Scotiabank. Your line is open. Please ask your question.

Speaker 7

Hi, good afternoon. Thanks for taking my question. Neil, you mentioned that The 6.4 month DOR in the AUGMENT-one trial could get better. I'm wondering if it is possible it could get worse. We haven't seen any capital minor curves, so just wondering what your thoughts are there.

Speaker 7

And then also in the SAVE trial, alluded to a previous question about The myelosuppression, wondering if those patients got any growth factor support and if growth factors were effective. Perhaps maybe revumentum had an impact on recovery or anything like that, if you could comment?

Speaker 3

Sure. Thanks for the question. So with respect to the first question, we've modeled it out in our A bit of noise on the line, but with respect to our expectation is that the median DoR can extend over time with additional follow-up, right? So we've modeled that out, running various Sorry, I'm blanking on the word, but statisticians have molded out looking at various different scenarios and we See multiple different scenarios under which the median Dior could extend over time. The to the second point, not to the best of my knowledge With respect to stem cell or with respect to growth factor support, that's not our understanding.

Speaker 7

Okay, great. And then one more if I could on axetilumab. The IPF study, can you just speak kind of high level about the design of that trial?

Speaker 3

Sure. I'll take that. Yes. So as Michael said in his remarks, it's randomized Phase 2. It's randomized, 135 patients is the target sample size, randomized 2:one, active axitomab to placebo On a background of best supportive care.

Speaker 3

So, very succinctly, that is the study design. We think that it's At an efficient way to address the proof of concept question.

Speaker 4

All right.

Speaker 7

Is that a 6 month study, 52 weeks? 26 weeks.

Speaker 3

That's right. 26 week primary endpoint analysis. Okay. Good. Thank you.

Speaker 2

You're welcome. Thank you, George.

Operator

Our last question is from Joel Beatty at Baird. Your line is open. Please ask your question.

Speaker 2

Hi, this is Ben on for Joel. Thanks for taking the question. What gives you confidence that payers would support or payers would cover post transplant Maintenance revumented therapy is not in the FDA label? Yes. Thanks for the question.

Speaker 2

Well, look, I think the Experience physicians have in treating patients for AML and providing maintenance treatment to those patients Again, are at high, high risk of relapse. That is seems to be a very important treatment decision granted by the given by the or taken by the physician. And none of these relapsed refractory agents that have been approved have a maintenance label. So it's a sort of a tried and true experience with other agents that gives us confidence that this is something That physicians can do and payers will abide by. I think there's a pharmacoeconomic analysis, of course, that Supports this.

Speaker 2

These are not inexpensive therapies, but these are very seriously ill patients who aren't able To get to a steady state and so if you can keep them in remission for a long period of time And keep them out of the hospital. That's a very positive driver for any payer. So I also mentioned that this Kind of experience can get into the guidelines and you see it in the guidelines as well. And so payers tend to abide by those guidelines In making the reimbursement decision. So, I think there are multiple factors in support of this paradigm.

Speaker 2

And I also mentioned that these are rare diseases and so payer not one payer is impacted dramatically Or disproportionately, I should say, by a high price therapy being given over an extended period of time. So I think that's That all kind of factors into the fact when we hear from physicians that they do this and they have very little intervention From payers to stop this from happening, there seems to be a supportive setup. So that's what I can tell you.

Operator

That completes the Q and A section of the call. I will now hand back to Michael for closing remarks.

Speaker 2

Thank you, operator. Thank you all. We appreciate you tuning in tonight and we look forward to seeing you at our planned investor events, including The Cowen Fall Oncology Summit tomorrow and the Stifel Conference on November 14, as well as the ASH meeting in December that we talked a lot about today. And with that, I wish you a great evening. Thank you so much.

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