Q4 2023 Syndax Pharmaceuticals Inc Earnings Call
Kept biotechnology company.
And with opportunities to expand well beyond the initial indications for <unk>, we envision creating long term value with these franchises for years to come.
On slide three let me take a moment to review some recent accomplishments.
With <unk>, our highly selective <unk> inhibitor, we made significant clinical and regulatory progress in the fourth quarter.
The 2023 American Society of Hematology annual meeting in December we presented robust data from the phase one and phase II portions of the augment 101 trial that included a late breaking oral presentation, highlighting pivotal results from the Kmt <unk> acute leukemia cohort as well as multiple phase one combination.
Asian trials that demonstrated <unk> ability to safely and effectively combined with standards of care.
In late December we announced the submission of an NDA filing for <unk> under the Fda's real time oncology review or <unk> program for the treatment of adult and pediatric relapsed or refractory <unk> rearranged acute leukemia.
Submitting the NDA under our tour insurers early engagement with the FDA throughout the review process, helping to Derisk, the submission and provide a potentially expedited timeline to <unk> approval.
We expect to receive a <unk> action date for <unk>, this quarter, which should align with a third quarter approval date.
For <unk>, our anti CSF Oner antibody I am excited to announce today that the FDA granted priority review and a <unk> action date of August 28, 2024 for the treatment of chronic graft versus host disease or gvhd. After failure of at least two prior lines of systemic therapy.
Positive data from the pivotal <unk> trial presented at a plenary scientific session at Ash in December form the basis of the BLA submission.
And last quarter, we also initiated a phase II double blind randomized clinical trial for the treatment of idiopathic pulmonary fibrosis or IPF that Neil will later detail in this call.
Financially we are in a very good position, we strengthened our balance sheet in the fourth quarter with an additional $258 million in cash and Keith will go into more detail in our financials later in this call.
We continue to prepare for commercialization in 2024, our first mover advantage is of high strategic importance and we are busy ensuring that we successfully execute two first and best in class drug launches.
For <unk>, we are focused on prelaunch activities and we are finalizing our go to market strategies for both <unk> and <unk> and we look forward to communicating in the coming months.
In January we exercised our option under our agreement with our partner insight to co commercialize <unk> in the United States and provide 30% of the commercial effort is there is a considerable benefit to promoting two products simultaneously to a highly overlapping and targeted physician prescriber universe.
2024 is shaping up to be a historical year for <unk> as we prepare to launch two first and best in class products and I am confident that we have the expertise resources and determination to achieve our goals.
Now, let's turn to slide four and I'll begin our recap of some recent clinical data for <unk> that investigators presented at the Ash annual meeting in December.
There was significant excitement for <unk> and the reaction to the data that investigators presented which clearly demonstrated <unk> potential to become a cornerstone for the treatment and NPM, one and Kmt <unk> acute leukemia.
The data presentations have translated to continued strong enrollment in our clinical trials through additional engagement from the medical community as well as additional requests for investigator sponsored trials that could ultimately expand the use of the drug once approved.
In the late breaker presentation for the augment 101 pivotal trial, we indicated that Kmt <unk> acute leukemia patients achieve clinically significant responses to treatment with a high overall response rate of 63% and responses were observed across all major subgroups.
<unk> delivered a high rate of deep responses with the CR cri rate of 23%, 70% of which were <unk> negative.
At the time of the data cutoff. The median duration of CR CRH response was $6 four months base based on the Kaplan Meier estimate with 46% or six patients remaining in response.
Moving to slide five in the augment 101 trial, 39% of the overall responder population proceeded to a stem cell transplant, which is higher than historical benchmarks in this population of less than 5%.
Many of these patients proceeded to transplant prior to achievement of a CR CRH at.
At the time of the data cutoff, 71% of patients who underwent a transplant had either restarted regimented or were eligible to restart as maintenance therapy a.
A few of these patients had been receiving maintenance treatment for as long as eight months with several continuing on therapy, highlighting the potential for long term treatment with <unk>.
Physicians with whom we have engaged our impressed by <unk> ability to rapid tumor clearance in heavily pretreated patients, enabling many of them to undergo a potentially curative bone marrow transplant treating physicians have repeatedly told us that they want to use revenue as early as possible during treatment to bring more.
As to transplant and then extend responses by continuing treatment following transplant and graph net.
Unanimously heard from Kols at our Ash Investor event and continue to hear from physicians today. Their belief that continued use of <unk> post transplant should lead to the best possible outcomes and it is an attractive option for these patients.
Turning to slide six.
The final pivotal cohort of the augment 101 trial continues to enroll relapsed or refractory <unk> mutant AML patients.
It is designed to enroll 64 patients and up to 20 pediatric patients with multiple.
Presentations, highlighting the consistency of Menin inhibition across <unk> mutations and <unk> rearrangements as a monotherapy agent.
And in combination with standards standards of care, we continue to see the excitement building for <unk> and <unk>.
We are quite pleased with the recruitment in the trial and are reaffirming our guidance of expected completion of enrollment in the late first quarter or early second quarter of this year we.
We expect to report topline data from the trial in the fourth quarter of 2024, and importantly, we continue to look forward to a potential approval in 2025 based on an NDA filing for <unk>. Following revenue managed anticipated initial approval in <unk> for acute leukemia.
The phase one NPM one data that we've reported for every minute supports our conviction that <unk> could be an important treatment for this AML population.
Across monotherapy and in combination we've generated consistent results between <unk> and NPM one acute leukemias.
In the phase one portion of augment 101, 50% of <unk> patients achieved an overall response and 36% achieved a CR for CRH and importantly, all patients with CR, CRH, where <unk> negative.
Consistent with the <unk> population revenue also enabled a high percentage of MTM, one responders to proceed to transplant, 43%.
And responses have been durable this.
This is despite many of the patients failing prior <unk> therapy, and receiving prior stem cell transplants.
It's worth noting that <unk> has been well tolerated in patients with relapsed or refractory <unk> AML.
In the phase one results there were no grade four or five Qt prolongation, no patients experienced more than great to differentiation syndrome, and no patients discontinued due to treatment related adverse events.
Now turning to slide seven.
We believe that <unk> will form the backbone of treatment for patients with <unk> and NPM, one acute leukemias, our clinical strategy extends beyond the initial relapsed or refractory indications and into the frontline and post transplant maintenance settings through combinations with approved therapies.
In the frontline setting there are basically two broad categories of patients those who are fit and can tolerate intensive chemotherapy and those who are deemed unfit for intensive chemotherapy and with traditionally received <unk> plus <unk>.
Our frontline strategy is to add revenue mounted on to standard of care treatments to show that revenue amount of can be used effectively in combination, thereby increasing efficacy without negatively impacting the tolerability or safety profile of those regimens.
We started combination development with <unk> plus <unk> in frontline unfit AML population in the beat AML trial.
The trial is expanding to validate the recommended phase two doses and we expect to have an additional data update for this trial later this year.
In parallel we are planning the <unk> plus as decided in pivotal trial that we expect to initiate by year end.
To address frontline AML patients fit enough to tolerate intensive chemotherapy, we initiated a phase one dose escalation trial of <unk> in combination with standard of care induction therapy, known as seven plus III.
Here, we also anticipate identifying and <unk> for <unk> and initiating a pivotal trial for this combination as soon thereafter.
On slide eight is the data from the beat AML trial, a phase one trial being conducted by the leukemia and lymphoma Society.
In this trial frontline AML patients who are unfit for induction chemotherapy are dosed with the triplet of <unk> <unk> and a decided in 28 day cycles.
In an interim look at data data from 13 patients.
100% achieved a complete remission for CRC.
And all patients for whom we had in MRV assessment achieved in <unk> negative response.
This is significantly higher than what would be expected from <unk> plus agent <unk> alone based on the results of the bi alloy trial, where patients achieved a 66% CRC rate and only 24% achieved in <unk> negative response.
Importantly, I'd like to emphasize that there are there was no impact on the safety or tolerability observed by adding <unk> to the doublet regimen.
Turning to slide nine.
<unk> was also evaluated and is another oral <unk> combination among patients with relapsed or refractory AML.
Interim data from this trial known as save AML was conducted by investigators from the MD Anderson cancer Center and presented at Ash.
The same trial evaluated the all oral combination of <unk> and a fixed dose combination of decitabine and <unk> in relapsed or refractory AML or mixed phenotype of acute leukemias.
In the interim presentation nine patients with either NPM, one Kmt <unk> or 98 mutations were enrolled into the trial.
These patients had received a median of three prior lines of therapy and over half of them had received prior <unk> and prior hyperventilating agents at.
At the interim assessment, 100% of patients achieved a response and 78% achieved a complete remission.
Importantly responses were observed across all three patient subset NPM, one Kmt <unk> four and <unk> 98.
Triple combination was also well tolerated at both active doses of <unk> met the trial, including the current monotherapy <unk> two dee with no new or increased safety signals observed beyond what would be expected with vanadic lax and our hypo methylated issue.
Now to slide 10.
<unk> one on acute leukemias represent up to 40% of all AML patients and there are no FDA approved targeted therapies for this population.
Inclusive of the expansion opportunities there is the potential to address upwards of 12000, NPM, one <unk> acute leukemia patients across various settings.
We believe relapse or refractory Kmt <unk> acute leukemia alone represents a $750 million market opportunity in the U S. The annual incidence of Kmt <unk> acute leukemia is about 2600 patients and the majority are refractory to frontline standard of care treatments we.
We estimate a median duration of therapy across the treated population of approximately nine months and we believe the clinical data supports pricing competitively with other targeted therapies in AML, such as the flip three or <unk> inhibitors.
We anticipate that with the only age and disease agnostic label in <unk> acute leukemia, along with no. Other treatment options approved in this population and no near no near term competition revenue met them should become the treatment of choice for patients with relapsed or refractory Kmt <unk> acute leukemia.
We expect that our first mover advantage and the experienced physicians will gain treating patients with <unk> could extend meaningfully beyond <unk> and allow us to build a formidable franchise and then in the next few years augmented by a second indication in <unk> AML.
Our market research suggests that if approved if approved oncologists or like is it likely to prescribe recommended as either the second or third line agent of choice for the treatment of <unk> AML.
We estimate that this population would be slightly larger than the relapsed or refractory <unk> acute leukemia population and based on our phase. One results. We also believe overall efficacy and treatment duration will be consistent between the <unk> and NPM, one relapsed or refractory population.
Having two distinct market segments in acute leukemia is available to us <unk> and NPM, one would create a total accessible population of.
Somewhere between 5000 6500 patients in the relapsed refractory setting and an addressable market opportunity.
We are also investigating the opportunity to expand to solid tumors. Our proof of concept signal seeking phase one clinical trial in metastatic colorectal cancer is ongoing. This trial is based on preclinical science that supports the role of Menin <unk> interaction and beta Katina.
<unk> driven tumors. We are following these patients and expect to provide an update on the on the progress of the dose escalation phase of the trial in the second quarter of 2024.
We would perceive single agent activity reflected as responses or prolonged stable disease is encouraging and this third line patient population.
Let me now turn to <unk>, our monoclonal antibody targeting the CSF one receptor beginning on slide 11.
As noted earlier, we're thrilled that the BLA for <unk> in adult and pediatric patients with chronic gvhd after failure of at least two prior lines of systemic therapy has been given a <unk> action date of August 28, 2024 by the FDA.
Data from the global pivotal agave tool one trial form the basis for this application.
<unk> to a one trial, which was showcased during the plenary scientific session at Ash met its primary endpoint of overall response rate by cycle seven day, one using the 2014 NIH consensus criteria for chronic gvhd across all three dose groups.
The overall response rate was 74% at a dose of <unk> three milligrams per kilogram administered every two weeks. The responses were durable with a median duration of response not yet reached at the time of data cutoff and 60% of responders were still responding at one year.
<unk> was well tolerated in the trial with a low 6% rate of discontinuation.
Most common adverse events for consistent with the on target effects observed in prior trials.
<unk> is differentiated from other approved therapies for chronic gvhd in that it is the first investigational chronic gvhd treatment to target inflammation and fibrosis through the inhibition of disease associated macrophages.
On Slide 12, you will note that responses, including Crs, we're seeing across all organs involved and notably in fibrosis dominated oregon's, including a soft esophagus joins fascia and lung.
Over 85% of patients reported a reduction in chronic gvhd related symptom burden and agave 201, which supports the potentially pronounced impact. This mechanism can have on patients suffering from chronic gvhd.
These results reinforce its potential as a first and best in class CSF, one our monoclonal antibody antibody in chronic gvhd.
I'll now turn the call over to Neal speak about the IPF trial that we started in late fourth quarter as well as the scientific rationale for the use of <unk> in IPF.
Thank you Michael.
Turning to slide 13.
We're excited about the opportunity to expand the development of <unk> until them up into fibrotic diseases, such as idiopathic pulmonary fibrosis or the monocyte macrophage macrophage cell lineage plays a key role.
IPF is a chronic fibrosis lung disease for which there are limited treatment options let me.
Two drugs have been approved on both have only been shown to slow, but not halt or reverse disease progression.
The opportunity for a cure is lung transplant, which is limited.
Less than 5% of patients.
With the estimated U S prevalence of IPF growing to over 180000 people by 2026.
Increasing need for a new well tolerated unaffected medications.
There are several reasons why we are excited to pursue fibrotic disease outside of chronic gvhd and why we have confidence that <unk> may provide meaningful benefit in IPF.
There is a growing understanding of the important role of macrophages that macrophages play is a master regulator of the fibrotic process.
There's a wealth of preclinical and clinical data, indicating that the CSF oner signaling pathway may play an important role in the development of pulmonary fibrosis.
One such preclinical dataset from an in vivo bleomycin pulmonary fibrosis model is shown in the panel on the left.
The bleomycin model is commonly used to investigate the potential of therapies to address the lung fibrosis and of this experiment animals were treated with an anti <unk> antibody or saline controlled nine days after the administration of bleomycin.
The histological section on the top left shows the normal lung with extensive flight aerospace Conversely, the bleomycin treated lung has extensive fibrosis as indicated by the dark colored materials.
Strikingly the lung treated with bleomycin, and then therapeutically with an anti CSF oner antibody and Danine has significantly less fibrosis markedly preserved Hoyt aerospace.
Analysis of the extent of fibrosis, using the Ashcroft score indicate indicates that significantly less damage to the lungs occurs in the presence of the anti CSF Oner antibody.
Even more encouraging are the clinical data fracs until now have been patients with pulmonary manifestations of chronic gvhd, where clinically notable improvements in lung function has been observed.
A panel on the right shows the data originally presented at the American Thoracic Society meeting last year from patients in the phase one two chronic gvhd trial of <unk>, who have chronic gvhd related bronchiolitis.
<unk> said from our POS as you can see most patients.
Patients experienced improvements or slowing of decline of pulmonary function, which is very unlikely to occur spontaneously. These.
These data in conjunction with the Oregon specific data from the agave to a one trial presented earlier strongly support the therapeutic potential of <unk> and interstitial lung diseases, including IPF.
Turning to slide 14.
Here, we lay out the design of our recently initiated multinational phase III trial of <unk> in IPF is a 26 week double blind placebo controlled multicenter trial, which aims to include 135 patients randomized two to one to receive <unk> three milligrams per kilogram of <unk> every two weeks or placebo on a.
<unk> of standard of care.
The primary endpoint is the annualized rates of decline in forced vital capacity or SEC key secondary endpoints include disease progression quality of life specific to patients with obstructive Airways disease and others.
We believe this study as robustly designed to demonstrate proof of concept <unk> IPF, thereby enabling us to advance the molecule into phase III pivotal development potentially let me now turn the call back to Michael.
Thank you Neil.
Turning now to slide 15, which highlights the broad clinical and commercial opportunity for <unk> at 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 wholly addressed with.
Current treatments there are no cures for this advanced population of chronic gvhd patients and patients who are initially treated with with corticosteroids are then cycled through a variety of additional therapies.
While patients may be treated with any of the approved therapies. The order in which they are used may depend on the physician's experience with how it given agent may address specific manifestations of the disease.
Newer entrants jakafi and <unk> have had successful commercial launches, which speaks to the unmet need in chronic gvhd and the substantial commercial opportunity for a differentiated agents such as <unk>.
<unk> suppresses monocyte derived macrophage activation and proliferation, which may provide more comprehensive control of the disease and currently approved therapies.
Addressing inflammation and fibrosis and one mechanism of action is a key differentiator and also supports moving <unk> earlier in the treatment paradigm to potentially prevent organ damage before it occurs.
Because <unk> is an antibody drug drug interactions are expected to be minimal and <unk> and the unique mechanism of action may offer the benefit of being an ideal combination partner with standard of care therapies currently used for the treatment of chronic gvhd.
The opportunity to expand to ex U S markets and into other high value indications could build significant additional value for <unk> over the next few decades.
We're looking forward to the insight led initiation of additional trials of <unk>, including a phase II combination trial with Jakafi and <unk> phase III combination trial with with corticosteroids, which is expected to commence in mid 2024.
I'll now turn the call over to Keith to review our financial results Keith Thank.
Thank you Michael.
Turning to slide 16.
As Michael mentioned earlier in the fourth quarter, we strengthen our balance sheet, adding $258 million, providing strong validation of <unk> potential from both existing as well as new high quality institutional investors.
The $600 million on the balance sheet at year end is expected to provide cash runway through 2026.
Turning to the income statement operating expenses for the fourth quarter were $77 9 million.
Comprised of $55 1 million of research and development expense and $22 $8 million of selling general and administrative expense in line with guidance.
Looking forward, our financial strength enables us to focus on the execution of advancing our pipeline and achieving an exceptional launch of <unk> and <unk> later this year.
Keeping in mind that we've always embraced a disciplined approach to resource allocation.
I'd like to provide financial guidance for the first quarter and full year 2024.
For the first quarter the.
Company expense expects research and development expense to be $56 million to $62 million and total operating expenses to be $82 million to $88 million.
For the full year 2024, the company expects research and development expenses to be $240 million to $260 million.
Total operating expenses to be $355 million to $375 million include.
Including approximately $43 million of noncash stock compensation expense.
With that let me now turn the call back over to Michael.
Thank you Keith.
As you've heard during the call 2023 was a landmark year for growth and execution.
As evidenced by our positive pivotal trial, Readouts and two regulatory submissions for our two lead drug candidates.
Both of which are first and potentially best in class treatments. This is only the beginning of what's to come for syntax.
We are in a significant transition into a fully integrated biopharmaceutical company, serving multiple patient populations of high unmet need both programs offer the potential for broad franchise opportunities beyond their initial registration indications, adding to its index as long term growth potential we have ambitious goals and milestones that I've set out for <unk>.
24, and that are laid out on slide 17, I am confident that we have the right plan and team in place to execute on them.
As always I would like to express my sincere appreciation to this index team collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs through your important work, we are getting closer to delivering on our mission of improving the lives of patients with cancer.
I'd also like to thank our committed long term investors, who continue to share our vision and support us in buildings index with that I'd like to open the call for questions operator.
At this time I would like to remind everyone in order to ask a question press star.
While the number five on your telephone keypad, if you would like to withdraw your question press bar number five.
Well pause for just a moment to compile the Q&A roster.
Our first question comes from Peter Lawson with Barclays. Please go ahead. Your line is open.
Hi, This is <unk> on for Peter Congrats on all the progress.
Ask that for ex <unk> can you comment on expectations for your launch and related to that it sounds like you're still expecting a thank you potential approvals over the next quarter.
And thats essentially possession for sales of <unk> potentially dependant on USA alrighty.
Got you.
Okay.
Thanks for the question.
So first off.
I think you broke up a little bit on the on the second question.
<unk>.
Do you want to take the first question on insurance.
So thanks for the question Shay This is Keith so.
For <unk> third quarter, you know we have the <unk>.
When the FDA actually.
<unk>.
The drug is still a question.
As we've laid out.
Earlier in the year, we've opted into the co promotion and as Michael said earlier to the co promotion of <unk> until the map. So we will be ready.
With our sales force prior to the approval of either product. So as you can see by looking at linked in or looking at our web site in the careers section. We're currently recruiting for all of the territory managers.
So that's public knowledge that will have them onboard and trained up prior to approval of either product with respect to your question around the timing of the initiation of <unk> of revenue and we will have to wait until later this quarter. When we received the <unk> date for its action date from the from the agents.
And I think at that time, we'll have a better idea of when to expect the initiation of revenue net of revenues.
Okay.
Does that answer your questions.
Okay.
Our next question comes from <unk> Rama with Jpmorgan. Your line is now open.
Hey, guys. Thanks, so much for taking my question.
Maybe expanding on <unk> comments, just now just remind us of where you are in terms of the sales force sales team build out what are your some of your pre commercial.
Plans here in the near term and then maybe just on expenses, how we think about the growth here quarter over quarter looking to 2020 for especially on the SG&A line as we think about the launches.
And if on thanks for the question I'll, maybe I'll take the first part in terms of sales force build out and then I'll leave the.
The rest to Keith to answer so so I think as we've said in the past we're building.
Building out our.
Commercial organization to accommodate both the launch of <unk> and now we've opted into the <unk>.
Co promote with insight around <unk> to provide up to 30% of the.
The ftes for that effort.
It's a overlapping as I said in my remarks, overlapping and highly targeted call point and so the opportunity here is with.
Roughly 40 to 50 representatives to cover the U S.
Quite extensively and also cover both products. So that's the build out of that sales force.
We will continue until the time of right up until we have approval on both agents, which and as Keith mentioned, we have a <unk>.
At the end of August for Fluor.
<unk> and we expect.
<unk> imminently for <unk> as well so we have we will be ready well in advance of.
Both of those to to put the sales force in place and leadership has been has been higher than this.
Doing extensive work to get ready, maybe Keith you want to handle the second one so on a pump with respect to your question on SG&A expense.
We gave guidance today on on total Opex for the year $3 55 to $3 75.
That includes noncash stock comp.
And then for R&D.
The $2 40 to $2 60, so based on that you can.
It's circa 100 slightly higher than total SG&A for the.
And all three combination trials were 113 milligrams.
Twice a day on 163 milligrams twice a day.
Different patient populations.
Obviously in the beat AML trial, there were newly diagnosed save we've just discussed they were.
Heavily pretreated relapsed refractory and on augment 102, there were heavily.
Pretreated relapsed refractory patients and in all three trials the dose limiting toxicity windows for both doses were cleared.
Okay. So.
And in with respect to beat AML.
The group is now doing is expanding those cohorts to further refine.
What the <unk>.
Would it be for a phase III trial, and we stated many times publicly that it is our intention.
Proceed to that phase III.
By the end of the year.
So.
Yeah. So so just just one final point those two doses 113, and 160 163 milligrams as the presumptive monotherapy full dose.
When administered with.
With a strong <unk> four inhibitor, okay and 113 milligrams is also highly a highly active also you have to recall that <unk>.
And decided in the beat AML trial was administered at full dose.
So there is.
The.
Okay.
There is no question in our mind that the combinability of <unk> with <unk> in the newly diagnosed as well as in the other two settings.
It's clear.
That's very helpful.
Makes it clear and then last question just on extra sales and marketing I think in your prepared remarks, you said.
<unk> is responsible for 30% of the marketing efforts.
I think on our pumps question, you said, 30% of Ftes.
How are the marketing efforts.
Was 30% of marketing efforts to find is that specifically, 30% of ftes or are there other metrics.
So next needs to deliver as well such as.
Touch points with physicians or a call point or something else.
Yes.
It over to Keith Phil Thanks for the question. So apologies if I wasn't clear if we werent clear.
So the.
Our partnership agreement with insight stipulates. So we have the ability to contribute 30% of the promotional effort.
From a from a sales call point perspective.
We'll be delivering 30% of that effort. So I mentioned it before in Ftes.
Because I didn't wanted to speak like in the number of reps, but we will be delivering 30% of that of that sales force effort, but don't forget it's a combined P&L right.
So we'll put our 30% the cost of that 30% effort into the combined P&L inside will put there are 70% of the cost of their effort into the P&L and then any any advertising and promotion expenses incurred by insight because they are taking the lead from that perspective would go into that joint P&L and that joint.
Some of that joint P&L called commercial profitability of the product is split 50 50.
Perfect Thats very helpful stent, they pick up.
Yeah. Thanks, Thanks for taking my questions.
Thank you Phil Thanks, Phil.
Yeah.
Our next.
Thomas from <unk>.
Your line is now open.
Good afternoon provided.
Provided peak sales opportunities, but how do you see the KMT two hour launch playing out this year things in terms of number of patients that are available in the relapsed refractory setting where they're concentrated in what to expect for the pace of uptake.
Alright. Thanks for the question I think maybe a little early to start speculating about the sales ramp and projection.
<unk> reserve.
The ability to give a little bit more guidance as we get closer to two.
To commercialization I think as we stated in our remarks, we think it's a <unk>.
Yes, it's a compelling opportunity commercially in the sense that we will have a first to market best in class product to address patients even earlier than they were tested in the clinical trial. So we're talking 2600 patients overall, probably about 2000 of which are are treated in the relapsed refractory setting we believe that we'll have.
The opportunity to address the vast majority of those patients.
And as we've pointed out.
In previous discussions that these patients are in dire need of therapy.
Many of them can go to transplant hopefully through the use of <unk>.
Treatment with <unk> with <unk>, and then potentially back on treatment in the post transplant setting. So there is we think a highly addressable population physicians seem to be quite motivated to use the drug.
And so we've seen that in our trials, but we've also heard that from physicians. So I think this sets up as a really interesting new opportunity for a drug to come to market with.
Really no competition at the current point at this current point too.
To get in the way of a very successful launch. So that's that's where we how we see it today and in terms of projections and launch and ramp.
We preserve that for future discussion.
Our next question comes from the line of Michael Schmidt with Guggenheim. Your line is now open.
Hey, guys. Thanks for taking my question I had one on the.
The first line setting for <unk> in combination with seven plus three.
In your opinion, what is the right way too.
To view, a frontline combo data.
With <unk> inhibitors.
Seven plus three and specifically given that.
One would expect very high CR rates, presumably on top of seven figure already.
What are what are other benchmarks that you said youre looking for in your on study.
Noting MRV status for example, transplants transplant rates or any other efficacy measures that are important in your opinion.
Yeah, Michael Thanks for the question.
Important one certainly to get a handle on I think the mid.
Seven plus three regimen as you know is highly effective.
In frontline patients <unk> in <unk> patients initially respond.
Upwards of 80% of patients respond.
To those treatment treatment. However, they don't usually respond for long so there's relapse that happens.
It happens with most of those patients.
Things to look for beyond just CR rates.
<unk> of course would be.
Would be Mardi and transplant rates, which.
We would be looking for obviously, we've seen high rates of both in relapsed refractory patients now we're moving it would be moving to frontline and you'd expect to see.
Equal or better rates of Mardi and certainly transplant in earlier line settings and so.
I think thats. The those are some really important measures duration.
Treatment of course.
Plus III to short course.
80 to treat with regimented and keep patients in remission for an extended period of time.
Obviously, something that we'd want to.
That we'd want to see of course, it's <unk>.
Days right. We haven't you haven't seen an amended inhibitor perform in the frontline seven plus three.
As of yet so I think it would be up to us to kind of set the trend for what what's the bar it looks like there, but certainly from a CRM perspective.
And a safety perspective, you kind of know what you'd want to see relatively clean relatively clean profile and highly effective but you need to continue on and <unk> deep durable responses as well Neil do you want anything yes. So maybe just two things I would add to that.
And I think there may have been a regulatory context to the question.
About what the puts.
The potential endpoint could be its certainly too soon to talk about that I think Michael has.
As mentioned.
<unk> negative Crs not as certainly an endpoint of interest.
Whether or not it could be an approvable endpoint remains to be seen and we will of course be engaging in discussions with the agency.
As we move closer to having now initiated our dose ranging trial as we move closer to initiating our phase III trial, and then the only other odd that I would that I would make would be.
If you look at the $7 three trials that have been conducted really over the last.
Sort of 10, 10 to 12 years going back as far as minus carnival component suited maintenance phases.
And you could assume that any seven three trial that we would conduct would also include the maintenance phase and in support of that what we have seen recall that what we've seen in the relapsed refractory setting post transplant.
That is patients who have remained on therapy for a protracted periods of time speaking to the tolerability of revenue amount of.
In a in a relapsed refractory setting and therefore, we anticipate that as we move towards the newly diagnosed setting patients who would be for instance, given monotherapy maintenance after induction consolidation therapy would probably would most likely tolerate the medicine very well as well.
The molecule rather.
Okay. Thank you.
Thank you Michael.
Our next question comes from William Dong that some of it with Citi. Your line is now open.
Hi, guys. This is <unk>. Thanks for taking my questions I have a few on <unk>.
First congrats on the Paducah date.
Wondering how involved you are in the regulatory process from this point out obviously, we know inside is leading the proceedings, but will it be part of the mid cycle review will you be able to weigh in on label negotiations how should we think about that.
Yes. So thanks for the question look we're very involved with obviously without <unk>.
We.
We generated the data and it's been a very close collaboration with with insight and so we are involved in the regulatory process.
And our <unk>.
Working with them closely to get this drug approved in all facets. So.
That youre thinking about label negotiated and things like that we are I would say suffice to say very involved with with what's going on so that's an exciting development for the company and obviously, we have great experience with the molecule you'd want to think that were involved so that's certainly what it is.
Was there a second part to your question or was that did I cover.
That's very clear I wanted to ask another one on IPF.
I'm, sorry for getting our simply.
It.
Just don't remember from prior calls but.
I know youre evaluating those airports <unk> per kg dose, which was obviously the dose that looked at us and above it to on.
Just wondering what kind of gives you confidence that's the right dose specifically for IPF.
Why why didn't you need to do dose optimization work or as a disease biology really similar enough that you felt.
Confident enough not to do that obviously, we're dealing with a different endpoint here. So just curious what your thoughts are.
Yes.
Yes, Hi, it's Neal.
The question. So it's a good question, we did have a long a long discussion internally about about the dose selection. So a couple of things.
Quite clearly the <unk> three milligram dose.
And a guy in the Agave trial was superior to the other two doses and we don't need to.
To go back over that quite clearly the superior dose in terms of.
In terms of efficacy as well as tolerability.
And what we have talked about a number of times.
Over the past year, and particularly before we announced the details of the IPF proof of concept trial that we talked about today was that we were looking for an efficient and efficient trial design.
And therefore.
The most efficient trial design, which would get us to.
Proof of concept.
Answer.
Efficiently, meaning efficiency in terms of.
The design of the trial, but also in the context of acute the trial was the one that we've described today and we felt that on the balance of.
The balance of everything that it was reasonable to go ahead with one dose.
In this trial and that those should be <unk> three milligrams I think one point that you would need it to yes, I think that there is sufficient overlap from a biological perspective to have made that decision and that sort of partly that has to that too.
To that decision.
All right, maybe I would add onto that.
You probably know that we did extensive dose ranging in the course of the phase one as well.
It will trial.
<unk> also looked at early on we looked at healthy volunteers, we know how this antibody behaves and so.
And the effect that it has on the macrophage.
And so I think the understanding.
Pharmacology here and therefore, how we think it would translate to patients in IPF kind of gave us some.
I think some good confidence that 0.3 would be the appropriate dose. In addition to what Neil has added.
Yeah.
Very helpful. Thanks, very much.
Thank you welcome.
Our next question comes from the line.
From Bank of America. Your line is now open.
Hey, guys. This is Alex <unk> on for Jason Thanks for taking my question.
Appreciating it's somewhat early but with regards to your regulatory submission for <unk> can you provide some color on what you expect to be included in the label or the eight efficacy evaluable AML and <unk> patients.
Trs <unk> warrant a tumor agnostic label.
And what are your base case expectations on central AP monitoring requirements Barrick DFS. Thanks Keith.
Prolongation. Thank you.
Okay, maybe I'll turn it over to Neil we talked a little bit about the label and then maybe talk about any kind of safety sure well our anticipation is that the label let.
Let me.
Presage, what I'm about to say by reminding everyone that we got BTB back in December 2022, four.
It came to <unk>.
AML and adults and kids so.
The development program moving moving forward from them those based on the phase one data.
The program moving forward from there was based around a premise that we would have a potential for a broad indication as you know, we actually pooled cohorts <unk> and.
And I and the submission for came to toy relapsed acute leukemias and it's based on on that pooled analysis, which of course includes AML.
Adults as well as pediatric patients. So our anticipation is and of course the agency has been fully unlocked.
Coming on that journey with us.
The whole way, including from BTB before <unk> and onwards.
So.
That's the indication that we're looking for so not the exact words, but came to <unk> rearranged acute leukemias in adults and children with respect to your second question about safety monitoring.
We don't we so first of all.
From a class perspective, our broad class maintaining targeted therapies in AML.
Anticipate we would probably anticipate a boxed warning for differentiation syndrome.
Since that is typical of of all of these agents in class right. It's on target.
Uh huh.
The agency knows that happens to us.
We.
We do not anticipate we anticipate.
Morning, a precaution for Qt, but that's it.
Our next question comes from cockpit Paypal with B Riley. Your line is now open.
Yeah, Hey, good afternoon, and thanks for taking the question.
Maybe a couple on the seven plus III combo study can you give us.
Some color on what goes so Ravi Menon your.
We are planning to start with.
And then.
The second question is how should we think about the enrollment.
Flip between the <unk> and the NPM, one population and that combo study would it be a <unk>.
50, 50 split or are you.
Are you anticipating hearing of.
The <unk> patients or is there more fit.
Yes, maybe I'll take the second question I'll give the first one to Neal yeah. So I think Thats I think you just said it in terms of <unk> versus <unk>, we don't really know, but I think it's.
Sure.
<unk> patients overall are more fit than that unfit, Brian so thats, where they skew whether or not we have.
Skewing in our population of patients to Kmt <unk> are not we don't know at this point, but we do expect representation of both.
And Neel do you want to talk about the seven plus three combo.
Starting dose yes.
And just to just one thing to add on it doesn't really matter.
The split between came to try and MQM one patient in the first instance, right, but we're actually seeking to demonstrate.
A demonstrated that.
The combined ability of revenue amount of about seven plus three.
The as we mentioned a little bit earlier on the call, but no. Other combination trials that we've described thus far there have been two doses tested 113 milligrams and 163 milligrams.
And those are the doses or the equivalent doses without the three or four.
Strong said three or four that we will be testing in the 7% to three trial as well.
I mean, we know we know based on the comments that we made around your own data that we presented before we know that they are combinable with.
Both chemotherapy and also vanilla flex space to HMA therapy.
Our next question comes from the line of Jeff Van <unk> with <unk>. Your line is now open.
Great. Thanks for taking our question. This is jeet Mukherjee on for Justin maybe just coming back to <unk> was hoping you could provide a little bit of a sense of the opportunity for <unk> in IPF the subset of patients perhaps best suited for this therapy and what you'd be looking for from an efficacy perspective.
Yes, I don't know the.
Angela do you want to take that question.
Sure I can.
Sorry.
Keith.
Ill preface this by saying that.
We need a little bit more efficacy data to really hone in on the expectation, but I think we know that Neil mentioned on the call. There's two drugs that are approved.
And so a lot of patients cycle through both of them and sometimes.
See them added onto one another all they do is slow the decline theyre not actually treating the disease and so there is still a huge unmet need in the in the marketplace.
A very large number.
IPF patients out there.
Today, even in the U S alone and we would expect to be able to.
Yes.
Doing the trial to add on to standard of care. So we'd be looking at a second or third line utilization.
And I think.
We would expect based on positive data.
Significant uptake in that population because of the large unmet need.
Got it that's helpful and maybe just one more on <unk> just any additional color perspective on the combo studies Youre doing what <unk> been.
Steroids or.
In collaboration with insight and just what you'd be looking there from an efficacy and safety perspective to move.
One or both of those forward ultimately.
Hey, Angela do you want to follow on there yes.
Yeah sure so.
Again.
Until that bringing this Charles fibrotic.
Effect.
Theyre on patients.
Hopefully helping to manage the impact of the disease, Oregon's and therefore potentially.
Shifting the question.
The disease is is what we're trying is what we're trying to change with that combination therapies are moving up earlier could you really have a bigger impact on patients.
And their overall disease profile going forward, we anticipate.
Getting some data out of this trial.
In the coming years.
I think that would govern what the uptake would look like but.
This is something that physicians are telling us they are really looking for right now the only thing they have is steroids.
And Unfortunately does do as much as they do that and so if you could if you could get.
Sean.
Efficacy out of that combination could you minimize the use of steroids.
Bring estimate of up to an earlier population I mean, we know that.
Current estimated prevalent pool is about 14000 patients and so you could access a big chunk of that population.
Good data.
Thanks for taking up.
And our next question. Our next question comes from George Farmer with Scotia Bank. Your line is now open.
Hi, there.
This is clearly on for George Thank you for taking our questions.
From us on revenue.
So all you.
Do you have any sense on whether the FDA is intending to hold an <unk> meeting to discuss.
Approval package and Kim to TUI or AML.
Or yellow.
And secondly could you speak to the prospects for other indications for <unk>.
Great. Thank you for the question. So in terms of <unk>, we don't expect that the FDA will hold an <unk> for <unk>.
From time to time for new mechanisms, they do that more as a showcase than they do for any other reason, but we don't expect and we haven't received any word from the FDA to indicate that we would have in <unk>. So I think thats. The answer to your first question and then secondly, you had asked about prospects for additional indications.
Presume that means outside of leukemia, and as I mentioned in my previous remarks.
We are looking at <unk> or sorry <unk>.
In in colorectal disease.
Third line metastatic colorectal cancer.
As a monotherapy agent is obviously, a very difficult disease state and were.
We're going to have some data in the second quarter of this year are to first get at whether whether there is sufficient activity there as a monotherapy agent and how and how the drug performs.
There is this.
Thesis that we're pursuing a beta containing up regulated.
Tumor types, which is a broadly implicated phenomenon and through a lot of different cancers colorectal cancer as one and so there could be other cancers that we.
We look to CRE.
Whether they are susceptible to revenue amount of treatment. So stay tuned there may be more to come I think the first step here is is certainly.
The colorectal cancer trial that we're running.
Okay got it thank you.
Thank you.
This concludes our question and answer session I will now turn the floor <unk> <unk> and Mr. Michael <unk> for any additional comments or closing remarks.
Thank you all we appreciate you tuning in Tonight, and we look forward to seeing you at our planned investor events, including.
The upcoming Cowen and Barclays healthcare conferences in March and with that I wish you all a very pleasant evening. Thank you.
This concludes today's conference call. Thank you and you may now disconnect.
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