Q3 2022 Syndax Pharmaceuticals Inc Earnings Call
It's all about and is focused on realizing their full potential given they're getting they're compelling clinical profile.
Starting with revenue our highly selective <unk> inhibitor.
Our pivotal phase III augment 101 trial evaluation regimented in patients with relapsed refractory <unk> mutant or MLR acute leukemia is ongoing.
We expect to report topline data from at least one of the cohorts from the phase II portion in the third quarter of 2023, and we continue to expect to file an NDA by the end of 2023.
This morning, we published a press release highlighting positive updates from the phase one portion of the augment 101 trial that we will that will be presented during two oral presentations at the American society of hematology or Ash annual meeting this December .
Beyond the augment 101 trial, the FCB effect of monotherapy in relapsed refractory disease revenue met him as the focus of several ongoing and planned trials that presents important expansion opportunities.
<unk> and.
In addition to acute leukemia is we are on track to initiate our first solid tumor proof of concept trial in colorectal cancer in the fourth quarter of this year.
Moving to <unk>, our antibody against <unk>.
Enrollment is now complete and our pivotal phase III <unk> trial evaluating <unk> in patients with chronic graft versus host disease, and we expect to report data from the trial in mid 2023.
We are working in collaboration with our partner insight to maximize the value of the <unk> program and this includes an expected BLA filing by the end of 2020 as pretty as well as initiating a trial testing the combination of <unk> and Russell witness and frontline chronic graft versus host disease.
Looking beyond C. Gvhd, we expect to begin a phase II trial of acetone and idiopathic pulmonary fibrosis or Ips in the fourth quarter of this year.
We also continue to assess potential business development opportunities to complement our existing pipeline.
Bar is quite high for in licensing drug candidates given the strength of our pipeline, we continue to evaluate potential opportunities to in license earlier stage targeted oncology compounds and we believe could become high value differentiated assets.
Let's now turn to slide four and I'll provide further details on our recommended approach.
First our pivotal phase III augment 101 trial is designed as three single arm phase II trials enroll independently and could each provide the basis for our KOL regulatory filing in the U S. The augment 101 to a trial is enrolling patients with relapsed refractory MLR ALLL to be us.
Enrolling patients with relapsed refractory MLR AML and <unk> is enrolling patients with relapsed refractory NPM one used in AML.
Each trial is designed to enroll approximately 64 patients adult patients and up to 10 pediatric patients aged one month or older as.
As cited staffing issues industry wide have impacted startup timelines in certain geographies, we have updated our guidance for when our first cohort in this trial will be fully enrolled and expect enrollment to extend into the first quarter of 2023.
Interest in the trial remains incredibly high with strong enrollment.
Investigators are finding it is challenging as we are to deal with the unfortunate resourcing issues at some other institutions and we are working collaboratively to resolve them. We now expect to present top line data in the third quarter of 2023 for at least one of the three cohorts in the augment one on one trial and importantly, we can.
We anticipate filing an NDA by the end of 2023.
We have agreement with FDA that for each cohort or trial. The primary endpoint will be the percentage of patients achieving CR CRH with secondary endpoints, including durability of CRC Orange response, transfusion independence overall survival and safety.
You'll also have agreement with FDA on the statistical design of each trial importantly, the trial design allows patients to be treated again with revenue after a bone marrow transplant. A design feature that provides data on the potential role of recommended in the post transplant maintenance setting.
I will now glad to hand, the call to <unk> to provide an update on the ash abstracts, which published earlier today.
Thanks, So much Michael if we turn to slide five I'd like to note that we are excited that regimented will be the focus of two oral presentations at the ash annual meeting on Saturday December 10th.
Isa from MTN or Kansas, MD Anderson Cancer Center will present updated results from the phase one portion of the augment 101 trial.
Also present are second half strength summarized in the outcomes of patients who achieved a response on recommended and then went on to bone marrow transplant.
A copy of the press release with an overview of the Ash abstracts is available on our website and I'll take a moment to talk through some of the key highlights of the data that you see on this slide.
At Ash in 2021 eight.
Hey, Todd Stein from Memorial Sloan Kettering Cancer Center presented the initial phase one data on 51 patients who had either in NPM, one mutation or an MLR fusion.
This was our efficacy evaluable population.
In the abstract released today there are now 60 patients evaluable for efficacy. The additional patients include eight patients with MLR AML and one patient with an <unk> mutant AML.
All of the patients are from so called arm a.
Patients who are enrolled not receiving a concomitant strong <unk> four inhibitor.
Additionally, all of the nine patients were treated at one of the two doses that had been determined to meet our predefined recommended phase II dose criteria.
As you can see the percentage of patients achieving a complete remission as defined by the CR CRH rate is now 30% versus the 24% previously reported at Ash last year.
In addition at the time of last year's Ash presentation. The median duration of response for patients who had achieved a CR or CRH had not yet been achieved.
And as the data has matured we now see a very impressive median duration of CR CRH response of nine one months at the time of the data cut off.
I would also point out that we continue to see a high mrna negative rate, 78% among patients achieving either CRC RH or CRP, which is quite meaningful in this patient population as it enables patients to proceed to a potentially curative bone marrow transplant.
Indeed, the second half distract described on site slide six specifically summarizes the outcomes of the 12 patients who achieved a complete response in <unk> and then went on to receive a stem cell transplant.
Impressively nine remained in remission as of the data cutoff with a median follow up of 12 three months.
Two additional transplant patients were treated with revenue net revenue amount of maintenance and the capacity that you setting following a stem cell transplant or non mild latest stem cell boost both of whom remained in remission for over a year as of the data cutoff.
Consistent with the data presented last year revenue continues to be well tolerated and there have been no discontinuation due to treatment related adverse events.
We believe the data continues to support revenue minutes compelling clinical profile and position it not only as a first in class best in class treatment.
And adds to our confidence in the ongoing pivotal trials.
Our principal principal investigators are highly encouraged by the data and believe that regimented could play an important role in the treatment of not only these refractory relapsed refractory patients, but can also play an important role in earlier treatment lines and in combinations given its clinical profile.
I'll hand, it back to Michael to talk more about that program.
Thank you Brian .
Slide seven highlights a few additional opportunities that were exploring move Ravi Mehta beyond used as a monotherapy agent in relapse or refractory acute leukemia.
Preclinical data demonstrate the potential benefit of amended inhibitor in combination with standard regimens and regiment is excellent safety and efficacy profile as well expanding its used in earlier settings and in combination with approved therapies.
Starting with the phase one beat AML trial.
As part of our collaboration with leukemia, and lymphoma Society <unk> is being combined with the <unk> side of the entries to treat newly diagnosed AML patients with an MTM, one mutation or ml rearrangement or unfit for induction chemotherapy.
Recommended but first menin inhibitor to be included in the trial, which will assess safety as well as initial efforts.
Enrollment is ongoing and we expect initial data from this trial available it's great.
Longer term, we expect that positive beat AML trial results would lead to a phase two three trial, which could serve as the basis for our future regulatory filings.
We're also currently enrolling patients in August one.
In the augment 102 trial designed to assess revenue management in combination with standard salvage chemotherapy for patients with relapsed or refractory MTM, one music or MLR rearranged acute leukemia, we expect to have initial data available from this trial in 2023.
Finally, the intercept trial. This trial is focused on investigating novel therapies to treat early relapse and clonal evolution as a preemptive therapy in AML is being conducted as part of the intercept faster clinical trial led by the Australia, Asia and leukemia and lymphoma group.
The trial is designed to explore the activity of recognize it as monotherapy in patients with AML, who have <unk> positive disease. Following initial treatment a group of patients patients at very high risk of relapse.
Of note <unk> is the first Menin inhibitor are included in the intercept and all that.
<unk> clinical trial.
The intercept trial was a very creative approach to treating early patients early in their disease course.
We continue to expect the Australia, and Asian leukemia, and lymphoma group to initiate dosing in the fourth quarter of this year.
And is it as detailed on slide eight we are committed to unlocking the full potential of revenue beyond the relapsed refractory acute leukemias day I'm moving it earlier in treatment and in combination.
These expansion opportunities, we see the potential to address upwards of 12000, MTO on mute MLR acute leukemia patients across these.
These two forms of acute leukemia, together represent up to 40% of the overall AML population, which to our knowledge will be the largest population of AML to be addressed by a new targeted therapy.
We anticipate that revenue minute to be one of the most important new franchises in the leukemia setting and we are looking for looking to explore revenue.
As a treatment in solid tumors as well.
We expect to initiate a proof of concept phase one clinical trial in colorectal cancer in the fourth quarter of this year.
This trial is designed as a signal seeking trial in 20% to 30 patients with refractory colorectal cancer to look for responses or disease stabilization. We are excited about this opportunity, giving the given the compelling preclinical science supporting the role of the Menin <unk> interaction and beta carotene endured the tumors such as colorectal.
Cancer.
Let me now turn to <unk>, our potentially best in class monoclonal antibody therapy targeting the CSF one receptor.
Slide nine provides an overview of the pivotal agave tool one dose ranging trial evaluating <unk> in patients with <unk> HD.
We're excited to announce that the trial has now completed enrollment of approximately 240 patients which exceeds the original enrollment target of 210 patients.
We believe this speaks to the enthusiasm that investigators have reps selling that as well as the unmet medical need among the gvhd patients.
Trial enrolled patients whose disease has progressed after two prior therapies.
We are at least two years of age and that overall entry criteria.
Patients were randomized to one of re treatment groups each investigating a distinct dose on that given either once every two weeks or once every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for <unk>, while secondary endpoints include duration.
In response and validated quality of life assessments using the modified lease since its Scott.
As you May recall the primary endpoint for the trial is response by cycle seven day, one measured approximately six months after the initial dose.
Assuming a few additional weeks for data analysis due to the over enrollment we are now comfortable guiding to topline data in 2023.
Are the terms of our collaboration agreement insight will be leading the regulatory filing in gvhd, which we expect will occur in the later part of 2023.
This trial is supported by positive phase <unk> data in 40 Gvhd patients that we presented at Ash in 2021.
The overall response rate was 68% and the median time on treatment was over six months.
Along with an excellent safety profile. These results were well received among thought leaders who recognize some amount is having a clinical profile that would be beneficial in the treatment of these heavily pretreated patients.
In collaboration with our partner insight, we are enthusiastic about expanding Arizona that program into frontline's Gvhd in combination with rux slip that we believe the non overlapping mechanisms of action of Russell index, suppressing T cell activation and <unk> inhibiting inflammatory monocytes and pro fibrotic macrophage.
<unk> may allow percentage synergistic clinical benefit in patients with <unk> HD.
The phase one combination trial in patients with newly diagnosed EMEA <unk> is currently in preparation and we expect the trials we initiated in the first quarter of 2023.
Beyond Gvhd C. Gvhd, we are excited about the opportunity to expand acetone out beyond graft versus host disease into fibrotic diseases, where the monocyte macrophage lineage plays a key role we continue.
To expect to initiate a robust phase II trial in IPF in the fourth quarter of this year.
This multinational trial will enroll 170 patients with IPF randomized one to one to receive <unk> or placebo over a 52 week double blind treatment period in <unk>.
<unk>, we believe this trial along with one additional phase III trial could form the basis for FDA approval in IPF.
Slide 10 highlights the broad clinical and commercial opportunities brackets on that.
We believe C. Gvhd represents a high unmet medical need.
Actual opportunity with approximately 14000 patients suffering from <unk> in the U S. Today.
The successful commercial launches of insights geography.
<unk> reservoir rock are encouraging both both posted meaningful early revenues begin to speak to the commercial opportunity in gvhd.
Despite recent advancements in this area to our knowledge assets all amount as the only agent in clinical development that specifically targets. The monocyte macrophage lineage. We added insight believe the data generated to date with accidents on that suggest it has the potential to play an important role in the treatment of CGP HD, both as a monotherapy and <unk>.
And safety profile in combination with complementary medicine grew.
Combinations in the frontline setting as well as the opportunity to expand to ex U S markets, we envision the seed gvhd opportunity growing meaningfully.
I'll now turn the call over to Keith to review our financial results.
Thank you Michael.
I'm going to take a few minutes to discuss our financial results for the third quarter 2022.
Turning to slide 11.
The results of operations for the third quarter of 2022, and the comparison to 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 report, which was filed earlier today on Form 10-Q.
I would like to point out that our net loss for the quarter was $35 4 million.
<unk> per share.
Compared to a net loss of $26 million or <unk> 40 per share the same period last year.
This difference is primarily attributed to $12 4 million.
In nonrecurring license revenue recognized in the third quarter of 2021.
As well as higher operating expenses in 2022, driven by increased employee related expenses as well as higher professional fees.
This was partially offset by lower third quarter, 2022, clinical development and manufacturing expenses.
In large part the result of <unk> cost sharing benefits from our partner insight.
We ended the third quarter with $337 8 million in cash equivalents and marketable securities.
And 61 3 million shares and pre funded warrants outstanding.
And we continue to forecast the cash runway into the second half of 2024.
Our current cash on hand supports our development and pre commercialization plans for both the <unk> and exits of Loopnet programs. During this period and provides us flexibility to decide to engage in business development.
I would note that we made a debt repayment in September in connection with the termination of a loan agreement with Hercules.
This did not have an adverse impact on our cash guidance.
Looking ahead I'd like to provide updated financial guidance for the full year 2022.
We now expect R&D expense to be $115 million to $125 million versus our previous guidance of $130 million to $140 million.
The reduction is driven largely by higher than expected cost offset from our exit cylinder development partner insight.
And for the full year 2022, we now expect total operating expense to be $145 million to $155 million, including approximately $15 million of noncash stock compensation expense.
The current operating expense guidance is lower than the prior guidance of $160 million to $170 million after accounting for the third quarter financials as well as the updated full year expense guidance.
With that let me now turn the call back over to Michael.
Thank you Keith.
As you can see we continue to make significant progress executing against our ambition ambitious goals and milestones that we have set forth and beginning this year and confident we have the right plan in place.
And that we are building the right team to execute on our long term goals.
<unk> has always been focused on delivering new medicines that extended improve the lives of people with cancer and we are in a unique position today with two ongoing registration programs with pivotal data within the next 12 months.
In addition, both programs offer the potential for broad franchise opportunity beyond their initial registration indications.
We believe revenue met or it could have utility across a wide range of clinical settings in acute leukemia potentially in solid tumors.
Our immediate goal of the company is to be first to market and best in class <unk> uses an MLR rearranged acute leukemia, and we are pleased to be able to share updated data from the phase one portion of augment 101 at ash, which continue to support our ambitions we.
We are actively engaged with physicians and we are laying the groundwork potential launches as we seek to take advantage of our leadership position. We plan to have a large presence at the Ash Congress and we are focused on educating physicians through multiple avenues, such as our disease awareness campaign that kicks off in the fourth quarter.
Beyond the relapsed refractory setting we intend to drive additional value potential by expanding its use in the newly diagnosed that maintenance setting in MTM on mutant and MLR acute leukemia, and perhaps into solid tumors.
Same franchise potential hold track to tell them that we're broad opportunity exist in various lines of therapy, and see gvhd and across a broad range of fibrotic diseases, starting with IVF.
We are indeed in a strong financial position with a balance sheet that allows us to deliver on key near term milestones.
I would like to close the call by expressing our deep appreciation for this 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 execute on our mission of realizing a future with which people with cancer live longer and better than ever before.
And I'd also like to thank our committed long term investors, who continue to share in our vision and support us in building sendek with that I'd like to open the call for questions.
At this time, if you'd like to ask a question. Please press the star and one on your Touchtone phone.
Remove yourself from the queue at any time by pressing star and Q. Once again that is star one to ask a question and we will go right into our first question from Phil Nadeau with Cowen. Please go ahead. Your line is open.
Hi.
Good afternoon, Thanks for taking my questions and congratulations on the progress.
Couple of questions on the abstract from this morning, it sounds like most of the patients who are either in the abstract or MMO.
MLR patients, which I think you said just one M. P M one patient being added.
Is the enrollment of NPM, one patient still so so low it does seem like that's a much larger population, we would have thought maybe you'd get more.
Christmas without genotype in the trial and then a related question I think we're all thinking 20% CR Cri just necessary, perhaps we're filing in that indication is that.
Individual genotype is that a fair assumption.
Thanks Bill Thanks.
Thanks for the question, So I guess I'll take the first one which.
The MTM won number of Mcl, one patients I think we've talked at length about the fact that.
The enrollment in phase one I think it was initially skewed more towards MLR patients and <unk> is the initial patients that the trial is quite well received the response with the MLR.
And then of course, we see patients come on as well in the phase one and doing quite well.
But the how they.
And how the phase one was set up where you have a certain number of slots and so forth are sort of kind of the cadence of enrollment kind of stay that way throughout the trial. So really no change there with the addition of the new patients I would also say importantly that we do have three phase II trial open individually rolling including <unk>.
<unk> and I think we are prioritizing enrollment in phase II, So I wouldn't expect anything to change.
With the ongoing phase one.
I think that's the that's how I would explain that I don't think I would characterize it as low.
That's our phase one experience phase two should be should be different based on having separate trials.
And your second question.
What is that 20% CRC reiterate needed for filing.
And that is an assumption based on based on precedence right and so I think.
Our trials.
Our statistics are satisfied.
Each of these three enrolling cohorts have the same statistical design and number of patients.
We haven't talked much about the <unk>.
Those statistics on a lower bar that work.
Looking to rule out, but you can surmise that the agency has given us similar direction and guidance around around.
Whats statistics, we need to achieve and what the point estimates are and so.
I think we feel very confident that.
Based on precedent.
Are there other drugs getting approved targeted therapies that are.
That have been approved I think that we feel that at 20% of our Iris certainly.
A decent a decent way to think about it but it's certainly not a hole right theres.
There has been.
I am sure they.
They take into account both not only the safety, but also the efficacy of these compounds risk benefit and certainly we'll have.
That will be part of the package so.
20% is sort of a reasonable assumption, but it's not it's not it's not the total.
The total situation.
Great and then one last question from US just curious whether you mentioned benefit risk calculation.
In your experience with physicians.
What risk of differentiation syndrome is acceptable given the efficacy that we're seeing from our new members.
Sure, maybe I'll turn it over to breakeven.
Yes.
Sure.
Yes, Hi, Phil Thanks for the question I don't think we've asked that we then sort of.
Market research on that specific question.
Obviously, there are other agents that are in clinical use today that half.
Differentiation syndrome is a component of their.
The risk benefit profile.
The related question that we would probably ask is not just what is the.
Percent that might be acceptable, but what is the severity of those events.
As you know we tend not to see very many differentiated syndrome event than the ones that we have seen to date in the phase. One trial are all faced are all great too so that.
Profile, what we've clearly heard from our investigators at least is.
Yes quite acceptable.
That's very helpful. Thanks for your perspective.
Congrats on the progress.
Thanks, So much appreciate it next we go to the line of <unk> Patel with B Riley Securities. Please go ahead. Your line is open.
Yes, Hey, good afternoon, and congrats on the Ash data set today.
I guess first starting with the Ash data set can you confirm that the AE profile was comparable to the prior data set.
As the data mature and I think you added maybe nine more patients with efficacy data.
And particularly the grade three or higher <unk> rates did they do they stay at the 7% range yourself.
Yes, Kevin Thanks for the question I think we can confirm that the safety and the.
New update.
Of course see the wholesale.
At Ash, but it was consistent with what we've shown in prior no new no new safety findings in this data cut it at we would expect to see similar to what <unk> seen.
Awesome.
Okay.
The efficacy part.
Nine more patients that you added at the recommended phase II doses.
If I did the math right four out of nine patients achieved ACR CRH, which is obviously a bit better than the overall population numbers. So the question is if you go back and look at just the patients at the recommended phase II doses is a CR CRH rate higher than the 30% that you.
You reported at the Ash data sets.
Yes, but briggs do you want to data once we have a question.
Yes, so again remember that the vast majority of patients treated.
<unk>.
Ah 60 patients the vast majority are treated at the recommended.
One of the doses that met the criteria of recommended phase two dose for the protocol. So.
In essence, what you're looking at.
Yes.
Of efficacy that we would anticipate at a recommended phase II dose.
Okay, and then maybe a follow up on the.
On Phil's question since you did end up enrolling more patients with <unk>.
<unk> R.
AML in the phase one portion is it safe to assume that this cohort.
It will likely be the first to read out next year for the pivotal trial.
Yes, we havent. Thanks for that question, but I think we haven't given any particular guidance on which the cohorts is going to read out first I think what we've said consistently is that AML is likely to report before ALLL.
Based on <unk>, a smaller much smaller patient population.
We'll have more to say about that as we get closer but.
I would assume that AML will be first.
Okay fantastic. Thanks for taking my questions and congrats on the data center.
Thank you so much.
Next we go to the line of Madhu Kumar with Goldman Sachs. Please go ahead. Your line is open.
Yes. Thanks for taking my question I wanted to follow up on Phil's question, Ryan Differentiations in terms of I guess, one we've been getting a lot recently is are there differences in your kind of prospective with using <unk> and differentiation syndrome rate and MLR will be arranged NPM one disease.
Craig would you address this question please.
Yes.
So, but do remember that.
So I would say, we havent actually presented that that breakdown, but.
I would say.
We see relatively little of it so it's kind of hard to say.
But the determinants are when it correlates with but given the <unk>.
Relatively few cases, we've seen.
It seemed to be a trend between the different mutations.
Okay, Great and then I guess kind of thinking about the <unk> program in chronic graft versus host disease.
How should we think about kind of duration of therapy from the phase one trial like what can we expect any updates between now and kind of the topline data middle of X. So like how do you think about kind of the duration of use of extra on them.
Yes, thanks for the question Madhu I think.
What we have reported data last year, obviously, it at ash and at that point patients that have been on six months or longer and so the duration of therapy looks favorable.
As to your question about whether there'll be an update on that.
Short of putting out our pivotal data, which of course, we announced today that we finished the trial.
And that data will be coming out in 2023.
Sorry, I finished enrollment.
The data mid 2023.
Yes, I think that that would be the next logical time to update other than a potential obligation which.
Could happen along the line along the way, but right now we are gearing up for the topline data for the pivotal trial.
Okay, and I guess, one last question is what kind of things, we will be focusing on from the ash presentation that will be different from the abstracts presented early at this point, but what are kind of key.
Highlights then people who may look at keeping an eye on.
You are asking about what what should we be looking for at the ash presentation itself.
Yeah.
English from the abstract yes.
Right. So just to be clear. This will be this is the data cut that will that we will have at the presentation. So theres not going to be new data.
Question.
But in terms of updates and additional details are of course will be additional details of what we presented today in the presentation.
What those are in particular im not at Liberty to say now.
Harvest from the data, but I would expect that there'll be some interesting things that have come out of that presentation as well.
And then in fact too.
Just kind of remind everyone. Two presentations, who offers just want on the transplant data that we presented where we at today as well as the clinical data.
Okay, great. Thanks, very much guys.
Thanks for that.
Next we go to the line of <unk>.
The chunghwa.
With Citi. Please go ahead your line is open.
Hi, Tim This is <unk> on for Yigal, Thanks for taking my questions and congrats on all the progress really great to see.
Just kind of going back to the.
The earlier NPM, one enrollment discussion.
I guess would you be able to characterize if enrolling NPM one patients versus MLR patients might be different in terms of maybe a competitive.
<unk>.
A competitive dynamic between maybe your trial versus the other trials out there I'm just wondering if there's any potential differences there.
Yes, no. Thanks for the question Oscar I don't know I think this is as I mentioned before this is not the dynamic where there is we feel like Theres a competitive.
Reached through between one trial versus another trough in these pages I think we have we have.
Trials up and running and we're enrolling patients across the three phase III as I mentioned I think the phase one experience with separate experience for all the reasons I mentioned earlier from the experience that we're seeing in phase II.
And.
There are only a couple of sites that overlap with competitive competitors. So.
I think there is it's much more of the dynamics of a phase one and how that was set up to enroll patients versus the phase III stocks.
Individually enrolling.
Okay, Alright, thats very clear.
Maybe I'll switch over to a question on duration on the on the 9.1 month of the already reported.
Could you maybe give us some color commentary on how compelling you think that duration has been.
Maybe can you give us a sense of the contribution.
The post transplant recruitment period for that duration number.
Maybe Brexit would you like to.
And so that cost pressure.
Yeah sure. So look I think if you look at the other.
For example, I think.
Phil asked at the beginning about is the 20% required for filing for a CR CRH. The other question that some have asked us what kind of durability do you need so I think with a K a.
30%.
CRH rate and a median duration of response.
Nine months.
Looking at other other approved drugs I think that's quite competitive quite favorable.
Of course, our investigators are quite excited about what theyre seeing I think your question of can you separate out what is the.
The duration of response in patients who were transplanted versus patients who were transplanted.
It's of course difficult to do because so many of the patients were transplanted.
And I think that's in part why.
The FDA guidance document recommends that.
People not sensor at the time of transplant, it's essentially unknowable, what the duration of response would have been if they hadn't been transplanted.
Okay, Alright, that's helpful.
Last one from me it.
It seems like you've pushed back your expected.
Top line data or at least for the for the pivotal cohorts to the third quarter next year.
I guess, what's driving the slight adjustment is it maybe the pace of enrollment or does there a need for additional regulatory discussions any color that would be very helpful.
Yes, thanks for the follow up answer so let me, let me dive into that a little bit more so I would I would characterize this as really no.
No shift in timelines whats important here is that the NDA filing by the end of 2023 with our prior guidance.
Data, we expect to fall into the third quarter and.
And enrolling.
Enrollment in the first quarter what.
What we expect I explained in my prior remarks related to the fact that there were some site enrollment couple of sites that didn't come on as quickly as we had projected.
In the latter part of the year as part of the year and so I think that is.
Put us off a little bit on our expected timeline to fully enroll the first of the three cohorts.
But ultimately I think we.
Through some.
Good efforts with the science and the investigators.
I'll be back on track now.
I would say that enrollment is strong I think the enthusiasm for the trial is really very good.
The results of our trial speak to that and really support that and so what youre seeing.
What we're seeing across.
Set of sites that are coming on is just <unk>.
<unk> of what we're experiencing in the industry.
Right.
The initiation resourcing issues.
<unk> companies, we really haven't been bitten.
At all much until we saw a couple of sites.
It coming on.
Last few months. So I think that's the that's the explanation I think we're still in excellent shape and again.
Our.
No.
On pace to deliver on what we think is.
The most important which is top line data that of course a filing.
Alright, great. Thanks for taking all my questions and congrats again.
Thank you so much.
Our next question or comment comes from the line of Peter Lawson with Barclays. Please go ahead. Your line is open.
Thanks, Thanks for taking the questions.
Thanks for the update just wonder if you can make any commentary around that.
And a durability differences between the MLR range in the <unk> patients.
And then as we think about filing NDA available.
Got it right to assume that the FDA is going to look at these is the two kind of independent different.
Separately genotype <unk> versus that combined number.
You've seen so far in the in the phase one.
Sure Peter Thanks for the question. So let me let me address the first one.
In order to potentially enable three separate filings. If we are in a position to put a few filings one or more together due to the timing of when they enroll that we could potentially do that but.
But our view is that we should bring the drug as quickly as possible to the agency to get it.
Actually approved and so we're not going to wait necessarily to combined datasets in order to to avail ourselves of that so so that's the that's the overall plan.
And are there any other questions related to that.
Yes, just really as regards to the ash update where.
What we see what additional data that we're going to see we're going to see kind of responses broken out by dose.
Durability potentially.
The MLP negativity between and pay more than they rearrange patients.
Yes, well as you know we've.
We've presented some of that information in the past I think.
We have tried to be consistent between what we presented.
From from meeting to meeting so that investors.
Ken.
It really track what.
What the data looks like and how it's how it's accrued over time.
What we actually and I did say that we would have some additional things.
<unk> to say, obviously at the Ash presentation in terms of details I am not at Liberty to say exactly what we will present at the meeting.
Suffice to say I think it's interesting information and it'll be.
Great all presentation.
But as I said, we're trying to be consistent trying to be consistent between the meeting last year. This year in terms of the depth of information that we prepare and then present to us.
Yes.
Great. Thank you so much thanks for taking the questions.
Thanks, Dave.
Yeah.
Next we go to the line of Joel Beatty with Baird. Please go ahead. Your line is open.
Hey, Congrats on the data first question is on augment 101. It does a cohort need to have efficacy data collected on all 64 adults to read out or could it read out what a smaller denominator than 64, if enough responses were achieved.
So thanks for the question the way it is set up today.
We are targeting 64 patients.
That's how it's designed.
And so a lower denominator is not contemplated as part of that also.
That's the target number of prevalence of course, we could.
We're enrolling but I don't believe that Thursday.
Charlie and opportunity to undergo at this point.
Got it thanks, Dan could you discuss the status of it.
Initiating clinical trials in doing the work to move into the first line setting for Revlimid.
Right. So Greg maybe do you want to if you want to describe the beat AML trial, a little bit and maybe some of the other things that we're thinking about.
Sure so.
Again, I think Joel your question about earlier lines of therapy, we tend to separate those into two buckets, those who are fit for.
Intensive chemotherapy tend to be younger patients and those who are unfit for induction chemotherapy, who tend to be older patients or patients with co morbid disease. So for the fit patients the standard of care today.
As its been for decades.
So called seven plus three induction.
Consolidation regimen.
So there is a keen interest to combine our drug there.
The safety profile that we've seen.
Yeah, we think is quite favorable for combining with chemotherapy. So we're in the process of thinking through how we.
We haven't yet said.
When that trial will start what the design is but we're working hard on it.
The second population as the unfit population who are in combination within Asia and Thats. The beat AML trial, that's going on now to try to determine in the phase one portion of that what's the appropriate dose of regimented to give in combination with the label dose of <unk>.
In Asia, and then the third population of patients that are again quite.
It's quite a need of additional therapies are those who.
Our.
They'll have residual disease by more sophisticated assays, the so called <unk>.
<unk> residual disease population and there as you know the intercept trial is essentially a single agent <unk> to see if we can convert those patients to <unk> negativity, which would.
Sort of predict that that will be of clinical benefit to them.
Great. Thank you.
Thank you Joe.
It appears we have no further questions at this time I'll now turn the program back over to Michael Metzger for any additional or closing remarks.
Great. Thank you operator.
On the call today.
We appreciate your interest in our story and we look forward to seeing many of you at our upcoming.
That's mainly meetings as well as of course at the Ash.
Meeting, where we will be presenting data that we talked about today.
Great great.
This does conclude today's program that we thank you for your participation you may disconnect your lines at any time.
Okay.
Yes.
Through the year.
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Okay.
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Yes.