Syndax Pharmaceuticals Inc. Q1 2023 Earnings Call
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Good day, everyone and welcome to the Sun Dax first quarter 2023 earnings conference call today's call is being recorded.
At this time I would like to turn the call over to Sharon <unk> head of Investor Relations at syntax Pharmaceuticals.
Thank you operator, welcome and thank you all for joining us today for viewers and that this first quarter 2023 financial and operating results I'm sure as Larry and with me. This afternoon to provide an update on the company's progress and to discuss financial results for.
Michael Let Scott Chief Executive Officer.
Doctor, Neil Gallagher, President and head of R&D.
And Keith go bad.
Financial Officer.
Also joining us on the call today for the question and answer session. Dr. Peter <unk>, Chief Scientific Officer, Dr. Angelique angle 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 would 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 1990, but.
Actual results may differ materially for 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 represents our views as of today Nate.
H 2023.
A replay of this call will be available on the company's website www, yeah and desktop I'm following its completion and with that I'm pleased to turn it over to Michael Metzger, Chief Executive Officer Index.
Thank you Sharon and thank you all for joining the webcast I want to also welcome Dr. Neil Gallagher to the call today is our new president and head of R&D.
Neil is a highly accomplished oncology drug developer and has deep deep experience across all stages of drug development and strong track record of successful drug approval will be instrumental in driving continued pipeline development and growth. Its index you will hear from Neil later in the call.
We also welcomed Kevin Mcmanus of the company as our new Chief people Officer, we look forward to benefiting from his extensive experience and vision in building our organization and culture.
Now turning to slide three where we provide a high level summary of our corporate our current corporate priorities.
The first quarter, we continued to execute on our clinical and corporate strategy. We are confident in our ability to deliver pivotal readouts and registration filings for our two lead drug candidates. Later this year, we are on the cusp of realizing the potential of our sign by delivering treatments that provide critical benefit patients where there is significant unmet medical need.
Diving into Rebbe minutes are highly selected Menin inhibitor.
Our pivotal phase to augment 101 trial evaluating <unk> in patients with relapsed refractory N. P. M. One meeting or at KMT two eight rearranged acute leukemia is progressing well we express we expect to report data from KFC to a rearranged acute leukemia patients and the augment 101 pivotal trial in the third quarter of this year.
Here, which could serve as the basis for a U S regulatory filing by year end.
We have several additional trials ongoing designed to expand the potential of revenue minutes beyond used as a monotherapy agent in patients with relapsed refractory acute leukemias, including combinations with standard of care regimens to treat these forms of acute leukemia, and we expect to have initial data from several of them by the year end.
I will provide details on each of these trials later in the call.
Moving tax the telematic, our antibody against CSF Oner.
We remain on track to report topline data in mid 2023, when the pivotal phase II Agave 201 trial evaluating <unk> in patients with chronic graft versus host disease or see gvhd and plan to submit a BLA filing by the end of 2020 three.
With insight we have the support of a strong pharmaceutical partner to help us advance the development of actually kill them out and successfully commercialized once approved.
The trials that we expect to initiate this year include eight days once your combination trial back to telematics and Jakafi and see Gvhd led by our partner insight as well as a phase two trial are actually kill a map and idiopathic pulmonary fibrosis or IPF that will be led by its index.
As we prepare to become a commercial stage biopharmaceutical company delivering two best in class products to patients in areas of high unmet medical need we continue to take a disciplined and thoughtful approach to building our organization with highly experienced and talented people.
We are well funded with $449 million in cash as of March 31, our cash balance enables us to expand beyond our core registration indications and provides us flexibility to selectively pursue business development opportunities.
As part of that effort, we continue to evaluate earlier stage targeted oncology compounds for potential in licensing. We believe that we have sufficient resources to acquire new early stage assets that have the potential they'll become high value differentiated drugs, but we have as we have conveyed a high bar for doing so.
Any compound would need to complement our current pipeline and align with our long term corporate strategy.
Let's now turn to slide four and I'll provide further details on the recommended program.
The phase two portion of augment 101 was designed as three single arm pivotal trials with distinct patient populations that enroll independently.
Populations include Cam teach you a rearranged a L. L. K M. Teach you a rearranged AML an M. P. M. One mutant AML. The primary end point of each is the percentage of patients achieving Crs CRH with secondary endpoints, including durability of CR of CRH response transfusion independence overall.
Rival and safety patients, who undergo transplant also have the opportunity to be retreated with Ravi Menon, and the phase two portion, which could be an important maintenance option for these patients given that they are at high risk of relapse.
Based on the broad breakthrough therapy designation, we received in December 2022, and conversations with regulators, we will pool data generated from the AML and a L. L. A M. Teach you a cohorts into a single NDA filing aimed at an indication to treat adult and pediatric relapsed refractory acute leukemia patients.
With a K M. Teach you a rearrangement, we expect to provide top line data from this pooled population in the third quarter of this year and plan to file an NDA for the treatment of relapsed refractory Kmt a acute leukemia in adults and pediatric patients by the end of 2023.
Separately, we continue to enroll relapsed refractory M. P. M. One mutant AML patients and expect completion of enrollment of this cohort in the second half of 2023.
I'm happy to report that in the first quarter, we completed the clinical pharmacology work that support the recommended phase two dose in any patient eligible for every minute.
We have determined the RP Judy in patients who are not in a strong step three or four inhibitor is 276 milligrams every 12 hours and now have agency agreement on including this does not want to want it.
This means that any patient can be treated with grabbing than whether or not they're receiving concomitant to three or four inhibitors. We would expect this dose to be incorporated into the recommended label at the time of approval.
Moving to slide five.
We are excited now to now have the phase one on augment 101 data published in nature.
Work lays out the biology, a regimented and provides a thorough review of the data and.
In these heavily pretreated patients who have received a median of four prior therapies, 30% of the efficacy evaluable population experienced the Crs your H with an impressive median duration of CRC or H response of $9 one months as of the data cutoff date.
The authors concluded that Ravi Menon, mono therapy was associated with encouraging clinical benefit, including deep molecular remission and durable responses with minimal toxicity in this heavily pretreated patient population.
Turning to slide six based on revenue met its compelling efficacy and safety profile, our clinical strategy is to expand beyond the relapsed or refractory setting into earlier settings, and post transplant maintenance as well as explore the combination of Ravi Mehta with approved therapies, we believe that Ravi Menon could become the backbone are treating.
For patients with Cam teach you a R and M. P M. One in acute leukemias and by unlocking the full potential of RMB manner, meaning that meaningful value would be at it Eric.
There are currently no FDA approved therapies targeting Cam teach you a R. R. M. P. M. One acute leukemia is a population that together represent up to 40% of AML patients.
Including the expansion opportunities, we see the potential to address upwards of 12000 M. P. M on mutant and can teach you a R acute leukemia patients across various settings because of this significant unmet medical need we are committed to bringing encouraging clinical benefits to even more patients.
Here, we highlight our ongoing trials of grabbing that are across the treatment landscape.
Starting with phase the phase one beat AML umbrella trial.
As part of our collaboration with the leukemia and lymphoma Society, where have you met him as being combined with NAFTA class eight society and to treat newly diagnosed AML patients with an M. P. M. One mutant or Cam teach you a rearrangement who are unfit for induction chemotherapy revenue met him as the first man an inhibitor to be included in this trial, which will assess.
So safety as well as initial efficacy enrollment is ongoing and we expect to report initial safety data from the trial by year end 2023.
Longer term, we expect that positive beat AML trial results could lead to a phase two three trial, which could serve as the basis for our future regulatory filings.
We are also currently enrolling patients in the augment one or two trial designed to assess revenue met or in combination with standard salvage chemotherapy for patients with relapsed or refractory M. P. M on mute or Cam teach you a rearranged acute leukemia, we expect expect to reach a recommended phase two dose and report initial data from this trial.
2023.
And the intercept trial continues to roll enroll patients as part of the Master clinical trial led by the Australia, Asia and leukemia and lymphoma group.
The trial is a creative approach to treating patients early in their disease course as it is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML.
It is designed to explore the activity of Ravi met at the first man an inhibitor to be included in this master trial as monotherapy in patients with M. P. M. One mutant or km teach you a rearranged AML who have <unk> positive disease. Following initial treatment a group of patients at very high risk of relapse.
Data from this trial could also provide additional support for use a regimented in a maintenance setting.
We also plan to initiate a trial of every minute in combination with standard of care intensive chemotherapy known as seven plus three in the frontline setting in the second half of this year.
Turning to slide seven beyond the market opportunity that we outlined here and acute leukemias. We are also exploring the use of <unk> as a treatment in solid tumors based on compelling preclinical science supporting the role of the men and M. L. One interaction and beta Katina and driven tumors enrollment is going well and our proof of concept signal seeking.
Phase one trial in metastatic colorectal cancer and we expect to have initial data from this trial by year end 2023.
Now I'd like to turn the call over to Neil to talk to briefly talk about product graft versus host disease and why we believe acts with telematics are potentially best in class monoclonal antibody therapy targeting the CSF one receptor could benefit patients diagnosed with this disease.
Ill.
Thank you Michael it's a pleasure to be part of this index team and to showcase today why we're so excited about the agave 201 top line data that we expect to be able to share in the middle of the year.
Slide eight.
There are approximately 14000 patients living with chronic gvhd in the U S. Today.
Well there are a number of recently approved agents that have real benefit to patients suffering from the disease. There remains a significant unmet medical need across all lines of therapy.
Following initial treatment with corticosteroids patients are usually cycled through a variety of therapies all of which are associated with high failure rates.
Consequently, chronic gvhd remains a significant cause of morbidity and mortality.
Patients following transplant.
Based on the phase one two data, which I will summarize shortly we believe actually until I mab vital differentiated effective and practice changing intervention for this underserved population.
In slide nine.
I'd like to give some background on the disease pathology and the central role that monocyte drives macrophages have been shown to play in chronic gvhd.
Activation proliferation and survival of these macrophage population is regulated through CSF, one receptor once localized the tissues, where active diseases occurring macrophages may take on either a pro fibrotic inflammatory role depending on localized signaling factors.
Therefore attenuation of CSF, one receptor signaling using a blocking antibodies such as exits fill them up is expected to reduce circulating monocytes and derived macrophages and consequently reduce disease pathophysiology.
The differentiated mechanism of action of extra till amount, combining anti fibrotic and anti inflammatory activity holds the promise to provide a new therapeutic option for chronic gvhd patients distinct from other approved therapies.
The mechanism of CSF one hour blockade also offers the potential for improving the outcomes of patients with chronic gvhd when combined with other currently used therapies.
Based on encouraging preclinical data, we conducted a phase one two trial back to fill them up in patients with chronic gvhd.
The results of the trial were published in the journal of clinical oncology last fall and are summarized in slide 10.
Patients included in the study were heavily pretreated with a median of four prior therapies alone.
Among patients treated in the phase II portion of the trial. The overall response rate by cycle seven day, one with 82% with a median time to response to four weeks.
At the time of data cutoff, the median duration of exposure to actually fill them up with 38 weeks and the median duration of response and not yet been reached.
Importantly, clinical responses were accompanied by a reduction in chronic gvhd symptom burden.
Actually until I Mab demonstrated a manageable safety profile in this refractory population and the most common adverse events reported were consistent with on target effects of CSF Oner inhibition.
These encouraging data that I just described prompted us to initiate the agave to a one trial the design of which is summarized on slide 11.
This is the pivotal dose ranging trial evaluating acetone I've been in patients with chronic gvhd.
The enrollment criteria for a guy that 201 was similar to the phase one two trial reported on the prior slide.
Trial enrolled 240 patients whose disease had progressed after two prior therapies were at least two years of age and that all other criteria.
Patients are randomized to one of three treatment groups each investigating indistinct does flex the telemark administered either once every two weeks or once every four weeks.
The primary endpoint is overall response rate by cycled seven day, one using the 2014 NIH consensus criteria for chronic gvhd.
Secondary endpoints include the duration of response and validated quality of life assessments using the modified lease symptom scale.
We are looking forward to being able to report topline data from the agave to a one trial in mid 2023, and anticipate making a regulatory filing in relapsed or refractory chronic gvhd by year end 'twenty two 'twenty three.
Partner insight will be leaving the regulatory activities as laid out in the terms of our collaboration agreements.
And with that I'll turn the call back to Michael Michael Yeah. Thank you Neal.
Mr ran off this section, let me briefly turn to slide 12, which highlights the broad clinical and commercial opportunity for us to tell them that.
The successful commercial launches of <unk>.
Jakafi and Sotheby's restaurant speak to the unmet medical need and see gvhd it translates to a large commercial opportunity.
We believe actually tell them that has the potential to drive meaningful clinical benefit in chronic gvhd patients refractory to multiple prior therapies through.
Through combinations in earlier settings, as well as the opportunity to expand to the U S markets. We envision that act to tell them that could create significant additional value C. G. P. H D.
We're looking forward to expanding the exits on that program to include a phase <unk> combination trial with Jakafi in Gvhd. The trial will be led by insight and is expected to begin in the second half of 'twenty two 'twenty three.
Yeah on C. G V. H D. We are also excited about the opportunity to expand actually tell them out is the fibrotic diseases, such as IPF, where the monocyte macrophage lineage plays a key role.
At this point I want to highlight that actually tell them that benefit and lung manifestations of C. Gvhd will be the focus of an oral session at the American Thoracic Society conference on May 24.
The presentation details the 15 patients in the phase one two trial that had C. Gvhd related bronchiolitis Obliterans syndrome, or Pos for the 2014 NIH C. G. P. H D consensus criteria.
Eight of these patients demonstrated a partial response and no patients experienced Pos progression as might be expected in the absence of an active therapy.
We believe these data support actually tell them that has therapeutic potential in interstitial lung diseases, such as IPF, where we intend to initiate a phase II trial in the second half of 2023.
I'll now turn the call over to Keith to review our financial results.
Thank you Michael let me take a few minutes to discuss our financial results for the quarter ended March 31st 2023.
Turning to slide 13.
Our results of operations for the first quarter of 2023.
The comparison to prior year's quarter included in our press release, so I won't repeat them in these remarks.
Additional financial details are available in our first quarter 2023 report.
Which was filed earlier today on Form 10-Q.
I'd like to point out that our net loss for the first quarter was $41 $1 million or.
59 per share.
Compared to a net loss of $37 $2 million or <unk> 63 per share for the comparable period last year.
This difference in our net loss was driven largely by an increase in employee related expenses as well as professional fees within both SG&A and R&D.
We ended the first quarter with $449 million in cash equivalents in marketable securities.
And $69 6 million shares and pre funded warrants outstanding.
Our current cash is expected to provide runway into the second half of 2025.
Which allows us to appropriately invest to maximize the value of our pipeline.
Pair for two potential U S commercial launches in 'twenty, 'twenty, four and pursue potential business development activities to build our pipeline.
Looking ahead I'd like to provide financial guidance for the second quarter and full year 2023.
For the second quarter, we expect research and development expenses to be $38 million to $43 million.
In total operating expenses to be $53 million to $58 million.
For the full year of 2023. The company continues to expect R&D expenses to be $160 million to $175 million and total operating expenses to be $225 million to $240 million.
Including approximately $30 million noncash stock compensation expense.
With that let me turn the call back over to Michael.
Thank you Keith.
23 is an incredibly significant year for syntax I'm 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.
In the near term, we are focused on delivering quality data readouts for our pipeline and potential registrational filings in 2023 for our two lead drug candidates both of which are first and potentially best in class treatments.
Additionally, we continue to look for ways to capture the maximum value of our current pipeline by expanding into opportunities beyond the initial registration indications.
Our goal is to bring them to potentially encouraging clinical benefits of our lead candidates to even more patients.
As always I want to express our deep appreciation to the syntax 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 in 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 sharing our vision and support us in buildings index and with that I'd like to open the call for questions.
Thank you at this time, if you would like to ask a question. Please press the star and 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 will pause for a moment to allow questions to queue.
We'll take our first question from Matthew Kumar with Goldman Sachs.
Hey, everyone. Thanks for taking my questions I wanted to start by thinking about other than one or two the salvage chemotherapy combo trial, so as that moves toward how do you envision using red Humana as monotherapy in relapsed or refractory leukemias person in combination with chemotherapy.
Madhu. Thanks for the question and maybe I'll turn it over to Neil to to address that.
Yeah. So obviously the first approval already recognized for being in the relapsed refractory setting is monetized, but we have a number of different combination studies either ongoing or planned.
To enable us to execute the strategy of moving our refining recognized into other other patients in combination.
So the combination the combination there really earnings for earnings.
Or do you say.
Hello.
Okay.
Yeah.
Okay, and maybe on that note I'm thinking about the beat AML frontline trouble, you're going to have initial safety data by year end.
Can you talk a little more about what specific adverse events you might be monitoring and think that a combination of revenue might add further than it is at.
Yes, particularly the question one thing I'd tell you is there any reason to expect Qt prolongation could be exacerbated in the combination setting relative to the mono PERC.
Okay. Thanks for the clarification, so yeah, we're anticipating data from.
But the combination of all of us.
Then as a.
During the course of this year.
We don't anticipate there's no reason to anticipate that that combination would not be feasible. It's just a matter of fact, the normal dose ranging.
So there's no technical reason to assume that we wouldn't be able to proceed into a larger phase.
Okay.
Three studies in combination with any of our society.
I guess I mean closing on that point do you expect like how how much dose reduction than it is on revenue and then it might one expect from the combination kind of given any preclinical work you all have done where it's a combination.
Well thanks.
I forgot I mean pretty chunky huh, you cant predict how many we're doing the experiment to do those strange yet.
Yeah.
Remiss of me to speculate.
Well, we have to say that I mean of course, we report them.
Uh huh.
Okay. Thanks, very much everybody.
Thank you.
And we'll take our next question from Eva Pinos Altos with TD Cowen.
Hi, good afternoon, and thanks for taking our questions.
We've been getting some questions about the recent paper on resistance mechanisms that are rising around 40% of patients treated with <unk> inhibitors. After a few cycles.
How should we think about this phenomenon in the context of you know.
The high efficacy in the high <unk> negativity rates that we've seen in any actual clinical trial.
Yeah.
It started and then I'll pass it over to Neil look I think.
The data that we've generated and Eva thanks for the thanks for the question I think the data that's been generated obviously published in nature.
It really shows the the efficacy of the molecule and the ability to generate.
You know remissions deeper emissions MRV negative remissions.
In a large subset subset of patients.
30% I think the idea of being overall response rate of over 50%. We are seeing some mutations and I think there is it's across all the the Menin inhibitor class. We believe will be affected by this but I think yeah. You had quoted a 40 up to 40% I think it was a subset of our patient data.
Important to note that.
The great efficacy that we're seeing in the population is really and in the presence of some resistance. So of course, some patients will have some resistance overtime to all targeted therapies. This is not uncommon. It's it's been shown with all therapies, even outside of Menin inhibitors. The idea here is that we have.
You know a highly effective treatment and the ability to combine our agent and move it earlier in treatment. It is a step in the direction of treating patients as early as possible to potentially.
Deal with mutations that arise, but it is a it's a small part of the population and I think importantly, we feel that our it's likely our baseline that these mutations were likely in a they were present in probably below the level of detection.
And they are probably their you know these are first line patients. So heavily pretreated and have received a lot of our proprietary so I think overall I think we are we're feeling that our data is quite strong our well obviously be first to market and.
It will have a great profile I think mutations arise with all of these therapies and the ability to combine it move it earlier in treatment well Ah yeah over time help us treat even more patients. So we're quite encouraged by the data and it's always good to be on the front end of the science of.
Knowing that we have Oh, we have a molecule and we have the ability to understand kind of why some patients actually don't respond.
Thank you for that.
Yes.
Yeah, and you mentioned moving to the to the earlier lines. How do you expect these resistance mechanisms to impact the U S and in the frontline setting in combo with other agents and also also perhaps in the maintenance setting.
Yeah, Let me, let me ask Neil to respond to that yeah. So thanks, Michael and thanks, David for the question. So you know as Michael touched on it's our working hypothesis is that a lot of these patients actually present, a baseline but remained below the limit of detection and so just to reiterate a little bit you know we don't anticipate any.
From what we've already reported that the mutation data were derived from the same study that we've reported clinical data on what the median duration of response at nine months.
Importantly, also remember that 80% of patients who had a CR cri each other.
And we're already negative this is incredibly important from a therapeutic perspective it in very heavily pretreated patient population as Michael also alluded to you know obviously, we're at the forefront of the science here, where we're we understand it well.
Learning more about it but we understand it to a large extent.
And we absolutely believe that moving to earlier lines of therapy quickly, which is what we're planning to do during the course of 'twenty 'twenty four and actually are laying down the plans for them for doing that with the combination studies that we just described is a little bit earlier about moving to earlier lines of therapy is important.
So because we also believe that combining that regimented with standards of care in earlier lines of therapy is more likely to eradicate any any problems that exist already.
Already and also to preclude the emergence of of of resistant clones, Ontario.
Thank you.
Thank you Eva.
Yes.
And we'll take our next question from Paul Rama with J P. Morgan.
Hey, guys. So much for taking the question I'm just thinking about both the Kmt to a data coming from augment 101 in the third quarter and the future readout for M. P. M. One.
How do we think about how much sort of post maintenance post transplant maintenance data, we might get from both sort of near term and long term from these cohorts. Thanks so much.
Yeah Ana Thanks for the question.
Look I think that the data suggests that or at least the data from phase. One suggests a lot of patients that go on to transplant and certainly the ones that had reached an emerging negative response at up to 40% or so had had moved onto transplant I think that's a that's a number that's rarely seen in targeted therapy and so I would expect.
And based on the change in the protocol as you know in the phase one we weren't permitted to put patients back on therapy or they were permitted to go back on therapy. That's a yes, a significant change from that between the phase one into phase two where we have the ability to put patients back on after an grafman. They have the ability to go back on therapy that goes for Kmt too.
As well as M. P M. One patients and so if you take that forward and relieves. The you know the tension point of not being able to go back on therapy you.
You should be seeing a higher yeah, I would say a significant portion of patients who go on to get successful transplant to be eligible and and go back on so I.
I can't give you specific numbers, but I would say that this is a emerging paradigm in this in this field at relapsed refractory disease and so we're excited to see you know what what portion of the phase. Two is a is as is and that is it in that camp. So yeah. It's time will tell.
Thanks, so much for taking our question.
Yeah. Thank you Ann.
And we'll take our next question from Yigal <unk> with Citigroup.
Hi, Mike and team thanks for taking the questions I just wanted to switch topics to accept so on that one.
You just spend a little bit of time talking about any differences in the patient populations between the phase one two.
<unk> got to have one trial.
So on patients more.
Elite retreated given the.
Uptake of Rux Lytton and resurrect.
And then secondly can you comment at all on what physicians and maybe even the regulators said with respect to study that's randomized, but does not have a control arm. Thank you.
Yeah. Thanks for the question. So let me first start off with the differences in the patient populations.
The lack thereof.
I think these are third line plus patients.
The phase one two that we enrolled and then read out last year had.
Had those patients in it.
The patients that we're enrolling in a Gaba a two or one have the same patients you did see patients who had a prior <unk> and also the Jakob He I'm sorry, the a reservoir rock drugs. So we are seeing patients in both trials that had prior if they're you know significant prior therapies, including the.
Only approved ones.
And and so we expect that the patient population to be quite similar.
And then on your second question relates to Hum.
Sorry, so, but yeah the regulator randomization.
Yeah. So as you point out in your implicit in your question is the fact.
The fact that the trial is randomized three doses.
Bobby two alone we're talking about.
But it is it is yes call. It single arm, it's not a it's randomized between the doses, but doesn't have a placebo arm that is in fact true I think yeah. This is the design very similar design to a reservoir rocks. The trial that the cabinet ran to get their drug approved very similar and obviously we've had.
Significant agency feedback and they've reviewed everything that we've done and we had alignment on that design. So we we expect that this will lead to a full approval. It's not a it's not an accelerated approval, but it is a full approval.
And of course, it's all dependent upon us having positive data in submitting a package so.
So I think that's the that's the easiest way to think about it.
The design is a sort of tried and true based on what others have done and where are you now we're following what the agency has guided us to.
Okay got it and then another important question, which I'm sure you've thought about a lot of your your I E Q2 week and obviously some of the other market participants are oral.
Just talk a little bit about how you see that in terms of.
Achieving strong uptake.
So number assuming you make it to market.
Do you think that this can be a therapy that would.
The extended into the community practice as well as to be the.
<unk> sensors.
Thanks.
Yeah. Thanks for the question.
Turn it over to Angela and she's going to ours.
Hey, guys. Thanks for the question no where we're very we've gotten very strong feedback from physicians about the overall profile of Fracs are telling them.
It is an IV you know NOL does mm approved therapies that are oil, but many of the prior treatments that physicians have been using to control. The disease included IV therapies as well as a there are very.
Difficult to use treatments and I think what really drives. These physicians is can I get this disease under control for my patients.
Yeah, the infusion fast until now that's pretty straightforward a 30 minute.
Bush infusion and in the trial that we're running physicians are able to change patients to a once monthly frequency after six months or so.
Maybe an option for patients in the real world as well, we're also thinking about subcutaneous formulation that could alleviate some of these differences awesome.
Okay. Thanks, and then just one quick clarifying one Mike.
You mentioned that 276 milligram you have that data.
So just to confirm you don't need to do any more clinical work with that dose to obtain that.
Label claim so that does not right.
Yeah. Thanks for your call.
We've we had said several months ago that we were undertaking a pretty extensive Quinn farm program, which is which is necessary for filing and this was part of that set of work the clean Pharm work and so we've enrolled a sufficient number of patients to generate the data that derives the dose that we talked about the <unk>.
276.
And so we expect to enroll patients in the.
In the.
Oh, sorry, the the phase III trial, the phase two trial sorry, the approval trial argument went to one that has additional patients not on a strong set three or four inhibitor that'll be included ultimately in the registration filing.
But in terms of actually having data to support what we need at $2 76 that have that in the label. We we we we believe we have sufficient data.
Great. Okay. Thank you.
Thank you Paul.
And we'll take our next question from Peter Lawson with Barclays.
Hey, Thanks, Thanks for taking my questions just a follow up around the.
If patients that you would need.
To file without that strong <unk> four inhibitor.
Yeah.
Yeah, Hi, Peter Thanks for the question no we haven't disclosed how many patients that that is I think we've said in the.
We'll enroll a sufficient number of which to justify the dose and we've done so when we talk to the agency of Naves. They are aligned with that and so we.
We feel very confident that we have now will have a label of course, the drug has to be approved but the label will show that any patient will have the right dose at the right time.
Okay. Thank you and then I don't know if you've ever mentioned this but if you ever have you seen responses.
In AML patients that have already failed another menin inhibitor.
Thanks for the follow up I don't think we've actually called that out in our dataset and I don't know.
I don't know the actual answer to that but we haven't specifically called out under a dataset. So it's a little hard for me to give you a specific answer for it.
Got you. Thank you and then just final question around accident them at.
On the box office success for the Rux, plus actually turn them out. So that's the first line phase one gvhd combination trial, what do you think that is.
What do I am sorry, Peter could you repeat the last part again, what do I think what what is exactly the boss of successful do you want to see.
Yep.
Right now it's a it's a fair question I.
Maybe I'll turn it over to Neil to respond to that I think we're.
We're talking about the phase two trial in a phase one phase two trial, yes.
Thanks, Michael I mean, this is being executed by the partner and so.
I I would address that question to them.
Ultimately the the the strategy longer term, it's going to be executed by by inside actually so I think it would be a probably better if you if you're asked insight.
Perfect. Thank you.
Thank you Peter.
And we will take our next question from Caltech Patel with <unk> Securities.
Yeah, Hey, good afternoon, thanks for taking the questions.
Maybe a couple on ax until a map in the top line readout do you do you expect to show any I know its topline read out but do you expect to show any data on the durability for the six months or so follow up results that you may have.
Yeah. Thanks for the question look.
Look I think what we're we haven't disclosed what our.
The what the actual data will be the breadth of the data I should say that we'll be disclosing on a on the topline I think suffice to say, where we're at we'll endeavor to put enough data out that are really speaks to the profile and allows people to have.
And accurate view on.
Not only have the drug in the trial, but also what are the long term potential is relative to <unk>.
The market opportunity and so.
It's a little bit early for us to speculate on exactly what that.
What we're gonna have and are in the topline disclosure, we do need to spend some time with our partner and align their so it'd be a little bit early for me to.
It's hard to kind of give you too much detail there, but I think suffice to say, what we're gonna put out enough data that.
Allows our.
Investors to understand the profile of the drug and what the long term potential looks like at least preliminarily. It allows us also to follow up with a presentation at a medical meeting that will be it will be circling around.
Got it and do you do you intend to apply for the real time Oncology review program to our tour.
Our program for the shrunk.
Yeah. Thanks for the follow up I think.
It's an open question and something will have to also align with our partner on <unk>. As you May know I believe cadman had applied for that is it was it was granted our tour.
With their review of our restaurant so.
It's something that we.
Yeah, we generally don't comment on our regulatory strategy. So much as to what we may or may not be able to accomplish.
But.
It's on the table and where well have some discussions about it relative to our with our partner.
Okay got it and then one on the combination trial.
Have you have you are inside decided if you'll have a control arm with with steroids and in that trial.
Thanks for the question I think it's still under consideration as today the exact design of a trial and we'll be saying more soon.
But little early again, a little early for us to disclose what the exact design of that trial.
Okay. Thank you.
Thanks, so much.
Once again, if you'd like to ask a question. Please press star and one on your Touchtone phone.
We'll take our next question from Joel Beatty with Baird.
Hi, Thanks for taking the question.
First one is on Rocky Mountain could you discuss the size of the market opportunity for the two separate registrational cohorts and how they compare with each other for both the initial you know I'm just if I can.
Near term label as far as our longer term potential.
Yeah. Thanks, Joe Thanks for the question I'm going to turn it over to Angela She described.
And your.
I'm thinking about the relapsed refractory setting and I think we feel that he can teach you a population and E. N. P. M. One population maybe closer than expected and given that more he can teach you a population is is likely to relapse.
And need additional.
<unk> therapy to address their disease.
So the correct assumption is it's closer than what you would expect given the initial diagnosis of MTN lending kandi today moving to frontline I think we've given the guidance in and a lot of publications suggest about 30% of them now is.
And Tim one well at closer to 10% as cancer today.
Got it. Thanks appreciate that and then a question.
Question on potential in licensing of new earliest stage agents.
We've heard about that for a number of partners.
The conference calls and and in fact, the two agents that you. Currently have are great successes that have come out of that but I suppose two programs move towards late stage with adult data coming in the next few months does that affect your company's appetite for going back in and licensing earlier stage engines at this point.
Yeah, Joel Thank you for that.
Look I think business development continues to be a really important component of our strategy long term.
As you pointed out we were successful in licensing the two agents that were working on.
We are moving them through registration trials, we do expect to do a fair amount of lifecycle that we mentioned earlier line trials for both agents are adjacencies other other indications such.
Such as IPF Fracs until a man.
Solid tumors are for a minute I think the idea to bring in additional early stage targeted oncology assets. We had we've been fairly descriptive about what that means we're talking about sort of preclinical stage lead stage preclinical through phase one.
These are the types of assets that are one we feel that our lens to our expertise.
And we can develop them efficiently.
To kind of grow them into assets that have meaningful value and.
In a reasonable period of time.
And also fit in with the overall kind of dynamic of our company, which is growing to accommodate.
Eight additional additional works, but certainly don't want to overwhelm the important work that's going on in the in the late stage setting our priority does remain our.
Our two key assets, but bringing on additional one or more additional assets of the early stage variety could add a tremendous amount of value in a reasonably short period of time and again it remains the future of syntax.
To be able to do that so we are keen to to to evaluate it and now I will say that the bar remains extremely high for us to trade off and even spend one marginal dollar on additional assets. While you have two approved we're approvable agents are in our midst. So we do remain quite interested.
But also.
Keep the bar very high to make sure that we bring only the best assets into the pipeline.
And I'll, let lastly, I'll say the team is quite focused on it here and of course. The addition of Neil to our team really well, we think add in that yeah that Friday. So we're again excited about business development and realize the scope of work is is significant for our current pipeline that looked at.
And overtime.
Thank you.
Thanks Joel.
And we'll take our next question from Brad <unk> with Stifel.
Hi, everyone. This is Don.
Our eyes are on for Brad Canino two questions from us.
On revenue.
Acting samples pre and post treatment for it.
Ounces of men, one resistance mutation and when should we expect a formula.
This is public data.
And on actually tell them what might be available and the top line.
It can help us confirm differential activity versus perhaps you're wrong.
Thanks, Dara until I think the answer to your first question is no. We're not we're not a we're.
We're not tracking that data.
And we're not you know yeah I think the.
The idea is that we published the data that we had and I think we shouldn't you shouldn't expect to see additional data coming out on on resistance any anytime soon from the from the current dataset.
And then I'm sorry, the second question.
Yeah, what might be available in topline for thinking about potential differential activity versus raws you're off for example, anti fibrotic benefit anything like that.
Yeah, maybe I'll turn it over to Neil to take that so with all the caveats of the dangerous a cross study comparison.
I think your main question is how much data are we going to topline. So you guys can actually yeah got it got it kind of idea about what you've done what you're going to see or our anticipation and of course. This has to be aligned with our partner our anticipation is to topline as much data as.
As we think we need for our you know to be useful to to the investment community and.
And the others are booked but you know one caveat is that we also want to preserve the ability to present the full dataset on a forthcoming medical meetings. So we don't want to compromise that either in fact are rapidly.
In discussions with insight, our our kind of parts of insight about what that might look like so.
So we're not going to be you know, it's not gonna be minimalist.
We willing to as much data there as we can get them to be at the caveats that I that I mentioned.
Because I think that at a medical meeting in the future.
Yeah very helpful. Thank you.
Thank you so much.
And we'll take our next question from Justin Zaman with B T I D.
Hi, guys. Thanks for taking the question and congrats on the progress here just a quick question on on <unk> is there.
Any demand or any interest in additional investigator sponsored studies in either AML or or other indications or other combinations that that we should be expecting out in the future.
Yeah, Justin first of all welcome to this index. Thanks for thanks for covering us and.
Look forward to working with you.
Look I think we we actually have a lot of interest in <unk> and then there's a whole assortment of work that.
Has either kicked off or will be kicking off are related to AML and somebody other disease states that we're looking at.
We haven't.
Really disclose that in any any natural for them yet so I think you'll you'll see some data are emerging.
Emerging over the coming months from some of these some of these trials that are some of the investigators are doing but.
But we havent been especially prescriptive about how that how that's going to roll out or what what those are yet so stay.
Stay tuned.
But I think there's a.
Suffice to say a lot of a lot of interest in what we're doing and the investigators around the world who are not only involved in our trials, but also some that are not that have asked us to do a particular trials of interest. So maybe Neil has a comment to make is well yeah. So thanks.
Thanks, Michael.
I mean, there's a lot of interest and Humana and the AML community and acute leukemia community M. L. A new York community.
So what I would say is that we are developing our my cycle management plans for for retina beyond the initial indication that as we've discussed a couple of times already on the call in terms of the combinations that we're doing at the moment what are the early phase studies looks like we're not ready to discuss the exact designs of the studies.
So there will be studies that we will sponsor and then there will be studies that will be conducted through ISS and our intention is to have an integrated evidence plan micro to be generating data across all relevant patient populations.
We can fully fully informed of scientific Oh, you provide broad scientific knowledge about C. A S. E molecule. So you know as we're as we're ready to reveal not only Ah.
The details of our own <unk> sponsored studies, but also the broader time, we'd be happy to do that in future.
Great I appreciate you taking the question. Thank you.
Welcome.
Thank you Joseph.
And it appears that we have no further questions at this time.
I will now turn the program back over to Michael Metzger for any additional or closing remarks.
Yeah.
Thank you all we look forward to seeing you at several upcoming medical conferences, including the American Thoracic Society annual meeting in May and the European Hematology Association annual meeting in June .
Also be attending the Goldman Sachs Healthcare conference in June as well as other investor events, which we hope you will join us that.
Have a great evening.
That concludes today's teleconference. Thank you for your participation you may now disconnect.
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Yeah.
Thank you Shelby.
Greatly appreciate it.
Yeah.
Yeah.
Okay.
Yeah.
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Uh huh.