Q3 2023 Syndax Pharmaceuticals Inc Earnings Call
Good day, everyone and welcome to this index 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 <unk> head of Investor Relations at Index Pharmaceuticals.
Thank you operator, welcome and thank you all for joining US today for a review of its indexes third quarter 2023 financial and operating results for Shashank, Larry and with me. This afternoon to provide an update on the company's progress and discuss financial results and Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher President.
And head of R&D.
Let's go then Chief Finance financial Officer.
Also joining us on the call today for the question and answer session are Dr. Peter or Denmark, Chief Scientific Officer, and Doctor Angelilli Gangly 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 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 made represent our views as of today November 2nd so in each.
93, only a replay of this call will be available on the company's website www <unk> com following its completion.
That I am pleased to turn the call over to Michael Metzger, Chief Executive Officer Cindy.
Thank you Sharon and thank you to everyone joining us on the webcast. This continues to be an exciting year for <unk> and I look forward to sharing a number of updates with you on the significant progress we've made.
Throughout the third quarter, we delivered on key pipeline milestones that are highlighted on slide three including reporting positive topline agave 201 pivotal data of <unk> for the treatment of chronic graft versus host disease.
We also reported positive topline pivotal augment 101 data for <unk> in adult and pediatric patients with relapsed refractory <unk> rearranged acute leukemia together. These results put us on a clear path to becoming a commercial stage biopharmaceutical company in 2024 with two potentially first and best in class <unk>.
<unk>.
We are also happy to provide data today from additional relapsed or refractory NPM one patients that were enrolled in the final stages of the phase one portion of the augment 101 trial.
Neil will walk us through the data a little later in this call but in summary, we are encouraged by the 36% CR CRH rate and deep responses that we're seeing in the M. P. M. One population responses elicited by revenue minute.
And the NPM one population are durable with some patients in remission beyond 'twenty two months further supporting the rationale that revenue managed can provide a meaningful benefit to NPM, one patients and emphasizing is blockbuster commercial potential across both <unk> and NPM one acute leukemia.
We continue our positive momentum heading into the end of 2023 with a primary focus on completing two potential regulatory filings by year end and launching both drugs in 2024.
This will put us index in a very unique position to create value as a smid cap biotech company.
We will 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 few days ago, we initiated the NDA submission of <unk> for <unk> acute leukemia under the Fda's real time oncology review program or <unk>.
We view our tour as a significant benefit for the <unk> program it.
Complements our BTT and fast track status for <unk> and provides a more efficient review process to ensure that Ravi minutes is available to patients as early as possible.
Under our tour the sponsor has consistent engagement with the FDA throughout this submission process drugs or 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.
In accordance with FDA guidance for AML and in line with the approvals of other AML agents in the relapsed refractory setting we anticipate revenue will be granted full approval based on the results of augment 101 with our partner insight. We also remain on track to complete the BLA filing for <unk> by year end.
As you saw from our press release earlier today data from both the agave 201, and augment 101 pivotal trials, including post transplant maintenance data along with revenue men have combination data from the save trial will be presented at the Ash meeting in December.
Beyond the Congress presentations, we will also have the opportunity to share additional data from ongoing revenue met a combination trials at our ash.
Investor event, which will further reinforce <unk> compelling clinical profile and meaningfully add to its value proposition.
We are well funded with $379 million in cash as of September 30, our current balance sheet not only supports our planned commercial launches in the trials that we have outlined but also allows us to expand beyond our core registration indications and pursue select business development opportunities.
Now, let's dive into <unk>, our highly selective <unk> inhibitor I'll ask Neal to provide a recap of the results from the augment 101 pivotal trial speak to the Ash Abstracts and review the data from the <unk> one patients in the phase one portion of the augment 101 trial Neil Thank.
Thank you Michael I will now review the augment 101 pivotal data in relapsed or refractory <unk> acute leukemia, beginning on slide four.
As previously reported the independent data monitoring committee reviewed the data and recommended that the trial 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 two thirds of these heavily pre treated patients achieved a clinically significant responses, enabling many to receive <unk>.
Density curative transplant importantly, I proportion of responders in the trial were started on revenue amount of in the post transplant maintenance setting the desire for physicians to restart revenue amount of this post transplant maintenance speaks to its efficacy and tolerability and their belief that it may offer a better outcome for their cancer acute leukemia patients importantly, the one.
<unk> of these heavily pretreated patients to both respond to tolerate revenue amount of therapy also underscores its potential to be adopted into frontline combinations.
Turning to slide five the majority of patients in the efficacy Evaluable population, which include adult and pediatric AML and <unk> patients achieved a clinically significant responses to treatment with a high overall response rate of 63% CR.
CRH rate in this population was 23% the response rates observed in Kmt two AML, specifically were consistent with those in the overall efficacy evaluable population with 65% achieving a response in 24, 5%, achieving CR or CRH, the <unk> negative rate amongst VR CRH responders with <unk>.
Also impressive at 70%.
At the time of the data cutoff, the median duration of CRC rates responses six four months across the efficacy evaluable in AML populations with 46% or six patients remaining in response.
Of note. This is a kaplan meier estimate and the data will continue to mature over time. Therefore, the median deal or may extend beyond six four months with additional follow up.
Turning to slide six not only did we observe a high overall response rate of 63%, but 39% of responding patients preceded to bone marrow transplant, which is notably higher than the historical benchmark in this population of less than 5%.
Eight patients were transplanted prior to achieving CR CRH at the discretion of the attending physician clearly physicians had decided to wait a little longer prior to transplant than more of these patients could have achieved a best response CR CRH. For example, if all eight of these patients had achieved CR CRH then the rate would have been 37%.
71% of these patients 10 of 2014, either restarted revenue amount of ore 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 eight months on several of our continue on therapy, which we believe speaks to revenue amount a compelling overall clinical profile and the potential for long term maintenance in this setting.
The ability of revenue amount up to rapidly induce blocked the responses in heavily pre treated patients, thereby enabling them to undergo potentially curious have bone marrow transplant, followed by post transplant maintenance represents a potential paradigm shift in the standard of care in this setting we have resolution at the ash meeting that will highlight revenue manner for post transplant.
Maintenance, including patients on therapy in remission beyond 18 months.
The data from augment 101 indicate that <unk> is well tolerated and the safety profile is consistent with what is what was previously reported.
We believe that the emerging benefit risk profile of the amount of support that <unk> 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.
Initial data are forthcoming will be forthcoming later this year.
Turning to slide seven today, we announced encouraging data from three additional patients with <unk> mutated relapsed or refractory AML included in the phase one portion of the augment 101 trial for a total of 14 NPM one patients treated at doses meeting the <unk> criteria.
These patients who are enrolled in phase one to complete the pharmacokinetic characterization of rescue medicine. Among these 14 patients seven achieved a response to treatment for a 50% overall response rate.
514 achieved a CR or CRH, a rate of 36% and 100% of the Cri CRH responders were <unk> negative.
On slide eight you may see that these responses.
Our durable with four or five off the patients remaining in response three already beyond six months, one beyond 'twenty two months and one over a 30 month photography analysis.
<unk> also enabled 43% of NPM, one responders to proceed to transplant.
One of the patients who preceded to transplant I've been enrolled following the augment 101 protocol update which allowed patients to restart regimented post post transplant. This patient remains on revenue amount of maintenance at the time of the analysis.
Similar to the phase II results observed with the <unk> population revenue and that bodes well tolerated in patients with relapsed refractory <unk> one a.
No there were no grade four or five keeps you prolongation is no patients experienced more than great to differentiation syndrome, and no patients discontinued due to treatment related adverse events as Michael said earlier. These data continue to support our conviction that Rev. Humana will be an important treatment for MTM, one AML as well as from <unk> acute leukemias and we.
The MTM one pivotal trial results will be consistent with the data generated to date and highly supportive of a first to market approval the.
The pivotal cohort of the augment 101 trial continues to enroll relapsed refractory <unk> mutant AML patients. The trial is designed to enroll 64 patients in up to 20 pediatric patients. While the trial continues to recruit well in the U S and internationally, we now forecast completion of enrollment in the late first quarter early second quarter next year to do to a few <unk>.
High enrolling sites in Europe coming online later than we expected in the third quarter, 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 well.
We are now looking forward looking to make up for any potential shortfall at our sites, but it is difficult for us to predict the impact that the evolving geopolitical situations may have on Oklahoma. Nonetheless, we expect to be in a position to report data in the fourth quarter of 2024 Unimportance. We continue to look forward to a potential approval in 2025 based on an <unk>.
S NDA filing falling revenue minutes anticipated initial approval in <unk>.
Turning to slide nine.
In addition to sharing the augment 101 pivotal data at Ash, we look forward to Dr. <unk> Isa highlighting his save trial results in an oral presentation on Saturday morning. During the meeting. This is an investigator sponsored phase <unk> trial conducted by Dr. <unk> at the MD Anderson cancer Center evaluating them all oral combination of <unk> with <unk>.
In a fixed dose combination of decided then a set of <unk> in children and adults with relapsed refractory AML are mixed phenotype acute leukemias at the timing of the data cutoff. The trial was enrolling at the current monotherapy <unk> of 163 milligrams every 12 hours with a strong sip three or four inhibitor in total eight patients with.
Either <unk> or <unk> 98 mutations were enrolled in the trial, having received $2 five median prior lines of therapy approximately two thirds of patients received prior vanadic lacks all patients on a strong sip three <unk> four inhibitor.
We're on a strong set three or four inhibitor and were therefore treated with revenue and either 113 milligrams Q12, early or 160 milligrams 63 milligrams Q12 already seven of eight patients were Evaluable for response, all seven 100% achieved a response six of seven achieved the CRC and two of seven.
<unk>.
28% achieved a CR CRH importantly responses were observed across relapsed or refractory M. P. M. One came to <unk> 98 acute leukemia patients.
Three patients transition to hematopoietic stem cell transplantation. Following response and to continue in remission and have started maintenance as of the data cutoff. We are highly encouraged by the combined ability of revenue amount of a fanatical acts on the hypermedia hydro.
The hydro methylated agent in this trial. This combination was well tolerated the active doses, including the current monotherapy <unk> I'll now turn the call back to Michael.
Thank you Neal turning to slide 10, we believe that revenue method could form the backbone of treatment for patients with <unk> rearranged and <unk> mutant acute leukemias.
And as demonstrated by its compelling efficacy and safety profile, 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 <unk> across various settings of <unk>.
And NPM, one acute leukemias, we're collaborating with cooperative groups and leading investigators in addition to the clinical trials that Syntaxes conducted.
In addition to the save trial that.
Neal described earlier, we plan to present initial data from the beat AML and augment one or two trials in the fourth quarter at our planned investor event at Ash.
Phase one beat AML trial as part of our collaboration with leukemia, and lymphoma Society and revenue managers being combined with <unk> and is decided in to treat newly diagnosed AML patients who are unfit for induction chemotherapy.
Enrollment is ongoing in the dose finding stage.
Of the trial to confirm the <unk> for this combination and we continue to expect to share data on safety and efficacy from the trial at our Ash investor event.
The augment 102 trial is designed to assess the safety of <unk> in combination with standard salvage chemotherapy for patients with relapsed or refractory acute leukemia, we anticipate presenting an update on the initial safety and potential RP to deepen the trial at our Ash investor event.
We look forward to initiating a trial of <unk> in combination with standard of care intensive chemotherapy known as seven plus three in newly diagnosed patients with acute leukemia in late 2023 or early 2020 for this trial will also include an option for maintenance with <unk> monotherapy.
On the acute leukemia trials, we've laid out here, we are enrolling a proof of concept signal seeking phase one clinical trial in metastatic colorectal cancer based on compelling preclinical science supporting the role of the Menin <unk> interaction and beta Katina driven tumors. The trial is advancing nicely through the dose escalation phase and we are nearing an RFP.
We would perceive responses or prolonged stable disease is encouraging in this difficult to treat patient population with the market with a mono therapy and we expect to follow these patients to gather sufficient efficacy into 2024, we anticipate be able to provide an update on the progress of the dose escalation phase of the trial in the first quarter of 2024.
Sure.
Now to slide 11.
<unk> and <unk> in 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 12000, NPM, one mutant <unk> rearranged acute leukemia patients across various settings. We are committed to bringing these encouraging clinical benefits to even more patients.
As this remains an area with significant unmet need.
We believe that relapsed or refractory <unk> acute leukemias alone represent a $650 to $750 million market opportunity in the U S. Based on the estimated patient population duration of treatment and current pricing assumptions <unk> rearrangements represent approximately 10% of AML <unk>, which <unk>.
Insights into an incidence of approximately 2600, <unk> rearranged acute leukemia patients a very high percentage of whom are refractory to frontline standard of care treatments.
Just on the enthusiasm we are hearing from physicians and the potential to shift the treatment paradigm in <unk> to incorporate maintenance treatment post transplant. We believe the median duration of therapy across the treatment population would be approximately nine months and we believe the data generated in augment 101 support pricing competitive with or above.
Other targeted therapies in AML, such as flip III or IV <unk> inhibitors with no treatment options approved for these patients and no near term competition revenue met it could easily become the treatment of choice for all patients with <unk> acute leukemia based on obtaining the only age and disease agnostic label and Kmt <unk> acute.
Leukemia.
We expect that our first mover advantage and experienced physicians will gain treating their patients with Ravi Menon could extend meaningfully beyond <unk> and allow us to build a formidable franchise in the next few years.
Supported by the compelling NPM one data we presented today, we believe <unk> will also provide meaningful benefit in relapsed or refractory <unk> patients. Our market research suggests that if approved oncologists are likely to reach for revenue manifest either their second or third line agent of choice for patients with <unk> mutant AML.
We estimate that this population will be slightly larger than relapsed refractory Kmt to any acute leukemia population and based on our phase. One results. We also believe overall efficacy and treatment duration will be consistent between the <unk> and NPM one populations, having first mover access to two.
Two distinct market segments, and acute leukemias, Kmt each way and NPM one creates a total accessible population of $5 to 6000 patients in the relapsed refractory setting and an addressable market opportunity of approximately $1 billion to $1 billion $5 for <unk> in the U S alone.
We anticipate that Ravi Mehta will begin to carve out a dominant share of the relapsed and refractory NPM one market starting in 2025.
Now, let's dive into <unk>, our monoclonal antibody targeting the CSF one receptor beginning on slide 12.
In collaboration with insight, we shared positive results from the global pivotal Agave 201 trial evaluating the efficacy safety and Tolerability of <unk> and 241 patients with active chronic gvhd, whose disease had progressed after at least two prior therapies.
As a reminder, the trial met its primary endpoint of overall response rate by cycle seven day, one using the 2014 NIH consensus criteria for chronic gvhd across all three dose groups.
Overall response rate or overall, our <unk> was 74% at a dose of <unk> three milligrams per kilogram administered every two weeks. The responses were durable with a median duration of response not yet reached at the time of data cutoff.
60% of responders were still responding at one year.
<unk> was well tolerated in the trial with a low 6% rate of discontinuation and the most common adverse events were consistent with the on target effects that were observed in prior trials I.
I want to remind you that robust efficacy was observed despite the patient is being very advanced and heavily pre treated as an example, I would highlight that there are meaningful differences in patient populations between the <unk> hundred one trial and the reservoir rock Star trial, both of which targeted patients with chronic gvhd, who have received two or more.
All lines of therapy, notably patients in <unk> hundred 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 that receive jakafi.
Patients included in the reservoir trial.
We believe these these points of differentiation underscore just how impressive the agave to a one trial results are and point to the significant value <unk> could bring to patients if approved.
These results not only support the promise of <unk> safety and efficacy profile, but reinforced its potential as a first and best in class CSF, one our monoclonal antibody in chronic gvhd <unk>.
<unk> is the first investigational chronic gvhd treatment to target inflammation and fibrosis through the inhibition of disease associated macrophages and the <unk> hundred 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.
It may have on patients suffering from chronic graft versus host disease.
In collaboration with insight, 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 14000 U S 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 arent wholly addressed with current treatments. 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 <unk> 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 <unk> could provide an effective differentiated practice changing intervention for this underserved population.
<unk> 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 <unk> earlier in the treatment paradigm.
<unk> prevent organ damage before it occurs.
<unk> is an antibody drug drug interactions are expected to be minimal and <unk> unique mechanism of action may offer the benefit of being an ideal combination partner with standard of care therapies currently used for the treatment of chronic gvhd.
The opportunity to expand to ex U S markets and additional high value indications as well as combinations in earlier settings in chronic gvhd, both in adult and pediatric pediatrics could build significant additional value for <unk>.
We are looking forward to the initiation of additional trials of <unk> <unk>, including a 26 week randomized placebo controlled phase II trial in 135, idiopathic pulmonary fibrosis patients expected to begin by year end as well as a combination trial to be conducted by insight in chronic gvhd patients with <unk>.
<unk> in mid 2024.
I'll now turn the call over to Keith to review our financial results.
Thank you Michael let.
Let me take a few minutes to discuss our financial results for the quarter ended September 32023.
Turning to slide 14.
The results of our operations for the third quarter 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 third quarter 2023 report, which was filed earlier today on Form 10-Q.
I would like to point out that our net loss for the third quarter was $51 1 million.
Or <unk> 73 per share compared to a net loss of $35 4 million or.
Or <unk> 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&A and R&D combined with increased clinical and manufacturing expenses.
We ended the third quarter with $379 $3 million in cash equivalents and short and long term investments.
And $69 9 million shares and pre funded warrants outstanding.
Our balance sheet is expected to provide runway into the second half of 2025.
It allows us to appropriately invest to maximize the value of our pipeline and importantly, it also allows us to transition into a commercial stage organization in 2024.
Looking ahead I'd like to provide financial guidance for the rest of this year.
For the full year of 2023.
The company expects to research and development expenses to be $160 million to $165 million.
And total operating expenses to be $225 million to $230 million, both of which are inclusive of approximately $30 million of noncash stock compensation expense.
Note that this is a reduction from our prior guidance of $160 million to $175 million for R&D expense and $225 million to $240 million for total operating expenses.
With that let me now turn the call back over to Michael.
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 101, <unk> hundred one datasets as well as data from several other combination trials at the Ash annual meeting and our planned investor event by year end we.
We are excited to provide positive final phase one results for regimen of treatment in relapsed refractory <unk> patients further demonstrating its best in class profile and another important indication with high unmet medical need.
Pivotal data from these trials will serve as the basis for potential U S. Registrational filings, including an NDA submission in relapsed refractory Kmt <unk> acute leukemia for revenue.
And an insight initiated BLA submission and chronic gvhd for <unk> by year end 2023.
<unk> and <unk> have significant market opportunities with the potential to gain quickly gained considerable market share and have a meaningful act 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 that need.
It has been a transformational year for <unk> 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 <unk> 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, which people with cancer live longer and better than ever before I'd also like to thank our committed long term investors who can.
To share in our vision and support us in buildings index with that I would like to open the call for questions operator.
And you would like to ask a question. Please press star.
Star to raise your hand.
STAAR filed to raise your hand to ask the question.
Our first question is from Brad.
Stifel. Your line is now open please ask your question.
Hi, and thank you for the questions looking forward to Ash I.
I have a two parter on the same trial actually the all oral triplet, where you had the abstract its first when you speak to AML physicians do you get the sense Theyre looking to use off label combinations in the relapsed refractory setting.
We on the street that are anchored T monotherapy data.
Guess, what might that then mean about the ultimate opportunity in this treatment line and relapsed refractory as we think about efficacy percentage transplant maintenance et cetera, and then I have a follow up.
Yes, Brad Thanks for the question I'm going to ask Neil to make a comment.
Yes look thanks.
Obviously this is a preliminary dose ranging.
There's more work to be done we see the value in the data that Dr. He says generating a couple of different ways. So.
So first of all.
The.
The demonstration of the combinability of revenue manner with <unk> agents I think it's very important.
<unk>.
And the studies ongoing with revenue amount of being administered at full dose and.
One is as mentioned in the in the abstract and bear in mind is that historically, if you look at this population.
They're quite heavily pre treated most of them have actually failed vanadic clocks escalating agent.
And.
One would expect the response rate therefore to <unk> plus in HMA to be quite low actually probably less than 10% and here, we're seeing much much higher response rates and a 28% CR cri rate. So this is extra.
Incremental progress, albeit based on early data incremental progress.
For those patients.
Great and then the second one.
Yes.
Safety for the regimen I guess is this higher and more prolonged myeloid suppression than would be expected from the components.
How are you thinking about this too is as we think about the frontline than as a combo that might be a different patient population in terms of how myeloma depression might affect them. Thank you.
Yes.
Thanks for the question just continuing on.
Well as the authors themselves conclude.
The safety profile as what you would expect from van in the hyper methylated agent.
So theres no.
No.
The triplet can call. It a triplet appears to be extremely tolerate sits right four four.
Mmm pretreated patients not just going to your point about what does this mean as we advanced the combinations in earlier stage patients I think it is.
Signals.
Good things right.
Because if heavily pretreated patients can actually.
Tolerate the combination than 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.
Our evolving some of the data that we've presented today, we're highly encouraged for the opportunity to advance.
The amount of into earlier stage combination therapies.
Okay.
Thanks, Brett.
Great. Our next question is from.
Rama at J P. Morgan Your line is open please ask your question.
Hi, this is actually on for.
On a pump.
Thank you for taking my question.
What additional data are you planning to present at patch on augment 101, Kmt two way.
Versus what we already know from the topline data. Thank you.
Yes, Michael Thank you for the question.
So as we had previously said and I think we had said in the remarks.
Obviously, we presented topline.
And in recent days and will be at Ash, we have an abstract.
It came out today that explains that will have a presentation at ash.
At our Investor event, I think would be the data that's been topline is the data cut but we will have additional analyses that I think go into more specific detail around.
Around that particular data cut.
And then not to speculate specifically around what we're going to present, but I think there are some important analysis that will allow people to get a even deeper.
For what for what we presented previously.
Stay tuned, but we will have.
More data at Ash and then.
Again at our Investor day.
Excellent. Thank you.
Our next question.
Our next question is from Chris you pretax Goldman Sachs. Your line is open. Please ask your question.
Hi, good afternoon. Thank you so much for taking our questions. This is Charlie on for Chris just to kind of follow up on the last question I'm wondering if you have the same data cut for the augment 101 presentation at ash. So it sounds like we're going to assume the same 57 patients that we have 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.
<unk>.
Yes, Charlie Thank you.
You are correct. It is the same data cut at Ash I mean, we're very focused now on on getting our NDA filed and as you noted under our tour we have a.
Pretty rigorous and short timeline to complete the filing by year end. So it is a it is a rolling submission.
Agency has very specifically.
<unk> to our data plan, which again efficacy.
You see on the 57 patients with safety on the overall 94, which we outlined when we topline the data.
And confirmed through our pre NDA meeting at our or towards the beginning or towards process. So.
The data will be they see all the data, but there there is no new data cut.
Acquired from an efficacy standpoint, and the safety, obviously will be submitted as so that's fine.
That's the way to look at it.
Okay, great. Thank you so much.
Thank you.
Our next question is from Yigal <unk> of it. Please on mute yourself ask your question.
Hi, Tim This is <unk> on for Yigal, Thanks for taking my question.
Just had one on the on the post transplant setting data you'd shared it seems like youre getting very long durability.
In terms of patients staying on drug for long periods of time post transplant, which is great. I guess, how are you thinking about the commercial opportunity sort of on average in terms of duration of treatment in the context of the.
<unk> transplant.
Thanks.
Yeah sure. Thanks for the question I'm going to turn it over to Angela to answer that please.
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.
Based on the data we are generating.
And they see that there's an opportunity to treat patients in the post transplant maintenance setting the judge is able to get patients to deep durable responses.
And they see no.
No downside for continuing them on therapy after transplant.
And I think would be to keep them on as long as possible, but the standard today is.
Assumed to be close to close to two years, obviously not every patient will achieve that in that every patient.
I was able to.
To successfully receive a transplant.
So we estimate that conservatively that duration on average for being close to 18 months.
Okay. That's very helpful. I guess, a conceptual question on the same topic.
What's the decision, making forward to position behind choosing <unk>.
Treatment in the post transplant setting as a disease progression.
Is there a pointed which they kind of determined the benefit.
Maybe.
Barring overtime.
Yes, thank you I'm going to risk off.
The disease progression.
Yes.
So Neil why don't you comment on it yes. Thanks. 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 has consistently been very good the feedback, we've obviously talked to investigators and other physicians about this.
They are very keen when we speak with them first of all they wanted this option just to remind you. They wanted this option in the city. It wasn't there in the earlier part of the study and we included it in phase III.
At the request of the investigators.
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. So they took about two years right for instance, but in fact.
This evidence to suggest the patients could stay on longer than that as well, so I think as long as patients.
And remember that these patients are extremely high risk very heavily pre treated that came through to a cohort.
We've presented that we reiterated today very heavily pretreated and therefore.
Theres no way to physicians and looking at it it's why take the risk of the patients or 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 why not just keep the patients on the drug that's the feedback that we're getting.
Got it very helpful. Thanks very much.
You're welcome thank you.
Our next question is from Phil and Joe Pagan.
<unk> Cohen your line is open please ask your question.
Good afternoon, a couple of questions first congrats on the 36% CR series trade with the three additional patients.
The pivotal trial and Pam one for every minute could you discuss in a bit more detail, what's the implications of the 16% of enrollment coming out of Israel is it.
This suspicious would be welcome follow up data will be lost.
Does that impact the timelines and.
The number of patients that you need to enroll.
Yes, thanks for the question so.
Look I think.
It's unfortunate set of events going there.
Our trial sites are still up and running.
In Israel the centralized so we have.
Obviously, good control over the data not the issue.
Implications, we think are hard to get a little bit hard to predict but we have a lot of other sites and we're doing quite well with enrollment and 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 first quarter early second quarter. So is it.
That's a little bit unfortunate, but but these as I said or Neil 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.
Got it that's helpful. And then a follow up question on the safe trial, if we'd be abstracts said that enrollment.
Continued and save an additional or updated data will be presented at the meeting.
What can we.
We expect in terms of patients at dose level one.
I think there were two in the abstract would there be another four dash or could those helpful. One enroll beyond the six that were enrolled that dose levels there.
Yes, Phil Thanks for the question.
It's little bit hard to answer at this point I think they are 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 quite strong and striking.
They are looking forward to expanding to additional.
Patients and that will be obviously presented at at at.
At Ash in the in the presentation, but.
But I can't give you specific numbers on how many patients will be expanded to I just don't have that detail.
Fair enough thanks for taking my questions.
Yes. Thank you so much.
Our next question is from Jason at Bank of America. Your line is open. Please ask your question.
Hi, This is Alexander <unk> and Anthony Thank you for taking my question.
Sort of data do you think is necessary before they can you can start to feel confident about.
Minutes comment ability profile, what do we need to see in terms of both safety and efficacy. Thank you.
Yeah. Thanks for the question.
Well look I think the.
The data that we generated to date, both as a monotherapy and now in <unk> and for <unk> really is.
Good source of.
Or I should say underpins well, what we would expect to see a contribution of components right. When you think about combining drugs.
Such as with <unk> and with chemotherapy. So we feel very confident that we have best in class monotherapy data and Thats a good starting point with combinations first things first that Neil made comments about this you need to be able to combine these drugs safely and effectively but full dose monotherapy dose getting to those levels.
A combination is extremely important and to save information to say trial information that came out today.
He supports that we'll have data at ash.
Sure.
With the beta for the beat AML trial, which is frontline patients to save trial, that's in relapsed refractory patients, but <unk> 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 would hope to be as good or better than what they see in the doublet.
That's that's what we're looking for and I would also say.
<unk> negativity as 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 Mardi negativity and Thats something we will look at in these combinations as well where patient.
Patients are not necessarily getting to full <unk> negative status. So there is those are the types of things that we'll look forward and we expect to have meaningful data for the end of the year or two.
To elucidate all that.
Our next question is from Peter Lawson at Barclays. Your line is open. Please ask your question.
Great. Thanks, so much thanks for the update.
On patients just.
Do you have enough data now to file for breakthrough designation.
Can we get an update this data at the Investor Day and then.
Ah patients going on to transplant.
Cause a downdraft in the CR Cri.
CRH rate in a pivotal trial.
Thank you.
Yes, Peter Thank you.
So I think you had a couple of different questions here.
One was taking it in reverse order here so.
Could patients go on to.
Do we see patients go to transplant I think the answer the NPM one patient I think the answer is obviously, yes, you can see that in the swimmers lane.
That we have on our slides as well as.
We've mentioned in the remarks, so patients are going to transplant three of the patients have to 14 went to transplant.
Many of them are staying on treatment.
Treatment for and also in remission. So I think that is that.
That is an important fact pattern also important to note our what we saw in the phase one sorry for the pivotal trial four Kmt <unk> Neil mentioned in his remarks, the the number of patients who didn't reach complete count recovery. So it didn't reach the our CRH as best response and we.
Taken to transplant very quickly that.
That actually ended up penalizing us a bit on the CRC RH rates as dealers marked it could have been as high as 37%. If all those patients had converted and Navy didn't go to transplant as quickly what we're seeing with NPM. One 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 Kmt <unk> younger patients.
We're actually not seeing if you look at the data we are not seeing patients.
CRP or incomplete hematological recovery points and so what youre seeing is all of our patients are <unk> and.
<unk> 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 is in NPM one patient so.
We don't think actually that's going to meaningfully impactful in.
The phase II in fact, we see it as the opposite we see that the <unk> could actually be more reminiscent of what we're seeing now it's in the mid <unk> or higher.
On NPM, one we'll have to see what the data bears out, but we don't think that.
Same treatment paradigm and in terms of the speed at which physicians take their patients to transplant is going to penalize them. The same way it did.
For us on the CRC our agent <unk>.
We will have an update.
This is the this is the data we may have some more to say at our investor event on NPM one but this is the data that we have in hand, and so we wanted to get it obviously out to you today.
But we haven't really bottomed out on what what else. We would we would analyze for our R&D day for our Investor day four.
In and around Ash and maybe there was another question on it.
Yes.
Right exactly right Peter Thank you so.
So look I think we've said in the past you need approximately 20% to 30 patients at the <unk> to file for breakthrough therapy designation.
As you see here. This is 14 patients at the break at the RP Judy So.
Right now we don't expect that we would be able to make that application. 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. Thank you so much.
Yes.
Our next question is from Michael Schmidt Guggenheim. Your line is open. Please ask your question.
Hey, guys. Good afternoon, thanks for taking my questions.
In the NPM one cohort.
How many patients had.
Overlapping call mutations other other genetic alterations and potentially you have had.
<unk> other targeted agents prior to receiving Remy manner, and how do you expect that dynamic to play out in that pivotal cohort and ultimately on the market. Thanks, so much.
Yes, Michael Thanks for the question. So we didnt break out that data in the in these swimmers.
Swimmers lane.
I'll tell you as you noticed in the we did say is that a lot of obviously a lot of prior therapy.
Are these patients.
In terms of co mutations I think the vast majority if not all were co mutated. So there were yes.
Obviously theres 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 muted.
Okay.
Yes.
As the representative of <unk>.
What you would think.
Okay and in order to how does that affect potential sequencing of therapies should the data be replicated in the pivotal study.
Approved in your opinion.
Yes, I think what youre getting at is whether.
Whether or not physicians will look at targeting the specific mutations.
For for treatment and obviously the paradigm for NPM, one at least in the unfit population or the hip population they get chemo or they get then as upfront and then physicians look to target their mutations with either three or an <unk> inhibitor.
And and we do expect that if these patients have those computations thats whats going to happen in the real world and in our trial as well. So what ended up resulting in I think the remarks that I made suggest this that physicians will be reaching for second or third line.
<unk> 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.
<unk> treated in call it the third line fourth line setting.
On our drug.
And as they.
Progress and get into very very late lines of therapy, which we've had some some patients also like that.
They don't do as well so.
I think the targeting of these mutations will likely come before recognize.
Thanks, so much.
Thank you.
Our next question is from Calvert to tell at B Riley. Your line is open. Please ask your question.
Yeah, Hey, good afternoon, and congrats on all the updates today.
Maybe a couple of more questions related to the maintenance use of recommended.
Now that you have all the post transplant data here.
How are you seeing the median duration of treatment for revenue.
Between the Qantas AIA populations and the MTM one populations.
Expect them to be very.
Very similar to each other.
Yeah, John Thank you for the question I think yes, I think we do think it is going to be very similar it's interesting how the data converges a bit right. So you have pay.
Patients in the <unk> population that great incentives go get a response high overall response rate.
<unk> taken to transplant and put back on drug and stay on drug do very very well the speed at which they get a best respond first and best response, and then move to transplant is noteworthy and <unk>, it's a beat slower.
With NPM, one, which probably allows their accounts to recover as I as I mentioned earlier, but.
But the paradigm is seems to be similar at least in relapsed refractory disease, where where physicians are interested in putting them back on once you get to a CR.
Are you take them to transplant and you put them back on drug.
I think that that's also new and it's a new paradigm, but its actually a very positive.
That 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 the App from the efficacy standpoint, and the Tolerability and safety standpoint to allow this to be the new paradigm. So it's it's quite interesting how it's turned out to be pretty similar.
Okay and then.
It's nice to see the additional responses in the NPM one patient population I'm. Just curious if you have any more NPM one patients after that I believe July.
Quite often more data in the phase one.
Yes, thanks for the follow up we do not that is it.
This is final data in terms of <unk>.
Patients. That's all we have we were looking to complete the pharmacokinetic work.
In the phase one 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.
Our next question is from Justin.
Your line is open please ask your question.
Hi, Thanks for taking my question and congrats on the progress here maybe.
Maybe a question just on the save AML study I think the abstract showed there wasn't much differentiation syndrome sitting here can you comment on whether you would expect differ.
Differentiation syndrome.
B reduce in the combination setting moving forward. Thank you.
Yes, Thanks Justin.
The answer is yes, I mean the data.
We've discussed the data are highly encouraging and I think that.
Clearly the combination with <unk> revenue amounted with with them.
Lighting agent is extremely well tolerated. So there's no reason to suspect that.
We would see a different pattern as we advance for instance, as we advance combinations have been methylated agents into earlier lines of therapy. So.
I think it's both expected and gratifying to see.
Great. Thanks, and congrats again on the plenary for exit toll map anything additional we should look out for at Ash beyond what we saw at the top line.
Justin I think yes. Thank you.
Obviously have the plenary at <unk>, which is very exciting.
I think we had five abstracts out today, so a lot of information save.
As we talked about but also some of the combinations.
And so just a lot of interesting information coming your way and obviously, we will have lots and lots of say at our event at ash as well so I'm looking forward to seeing everybody there.
Great. Thanks for taking my questions.
Thank you.
Our next question is from George Farmer at Scotia Bank.
Is open please ask your question.
Hi, good afternoon, Thanks for taking my question.
Neil you mentioned that.
Six four months.
And the augment one trial.
Could you get better I'm wondering if is it possible could get worse, we haven't seen any kaplan Meier curve. So just wondering what your thoughts are there and then also in the save trial.
Alluded to a previous question about the miles depression wondering if those patients got any growth factors support and growth factors were effective.
Perhaps maybe <unk> had had an impact on on on recovery or anything like that if you could comment thanks.
Sure. Thanks for the question so.
With respect to the first question are we model it out.
Theres been a noise in the line but.
With respect to our expectation is that.
The median DLR can extend over time with additional follow up right.
So we've modeled that out.
Running.
Various.
Sorry, I'm blanking on the words, but statisticians have modeled without looking at various different scenarios.
We.
<unk> multiple different scenarios under which the median dor extend over time.
To the second point.
Not to the best of my knowledge with respect to stem cells are with respect to growth factors support.
Yes.
Not our understanding.
Okay, Great and then one more if I could on X <unk>.
PFS study can you just speak kind of high level about the design of that trial.
Sure.
Yes.
I'll take that yes, so as Michael said in his remarks.
A randomized phase II.
It's randomized 135 patients with a target sample size randomized two to one.
Active actually tell them up to placebo on a background of best supportive care. So very simply that is the that is the study design, we think that it's.
And efficient way to address the proof of concept question.
Is that a six month study 52 weeks six weeks, that's right 26, 26 week primary primary endpoint analysis okay.
Thank you.
Youre welcome. Thank you George.
Our last question is from Joel Beatty of Baird. Your line is open. Please ask your question.
Hi, This is Ben on for Joel Thanks for taking the question.
What gives you confidence that payers would support payers recover post transplant maintenance revenue management therapy, if not not in the FDA label.
Yes, thanks for the question.
Well look I think the experienced physicians have been treating patients for AML and.
Providing betas.
Maintenance treatment to those patients who again are at high high risk of relapse that is seems to be a very important treatment decision granted by the given by the.
Are taken by the physician.
<unk>.
None of these 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 will abide by it I think.
Theres a pharmacodynamic analysis of course that supports this.
These are not inexpensive therapies, but this is these are very seriously ill patients too.
Aren't able to.
To get to.
No.
Our steady state and so if you can keep them in remission for a long period of time.
A hospital, that's a very positive driver for any payer so.
I also mentioned that debt.
This kind of experience can get into the guidelines and you see it in the in the guidelines as well and so payers tend to abide by those guidelines and in.
<unk> been making the reimbursed reimbursement decisions. So I think there are multiple factors in.
In support of.
This paradigm.
And I also mentioned that these are rare diseases, and so payers not one payer has impacted dramatically or disproportionately I should say by the high priced therapy be given over an extended period of time, So I think thats that all kind of factors into that.
When we hear from physicians that they do this in a very.
Very little.
<unk> from from payers to to stop this from happening and there seems to be a supportive supportive setup. So that's that's what I can tell you.
That concludes the Q&A section of the call I'll now hand back to Michael for closing remarks.
Yes. 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 for oncology Summit Tomorrow, and the Stifel Conference on November 14th as well as the Ash meeting in December that we talked a lot about today.
With that I wish you a great evening. Thank you so much.
Okay.
Yes.
Okay.
Okay.
Thanks.
Yes.
Okay.
[music].
Yes.