Q2 2023 Syndax Pharmaceuticals Inc Earnings Call
Section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC.
Forward looking statements made represent our views as of today August 3rd 20.
These three only a reported this call will be available.
So excuse me a replay of this call will be available on the company's website Ww that sendak dot com. Following its completion with that I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer.
Thank you Sharon and thank you all for joining the webcast.
This is a transformational time for US index, we are making excellent progress executing on our milestones and corporate priorities all of which put us on a path to becoming a commercial stage biopharmaceutical company with two potentially best in class products throughout the second quarter, we continued to deliver on our development strategy and we.
Started off the third quarter in a great position, having recently reported positive pivotal Gaba <unk> hundred one data with <unk> in chronic graft versus host disease, we look forward to presenting the full agave 201 dataset at a future medical meeting.
As you can see on slide three we are looking forward to reporting data from the <unk> population of the augment 101 trial of <unk> in acute leukemia is later this quarter further we expect to have data from several several of our trials. The revenue method by by year end, which we believe could meaningfully add to its value proposition.
And support its best in class profile.
Once we have pivotal data from both revenue.
And <unk> in hand, <unk> will be in a very unique position as a smid cap company with the opportunity to submit two potential regulatory filings by year end and if approved launch both drugs in 2024.
We are well funded with $418 million in cash and equivalents as of June 30.
This amount of cash not only fund our planned commercial launches and the trials we have laid out on slide three but also enables us to expand beyond our core registration indications and selectively pursue business development opportunities.
We continue to evaluate earlier stage targeted oncology compounds to add to our pipeline, but as we have previously conveyed our board our bar for consummating a transaction as high as any new opportunity, we need to be differentiated and create substantial future value to align with our long term corporate strategy.
Let's now turn to slide four to dive into revenue are highly selective <unk> inhibitor, our pivotal augment 101 trial evaluating <unk> in patients with relapsed refractory <unk> mutant or at Kmt <unk> rearranged acute leukemia is ongoing we continue to expect to report data from the interim Kmt.
<unk> rearranged acute leukemia patients in the augment 101 pivotal trial in the third quarter of this year, which could serve as the basis for our U S regulatory filing by year end.
The phase II portion of augment 101 was designed as three single arm pivotal trials with distinct patient populations that enroll independently.
These populations include Kmt <unk> rearranged ALLL, Kmt <unk> rearranged AML and <unk> mutant AML each trial is enrolling patients aged one month or older.
The primary endpoint of these of each of these is the percentage of patients achieving CR CRH with secondary endpoints, including durability of CR CRH response transfusion independence overall survival and safety.
Patients, who undergo transplant have the opportunity to continue treatment with <unk>. Following successful in graft meant which could be an important maintenance option for these patients given that they are at a high risk of relapse.
As a reminder, in the phase one experience we have had patients remain on treatment and response for nearly two years, which is possible due to revlimid revenue minutes compelling safety and Tolerability profile.
As previously reported in December 2022, we received breakthrough therapy designation covering all Kmt <unk> rearranged acute leukemia patients and subsequent conversations with the FDA. We reached agreement whereby we will pool a subset of data generated from the from the AML and Alo Kmt two cohorts into a single <unk>.
NDA filing aimed at an indication to treat adult and pediatric relapsed refractory acute leukemia patients with <unk> rearrangement we.
We expect to provide top line data in relapsed refractory adult and pediatric <unk> patients this quarter and to file an NDA for this population by the end of 2023.
Our goal for the top line data disclosure will be to provide enough data on efficacy and safety. So that all stakeholders understand the drug profile, while still preserving enough of the details for presentation at a future medical meeting.
Topline release will likely include the primary endpoint along with secondary endpoints of interest.
Separately, we continue to enroll relapsed refractory <unk> mutant AML patients and expect completion of enrollment of this cohort by year end.
As we look at the competitive landscape and engaged with experts in the field, we believe <unk> compelling clinical profile as demonstrated in the robust phase one experience published in nature in March and highlighted on slide five positions revenue method to not only be a first in class, but also a best in class treatment.
As a reminder, the phase one augment 101 data demonstrated that patients who received a median of four prior therapies. The CRC array treated in both the Kmt <unk> subsets at the <unk> was 27% with a median duration of response of $9 one months.
Experts in the field also point to the high <unk> negative rate of 78% among patients achieving a CR CRH since <unk> negativity is associated with improved outcomes of potential curative bone marrow transplant.
While the phase one trial wasn't designed for re treatment. Following transplantation. Several of these patients went on to receive <unk> maintenance therapy in the compassionate use setting and thus we included this option in the pivotal portion of the augment 101.
At the request of the treating physicians.
Turning to slide six.
We believe that <unk> could become the backbone of treatment for patients with Kmt <unk> arrangement and NPM, one mute and acute leukemias.
Based on <unk> compelling efficacy and safety profile, our clinical strategy has expanded beyond the relapsed and refractory setting into earlier settings, and post ramped and post transplant maintenance, including combinations with approved therapies. In addition to the clinical trials. That's indexes conducting we are working with cooperative groups and leading investigators.
Gators to further accelerate the generation of evidence of clinical benefit seen with revenue across various settings at Kmt <unk> and MTN, one acute leukemias, let me take a minute to highlight these for you.
Starting with the phase one beat AML umbrella trial.
Revenue met him as being combined with <unk>, <unk> and <unk> to treat newly diagnosed AML patients who are unfit for induction chemotherapy as part of our collaboration with the leukemia and lymphoma Society.
Enrollment is ongoing and we continue to expect to receive data on safety and a potential <unk> from the trial by the year end 2023.
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 expect to provide an update on the initial safety data and potential <unk> from the trial by year end 2023.
The safe trial is an interesting combination trial of all of an all oral regimen regimented within collector and in covey and oral hypo methylated agent in relapsed refractory acute leukemia being led by Dr. <unk> at MD Anderson Anderson Cancer Center.
In the intercept trial is enrolling patients as part of the Master clinical trial led by the Austral Asian leukemia and lymphoma group.
It is designed to explore the activity of revenue.
As monotherapy maintenance in patients with AML, who are <unk> positive disease following initial treatment and.
And finally, we plan to initiate a trial of <unk> in combination with standard of care intensive chemotherapy known as seven plus three in newly diagnosed patients with acute leukemia by year end 2023. This trial will also include an option for maintenance with <unk> monotherapy.
Turning to slide seven.
Currently no FDA approved therapies targeting <unk> or NPM, one acute leukemias, a population that together represents up to 40% of AML patients.
Including the expansion opportunities, we see the potential to address upwards of 12000 NPM one in <unk> acute leukemia patients across various settings. This is an area of significant unmet need and we are committed to bringing these encouraging clinical benefits to even more patients.
In addition to the market opportunity in acute and acute leukemia.
We're also exploring the use of <unk> as a <unk>.
Treatment in solid tumors based on compelling preclinical science supporting the role of the men and MLR, one interaction and beta katina and driven tumors to that end, we are enrolling a proof of concept signal seeking phase one clinical trial in metastatic colorectal cancer.
The trial is proceeding through the dose escalation phase and we would view responses or stable disease as promising in this difficult patient population we expect.
To provide an update on the progress of the phase one trial before year end 2023.
I will now ask Neal to provide a brief recap of our recently reported pivotal data for <unk> Neil.
Hey, Michael moving NASDAQ until about a monoclonal antibody targeting the CSF one receptor beginning on slide eight I'll.
I'll provide a brief recap as I expect that many of you joined us for the recent data call.
Last week, we shared positive results from our global pivotal <unk> trial evaluating the efficacy safety and Tolerability of back filling them up and 241 patients with active connect gvhd, whose disease had progressed after.
Two prior therapies.
All three dose cohorts of agave till one met the primary endpoint of overall response rate by FICO seven day, one using the 2014 NIH consensus criteria for chronic gvhd.
Patients were stratified at baseline based on prior exposure to Ibrutinib Rux, Loopnet, a bear market deal as well as disease severity and then treated until progression.
The primary endpoint of the <unk> trial was objective response rate by cycle seven day, one with six months of treatment. The trial randomized patients to one of three treatment each investigating a different dose.
These were <unk> three milligrams per kilogram or one milligram every two weeks and three milligrams per kilogram every four weeks.
Because macrophages play an essential role in maintaining physiological homeostasis. These regimen were chosen until that time for recovery of the macrophage population, thereby potentially minimizing adverse events, while maintaining robust efficacy.
Is there a 0.3 milligrams per kilogram dose selected in consultation with the FDA as an intermediate to represent the lower end of the range that we've explored in a phase one trial of responses were observed in patients who received <unk> five and <unk> five milligrams per kilogram every two.
This is also supported by PK PD data from a previous phase one trial in healthy volunteers.
After six months on trial patients.
0.3 milligrams per kilogram and one milligram per kilogram doses the option to switch to a dose proportional once monthly regimen.
Turning to slide nine I want to reemphasize.
Rather our excitement around the overall success of the trial all three cohorts in the agave to one pivotal trial met the primary endpoint of overall response rate and response rate was 74% in patients treated at <unk> three milligrams per kilogram of RMB, 267% in patients treated at one milligram per kilogram every two and 50% in.
At three milligrams per kilogram every four weeks.
While we have not yet annualized exposure response relationship. These data support our belief that lower doses. Given every two weeks to provide a greater opportunity for macrophage recovery between doses and may be key to improve tolerability as well as higher responses, particularly at <unk> three milligrams per kilogram dose level.
As I just mentioned at the <unk> three milligram per kilogram dose dose level. The response rate by cycle 70, 174%. Moreover.
The observed responses were durable with a median duration of response not yet reached at the time of data <unk>.
60% of patients who responded back filling up we're still responding at one year.
The responses were accompanied by a reduction in symptom burden as measured by the modified lease symptom scale <unk> was well tolerated with a low rate of discontinuation.
And the most common adverse events were consistent with the on target effects that were observed in prior trials.
On slide 10, I'd like to highlight that robust efficacy was observed. Despite the fact that these patients were very advanced in heavily pre treated. It is notable that patients included in the agave to own firewall more advanced more heavily pretreated patients included in pivotal trials with the approved agents.
This slide shows the cross study comparison with Rockstar pivotal trial of <unk> with targeted a similar population of patients with chronic gvhd received two or more prior lines of therapy.
See there are meaningful differences in patient population between the reservoir rock Star trial, and the exits in the <unk> one trial.
Patients in the agave to own trial had a longer median time since diagnosis.
More severe chronic gvhd and as the season more prior lines of therapy, including a greater number of patients that received jakafi.
We believe that these important 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.
Ill turn the call back to Michael.
Thank you Neil.
Slide 11 details the market opportunity for <unk>.
We estimate that approximately 14000 U S patients suffer from chronic gvhd, 50% of whom require treatment beyond second line due to disease progression inadequate response or disease manifestations that arent fully addressed with current treatments. Unfortunately, no cures for this advanced population of chronic gvhd patients.
Following initial treatment with corticosteroids patients are cycled through a variety of additional therapies essentially patients may be treated with several of the approved therapies. So 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.
The successful commercial launches of Jakafi and <unk> speak to the unmet need in chronic gvhd that translates to a large commercial opportunity.
We believe that <unk> could provide a differentiated effective and practice changing intervention for this underserved population.
<unk> ability to suppress monocyte derived macrophage activation and proliferation may provide more comprehensive control of the disease and currently approved therapies.
Not only is this is a key differentiator, but it also supports moving <unk> earlier in the treatment paradigm to potentially prevent organ damage before it occurs.
<unk> unique mechanism of action May also offer the advantage of being an ideal combination partner with standard of care therapies. Currently used for the treatment of chronic gvhd as there are no theoretical concerns in terms of drug drug interactions and overlapping mechanisms of action.
Combinations in earlier settings, both in adults and pediatrics as well as the opportunity to expand to the ex U S markets could build significant additional value for <unk> in chronic gvhd.
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 June 32023.
Turning to slide 12.
The results of our operations for the second 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 second quarter 2023 report.
Which was filed earlier today on Form 10-Q.
I would like to point out that our net loss for the second quarter was $44 6 million or <unk> 64 per share.
Compared to a net loss of $37 6 million or <unk> 62 per share for the comparable period last year.
This difference in our net loss was largely driven by an increase in employee related expenses and professional fees within both SG&A and R&D.
We ended the second quarter with $418 $3 million in cash equivalents and short and long term investments 60.
$69 7 million shares and pre funded warrants outstanding.
Our balance sheet is expected to provide runway into the second quarter of 2025, which allows us to appropriately invest to maximize the value of our pipeline and pursue potential business development opportunities to build the pipeline.
Importantly, it will also allow us to transition into a commercial stage organization in 2024.
Looking ahead I'd like to provide financial guidance for the third quarter and full year 2023.
For the third quarter of this year, we expect GAAP research and development expenses to be 39% to $43 million.
And total operating expenses to be $57 million to $62 million.
For the full year 2023, the company continues to expect research and development expenses to be $160 million to $175 million.
Total operating expenses to be $225 million to $240 million, which is inclusive of approximately $30 million of noncash stock compensation expense.
With that let me now turn the call back over to Michael.
Yes, Thank you Keith.
Before opening up to questions I'd like to briefly summarize what we presented today in the near term we remain highly focused on delivering quality data readouts for our pipeline and we're looking forward to reporting our next pivotal readout data from the <unk> population and the augment 101 trial later this quarter we.
We expect pivotal data will serve as the basis for potential U S. Registrational filings by year by year end 2023 for our two lead drug candidates both of which have the potential to make a significant impact on patient care in each setting and build considerable market share. In addition, we continue to explore ways to capture the maximum value of our current pie.
<unk> by expanding into opportunities beyond the initial registration indications in doing so we aim to bring the encouraging clinical benefits of our lead candidates to even more patients in need.
It has been an exciting year to date for <unk> and we expect this positive momentum to continue in the coming months with critical value generating milestones on the horizon.
I remain confident that we have the expertise and resources to execute on our goals and on the strategic long term vision that will allow us to successfully transition to a commercial stage biopharmaceutical company.
As always I would like to express our sincere appreciation to the index team collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs as all of you who help us to achieve our mission of realizing a future in which people with cancer live longer and better than ever before and also like to thank our committed long term.
Investors, who continue to share our vision and support us in building <unk>.
With that I'd like to open the call for questions.
Operator.
At this time, if you would like to ask a question. Please press star one on your Touchtone phone.
You may remove yourself from the queue at any time by pressing star two.
Once again that is star one to ask a question, we'll pause for a moment to allow questions to queue.
The first question today comes from from Phil Nadeau with TD Cowen. Please go ahead.
Good afternoon, thanks for taking our questions and congrats on the progress.
From us first on the upcoming pivotal data in the <unk> cohort.
You disclosed the statistical requirements for that cohort to be positive as they were.
Response rate that has to be excluded or below the lower bound of the 95% confidence interval in order for data technically to be positive.
Yes, Thanks, Phil for the first question.
We have not disclosed.
The lower bound nor that target rates of the statistics, we haven't we haven't talked about I think people have asked us sort of what's the regulatory bar.
Which of course is a little bit of an open question.
And generally our guidance is that we look at the precedent of what has been approved in this space in AML.
I think the lower end of that guidance has been about 20% Cri CRH.
And obviously if people have done better than that somewhere between 20%, 30%, but we haven't given specific guidance.
On the lower bound and what the target is for the trial.
Second question on the pivotal study I think most investors are going to use the Kmt <unk> data as a proxy for what will be shown in the NPM one population.
Next year is there a reason why we shouldnt do that do you think that is a fair.
Fair assumption that what you've shown Kmt <unk> likely to be repeated and pay more.
Thanks for the question, Yeah look I think our phase one experience was that the data looked the same very very similar to the point estimate was 27% at the <unk>. So.
That rationale would make some sense to us and so.
Sure I think it's reasonable to think that they would be roughly the same.
Great and then last question from Us on <unk>.
The press release.
So is that <unk> is going to receive the safety data.
The recommended phase II dose.
2023.
Do you plan to disclose it when you receive it or is there a specific venue at which investors will learn about the initial results from BMO.
Yes. Thanks for that question, Phil the beat AML trial is obviously, a cooperative group trial and so we.
We have close collaboration with that group.
We have the expectation that we will have some information related to safety and the <unk>.
Before the end of the year and we will look for a way to communicate that appropriately, but we haven't committed to.
Venue that will be done it.
Great. Thanks for taking my questions.
Thank you Phil.
The next question comes from <unk> Rama with Jpmorgan. Please go ahead.
Hey, guys. Thanks, so much for taking my question and congrats on the progress and look forward to the upcoming updates.
Maybe two quick ones from me so as we think about agave tool one data the full update later this year.
Can you remind us of what additional analyses you are thinking about presenting later in yard to provide some insights on some the emerging profile of <unk> and then what do you think the street is kind of missing on the market potential.
<unk>, Michael maybe following up on your sort of opening comments.
And what are the key underappreciated levers here in terms of the market. Thanks, so much.
Great. Thanks, So maybe the first question related to the Agave 201 trial and the full update.
Maybe I'll ask Neil to cover that please.
Sure. Thanks, Michael and thanks for the question. So we have not yet disclosed for instance response rate by disease.
My organs effected we haven't.
We haven't disclosed response rates by prior therapy for instance, although we don't think that.
We think that.
Given the extent of prior therapy and the high overall response rate.
It would be anything concerning in there, but we haven't we haven't yet.
<unk>.
Our plan as I mentioned, we haven't.
Perform the exposure response analyses with yet we expect to be able to do all of that.
At a meeting.
In the future.
And on top of that.
We will disclose whatever whatever data we have to hand that could be of use.
<unk> two is the prescribing community obviously in discussion with their with their partner.
Great and maybe.
The second question I had a problem was related to market potential in what.
What.
The market may be missing relative to what we've presented thus far and maybe I'll ask Angela to address that.
Okay. Thanks, everyone.
I think we said and Michael said in his prepared remarks.
Current estimate is about pricing and patients living with chronic kidney stable.
We believe that at least 40% of them will advance to that.
Your line setting and beyond.
That was the population we enrolled in the <unk>.
<unk>, one trial and what we expect.
To to have for a label facts until Nab and I think what we showed in the top line release last week is that I was told that it is very effective in patients refractory chronic gvhd.
And in a population, which mimics the current real world treatment paradigm over 70% of these patients had seen prior racks and 25% to 30% had prior <unk> and.
Exposure.
Despite enrolling a population very severe currency these team.
Foreign currency diagnosis in multiple prior therapies that drug was extremely however, especially at the <unk> printing deaths.
Very low rate of discontinuation.
Extra meaningful and durable and we know physicians are excited about this profound eager to have access so that is an option for their patients.
And then the fulsome data set a firm agave.
Just talk to that is likely to provide.
More exact differentiation for acetone Abbott, but based on what we know about its differentiated mechanism targeting monocytes and macrophages versus cytokines and signaling pathways.
Provide the potential to deliver a disease modifying treatment for patients and gives us confidence that Exxon that will be seen as a very important tool for treating refractory gvhd.
And as Michael said, we know, it's Profilers and antibody Oliver safer combinability experiments promise to deliver disease modifying effects earlier patients.
We'll be working on that trial and generating that data of the kind that even today, we think is going to be insignificant.
Value at Exterran that brings to these patients.
Anything else <unk>.
Thanks, so much for taking my questions.
Yes. Thank you.
The next question comes from Yigal <unk> with Citi. Please go ahead.
Question Akshay for Barak on for Yigal, Thanks for taking my questions. It sounds like the upcoming data for the <unk>.
Cohort will be more of a top line release.
We'll get we'll see our CRH data, but I'm curious will get a breakdown by leukemia type and more importantly, while the top line release include a look at median duration of response.
Yes, thanks for the question.
So look I think our goal here is to provide as I said in my remarks provide meaningful information in the top line such that physicians and stakeholders can really understand the full profile of the drug and there will be information that is not included in the top line I think.
Primary endpoint.
CRH and duration.
Likely to be a part of that release.
But I think beyond that.
<unk>.
It's hard to say at this point what will be provided but we know we were pretty.
Pretty.
Attuned to what people are looking to see and we will hope to provide that as much as possible in the top line.
Okay I understand.
Maybe one operating question. It does seem like you spent less on Opex I mean, you're sort of guiding for the second quarter. Just curious if anything in particular drove that.
Given your full year guidance unchanged I'm, just wondering how we should be thinking about spending for the rest of the year, maybe we should be sort of assuming both the lower end of the range.
Yes. Thanks for the question I'll ask Keith to trust assets.
Regarding the second quarter you go sorry.
Regarding the second quarter.
Their remarks.
In the press release and in the Q that spoke to.
Some lower spending on manufacturing.
While at CMC.
Primarily timing timing issue.
So we commented in the Q, how that was part of the contributor to a lower spend.
<unk> and R&D expense in the second quarter, which led us to come in under guidance with respect to your question on full year.
Appreciate that we do come in in the quarter under but.
Just look to us reaffirming the full year guidance.
Not going to make further comments.
For R&D and Opex beyond that.
Okay, Great. That's very helpful. Thanks very much.
Thanks for the questions. Thank you.
The next question comes from Brad Canino with Stifel. Please go ahead.
Good afternoon.
As you talked about in your remarks, the revenue restarts after transplant and that post transplant durability number will be important information and I think it's going to take time to gather those data after the topline release this quarter. So in the interim what have you learned in the real world as you've done your <unk>.
<unk> about rates of <unk>.
<unk> and <unk> inhibitors, specifically in the relapsed refractory setting in the post transplant setting in terms of.
The proportion that of patients that get restarted and how long they stay on those therapies. Thank you.
Yes, Brad Thanks for the question.
Let me ask Angela to comment on that that question, yes. Thanks.
So I think that.
Difference between.
In the relapsed refractory setting.
<unk> inhibitors.
<unk> inhibitors had meaningful transplant rates.
Many pencils that actually would go had the opportunity to go back up.
And I think that we're at.
Our <unk> revenue that is bringing a very differentiated profile and opportunity.
<unk> annually.
Benefit for these patients.
Okay.
And maybe just another question on clarification.
For the beat AML triplet when you say.
Safety and <unk> does that mean.
Mean to imply that you will not receive drug activity data.
Or does it imply that you believe the focus of the data given it's a phase one should be on safety.
Yes, Brian I think it's the latter thanks for the question I think what we're trying to have it as a phase one dose escalation.
Right. So the focus is always on safety, we're pretty consistent in saying so in phase one and obviously we're trying.
The goal is to get through dose escalation to get to an <unk> and we hope to inform on on that experience.
Before the end of the year.
Okay, but I do have several investor conversations that referenced like the foot III and IV H triplets, where those phase one results were 90% plus CR as high rates of <unk> negativity. So.
I want to know from you are these the right precedent comps to think about for your triplet at this stage and what other caveats would you suggest we think about as we try to compare those data.
Yes.
<unk>.
It's going to be tricky with a small patient population when you're adding onto an already effective.
Tim anything meaningful differences.
<unk>.
We think theres going to be all benefit from the triple.
Well that.
Plays out exactly where the enhancement.
There are a handful of patients I think what we're waiting to see.
Yes, I think just to add on Tangela.
I think we need to caution everyone to again. These are late line patients or sorry, there are early patients, but they're not a lot of them. So we're not we're not going to assume too much on the efficacy side. I think this is again as well see still see efficacy, but we are more intent on obviously, how the drugs combined and if we can get to an RPT.
That's meaningful.
Okay I appreciate it thank you.
Great. Thanks, Brad.
The next question comes from Michael Schmidt with Guggenheim. Please go ahead.
Hey, guys. Thanks for taking my questions.
I have a few follow up along the same lines so in.
101, then they can teach you a cohort in the pivotal cohort is the percentage of patients receiving transplant and substitute Glenn.
Mens similar to that in your phase one study.
I'm just thinking about <unk> in terms of the the DLR in that pivotal study.
Yes.
Alright, thanks for that Michael So just a reminder, so in the phase one we didn't have patients going back on on drove post transplant that was not part of the protocol. So one of the major changes between phase one and phase two portion of the augment trial is that in phase two we were able to.
Have patients go back on treatment post and graph net so that is that is the major change and obviously when you measure duration of therapy median duration.
<unk> account for the fact that patients go it really you're measuring.
How long patients stay on therapy.
Therapy.
Until relapse so.
That's really the measure and that measure includes whether or not they go to transplant. So theyre not censored at the time of transplant. They continue it's as if they are on one line of therapy, so there'll be patients who receive therapy and don't get transplanted and progress there'll be patients, who get transplant and continue on and.
And don't get retreated with revenue management, and then there'll be some patients who obviously get transplant and then get retreated with <unk> stay on treatment and we'll track those as well so that'll be.
Different experiences in the phase III.
<unk>.
I would say some of those patients enabled by the fact that they are able to go back on treatment and be treated as maintenance.
Got it understood. Thanks, and then.
Regarding the.
The question the regulatory bar the efficacy hurdle.
My question is the efficacy hurdle in relapsed refractory AML and the <unk>.
PM, one subset different than in that <unk> given.
Some overlap there.
<unk> and <unk> mutations for other treatments are available.
Yes. Thanks for the question Michael I think the of course, there are no drugs that are approved specifically for either NPM, one Kmt in the relapsed refractory setting.
I would make this comment with fourth fifth line patients once they get to that.
Really refractory.
Stage of their disease.
Our view is that.
The hurdle rate for four approval is likely to be similar now.
Again, we haven't provided the statistics of our trial, but they are each of the individual cohorts do have the same number of patients.
In them, so that should give you some some understanding that our statistics are set up.
In the same way so.
Again, I think regulatory precedent in AML is one thing.
And you can maybe do us.
Something from them.
Construction of our trials as well.
Okay Super and then lastly on the beat AML safety data later this year or early next.
Yes.
Let me see the safety data.
What what frequency.
Thanks.
What type of safety profile.
Would you view as acceptable is there a particular rate of thrombocytopenia for example that.
That you would view as kind of the upper the upper end of what acceptable in order to advance in this constellation into registration studies.
Yes. Thanks for that last question. So I would I would just say that at this stage before we have data and before we've actually disclosed anything.
We'll be looking at the totality of the data and obviously the safety and Tolerability is going to be really really important to understand how these drugs combined.
We're not sort of a priori.
Looking for any one particular side effect I think the drugs, we think in our mind it should.
Combined nicely and so.
We'll have to see what the overall profile looks like at the time that we present the data.
Okay, great. Thank you so much.
Thank you Michael.
The next question comes from Peter Lawson with Barclays. Please go ahead.
Great. Thanks, so much.
Just to follow up around the Gvhd side of things just when we should expect that.
The full data set there that's kind of an ash event.
If this.
Kind of what we should be focused around that data set.
Kind of the differentiation kind.
Kind of stuff's emerging between you and the reservoir.
Yes, Thank you Peter and thanks for the question so.
Without giving away exact meetings, because we tend not we haven't disclosed what exact what meeting that dataset is likely to be presented at but we did say before the end of the year is our target and so I think that's probably an indicator of where that will be.
And then maybe I'll ask Neil to follow up on the question about.
Additional information and differentiation.
Yes, thanks for the question.
I already pointed to the fact that we would we haven't yet disclosed for instance.
Responses are cost effective disease organ.
And I would anticipate that when we get to presenting data.
At.
Medical meeting, but those data will be included.
Just to recap and as we alluded to during the prepared remarks in the presentation.
The population that was included in the run rate to one study.
Really heavily more severe and more heavily pre treated.
And those patients included in prior pivotal studies with the approved agents.
So reiterate or all of them all of the data points, but in terms of.
Disease severity as I've mentioned, the number of prior therapies the time from diagnosis.
<unk>.
But also I would point to.
The.
Safety data that we've.
Already.
Disclosed in particular, the low rate of discontinuation, particularly at airports, where you maybe.
Q2 weekly, we're only six patients discontinued.
Local adverse events, but I think you can.
<unk> expect as I said.
More extensive data data disclosure at that meeting.
We will make every effort with our with our partner insights includes all of the relevant information that could be helpful to you in.
And the medical community and patients.
Great. Thank you and then just.
One side of the story.
Should we expect to see that data in <unk>.
2024, and so that kind of before after a potential funding for the <unk>.
Approval.
Yes, thanks for the question Peter So NPM one.
Our guidance is 2024, we havent narrowed that at this point.
And in terms of I'm, sorry, what the second part of your question.
Alright.
Kind of trying to narrow it down actually whether it comes before after the potential filing of <unk>.
Right of course, so yes.
Yeah, that's a that's a difficult one to answer of course because.
We have to actually get the drug filed the case for <unk> and then we will have to see what that timing looks like but.
I would say, it's relatively close proximity.
Okay.
That would be in close proximity.
The approval.
Okay.
To the best of our understanding it'll be some time, yet both will happen in 2024, we don't think there'll be too far apart.
Great. Thank you thanks, so much and goodbye.
Thank you.
The next question comes from Calvert Patel with B Riley Securities. Please go ahead.
Hi, This is really more on for <unk>. Thank you for taking our questions.
Just one from US quick follow up actually on for your Gvhd.
Should we expect alignment on what dose or doses will be filed for <unk> and strategically do you think it's best to file for just one dose or are is there an advantage for multiple dosing regimens on the label.
Thank you William let me ask Neil to please comment on that when both of your questions.
So.
Obviously the agreements.
Well, let me let me just start by saying as I mentioned, we are currently conducting additional analyses to effect the benefit risk across all three doses.
As you've seen the efficacy that we've observed at <unk> three milligrams and one most of them are pretty similar.
The safety profile of the zero three Meg per kg doses is excellent.
We can't comment on which dose we would.
File or whether we would buy one or two doses because we are in the house to discuss with the agency.
I think that.
Our objective would be to file the optimal dose.
As the recommended dose, but a substantial recommended dose.
That will be predicted discussion between.
While actually insight will be meeting the regulatory efforts between.
Insight on BSA.
That's all really.
Yes.
Is there a second part of your question.
Yes.
I appreciate it.
Thank you much thank you.
Thank you.
The next question comes from Justin <unk> with BTG. Please go ahead.
Hi, Thanks for taking the questions and congrats on the progress here, maybe just a clarification question just on Michael's earlier, one just about the augment 101 of duration of response so.
We see that data, we should assume that's inclusive of patients who have gone on transplant is that correct, Bob can be broken that out by whether they would receive a transplant or not is that correct.
Justin Thanks for the question.
It's probably a little early to say, how we will present that data per se, but I would say that the patients who were looking at the overall patient experience and that will include patients that have gone on to transplant and so I would expect that if we're reporting if we are reporting duration.
We would include that.
Those patients in the calculation as well so I'm, just maybe a little bit speculating.
I haven't in this remark I haven't said exactly that will be what will be breaking out I'm, just saying that if we are including those patients in the trial then naturally they would be included in the duration of assessment.
Got it okay that makes sense to me.
Naturally the maintenance setting here the large market I'm just curious if you talked about when we might see data either from the intercept study or the seven plus three.
Combination study in the maintenance setting.
If it's too early to say yet.
Yes, I think I hit the.
A little early to say, we're just going to get the seven plus three trial up and running.
Before the end of this year and intercept is a cooperative group trial, which is ongoing and I think we had said for the beginning of that would take a little bit of time. So just a little early we'll probably have more to say in 2000 early in the year in 'twenty for how things are progressing and we will try to put a little finer and finer detail around that.
That makes sense to me and congrats also on the very positive.
So on that data just curious if you could comment on the subcutaneous formulation. If you have any updates there or when we might see that.
<unk> formulation being ready for clinical studies.
Yes, thanks for the follow up the sub Q.
Progressing nicely I think both inside and syntax or working in tandem to to bring that forward and are progressing.
We haven't put a timeline around that just yet again stay tuned as.
As we get little bit closer here, but yes. It is.
Potential option that we think we can bring bring alongside the.
File dose or doses that we take forward.
Great well, thanks for taking my questions. Congrats once again and looking forward to the data.
Thank you Joseph Bill I appreciate it.
The next question comes from George <unk> with Scotiabank. Please go ahead.
Hi, good afternoon.
Thanks, George Farmer.
Just two from us.
First on <unk>.
AML, so keeping your data so far I talking about competitors data in hand.
Can you speak to your level of confidence about penetrating in dominating both excellent. Thank you and then one for BMO I'm, assuming approval or do you think.
More conditioned to come in higher market share in one sense that prices there.
Reasoning behind that.
And the second question was on <unk>.
Just your comments on what your contribution.
Commercial efforts.
Right.
Great. Thank you so much for the questions. So first of all.
Look I think what's apparent to us at least and I think many is that we will be the first drug approved.
And this space first met inhibitor approved.
For AML and <unk> patients.
Patients and the.
The first indication will be Kmt to add I think we believe will be first to market there.
And best in class and I think that extend the <unk> one as well I think we believe we'll reach the market first and have a best in class profile. So from our vantage point.
We see execution in front of us and feel very confident that we can get this done based on the data that we've presented thus far.
And I would underline the fact that robust data set in phase one presented at ash.
Really I think sets us up very nicely to be.
To be a top contender and really lead the field.
<unk>.
So that's how we feel and we.
As of today, there is really not a lot of data out there that would suggest otherwise.
So that's that's where every minute with.
With <unk>.
Our setup with.
Ranger with insight is that we can participate we have an option to participate in the commercialization of <unk> of up to 30% of the commercial effort and.
Thats an election that.
We will be making over the next.
A quarter or two so.
Relatively soon.
Make that election.
Its a interesting setup commercially for us because as we've talked about there we have two drugs coming to market.
Pretty much the same time.
And it's a very similar overlapping call point.
Physicians that will be calling on.
Could be.
The detail with both drugs. So it's for a small company our size it provides a very meaningful.
Commercial opportunity.
Rich.
We would look to take advantage of it. So again, that's an election that will make.
In the next few quarters, but it does provide an advantage to us and it was done with purpose.
Doing this transaction with insight.
Got it. Thank you and just a quick follow up what are some of these.
The key drivers behind the decision so what are.
Some of the factors.
Taking into account.
Okay.
So what are the what are the key drivers to consider for a commercial launch for us.
And did I hear your question for those activities.
Some of the key factors you take into account the Farmington that election decision.
Yes, thanks for that.
Well I think it comes down to.
There is no difference in the economics for US. It's a 50 50 profit split for us in the U S.
So we are contributing to the cost of commercialization, regardless of whether we provide reps or not.
<unk>.
As I mentioned it is inefficient.
Setup for us and that we have both products.
Sales reps will be calling on the same positions for both products. So there is overlap there. So we wanted to ensure that that was indeed, the case and we have and so.
So certainly the efficiency of which.
We can deploy our reps.
And and how how meaningful that will be for us and our commercial.
<unk> effort for <unk> as well that is kind of what we're thinking about.
It's probably not as complicated as one would think it's pretty straightforward. So I'll just leave it there.
Got it thank you so much.
Thank you.
This does conclude today's question and answer session I will now turn the call back over to Michael Metzger for any additional remarks.
Great.
Well, thank you operator, and thanks for all the questions today, we look forward to seeing many of you at the upcoming conferences in August and into September and look forward to the data disclosure, which we talked about today for <unk> in the near future. Thank you very much and have a great evening.
This does conclude today's program. Thank you for your participation you may disconnect at any time.
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