Q1 2022 Syndax Pharmaceuticals Inc Earnings Call

May 9, 2022

Good day and welcome to the Syndax First Quarter 2022 Earnings Conference call.

Good day and welcome to this index first quarter 2022 earnings conference call. Today's call is being recorded at this time I would like to turn the call over to Megan Meyers of Argot partners. Please begin.

Today's call is being recorded.

At this time, I would like to turn the call over to Megan Myers of Argo Partners.

Please begin.

Thank you, Operator.

Welcome, and thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax's First Quarter 2022 Financial and Operating Results.

Thank you operator.

Welcome and thank you to those of you joining us on the line and the webcast. This afternoon for a review of <unk> first quarter 2022 financial and operating results.

I'm Megan Myers with Argo Partners, and with me this afternoon to discuss the results and provide an update on the company's progress are Michael Metzger, Chief Executive Officer, Dr. Briggs Morrison, President and Head of R&D, and Alex Milti, Chief Accounting Officer.

I am Megan Myers with Argot partners and with me. This afternoon to discuss the results and provide an update on the company's progress and Michael Metzger, Chief Executive Officer, Dr. Briggs Morrison, President and head of R&D, and Alex <unk>, Chief Accounting Officer.

Also joining us on the call today for the question and answer session is Dr. Peter O'Dutleck, Chief Scientific Officer, and Dr. Anjali Ganguli, Chief Business Officer.

Also joining us on the call today for the question and answer session is Dr. Peter <unk> Chief Scientific Officer.

And Dr <unk> <unk> Chief business Officer.

This call is being accompanied by a slide deck that has been posted on the company's website, so I would ask you to please turn to our forward-looking statements on slide two.

This call is being accompanied by a slide deck that has been posted on the Companys website.

I would ask you to please turn to our forward looking statements on slide two.

Before we begin, I would like to remind you that any statement made during this call, that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation and Reform Act of 1995.

Before we begin I would like to remind you that any statements made.

During this call.

Are not that are not historical are considered to be forward looking statements within the meaning of the private Securities Litigation Reform Act of 90 95.

Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC.

Actual results may differ materially from those indicated by these statements.

As a result of various important factors.

Including those discussed in the risk factors section in the company's most recent quarterly report on Form 10-Q.

As well as other reports filed with the SEC.

Any forward-looking statements represent our views as of today, May 9, 2022, only.

Any forward looking statements represent our views as of today may nine 2022 only.

A replay of this call will be available on the company's website, www.synvax.com, following this call.

A replay of this call will be available on the Companys website www Dot <unk> dot com following this call.

With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of SYNVAX.

With that I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of setbacks.

Thank you, Megan, and thank you to everyone joining us on today's call and webcast.

Thank you Megan and thank you to everyone joining us on today's call and webcast on the heels of a transformational 2021, we're off to a strong start for 2022 and I look forward to sharing with you today, our recent progress in several key developments.

On the heels of a transformational 2021, we're off to a strong start for 2022, and I look forward to sharing with you today our recent progress and several key developments.

I'm especially excited to report that SYNVAX is now on pace to deliver two U.S. applications for potential drug approvals in 2023, a distant and aspirational goal for most biotech companies, and yet a near-term and highly achievable one for SYNVAX.

Especially excited to report that <unk> is now on pace to deliver two U S applications for potential drug approvals in 2023, a distant an aspirational goal for most biotech companies and yet our near term and highly achievable one for Sundar.

Despite the challenging market backdrop, we currently find ourselves with a solid balance sheet, and the support of a strong pharmaceutical partner to advance the development of one of our lead molecules.

Despite the challenging market backdrop, we currently find ourselves with a solid balance sheet and the support of a strong pharmaceutical partner to advance the development of one of our lead molecule.

We are well-positioned to expand both of our lead assets into new indications, and to build out a commercial organization to support the potential launch of these first and potentially best-in-class products.

We are well positioned to extend both of our lead assets into new indications and to build out a commercial organization to support the potential launch of these first and potentially best in class products.

We also have the flexibility to selectively pursue We also have the flexibility to selectively pursue business development opportunities, to augment our pipeline with additional promising molecules to complement the ones we have.

We also have the flexibility to selectively pursue business development opportunities to augment our pipeline with additional promising molecules to complement the ones we have.

The momentum is building at SYNVAX, and it is indeed a very exciting time for the company.

The momentum is building its syntax syntax and it is indeed, a very exciting time for the company.

Now, turning to slide three, we provide a high-level summary of our current corporate, priorities as we strive to realize a future in which people with cancers live longer and better than ever before.

Now turning to slide three.

We provide a high level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before.

Starting with Revumenib, our official generic name for SNDX5613, our highly selective menin inhibitor.

Starting with revenue minute, our official generic name for F&B X 50, 613, our highly selective <unk> inhibitor.

Enrollment in our three pivotal Phase II trials in patients with relapsed refractory MPM1 or MLR, acute leukemia, which we call Augment 101, 2A, 2B, and 2C, remains on track.

Enrollment in our three pivotal phase II trials in patients with relapsed refractory NPM, one or MLR acute leukemia, which we call augment 101, two a two b and <unk> remains on track.

We're also pleased to announce that we have enrolled our first patients in the BEAT AML and Augment 102 trials, which represent important expansion opportunities for the franchise in combination with other approved agents and begin to move us into newly diagnosed patients.

Also pleased to announce that we have enrolled our first patients in the beat AML and augment 102 trials, which represent important expansion opportunities for the franchise in combination with other approved agents and begin to move us into newly diagnosed patients.

Beyond acute leukemia, we will be initiating a proof of concept trial later this year in colorectal cancer to our knowledge represents the first assessment.

Beyond acute leukemia, we will be initiating a proof-of-concept trial later this year in colorectal cancer, to our knowledge, represents the first assessment of a menin inhibitor in patients with solid tumors.

Menin inhibitor in patients with solid tumors. This is an exciting development and Briggs will discuss this effort further in a few minutes.

This is an exciting development, and Briggs will discuss this effort further in a few minutes.

Moving to Axitilumab, our antibody against CSF1R.

Moving to act with Telematic, our antibody against CSF one are.

Enrollment is ongoing in our pivotal agave 201 trial in patients with chronic graft versus host disease with topline data expected in 2023 and.

Enrollment is ongoing in our pivotal Agave 201 trial in patients with chronic RAF versus host disease, with top-line data expected in 2023. In addition, we are excited to announce today that we recently received Fast-Track designation for Axitilumab for the treatment of CGVHD.

In addition, we are excited to announce today that we recently received fast track designation for <unk> for the treatment of C. Gvhd.

We are currently making, progress, working closely with our partner, Insight, to maximize the value of this important program, and expect to begin trials to move Axitilumab into earlier lines of CGVHD later this year.

We're currently making progress working closely with our partner insight to maximize the value of this important program and expect to begin trial to move <unk> into earlier lines of <unk> later this year.

And beyond RAF versus host disease, we remain on track to commence a phase two proof-of-concept trial of Axitilumab in idiopathic pulmonary fibrosis, or IPF, in the fourth quarter of this year.

And beyond graft versus host disease, we remain on track to commence a phase II proof of concept trial of <unk> in idiopathic pulmonary fibrosis or Ips in the fourth quarter of this year.

Again, I want to emphasize that we now have two registrational programs ongoing for two first-in-class and potentially best-in-class medicines in two areas of unmet medical need.

Again, I want to emphasize that we now have two registrational programs ongoing for two first in class and potentially best in class medicines in two areas of unmet medical need.

With filings for both programs expected in 2023, we are starting to expand the organization to, support the potential commercial launch of both molecules in the U.S. Later this year, we expect to hire the company's first chief commercial officer to lead the additional build-out of our commercial organization.

With filings for both programs expected in 2023, we're starting to expand the organization to support the potential commercial launch of both molecules in the U S.

Later this year, we expect to hire the company's first chief commercial officer to lead the additional build out of our commercial organization.

Let's now turn to slide four and provide further details on where we are with RevuMenid.

Let's now turn to slide four and provide further details on where we are with revenue minutes.

First, we are conducting three single-arm phase two trials that FDA has agreed may each serve as a pivotal trial. Each of these single-arm phase two trials represent an independent path to a separate indication. The Augment 101-2A trial is enrolling patients with relapsed refractory MLLR ALL, 2B is enrolling patients with relapsed refractory MLLR AML, and 2C is enrolling patients with relapsed refractory MPM1 AML. Each trial is open to, patients aged one month or older, and each trial will enroll independent of the other two.

We are conducting three single arm phase II trials that FDA has agreed may each serve as a pivotal trial. Each of these single arm phase II trials represent an independent path to a separate indication the.

The augment 101 to a trial is enrolling patients with relapsed refractory MLR.

<unk> <unk> is enrolling patients with relapsed refractory MLR AML and TC is enrolling patients with relapsed refractory NPM one AML.

Each trial is open to patients aged one month or older in each trial will enroll independent of the other two.

We may seek initial regulatory approval for RevuMenid based on the results of any one of, these trials should one trial enroll faster than the others, or we may seek initial regulatory approval with any two or three depending on when they complete enrollment. We are happy to report that additional site initiation and patient accrual across the individual trials is going well, and we are optimistic that we will be able to complete enrollment in at least one of these trials this year.

We may seek initial regulatory approval for <unk> based on the results of any one of these trials should one trial enrolled faster than the others or we may seek initial regulatory approval with any two or three depending on when they complete enrollment.

We are happy to report that additional site initiation and patient accrual across the individual trials is going well and we are optimistic that we will be able to complete enrollment in at least one of these trials this year.

Given our current trajectory and our view of the competitive landscape, we anticipate being the first company to achieve regulatory approval for RevuMenid inhibitor. Needless to say, we believe being first to market is important and accretive to the long-term value, of syndrome. We have agreement with FDA that for each trial, the primary endpoint will be the percentage of patients achieving CR-CRH, with secondary endpoints including durability of CR-CRH response, transfusion independence, overall survival, and safety. Importantly, the trial design allows patients to be treated with RevuMenib after bone marrow transplant, a design feature that allows us to start to understand the role of RevuMenib in the post-transplant maintenance setting.

Given our current trajectory and our view of the competitive landscape, we anticipate being the first company to achieve regulatory approval for amended inhibitor Needless to say we believe this is we believe being first to market is important and accretive to the long term value of syntax.

We have agreement with FDA that for each trial. The primary endpoint will be the percentage of patients achieving CR CRH with secondary endpoints, including durability of CR CRH response transfusion independence overall survival and safety.

Importantly, the trial design allows patients to be treated with revenue mounted after bone marrow transplant. A design feature that allows us to start to understand the role of <unk> in the post transplant maintenance setting.

We also have agreement with FDA on the statistical design of each trial. Each trial will enroll 64 adult patients and up to 10 pediatric patients.

We also have agreement with FDA on the statistical design of each trial. This trial will enroll 64 adult patients in up to 10 pediatric patients.

Beyond the augmented pivotal program in relapsed refractory disease, slide five highlights some of the additional opportunities we are exploring with RevuMenib, all of which build on the excellent safety and efficacy profile we have seen thus far with RevuMenib.

Beyond the augment pivotal program in relapsed refractory disease slide five highlights some of the additional opportunities we are exploring with revenue minimum all of which build on the excellent safety and efficacy profile, we have seen thus far with revenue Madam.

As I mentioned at the start of today's remarks, we are excited to share that enrollment is now underway in both the BEAT AML and Augment 102 trials. The Phase I BEAT AML Umbrella Trial is a collaboration with Leukemia and Lymphoma Society.

As I mentioned at the start of today's remarks, we're excited to share that enrollment is now underway in both the beat AML and augment one or two trials.

As one beat AML umbrella trial is a collaboration with leukemia and lymphoma society as part of the collaboration <unk>. The first <unk> inhibitor to be included in the trial will be combined with <unk> and the Asa siding diagnosed newly diagnosed AML patients who are unfit for induction chemotherapy. This trial will assess.

As part of the collaboration, RevuMenib, the first MEN inhibitor to be included in the trial, will be combined with venetoclax and the asositidine in newly diagnosed AML patients who are unfit for induction chemotherapy. This trial will assess safety as well as initial efficacy with top-line data expected next year.

<unk> safety as well as initial efficacy with topline data expected next year.

We expect a Phase II-III trial, which could serve as the basis for a regulatory filing, to follow soon after completion of the Phase I trial.

We expect a phase two three trial, which could serve as the basis for our regulatory following filing to follow soon after completion of the phase one trial.

The middle panel of the slide highlights our Augment 102 trial, which is designed to assess RevuMenib in combination with standard salvage chemotherapies used for pediatric patients with ALL or AML. I am pleased to report that patients have begun accruing in this trial as well.

The middle panel of this slide highlights our augment one or two trial, which is designed to assess <unk> in combination with standard salvage chemotherapy used for pediatric patients with AML or AML.

Im pleased to report that patients have begun accruing this trial as well.

Both the Augment 102 and BEAT AML trials are supported by preclinical data, which demonstrate the potential benefit of a MEN inhibitor used in combination regimens in these settings, and we are excited to see how these data translate in the clinic.

Both the augment 102 and beat AML trials are supported by preclinical data, which demonstrate the potential benefit of amendment inhibitor used in combination regimens in these settings and we're excited to see how these data translate in the clinic.

The third panel on the right illustrates the Intercept trial, which is designed to explore the activity of RevuMenib in patients with AML who have MRD-positive disease.

The third panel on the right illustrates the intercept trial, which is designed to explore the activity of <unk> in patients with AML, who have <unk> positive disease. This trial is being conducted as part of the intercept master clinical trial being led by the Australian leukemia, and lymphoma group and were expected and we expect patients to begin enrolling.

This trial is being conducted as part of the Intercept Master Clinical Trial, being led by the Australian Leukemia and Lymphoma Group, and we expect patients to begin enrolling into that trial later this quarter.

And so that trial later this quarter.

The Intercept trial is focused on investigating novel therapies to target early relapse and clonal evolution as a preemptive therapy in AML. The trial will enroll patients with measurable residual disease progression following initial treatment, a group of patients at very high risk of relapse that represents an important unmet medical need. The general tenet in cancer treatment is that the earlier you treat the patient's disease, the better patients do and the longer the patients stay on medicine.

The intercept trial is focused on investigating novel therapies to target early relapse and clonal evolution as a preemptive therapy in AML.

While we enroll patients with measurable residual disease progression. Following initial treatment a group of patients at very high risk of relapse that represents an important unmet medical need.

In general tenant in cancer treatment is that the earlier you treat the patients disease, the better patients do and the longer the patient stay on medicine. The intercept trial is a very creative approach to treating patients early in their disease course I'll also note that regimen is the first <unk> inhibitor to be included in the intercept AML Master clinical trial we.

The Intercept trial is a very creative approach to treating patients early in their disease course.

I'll also note that RevuMenib is the first menin inhibitor to be included in the Intercept AML Master Clinical Trial.

We believe the selection of RevuMenib for inclusion in two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with RevuMenib.

Believe the selection of revenue method for inclusion in two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with revenue minutes.

As we have previously communicated, we are committed to unlocking the full potential of Revumenib beyond the relapsed refractory acute leukemia setting.

As we have previously communicated we are committed to unlocking the full potential potential of revenue beyond the relapsed refractory acute leukemia setting slide six highlights our goals as a company to be the first to market in the relapsed refractory disease setting beyond that we intend to pursue approval in indications and additional value enhancing indications.

And patients with MLR in <unk> mutant acute leukemias, including the newly diagnosed and maintenance settings.

Slide 6 highlights our goals as a company to be the first to market in the relapsed refractory disease setting.

As we continue to develop revenue manner for use beyond treatment of relapsed refractory patients and into the first line treatment setting we see the opportunity to treat up to 12500 patients identified each year with the two forms of mutant acute leukemia NPM.

<unk>, an MLR represent up to 40% of the overall AML population, which to our knowledge will be the largest sub population of AML can be addressed by a new targeted therapy.

Beyond that, we intend to pursue approval and additional value-enhancing indications in patients with MLR and MPM1 mutant acute leukemias, including the newly diagnosed and maintenance settings.

Our goal is to engage patients early in their treatment journey get them into remission and maintain them in that state for months, if not years that emerging potential for revenue minimum is why we believe it could be one of the most important new franchises and largest market opportunities in hematology and certainly worthy of significant investments.

As we continue to develop Revumenib for use beyond treatment of relapsed refractory patients and into the first-line treatment setting, we see the opportunity to treat up to 12,500 patients identified each year with these two forms of mutant acute leukemia.

As I mentioned earlier, we are also preparing to start an initial proof of concept trial in solid tumors, yet another exciting new area of exploration for Ravi Menon, I'll now turn the call over to Briggs, who will walk through the biologic rationale development strategy and market opportunity for revenue and colorectal cancer.

Great.

MPM1 and MLR represent up to 40% of the overall AML population, which, to our knowledge, will be the largest subpopulation of AML to be addressed by a new targeted therapy.

Thanks, very much Michael.

But given that we've already established that are driving that because both in NPM, one MLR leukemias and have initiated a series of trials to explore the use of <unk> in earlier lines of leukemia therapy. We believe now is the time to turn our attention to exploring the utility of <unk> inhibition in diseases beyond leukemia.

Our goal is to engage patients early in their treatment journey, get them into remission, and maintain them in that state for months, if not years.

As we've continued to assess the emerging science across a range of opportunities we've decided that our initial clinical program.

That emerging potential for Revumenib is why we believe it could be one of the most important new franchises and largest market opportunities in hematology and certainly worthy of significant investment.

Thanks, Greg.

Advanced colorectal cancer.

On slide seven we note that colorectal cancer is the third most frequently diagnosed cancer and is the second leading cause of cancer death in the U S.

As I mentioned earlier, we are also preparing to start an initial proof-of-concept trial in solid tumors, yet another exciting new area of exploration for Revumenib.

When you look at unmet medical need.

Most notably in patients with metastatic disease.

It's well established that the beta continued pathway is a key driver of essentially all of them.

Final common pathway B data companion transcriptional activation of several transforming genes.

I will now turn the call over to Briggs, who will walk through the biologic rationale, development strategy, and market opportunity for Revumenib in colorectal cancer.

What has become increasingly clear.

What is required for beta Catania biotech.

Cancer, and the molecules like Ravi Menon, which disrupt the binding of MLR one committed to <unk>.

<unk> <unk> from transcriptional start sites.

Farming.

Briggs?

What's really quite remarkable is that one MLR one is displaced from the beta Catania complex colon cancer cells differentiate into normal colonic cells and lose their ability to proliferate.

This differentiation is highly reminiscent of what we see both pre clinically and clinically with revenue.

Differentiation.

Thanks very much, Michael.

Consolidated <unk> illustration of what we believe is happening in colorectal cancer cells in the panel on the left and not all one as a component of the beta continuing trends.

Given that we have already established that our drug is active both in MPM1 and MLR leukemias and have initiated a series of trials to explore the use of Revumenib in earlier lines of leukemia therapy, we believe now is the time to turn our attention to exploring the utility of mending inhibition in diseases beyond leukemia.

Jean like Mick and cycling that drives cell division and.

In the panel on the right and the presence of <unk>.

We see a disruption of the beta <unk>.

With eight to a loss of expression and cell differentiation.

Given this emerging science slide nine shows our development strategy for <unk> in colorectal cancer the.

As we have continued to assess the emerging science across a range of opportunities, we have decided that our initial clinical program, advanced colorectal cancer. On slide 7, we note that colorectal cancer is the third most frequently diagnosed cancer and is the second leading cause of cancer death in the U.S.

We have a significant unmet medical need, most notably in patients with metastatic disease. It is well established that the beta-catenin pathway is a key driver of essentially all final common pathway being beta-catenin transcriptional activation of several transforming genes.

The initial study will be a signal seeking trial in patients with it.

Given what has been described pre clinically we think we might see tumor responses actual tumor shrinkage, but given the differentiation that I've mentioned earlier. It's also possible that we will not see actual responses, but rather we will see a lack of progression as the cancer cells differentiate and lose their ability to proliferate.

Therefore, designed as signal seeking portion of the trial to look for either responses or disease stabilization.

<unk> are assessed using a well known resist assessments and disease stabilization as assessed by the disease control rate at six months.

I should note that the standard of care in this population of patients provides a very low response rate about 5% and the disease control rate at six months is only about 15% if.

If we start to see responses, we believe there could be a very rapid path to accelerated regulatory approval based upon <unk> and duration of response.

Illustrated as one option coming out of our proof of concept trial.

We don't see a significant response rate, but do see a cap rate.

First by the Dcs control right. The other option is to proceed to a small randomized trial to confirm the clinical activity of using PFS.

Okay.

We're currently finalizing the protocol for this trial and expect to start enrolling patients in the fourth quarter of this year with possible data anticipated by the end of 'twenty three.

What has become increasingly clear is that this travel is required for beta-catenin biotransferable cancer and that molecules like Revumenib, which disrupt the binding of MLR1 to Menin, displace MLR1 from transcriptional start sites, transforming genes.

I want to emphasize that the preclinical science supporting the role of Menin, <unk> interaction and beta Catania, and driven tumors such as colorectal cancer is quite compelling and we are eager to translate the science to the clinic. Nonetheless, we are taking a staged approach to studying this in the clinic starting with what we believe is a modest investment in a signal seeking trial.

What is really quite remarkable is that when MLR1 is displaced from the beta-catenin complex, the colon cancer cells differentiate into normal colonic cells and lose their ability to proliferate.

This differentiation is highly reminiscent of what we see both pre-clinically and clinically with red and pink cell differentiation.

This slide is a diagrammatic illustration of what we believe is happening in colorectal, cancer cells.

In the panel on the left, MNR1 is a component of the beta-catenin transformation of genes, like MYC and cyclins that drive cell division.

Let me turn the call back over to Michael.

In the panel on the right, in the presence of revumenib, we see a disruption of the beta-catenin, concept, which leads to a loss of expression and cell differentiation.

Yes, Thanks Briggs.

In this emerging science, slide 9 shows our development strategy for revumenib in colorectal, cancer.

Before we move on let me further emphasize that seeing disease control rates above standard of care, even seeing a few responses in these metastatic colorectal patients will indeed be a very exciting results.

The initial study will be a signal-seeking trial in patients with—given what has been, described preclinically, we think we might see tumor responses, actual tumor shrinkage, but given the differentiation that I mentioned earlier, it's also possible that we will not see actual responses, but rather we'll see a lack of progression as the cancer cells differentiate and lose their ability to proliferate. We've therefore designed a signal-seeking portion of the trial to look for either responses, or disease stabilization. Responses are assessed using the well-known resist assessments, and disease stabilization, is assessed by the disease control rate at six months.

As you May know this is an area of high unmet medical need where current therapies are not particularly effective.

I should note that the standard of care in this population of patients provides a very, low response rate, about 5 percent, and the disease control rate at six months is only about 15 percent.

If we start to see responses, we believe there could be a very rapid path to accelerated, regulatory approval based upon ORR and duration of response. That's illustrated as one option coming out of our proof-of-concept trial.

Right and the science translates into clinic. This discovery would enable us to next to meaningfully expand the market opportunity for <unk> inhibition beyond hemolytic disease.

If we don't see a significant response rate but do see high rates, that's assessed by, the disease control rate.

Let me now turn to <unk>, our potentially best in class monoclonal antibody therapy targeting the CSF one receptor.

The other option is to proceed to a small, randomized trial to confirm the clinical activity, using PFS. We're currently finalizing the protocol for this trial and expect to start enrolling patients, in the fourth quarter of this year, with possible data anticipated by the end of 2023. I want to emphasize that the preclinical science supporting the role of MEN and ML-L1 interaction, in beta-catenin-driven tumors, such as colorectal cancer, is quite compelling, and we're eager to translate this science to the clinic.

Nonetheless, we are taking a staged approach to studying this in a clinic, starting with, what we believe is a modest investment in a signal-seeking trial.

Let me turn the call back over to Michael.

Slide 10 is our pivotal trial for <unk> and C Gvhd.

Yeah, thanks, Briggs.

This trial is the <unk> for graft versus host disease trial called the <unk> hundred one.

Before we move on, let me further emphasize that seeing disease control rates above standard, of care, even seeing a few responses in these metastatic colorectal patients, will indeed be a very exciting result. As you may know, this is an area of high medical need where current therapies are not particularly, effective.

The trial is enrolling patients with <unk>, whose disease has progressed after two prior therapies.

If we are right and the science translates in the clinic, this discovery would enable, Syndex to meaningfully expand the market opportunity for MEN and inhibition beyond heme malignancies.

Let me now turn to axotilumab, our potentially best-in-class monoclonal antibody therapy, targeting the CSF1 receptor.

Patients must be at least two years of age and have net overall entry criteria. This is a pivotal dose ranging trial in which patients will be randomized to one of three treatment groups. Each investigating a distinct dose of <unk> given every SKU either every two weeks or every four weeks the primary.

Slide 10 is our pivotal trial for axotilumab in CGVHD. This trial is the axotilumab for graft-versus-host disease trial, called AGAVE-201. The trial is enrolling patients with CGVHD whose disease has progressed after two prior, therapies.

Patients must be at least two years of age and have met overall entry criteria. This is a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axotilamide given either every two weeks or every four weeks. The primary endpoint is response rate using the 2014 NIH consensus criteria for CGVHD. Secondary endpoints will include duration of response and validated quality-of-life assessments using the Lee-Simpson scale.

Endpoint is response rate using the 2014 NIH consensus criteria for CGP HD.

Secondary endpoints will include duration of response and validated quality of life assessments using the least symptom scale enrollment to the study is going well and we are on track to deliver top line data in the first half of 2023.

Enrollment of the study is going well, and we are on track to deliver top-line data in the first half of 2023.

We're also delighted to announce late last year that we closed our global collaboration with Insight. This collaboration brings together two companies with a solid track record of innovation to accelerate and maximize the development of axotilamide.

We're also delighted to announce late last year that we closed our global collaboration with insight. This collaboration brings together two companies with a solid track record of innovation to accelerate and maximize the development of exits allomap.

Our Phase I-II CGVHD data presented at ASH in December of last year received very positive feedback from the investigator community, and further underscores its best-in-class profile.

Our phase one two C. Gvhd data presented at Ash in December of last year received very positive feedback from the investigator community and further underscores its best in class profile.

Through our collaboration, Syndax and Insight will pursue an expanded set of indications in CGVHD and other fibrotic diseases.

Through our collaboration <unk> and insight will pursue an expanded set of indications and see gvhd and other fibrotic diseases.

Together, we plan to assess novel combinations of axotilamide and Insight's JAK inhibitors, with the goal of establishing axotilamide in earlier settings within CGVHD and expanding its market opportunity.

Together, we plan to assess novel combinations of <unk> and insights JAK inhibitors with the goal of establishing <unk> in earlier earlier settings with within C gvhd and expanding its market opportunity.

As we previously mentioned was our intention, we plan to initiate a robust Phase II trial in IPF in the fourth quarter of this year.

As we've previously mentioned was our intention we plan to initiate a robust phase II trial in IPF in the fourth quarter of this year.

The first expansion outside of establishing CGVHD is a beachhead into other fibrotic diseases, where we believe axotilamide could have a significant impact.

First expansion outside of establishing <unk>.

Gvhd is a beachhead into other fibrotic diseases, where we believe <unk> could have a significant impact.

Successful development in IPF could lead to an additional approval and a very important indication of considerable value, and would provide support for axotilamide and other fibrotic-driven diseases that Syndax and Insight could explore over the course of the collaboration.

Vessel development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support for <unk> in other fibrotic driven diseases, that's index and insight could explore over the course of the collaboration.

Slide 11 highlights our view of the broad clinical and commercial opportunity for axotilamide.

Slide 11 highlights our view of the broad clinical and commercial opportunity for <unk> that.

We believe CGVHD represents a high unmet medical need and an important commercial opportunity, with approximately 14,000 patients suffering from CGVHD in the U.S. today.

We believe C. Gvhd represents a high unmet medical need and an important commercial opportunity with approximately 14000 patients suffering from CGP HD in the U S. Today. The recent approvals in early successful commercial launches of insights Jakafi and <unk> have begun to delineate the commercial.

The recent approvals and early successful commercial launches of Insight's Dacafi and Sanofi's Resiroc, have begun to delineate the commercial opportunity in CGVHD.

Opportunity and see Gvhd despite.

Despite recent advancements in this area, to our knowledge, axotilamide is the only agent in clinical development, that specifically targets the monocyte macrophage lineage.

Despite recent advancements in this area to our knowledge <unk> is the only agent in clinical development that specifically targets. The monocyte macrophage lineage Bolsa index and insight believed the data generated to date with <unk> Telematics suggests it has the potential to play an important role in the treatment of C. Gvhd, both as a monotherapy.

Both Syndax and Insight believe the data generated to date with axotilamide suggests it has the potential to play an important role, in the treatment of CGVHD, both as a monotherapy and, given its safety profile, in combination with complementary medicines such as Dacafi or other JAK inhibitors within the Insight portfolio.

And given its safety profile in combination with complementary medicines, such as Jakafi or other JAK inhibitors within the insight portfolio.

Through combinations in the frontline setting, as well as the opportunity to expand XUS, we envision the CGVHD opportunity more than doubling as shown on this slide.

Through combinations in the frontline setting as well as the opportunity to expand ex U S.

We envision the CGP HD opportunity more than doubling as shown on this slide.

As we move axotilamide into additional indications, starting with IPF, we really see axotilamide contributing materially to the value of our company moving forward.

As we move <unk> into additional indications starting with IPF, we really see <unk> contribute contributing materially to the value of our company moving forward.

Finally, on slide 12, this summarizes the transactions that led to the acquisition of the Menin MLR and Axitilumab programs. We believe these transactions underscore our robust capabilities to identify and evaluate high-value differentiated assets, as well as the clinical development expertise to bring these compounds through key value inflection points.

And finally on slide 12 summarizes the transactions that led to the acquisition of the Menin MLR and exit telling that programs. We believe these transactions underscore our robust capabilities to identify and evaluate high value differentiated assets as well as the clinical development expertise to bring these compounds through key.

Inflection points, we anticipate in 2022 that we'll be able to continue to expand our pipeline through in licensing of earlier quality differentiated assets, we expect that.

We anticipate in 2022 that we will be able to continue to expand our pipeline, through in-licensing of earlier quality differentiated assets.

We expect to remain among preferred partners of such transactions.

To remain among preferred partners of such transactions.

I'm going to now turn the call over to Alex to review our financial results.

I'll now turn the call over to Alex to review our financial results Alex.

Alex?

Thank you Michael.

Thank you, Michael.

Let me now take a few minutes to discuss our financial results for the first quarter of 2022.

The results of our operations for the first quarter of 2022, and the comparison to the prior year quarter are included in our press release. So I wanted to repeat I mean these remarks.

The results of our operations for the first quarter of 2022 and the comparison to the prior year quarter are included in our press release, so I won't repeat them in these remarks.

Additional financial details are available in our first quarter report, which was filed today. I would like to point out that our net loss for the quarter was $37.2 million, or $0.63 per share, compared to our net loss of $27.7 million, or $0.54 per share, for the same period last year. This difference is primarily attributed to the increased clinical and CMC activities for both of our programs.

Additional financial details are available in our first quarter report, which was filed today.

I would like to point out that our net loss for the quarter was $37 2 million or.

<unk> 63 per share.

To a net loss of $27 7 million.

<unk> 54 per share for the same period last year.

This difference is primarily attributed to the increased clinical and CMC activities for both of our programs.

Turning to slide 13, we ended the first quarter with $397 $9 million in cash and cash equivalents at <unk>.

Turning to slide 13, we ended the first quarter with $397.9 million in cash-in-cash equivalents, and 59 million shares in pre-funded warrants outstanding. Our current cash runway now extends into the second half of 2024, and supports our expanded development and early commercialization plans for both the Exit DLMF and the MNIM programs during this period and provides us flexibility for continued business development.

59 million shares and pre funded warrants outstanding.

Our current cash runway now extends into the second half of 2024.

And so for us our expanded development and early commercialization plans.

For both <unk> and <unk> programs during this period.

It provides us flexibility for continued business development.

Looking ahead, I'd like to provide financial guidance for the second quarter and full year of 2022. For the second quarter of 2022, we expect R&D expense to be $30 to $35 million, and total operating expense to be $38 to $42 million, including approximately $4 million of non-cash stock compensation expense.

Looking ahead I'd like to provide financial guidance for the second quarter and full year of 2022.

For the second quarter of 2022, we expect R&D expense to be $30 million to $35 million and total operating expenses to be $38 million to $42 million.

Including approximately <unk> <unk>.

$4 million of noncash stock compensation expense.

For the full year 2022, we expect R&D expense to be $130 to $140 million, and total operating expense to be $160 to $170 million, including approximately $14 million in non-cash stock compensation expense for the full year of 2022. The increase in R&D and operating expense in 2022 compared to the prior year period, is driven by the expansion of both Exit DLMF and MNIM into registration trials, expansion into new indications, and initiation of prelaunch commercialization activities.

For the full year 2022.

R&D expense to be $130 million to $140 million.

Total operating expense to be 160 to 170 million, including approximately $14 million in noncash stock compensation expense for the full year of 2022.

The increase in R&D and operating expense in 2022 compared to the prior year periods is driven by the expansion of both exit settlement.

And into registration trials expansion into new indications and initiation of pre launch commercialization activities.

With that, let me now turn the call back over to Michael.

With that let me now turn the call back over to Michael.

Thank you, Alex.

Thank you Alex.

Let me close the call by again emphasizing the tremendous progress we have made as a company.

Let me close the call the call by again, emphasizing the tremendous progress we have made as a company.

GenX has always been focused on delivering new medicines, that extend and improve the lives of people with cancer and other serious diseases.

<unk> has always been focused on delivering new medicines that extend and improve the lives of people with cancer and other serious diseases and today with two high value ongoing registration programs. A notable achievement in its own right. We stand on the precipice of realizing this goal.

And today, with two high-value ongoing registration programs, a notable achievement in its own right, we stand on the precipice of realizing this goal. And the potential of these programs extends well beyond their initial registration indications, with both offering broad franchise opportunities.

And the potential of these programs extends well beyond their initial registration indications with both offering broad franchise opportunities.

We believe RevuMenib could have utility across a wide range of clinical settings in acute leukemia, as well as potentially in some solid tumors.

We believe revenue minutes could have utility across a wide range of clinical settings in acute leukemia as well as potentially in some solid tumors. Our immediate goal as a company is to be the first to market in relapsed refractory acute leukemia, and then drive additional value potential by expanding its use into newly diagnosed and maintenance settings and NPM one in MLR.

<unk> leukemias.

Our immediate goal as a company is to be the first to market and relapse refractory acute leukemia, and then drive additional value potential by expanding its use into newly diagnosed and maintenance settings in NPM1 and MLR acute leukemias.

The same franchise potential hold track, the telematics, where broad opportunity exists both in the various lines of therapy, and CG Phd and across a broad range of fibrotic diseases, starting with IPF.

Underpinning all of these efforts we have the balance sheet to aggressively advance our programs through key near term milestones.

And lastly, we remain confident in our ability to identify and bring in novel molecules to deepen our portfolio, particularly in a more challenging market where competition for high quality assets may be diminished.

A proven track record of delivering on this pillar of our corporate strategy and I believe this is a core strength of our company and management team.

The same franchise potential holds for axotilamide, where broad opportunity exists both in the various lines of therapy in CGVHD and across a broad range of fibrotic diseases, starting with IPS.

In addition, I would like to thank the many committed long term investors, who continue to help us in building this great company.

With that I'd like to open the call for questions.

Underpinning all of these efforts, we have the balance sheet to aggressively advance our programs through key near-term milestones.

As a reminder to ask a question you will need to press star followed by one on your telephone keypad.

We could not accomplish what we have and what we hope to achieve without our wonderfully talented team here at Syndax, our collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs.

If your question has been answered or you wish to withdraw your question Ross.

Again, Thats star one to ask a question.

In addition, I would like to thank the many committed long-term investors who continue to help us in building this great company.

Your first question comes from the line of Madhu Kumar from Goldman Sachs. Your line is now open.

And with that, I'd like to open the call for questions.

One cohort or several cohorts in the first half of 2023, given the kind of roku maintained it you've seen so far do you expect the reported one versus multiple at one go how are you thinking about that today.

Yes, Madhu thanks for the question.

Look I think.

What we were referring to was actual enrollment in the trial and how the cadence kind of rolls forward from there. So we have three independent as you pointed out we have three independent trials that are enrolling we haven't we haven't given guidance as to whether one is enrolling more quickly than the other I think we had said that.

AML cohorts would probably finished earlier than the ALLL cohorts, but we haven't given any guidance as to whether MLR NPM, one will be first or second.

So I think the.

The concept of having one or more of the individual trials finish enrollment. This year is still operative and certainly what follows from that is.

Additional follow up and.

<unk> filing or two perhaps in the.

In the 2023 timeframe, but we do think that we'll have top line data starting in the first half of 'twenty three.

Okay and one follow up question you mentioned that you have agreement with the FDA on our statistical plan for the <unk> III augment 101 card can you give us some details on how to think about that in terms of like is there like an effective Trs CRA trade that needs to be seen is there.

Durability that youre kind of looking at like how should we think about those kind of parameters for evaluating augment 101 based on your interactions with the regulators so far.

Great maybe I'll ask Briggs to address that question.

Yes, so maybe for some of your partners I guess my line is breaking up a little bit but there is a statistical hypothesis as you could imagine that we have agreed to.

Lower bound to have to be ruled out.

That's the primary endpoint there is still.

Pre specified requirement for durability as we've talked about with you previously.

There's regulatory precedent for.

Both CRA traits and durability from other targeted agents in AML and that sort of what we've been.

Thinking about.

Okay, great. Thank you very much everybody.

Thanks Madhu.

As a reminder, to ask a question, you will need to press star followed by 1 on your telephone keypad.

Next question comes from.

Phil Nadeau.

Halloween and company your line is now.

Fiona Adobe Cowen <unk> Company. Your line is now open.

Operator, maybe we'll put them back in the queue and we will circle back.

If your question has been answered or you wish to withdraw your question, press the pound key.

Are you online you are now your line is now open Hi can you hear me now.

Again, it's at star 1 to ask a question.

Your first question comes from the line of Madhu Kumar from Goldman Sachs.

Yes, great.

Your line is now open.

Hey, everyone.

Sorry, but I don't know what happened there.

I guess just a follow up first on <unk> question.

In terms of.

The durability that you need to filing for approval when can you remind us what that is and then second.

What's your data disclosure strategy will you wait till you have the full.

Duration of durability, that's necessary or will you give us a preliminary look on the data from augment 101 before it's fully mature.

Right again, I guess, maybe I'll ask Greg to follow up thanks for the question Phil.

Alright, so far there is no durability that's required for filing I think if you look at the precedent for some of the other targeted agents.

Median duration of response.

Leased four to six months has been acceptable in the past.

So I think that's.

Sort of the lower bound of what people would see as you will recall the data we showed at ash.

The Kaplan Meier estimate for durability of response, even at six months was greater than two around 70%. So if the data for our filing holds up similar to what we presented at Ash I think we're at very very good shape from a regulatory point of view in terms of data disclosures again as Michael pointed out once a cohort has completed enrollment.

The idea is it would.

We will file the patients from six months from the last patient enrolled.

And that would be the data set that we would consider at our filing dataset. Obviously, there would be continued to follow up on those patients over time, but the.

Finally data set would be six months after the last patient is enrolled.

So that's approximately when we as investors should expect to see the data about six months. After you get the last patient for each cohort.

Exactly okay.

Okay and then second question is on the intercept trial, how is MLD negativity being assessed for the different genotypes. There is regulatory precedent for MRV negative negativity for NPM one.

AML patient established by Kronos, but I don't believe <unk> ever said, what or how do you assess MLR sorry.

<unk> negativity for MLR.

The intercept trial doing that.

So maybe if Peter is on the line Peter maybe you want to comment on that one.

Yes, the sphere.

For the MLR, there might be a little.

As you know just because of that.

They drive nature of the different occasion can occur I believe by flow cytometry predominantly for the MLR patients.

Great. That's very helpful. And then last question we saw that the trial was on clinical trials trial stuck up now.

Can you remind us what the rationale is for looking at combinations with <unk> 77.

Why choose that as one of the agents that you first.

Moving into combo studies with.

Yes, Phil.

Of all.

Investigator sponsored trials so that's.

That's part of the equation here, but maybe I'll ask.

Briggs or Peter to comment on the rationale.

Yes, I'd be happy to sell further.

The logic is the same as it has been Asia right essentially the asset molecule is essentially an oral Asia.

So I think the MD Anderson team as Michael said, it's an investigator sponsored trial they were quite interested in being able to potentially develop an all oral regimen.

Without having to get parenteral decided it so the scientific rationale for the combo is the same as for the vent Asia why that molecule specifically I think they are quite interested in it and an all oral regimen.

Perfect. Thanks for taking our questions and congrats on purpose.

Thanks for taking our questions.

Thank you Bill.

I guess our first one relates to the cadence of recruitment into the Phase II arms of the Augment 101 trial. So you mentioned that you could either disclose one cohort or several cohorts in the first half of 2023.

Next question comes from Bert Hazlett with <unk>.

Given the kind of recruitment cadence you've seen so far, do you expect to report one versus multiple in one go?

Your line is now live.

Thank you.

Thanks, Thank you for taking the questions.

How are you thinking about that today?

A couple on $56 13 forgive me for not.

Yeah, Madhu, thanks for the question.

<unk> excuse me.

The.

Look, I think what we were referring to was actual enrollment in the trial and how the cadence kind of rolls forward from there.

Could you just maybe provide benchmarks I think you may have done this previously but for the beat AML trial with regard to frontline Ben as though the combination with frontline venues.

Specifically in.

NPM, one or MLR patients.

What should be the benchmarks were considering for meaningful activity in.

That patient group with frontline.

Yes.

Greg you want to take that one.

Yeah. So so we can send you the <unk> trial, which was the does that Asia versus as a first line trial.

So we have three independent, as you pointed out, we have three independent trials that are enrolling.

We haven't given guidance as to whether one is enrolling more quickly than the other.

I think we had said that the AML cohorts would probably finish earlier than the ALL cohorts, but we haven't given any guidance as to whether MLLR or MPM1 will be first or second.

The overall response rate.

If I remember correctly, it was sort of into the mid <unk>.

We are the actual CR cri CR rate was lower than that.

There are some subsequent publications, where they break it out by mutational status, but as you can imagine the number of patients in each one of those is.

It's smaller.

I think an early look at the data.

Looking at the negative rate.

And then the.

Okay.

Looking at it.

Our CR cri rate, but we'll send you the vitality paper and supporting information.

And so I think the concept of having one or more of the individual trials finish enrollment this year is still operative.

Okay.

Helpful and then one kind of strategically given the effort.

Into solid tumors here with CRC is this foreshadowing.

Some additional combination therapy or potential combinations.

Licensing potential with.

Revenue and other.

Other molecules that focus on the <unk> beta catenin pathway or is this moving into CRC or how should we think about what this initial step means strategically for the development of revenue made up.

And certainly what follows from that is additional follow-up and a filing or two, perhaps in the 2023 timeframe.

Yes. Thanks for the question I'll, just say over overall strategy here is we're following we think we're following good science into.

But we do think that we'll have top-line data starting in the first half of 2023.

A particular form a solid solid tumor.

<unk> and I think that that's where we find.

We think that this will be something to explore it as a signal seeking phase one trial limited investment as Briggs pointed out in his remarks.

So market opportunity is quite significant there's a lot of unmet medical need in this area of colorectal cancer and <unk>.

We think the mechanism has very strong rationale we will find out essentially if it if it works, but in terms of a larger strategy in solid tumors I think where we are.

We're being strategic and surgical about how we go into certain other areas outside of hematology.

And leukemia I should say.

So I think I think this is a this is one such opportunity there may be others, but again, we're focused very much focused on the biology at hand, and where it takes us.

With of course, our first focus being.

Very much in leukemia space, So I don't know.

Tracey do you want to add anything to that.

No no I think that's right.

Sure.

I wouldn't necessarily think about novel.

And we wanted to just sort of see is it.

It does look preclinical data.

Clinic.

We're obviously is it additional opportunities if it does work in the beta continued pathway beyond colorectal cancer.

Yes.

Fair enough and then just one more kind of big picture and the.

This class in general how do you see.

Clearly in the lead with a number of these indications and certainly to move into.

Colorectal in the space, how do you see the competitive landscape evolving.

<unk> inhibitor space. Thanks.

Yes, thanks Bert.

Look I think you pointed to us what you point out what we believe to be true, which is that we are in the lead in.

In terms of developing our drug and becoming the first met inhibitor approved potentially.

That's the thrust of our effort.

And in terms of looking at other indications front.

Frontline.

Maintenance what have you that's.

Those are areas that will go into as well.

And then we've talked about today, we talked about colorectal cancer.

There may be other areas to exploit as Bridgepoint just pointed out.

Around in solid tumors.

Essentially I think we feel like we are.

We're able to leverage our first mover advantage exploit the attributes of our agent, which we think are pronounced and an end.

We'll have a good opportunity to to.

Show that in the market.

Others have to put up data and.

And we will look forward to seeing seeing what they have when they actually.

The data and presented at conferences.

Alright, thank you.

Thanks, Brett next.

The next question comes from the line of Thomas.

Some of it.

From Citigroup. Your line is now open.

Hi, Tim This is Chuck Mubarak on for Yigal, Thanks for taking my questions.

A bit of a basic one but regarding your new plant study in colorectal cancer does there need to be an MLR rearrangement to support I guess aberrant activation of the beta katina and pathway or is it all just wild type and maybe what proportion of the CRE COPD population do you think is addressing yet yes.

Yes, it's more akin to the NPM one story, it's not there's not a fusion protein, it's more akin to <unk>, where the NPM one driven transformation is dependent upon that.

Sure.

For <unk>, it's similar to.

Okay.

<unk> do you think is addressable with <unk> inhibition.

Alright, so if you look at.

Hello.

Thank you.

It's Sean.

Okay to continue that pathway and CRC and whether we should be taking a biomarker selected population, but the vast majority of colorectal cancers.

Either.

Haven't activation definitely it would have an activation of the beta continue the pathway. So we think it's actually the majority the vast majority of patients have this pathway activated.

Okay, maybe one last one for me.

How do you how do you expect revenue to behave in solid tumors versus leukemia.

And maybe do you think you would need to dose with us three or four based on your prior work with.

Thanks.

Yes, so the dosing and it should be.

Thank you Michael.

Yes so.

So the dosing should be the same again, you're just blocking the interaction of men with NOL.

As we do with NPM, one where the dosing is the same.

The dose.

Yes.

Whether you see responses or whether you see differentiation and as we see in AML is one that will be very interesting.

Pre clinically you actually see a very similar differentiation.

With that now.

Okay, and then maybe the last point on leaving us with three or four.

Yes.

No again so.

Okay.

Just to clarify it sounds like maybe the ships.

Got you.

It depends on whether they are also taking a <unk> four inhibitor. So we think that that.

Those your response should be the same.

So again, we don't need three or four inhibitor, we just need to know what the doses with or without and that should be the same in colorectal cancer.

Okay, sorry, I think the connection wasn't great, but I appreciate the answers.

Yes, we can follow up afterwards, if need be.

Next question is from.

Joe <unk> with Baird. Your line is now open.

Hi, Congrats on the progress and thanks for taking my questions.

First one is on augment 101 and with a lower bound there has to be ruled out when you submit the data to FDA do you see any potential for the enrollment size any of the three arms to change based on early data and how it looks.

Yes, Joel Thank you for the question.

Well as you know.

This is a pivotal trial. So we are not looking at the data I think I think the.

The concept is that we have.

And I think I mentioned in my remarks, 64 patients enrolled in each of the trials individual trials and up to 10 pediatric patients. So that's sort of.

The statistics are set around the 64 patients.

And.

As of today there is no we don't see any reason why that would move.

And that obviously is driven all the powering is done after the lower bound so.

While we haven't disclosed what that is we feel like it statistics hold and we have agreed with FDA on the design so.

Mind it we don't see any reason why we change.

Okay, Great and then a question on business development.

You've mentioned how that could be a bigger focus for this year.

How long is the recent biotech downturn affected the outlook for that.

Yes, thanks for the question Joel.

I mentioned that obviously, we're in a tough environment.

And I don't think many companies are immune to that but I do think that.

Our business model is to in license or acquire other assets we have.

Generally focused on early stage assets call it.

Lead stage preclinical through phase one. So these these are assets that allow us to do some very good development work.

And not spend as much on.

On development at the early stages until we get to a point of value inflection.

And so I think that's the area that we tend to focus on and I think those are the assets that perhaps are not getting as much attention in the down market and so.

We continue to be encouraged by some of the things that we're seeing and we're being very selective.

On the types of assets and what we're what we could potentially bring into <unk> and so it's.

And that way I think we're feeling we're feeling good about our goals for the future and building our pipeline.

Great. Thank you.

Thanks, Phil.

Thanks.

Final question comes from the line of Peter Lawson.

Barclays. Your line is now open.

Great. Thanks for taking my questions.

I guess the first one is just around whether we would see any.

Updated phase one data.

The Menin inhibitor.

This year or.

Early next.

Yes, Thank you Peter for the.

For the question.

<unk>.

In our mind.

We're pretty much focused on enrolling and doing all the work that's required.

Now in the phase III to get they get the drug.

Get the drug ultimately approved and so that's where our focus is.

I guess the.

Only real question and there are some questions that I'm sure people have but the question that.

Something we could potentially talk about.

Coming out of the phase one is maybe just an update on the.

On the durability of the endpoint of CRC, our age, which we reported on at Ash as of now we don't have specific plans to.

To update the market on that again, because our focus has turned to the phase III.

But if that were to change obviously, we would let people know.

You shouldnt be an expectation necessarily that we would do that so.

Other than that I don't think theres much to say about the phase one at any particular time this year, but again if that were to change we'll certainly let people know.

With the durability kind of help with the enrollment for the <unk> study in any way you think to help.

Investigators.

I guess greater comfort around the durability of these drugs.

Yes, thanks for that question too I do think that.

More data helps whatever the data is if it's positive about your program.

And people are interested in your program they tend to notice.

Yes.

The data that you put out.

And so.

Could that help I would imagine there could be some positive some benefit to that.

I would also offer that physicians are extremely excited today about what we've what we've put out.

From the phase one and we did that at ash and the the follow through has been tremendous.

Our trials are enrolling well so I think we feel very encouraged by.

The interest of physicians and investigators and so.

That's just where we are today, but additional data never hurts as long as it is supportive of your program.

Thank you and then the assumption to solid tumor indications.

Curious if you see any preclinical data for CRC or other indications.

Or do you think there's any preclinical evidence that they could work better with the.

CSC mutations such as the <unk>.

<unk>.

Maybe I'll, let I'll, let <unk> take that question.

Yes.

Yes, so Peter we can send us.

Okay.

Come out.

Okay.

Have you given us a lot of confidence in this mechanism.

Again, as I mentioned earlier, I think combinations with other agents in colorectal cancer.

Thank you Bob.

Thanks.

Yes.

Okay.

Perfect.

Is there anything coming out from your own work.

We could potentially see this year.

Clinically.

Potentially potentially yes.

I wouldn't I wouldn't set an expectation, but the team is.

Doing some additional work to validate some of the things that we've seen in the literature.

Don't know when that will be ready.

Perfect. Thank you so much.

Taking the question.

Thank you Peter.

This concludes the Q&A portion of the call I will now turn the call back.

Michael Metzger, who will make a few closing remarks.

Great. Thank you operator, and thank you for joining us on the call. This afternoon, we look forward to seeing many of you at the upcoming conferences this spring and as well as on any future calls.

Again have have a great evening and thanks for joining us.

Correct.

This concludes today's conference call. Thank you all for your participation you may now disconnect.

Okay.

[music].

<unk>.

Okay.

[music].

Okay.

Yes.

Okay.

[music].

Thanks.

[music].

Okay, and one follow-up question.

You mentioned that you have agreement with the FDA on a statistical plan for these three Augment 101 cohorts.

Can you give us some details on how to think about that in terms of like, is there an effective CR-CRA trade that needs to be seen?

Is there a durability that you're kind of looking at?

Thank you operator.

Like, how should we think about those kind of parameters for evaluating Augment 101 based on your interactions with the regulators so far?

And thank you to those of you joining us on the line and the webcast. This afternoon for a review of syntax its first quarter 2022 financial and operating results.

Great.

I'm, Megan Myers with Argot partners.

With me this afternoon to discuss the results and provide an update on the company's progress and Michael Metzger, Chief Executive Officer, Dr. Briggs Morrison, President and head of R&D, and Alex <unk>, Chief Accounting Officer.

Also joining us on the call today for the question answer session is Dr. Peter <unk>, Chief Scientific Officer and.

And Dr <unk> <unk> Chief business Officer.

This call is being accompanied by a slide deck that has been posted on the company's website.

I would ask you to please 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.

Are not that are not historical Arkansas to be forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these statements.

As a result of various important factors.

Including those discussed in the risk factors section in the company's most recent quarterly report on Form 10-Q.

As well as other reports filed with the SEC.

These forward looking statements represent our views as of today may nine 2022 only.

A replay of this call will be available on the company's website www dot <unk> dot com following this call.

Maybe I'll ask Briggs to address that question.

With that I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of setbacks.

Okay, great.

Yeah.

Thank you Megan and thank you to everyone joining us on today's call and webcast.

Thanks very much, everybody.

On the heels of a transformational 2021, we're off to a strong start for 2022 and I look forward to sharing with you today, our recent progress in several key developments.

Thanks, Madhu.

The next question comes from Phil Nadeau with Cowen & Company.

I am, especially excited to report that <unk> is now on pace to deliver two U S applications for potential drug approvals in 2023.

An aspirational goal for most biotech companies and yet our near term and highly achievable one for Sundar.

We also have the flexibility to selectively pursue business development opportunities to augment our pipeline with additional promising molecules to complement the ones we have.

The momentum is building its syntax syntax and it is indeed, a very exciting time for the company.

Your line is now open.

Now turning to slide three.

We provide a high level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before.

Phil Nadeau, are you online?

Starting with revenue minute, our official generic name for F&B X 50, 613, our highly selective <unk> inhibitor.

Enrollment in our three pivotal phase II trials in patients with relapsed refractory NPM, one or MLR acute leukemia, which we call augment 101, two a two b and two C remains on track. We're also pleased to announce that we have enrolled our first patients in the beat AML and augment 102 trials.

Your line is now open.

Hi.

Can you hear me now?

Yes.

<unk>, which represent an important expansion opportunities for the franchise in combination with other approved agents and begin to move us into newly diagnosed patients.

Beyond acute leukemia, we will be initiating a proof of concept trial later this year in colorectal cancer to our knowledge represents the first assessment.

Menin inhibitor in patients with solid tumors. This is an exciting development and Briggs will discuss this effort further in a few minutes.

Moving to <unk>, our antibody against CSF one are.

Enrollment is ongoing in our pivotal agave 201 trial in patients with chronic graft versus host disease with topline data expected in 2023 and.

In addition, we are excited to announce today that we recently received fast track designation for <unk> for the treatment of Gvhd.

And beyond graft versus host disease, we remain on track to commence a phase II proof of concept trial accent filling that in idiopathic pulmonary fibrosis or Ips in the fourth quarter of this year.

Again, I want to emphasize that we now have two registrational programs ongoing for two first in class and potentially best in class medicines in two areas of unmet medical need.

With filings for both programs expected in 2023, we're starting to expand the organization to support the potential commercial launch of both molecules in the U S.

Later this year, we expect to hire the company's first chief commercial officer to lead the additional build out of our commercial organization.

Let's now turn to slide four and provide further details on where we are with revenue method.

The augment 101 to a trial is enrolling patients with relapsed refractory MLR ALLL <unk> is enrolling patients with relapsed refractory MLR AML and TC is enrolling patients with relapsed refractory NPM one AML.

Each trial is open to patients aged one month or older and each trial will enroll independent of the other two.

We may seek initial regulatory approval for <unk> based on the results of any one of these trials should one trial enrolled faster than the others or are we may seek initial regulatory approval with any two or three depending on when they complete enrollment.

Importantly, the trial design allows patients to be treated with revenue minute. After bone marrow transplant. A design feature that allows us to start to understand the role of <unk> in.

In the post transplant maintenance setting.

We also have agreement with FDA on the statistical design of each trial. This trial will enroll 64 adult patients in up to 10 pediatric patients.

Beyond the augment pivotal program in relapsed refractory disease slide five highlights some of the additional opportunities we're exploring with revenue all of which build on the excellent safety and efficacy profile, we have seen thus far with Ravi Madam.

Great.

As I mentioned at the start of today's remarks, we're excited to share that enrollment is now underway in both the beat AML and augment one or two trials.

Sorry about that.

I don't know what happened there.

Phase one beat AML umbrella trial is a collaboration with leukemia and lymphoma society as part of the collaboration revenue manner that first met inhibitor to be included in the trial will be combined with <unk> and the Asa siding diagnosed newly diagnosed AML patients who are unfit for induction chemotherapy. This trial will assess.

So I guess just a follow-up first on Madhu's question.

In terms of the durability that you need to file in for approval, one, can you remind us what that is?

And then second, what's your data disclosure strategy?

Will you wait until you have the full duration of durability that's necessary, or will you give us a preliminary look on the data from Augment 101 before it's fully mature?

<unk> safety as well as initial efficacy with topline data expected next year.

Right.

We expect a phase two three trial, which could serve as the basis for our regulatory following filing to follow soon after completion of the phase one trial.

Again, I guess maybe I'll ask Briggs to follow up.

Thanks for the question, Phil.

The middle panel of this slide highlights our augment 102 trial, which is designed to assess <unk> in combination with standard salvage chemotherapy used for pediatric patients with AML or AML.

Right.

So, Phil, there is no durability that's required for filing.

I think if you look at the precedents for some of the other targeted agents, a median duration of response of at least four to six months has been acceptable in the past.

I'm pleased to report that patients have begun accruing this trial as well.

In terms of data disclosures, again, as Michael pointed out, once a cohort has completed enrollment, the idea is it would follow the patients from six months from the last patient enrolled, and that would be the data set that we would consider as our filing data set. Obviously, there would be continued follow-up on those patients over time, but the filing data set would be six months after the last patient's enrolled.

How is MRD negativity being assessed for the different genotypes?

Both the augment 102 and beat AML trials are supported by preclinical data, which demonstrate the potential benefit of our menin inhibitor used in combination regimens in these settings and we are excited to see how these data translate in the clinic.

There is regulatory precedent for MRD negativity for an NPM1 AML patient established by Cronos, but I don't believe the FDA has ever said how you assess MRD negativity for MLR.

How is the INTERCEPT trial doing that?

So maybe if Peter is on the line, Peter, maybe you want to comment on that one.

And so that trial later this quarter.

Yeah, I hit the spear.

The intercept trial is focused on investigating novel therapies to target early relapse and clonal evolution as a preemptive therapy in AML and <unk>.

For the MLR, the MRD is a little tricky, as you note, just because of the individualized nature of the different infusions that can occur.

Jill will enroll patients with measurable residual disease progression. Following initial treatment a group of patients at very high risk of relapse that represented an important unmet medical need.

In general tenant in cancer treatment is that the earlier you treat the patients disease, the better patients do and the longer the patients stay on medicine. The intercept trial is a very creative approach to treating patients early in their disease course I'll also note that revenue <unk> is the first <unk> inhibitor to be included in the intercept AML Master clinical trial we've.

I'll leave the selection of revenue management for inclusion in two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with revenue minutes.

As we have previously communicated we are committed to unlocking the full potential potential of revenue.

Beyond the relapsed refractory acute leukemia, setting slide six highlights our goals as a company to be the first to market in the relapsed refractory disease setting beyond that we intend to pursue approval in indications and additional value enhancing indications and patients with MLR in <unk> mutant acute leukemias, including the newly diagnosed and <unk>.

I believe it's by flow cytometry predominantly for the MLR patients.

And incentives.

Great.

That's very helpful.

<unk> and MLR represent up to 40% of the overall AML population, which to our knowledge will be the largest sub population of AML to be addressed by a new targeted therapy.

And then last question, we saw that the SAVE trial is on clinicaltrials.gov now.

Our goal is to engage patients early in their treatment journey get them into remission and maintain them in that state for months, if not years that emerging potential for Ravi Menon is why we believe it could be one of the most important new franchises and largest market opportunities in hematology and certainly worthy of significant investments.

This is what the rationale is for looking at combinations with ASTX727.

Why choose that as one of the agents that you're first moving into combo studies with?

Great.

Yeah, Phil, first of all, it's an investigator-sponsored trial, so that's part of the equation here.

Thanks, very much Michael.

But maybe I'll ask Briggs or Peter to comment on the rationale.

But given that we've already established that are driving that because both in NPM, one and MLR leukemias and have initiated a series of trials to explore the use of rescue pen in earlier lines of leukemia therapy. We believe now is the time to turn our attention to exploring the utility of <unk> inhibition in diseases beyond leukemia.

Yeah, I'll be happy to.

The logic is the same as Venasa, right?

Essentially, the ASTX molecule is essentially an oral ASA.

And we'll continue to assess the emerging science across a range of opportunities.

You guided that our initial clinical program.

So I think the MD Anderson team, as Michael said, it's an investigator-sponsored trial. They were quite interested in being able to potentially develop an oral regimen, without having to give parenteral ASA cytidine.

So the scientific rationale for the combo is the same as for the Venasa.

Advanced colorectal cancer.

On slide seven we note that colorectal cancer is the third most frequently diagnosed cancer and is the second leading cause of cancer death in the U S.

Okay unmet medical need.

Most notably in patients with metastatic disease.

Why that molecule specifically?

It's well established that the beta continued pathway is a key driver of essentially all of them.

I think they're quite interested in an oral regimen.

Perfect.

Final common pathway would be data companion Transco.

Transcriptional activation of several transforming change.

Thanks for taking our questions, and congrats on the progress.

What has become increasingly clear.

What is required for beta catena in biotech.

Okay.

Thank you, Phil.

And the molecules like Ravi Menon, which disrupt the binding of MLR one committed dispute.

Next question comes from Bert Hazlitt with BDIG.

Displace MLR wanted from transcriptional start sites.

Farming change.

Your line is now open.

It's really quite remarkable is that one ml. All one is displaced from the beta Catania complex.

Colon cancer cells differentiate into normal colonic cells lose their ability to proliferate.

This differentiation is highly reminiscent of what we see both pre clinically and clinically with revenue.

How differentiation.

It's always a diagram that illustration of what we believe is happening in colorectal cancer cells in the panel on the left and that all one as a component of the beta containing transfer.

Jeans, like Nick and cycling that drives cell division.

In the panel on the right and the presence of <unk>.

We see a disruption of the <unk> prospect, which is to a loss of expression and cell differentiation.

Do you think this emerging science slide nine shows our development strategy for <unk> in colorectal cancer.

Actual study will be a signal seeking trial in patients with it.

Given what has been described pre clinically we think we might see tumor responses actual tumor shrinkage, but given the differentiation that I've mentioned earlier. It's also possible that we will not see actual responses, but rather we'll see a lack of progression as the cancer cells differentiate and lose their ability to proliferate.

Therefore, designed as signal seeking portion of the trial to look for either responses or disease stabilization responses are assessed using the well known resist assessments and disease stabilization as assessed by the disease control rate at six months.

I should note that the standard of care in this population of patients provides a very low response rate about 5% and the disease control rate is six months is only about 15%.

If we start to see responses, we believe there could be a very rapid path to accelerated regulatory approval based upon <unk> and duration of response.

Illustrated as one option coming out of our proof of concept trial.

We don't see a significant response rate, but do see a pathway.

That's assessed by the disease control rate. The other option is to proceed to a small randomized trial to confirm the clinical activity of using PFS.

Glenn.

We're currently finalizing the protocol for this trial and expect to start enrolling patients in the fourth quarter of this year with possible data anticipated by the end of 'twenty three.

I want to emphasize that the preclinical science supporting the role of men and.

Interaction and beta Catania, and driven tumors, such as colorectal cancer is quite compelling and we're eager to translate the science to the clinic. Nonetheless, we are taking a staged approach to studying this in the clinic starting with what we believe is a modest investment in a signal seeking trial, let me turn the call back over to Michael.

Thanks.

Thank you for taking the questions.

Yes, Thanks Briggs.

I have a couple on 5613.

As you May know this is an area of high unmet medical need where current therapies are not particularly effective.

And the science translates into clinic. This discovery would enable sit next to meaningfully expand the market opportunity for <unk> inhibition beyond hemolytic disease.

Forgive me for not revumented.

Let me now turn turn tax until a map our potentially best in class monoclonal antibody therapy targeting the CSF one receptor.

Excuse me.

Slide 10 is our pivotal trial for <unk> and C Gvhd.

Could you just maybe provide benchmarks?

This trial is the <unk> for graft versus host disease trial called the <unk> hundred one.

I think you may have done this previously, but for the BEAT AML trial with regard to front-line Venasa, the combination with front-line Venasa, and specifically in NPM1 or MLLR patients, what should be the benchmarks we're considering for meaningful activity in that patient group in front-line?

Greg, do you want to take that one?

Trial is enrolling patients with <unk>, whose disease has progressed after two prior therapies.

Yeah.

So, Bert, we can send you the Vialla A trial, which was the Venasa versus Asa first-line trial.

The overall response rate, I think if I remember correctly, was sort of in the mid-60s.

Every two weeks or every four weeks. The primary endpoint is response rate using the 2014 NIH consensus criteria for <unk> HD.

Secondary endpoints will include duration of response and validated quality of life life assessments, using the least symptom scale enrollment to the study is going well and we are on track to deliver top line data in the first half of 2023.

The actual CR rate was lower than that.

We're all we're also delighted to announce late last year that we closed our global collaboration with insight. This collaboration brings together two companies with a solid track record of innovation to accelerate and maximize the development of exits allomap.

There are some subsequent publications where they break it out by mutational, status, but as you can imagine, the number of patients in each one of those is smaller.

So I think in an early look at the data, looking at an MRD negative rate than the, Looking at the CRI rate, but we'll send you the YLA paper and all the supporting information.

Our phase one two C. Gvhd data presented at Ash in December of last year received very positive feedback from the investigator community and further underscores its best in class profile.

Okay, that's helpful.

Then one kind of strategically, given the effort into solid tumors here with CRC, is this foreshadowing some additional combination therapy or potential combinations or licensing potential with Revumenib and other molecules that focus on the Wnt beta-container pathway, or is this moving into CRC, or how should we think about what this initial step means strategically for the development of Revumenib?

Yeah, thanks for the question, Bert.

Through our collaboration in an accident insight will pursue an expanded set of indications and see gvhd and other fibrotic diseases.

I'll just say overall strategy here is we think we're following good science, into a particular form of solid tumor biology, and I think that's where we find we think that this will be something to explore.

Together, we plan to assess novel combinations of <unk> and insights JAK inhibitors with the goal of establishing <unk> in earlier earlier settings with within <unk> and expanding its market opportunity.

It is a signal-seeking Phase I trial, limited investment, as Briggs pointed out in his remarks.

As we previously mentioned was our intention we plan to initiate a robust phase II trial in IPF in the fourth quarter of this year the first expansion outside of establishing.

So market opportunity is quite significant. There's a lot of unmet medical need in this area of colorectal cancer, and we think the mechanism has very strong rationale.

We'll find out, essentially, if it works.

But in terms of a larger strategy in solid tumors, I think we're being strategic and surgical about how we go into certain other areas, outside of hematology and leukemia, I should say.

<unk> as a beachhead into other fibrotic diseases, where we believe that <unk> could have a significant impact success.

So I think this is one such opportunity.

Successful development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support for <unk> in other fibrotic driven diseases, that's index and insight could explore over the course of the collaboration.

Slide 11 highlights our view of the broad clinical and commercial opportunity for <unk>.

We believe C. Gvhd represents a high unmet medical need and an important commercial opportunity with approximately 14000 patients suffering from CGP HD in the U S. Today.

The recent approvals in early successful commercial launches of insights geography, and <unk> have begun to delineate the commercial opportunity and see gvhd. Despite recent advancements in this area to our knowledge <unk> is the only agent in clinical development that specifically targets the monocyte macrophage linear.

Both index and as I believe the data generated to date with telematics suggests that has the potential to play an important role in the treatment of <unk> HD, both as a monotherapy and given its safety profile in combination with complementary medicines, such as Jakafi or other JAK inhibitors within the insight portfolio.

Through combinations in the frontline setting as well as the opportunity to expand ex U S.

We envision the gvhd opportunity more than doubling as shown on this slide.

There may be others, but, again, we're very much focused on the biology at hand and where it takes us, with, of course, our first focus being very much in the leukemia space.

As we move <unk> into additional indications starting with IPF, we really see acts until Nab contributed contributing materially to the value of our company moving forward.

And finally on slide 12 summarizes the transactions that led to the acquisition of the Menin MLR and exit tolling that programs. We believe these transactions underscore our robust capabilities to identify and evaluate high value differentiated assets as well as the clinical development expertise to bring these compounds through key.

So, I don't know.

Briggs, did you want to add anything to that?

Inflection points, we anticipate in 2022 that we'll be able to continue to expand our pipeline through in licensing of earlier quality differentiated assets, we expect.

No, no, I think that's right.

To remain among preferred partners of such transactions.

I mean, I wouldn't necessarily think about novel, but what I would want to just sort of see is does the preclinical data come from the clinic?

I'll now turn the call over to Alex to review our financial results Alex.

Or, obviously, is there additional opportunities if it does work in the beta-catenin pathway beyond colorectal cancer?

Thank you Michael.

Fair enough.

I will take a few minutes to discuss our financial results for the first quarter of 2022.

And then just one more kind of big picture in this class in general.

The results of our operations for the first quarter of 2022, and the comparison to the prior year quarter are included in our press release, So I wanted to repeat them in these remarks.

You're clearly in the lead with a number of these indications and certainly the move into colorectal and the other space.

Additional financial details are available in our first quarter report, which was filed today.

What's the competitive landscape evolving in these menin interaction inhibitor space?

I would like to point out that our net loss for the quarter was $37 2 million or.

<unk> 63 per share.

To a net loss of $27 7 million.

<unk> 54 per share for the same period last year.

This difference is primarily attributed to the increased clinical and CMC activities for both of our programs.

Turning to slide 13, we ended the first quarter with $397 $9 million in cash and cash equivalents at <unk>.

59 million shares and pre funded warrants outstanding.

Our current cash runway now extends into the second half of 2024.

And so for US our expanded development and early commercialization plans for both <unk> and the managed programs during this period.

It provides us flexibility for continued business development.

Looking ahead I'd like to provide financial guidance for the second quarter and full year of 2022.

For the second quarter of 2022, we expect R&D expense to be 30% to $35 million and total operating expense to be 38 to 42 million.

Including approximately $4 million of noncash stock compensation expense.

For the full year 2022.

R&D expense to be $130 million to $140 million and total operating expense to be 160 to 170 million, including approximately $14 million in noncash stock compensation expense for the full year of 2022.

The increase in R&D and operating expense in 2022 compared to the prior year periods is driven by the expansion of both exit settlement.

It into registration trials expansion into new indications and initiation of pre launch commercialization activities.

With that let me now turn the call back over to Michael.

Thank you Alex.

Let me close the call the call by again, emphasizing the tremendous progress we have made as a company.

Thanks.

Yeah, thanks, Bert.

And the potential of these programs extends well beyond their initial registration indications with both offering broad franchise opportunities.

<unk> leukemias.

The same franchise potential whole track to tell them that we're broad opportunity exists both in the various lines of therapy in Cte Phd and across a broad range of fibrotic diseases, starting with Ips and.

Underpinning all of these efforts we have the balance sheet to aggressively advance our programs through key near term milestones.

We have a proven track record of delivering on this pillar of our corporate strategy and I believe this is a core strength of our company and management team.

We could not accomplish what we have and what we hope to achieve without our wonderfully talented team here its index, our collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs. In addition, I would like to thank the many committed long term investors, who continue to help us in building this great company and with that.

Look, I think you pointed to us.

You point out what we believe to be true, which is that we're in the lead in terms of developing our drug, and becoming the first menin inhibitor approved, potentially, and that's the thrust of our effort.

I'd like to open the call for questions.

As a reminder to ask a question you will need to press star followed by one on your telephone keypad.

If your question has been answered or you wish to withdraw your question.

Keith.

Ken.

And in terms of looking at other indications, front line, maintenance, what have you, those are areas that we'll go into as well.

I want to ask a question.

And then we've talked about today, we've talked about colorectal cancer.

Your first question comes from the line of Madhu Kumar from Goldman Sachs. Your line is now open.

Hey, everyone. Thanks for taking our questions. So I guess, our first one relates to the cadence of recruitment into the phase two arms of the augment 101 trial. So you mentioned that you could either disclose one cohort or several cohorts in the first half of 2023, given the kind of roku maintained it you've seen so far do you expect to report one versus.

Multiple at one go how are you thinking about that today.

Yes Madhu.

Thanks for the question.

Look I think.

The AML cohorts would probably finished earlier than the ALLL cohorts, but we haven't given any guidance as to whether MLR or NPM, one will be first or a second.

And so I think the big.

Concept that having one or more of the individual trials finish enrollment. This year is still operative and certainly what follows from that is.

Additional follow up and <unk>.

Filing or two perhaps in the.

In the 2023 timeframe, but we do think that we'll have top line data starting in the first half of 'twenty three.

Okay and one follow up question you mentioned that you have agreement with the FDA on a statistical plan for the <unk> III augment 101 card can you give us some details on how to think about that in terms of like is there like an effective Crs CRA trade that needs to be seen is there.

Durability that youre kind of looking at like how should we think about those kind of parameters for evaluating on that one.

But based on your interactions with the regulators so far.

Great maybe I'll ask Briggs to address that question.

Yes, so maybe for some of your partners I guess my line is breaking up a little bit but there is a statistical hypothesis as you could imagine that we have agreed to.

Is there a lower bound to have to be rolled out.

Primary endpoint there is still.

Pre specified requirement for durability as we've talked about with you previously.

Yes.

<unk> precedent for.

Both CRH rates and durability from other targeted agents in AML and that sort of what we've been.

Thinking about.

Okay, great. Thank you very much everybody.

Thanks Madhu.

Next question comes from Seattle.

There may be other areas to exploit, as Briggs just pointed out, around in solid tumors.

Phil Nadeau.

Allen <unk> company your line is now.

But essentially, I think we feel like we are able to leverage our first mover advantage, exploit the attributes of our agent, which we think are pronounced, and we'll have a good opportunity to show that in the market.

Others have to put up data, and we'll look forward to seeing what they have when they actually produce the data, and present it at conferences.

Phil Nadeau with Cowen <unk> Company. Your line is now open.

Operator, maybe we'll put them back in the queue and we'll circle back.

Thank you.

Are you online Youre now your line is now open Hi can you hear me now.

Next question comes from the line of Yigal Nochomovitz from CD Group.

Your line is now open.

Yes, great.

Hi team, this is Ashiq Mubarack on for Yigal.

Sorry, but I don't know what happened there.

Thanks for taking my questions.

I guess just a follow up first on <unk> question in terms of the durability that you need to filing for approval. One can you remind us what that is and then second.

A bit of a basic one, but regarding your new plant study in colorectal cancer, does there need to be an MLL rearrangement to support, I guess, aberrant activation of the beta-catenin pathway, or is it all just wild type?

What's your data disclosure strategy will you wait till you have the full.

Duration of durability, that's necessary or will you give us a preliminary look on the data from augment 101 before it's fully mature.

Right again, I guess, maybe I'll ask Greg to follow up thanks for the question Phil.

So far there is no durability that's required for filing I think if you look at the precedent for some of the other targeted agents.

Median duration of response.

At least four to six months has been acceptable in the past.

I think thats.

Sort of the lower bound of what people would see as you will recall the data we showed at ash.

Kaplan Meier estimate for durability of response, even at six months was greater than two around 70%. So if the data for our filing holds up similar to what we presented at Ash I think we're in very very good shape from a regulatory point of view in terms of data disclosures again as Michael pointed out once a cohort has completed enrollment.

The idea is it would.

We'll follow the patients from six months from the last patient enrolled.

That would be the data set that we would consider as our filing dataset, obviously, there would be continuing to follow up on those patients over time, but the filing data set would be six months after the last patient enrolled.

So that's approximately when we as investors should expect to see the data for about six months. After you get the last patient for each cohort.

Exactly okay.

And then second question is on the intercept trial, how is Mardi negativity being assessed for the different genotypes. There is regulatory precedent for MRV negative negativity for NPM one.

AML patient established by Kronos, but I don't believe <unk> ever said, what or how do you assess MLR sorry.

<unk> negativity for MLR.

Intercept trial doing that.

So maybe.

Peter is on the line Peter maybe you want to comment on that one.

Yes, that's fair.

For the MLR, there might be a little tricky.

Note just because of that.

They drive nature of the different occasion can occur I believe by flow cytometry predominantly for the MLR patients.

Great. That's very helpful. And then last question, we saw that the safe trial as our clinical trial trials stuck up now.

Can you remind us what the rationale is for looking at combinations with <unk> 77.

Why choose that as one of the agents that you first.

Moving into combo studies with.

Yes, Phil first of all.

Investigator sponsored trials so that's that.

It's part of the equation here, but maybe I'll ask.

Briggs or Peter to comment on the rationale.

Yes, I'd be happy to do so.

The logic is the same as it has been Asia right essentially the assets molecule is essentially an oral Asia.

I think the MD Anderson team as Michael said, it's an investigator sponsored trial they were quite interested in being able to potentially develop an all oral regimen.

Without having to get parenteral had decided to do so.

Scientific rationale for the combo is the same as for the vent Asia why that molecule specifically I think they are quite interested in it and an all oral regimen.

Perfect. Thanks for taking our questions and congrats on progress.

Thank you Bill.

Next question comes from Bert Hazlett with <unk>.

Your line.

Yeah.

Thanks, Thank you for taking the questions.

A couple on 50 613 forgive me for not.

<unk> excuse me.

Could you just maybe provide benchmarks I think you may have done this previously but for the beat AML trial with regard to frontline Ben <unk>.

Combination with frontline been Asia and specifically in.

NPM, one or MLR patients what should be the benchmarks were considering for meaningful activity.

That patient group with frontline.

Yes.

Greg you want to take that one yeah. So so we can send you the <unk>.

A trial, which was the <unk>.

And then Asia versus as a first line trial.

The overall response rate.

If I remember correctly, it was sort of into the mid <unk>.

Our actual CR Cri CR rate was lower than that.

There are some subsequent publications, where they break it out by mutational status, but as you can imagine the number of patients in each one of those is.

Smaller so I think in an early look at the data.

Looking at the negative rate.

And then the.

Okay.

At this.

Our CR cri rate, but we'll send you the vitality paper.

Sporting information.

Okay.

Helpful and then one kind of strategically given the effort.

Into solid tumors here with CRC.

Is this foreshadowing.

Additional combination therapy or potential combinations.

Licensing potential with <unk>.

<unk> and other.

Other molecules that focus on the <unk> beta catenin pathway or is this moving into CRC or how should we think about what this initial step means strategically for the development of revenue made up.

Yes. Thanks for the question Bert I'll, just say over overall strategy here is we're following we think we're following good science into.

No particular form a solid solid tumor.

Biology, and I think that that's where we find.

We think that this will be.

Something to explore it as a signal seeking phase one trial limited investment as Briggs pointed out in his remarks.

So market opportunity is quite significant there's a lot of unmet medical need in this area of colorectal cancer and <unk>.

We think the mechanism has very strong rationale will find out essentially if it if it works, but in terms of a larger strategy in solid tumors I think where we are.

We're being strategic and surgical about how we go into certain other areas outside of hematology.

And leukemia I should say.

So I think I think this is a this is one such opportunity there may be others, but again, we're focused very much focused on the biology at hand, and where it takes us.

With of course, our first focus being.

Very much in the leukemia space I don't know.

Briggs do you want to add anything to that.

No no I think that's right.

Yes.

I wouldn't necessarily think about novel.

And we wanted to just sort of see is this.

It does really preclinical data.

Clinic.

We're obviously is it additional opportunities if it does work in the beta continued pathway beyond colorectal cancer.

Yeah.

Fair enough and then just one more kind of big picture and the.

In this class in general how do you see you're currently in the lead with a number of these indications and certainly to move into.

Colorectal in the space, how do you see the competitive landscape evolving.

<unk> inhibitor space. Thanks.

Yes.

Yes, thanks Bert.

Look I think you pointed to us as you pointed out what we believe to be true, which is that we are in the lead in.

In terms of developing our drug and becoming the first met inhibitor approved potentially.

That's the thrust of our effort.

And in terms of looking at other indications front.

Frontline.

Maintenance what have you that's.

Those are areas that will go into as well.

And then we've talked about today, we talked about colorectal cancer, there may be other areas to exploit as Briggs <unk> just pointed out.

Around in solid tumors.

But essentially I think we feel like we are.

We're able to leverage our first mover advantage exploit the attributes of our agent, which we think are pronounced.

We'll have a good opportunity to show that in the market.

Others have to put up data and.

And we will look forward to seeing seeing what they have when they actually.

Produced the data and presented at conferences.

Alright, thank you.

Thanks Bert.

And maybe what proportion of the CRT population do you think is addressable with menin?

Next question comes from the line of golf.

From Citigroup. Your line is now open.

Yeah, it's more akin to the NPM1 story.

Hi, Tim This is Ashok Mubarak on for Yigal. Thanks for taking my questions a bit of a basic one but regarding your new plant study in colorectal cancer does there need to be an MLR rearrangement to support I guess aberrant activation of the beta katina and pathway or is it all just <unk>.

Wild type and maybe what proportion of the Cri CRH population do you think is addressing yet with amendment yes.

There's not a fusion protein.

Yes, it's more akin to the NPM one story, it's not there's not a fusion protein it's more akin to NPM, one where the NPM one driven transformation is dependent upon that.

Sure.

For <unk>, it's similar to.

Okay.

<unk> do you think is addressable with <unk> inhibition.

Alright, so if you look at.

Hello.

Thank you.

It's Sean.

Okay to continue that pathway and CRC and whether we should be taking a biomarker selected population, but the vast majority of colorectal cancers.

Either.

Have an activation necessarily with the activation of the beta continue the pathway. So we think it's actually the majority vast majority of patients have this pathway activated.

Okay, and maybe one last one for me.

How do you how do you expect revenue amount up to behave in solid tumors versus leukemia.

And maybe do you think you'd need to dose would sit three or four based on your prior work with.

Thanks.

It's more akin to NPM1 where the NPM1-driven transformation is dependent upon it.

Yes, so the dose or it should be.

Let me take you off Michael.

Yes, so the dosing should be the same again youre just blocking the interaction of men with MLR just as we do with NPM, one where the dosing is the same.

The dose.

So whether you see responses or whether you see differentiation and as we see in AML is one that will be very interesting.

Pre clinically you actually see a very similar differentiation.

With that now.

Okay, and then maybe the last point on leaving us with three or four.

Yeah.

No again so.

Okay.

Just to clarify it sounds like either ships.

Got you.

It depends on whether they are also taking a <unk> four inhibitor. So we think that that exposure response should be the same.

EMEA. So again, we don't need three or four inhibitor. If we just need to know what the doses with or without and that should be the same in colorectal cancer.

Okay, sorry, I think the connection is on grade, but I appreciate the answers.

Yes. Thanks.

We can follow up afterwards, if need be.

For beta-catenin, it's similar to it.

Next question is from.

Joe BD with Baird. Your line is now open.

Okay, and what proportion do you think is addressable with menin inhibition?

Alright, congrats on the progress and thanks for taking my questions.

First one is on augment 101 and with a lower bound it has to be ruled out when you submit the data. The FDA do you see any potential for the enrollment size any of the three arms to change based on early data and how it looks.

Yes, Joel Thank you for the question.

Well as you know it is.

This is a pivotal trial. So we are not looking at the data I think I think.

The concept is that we have.

And I think I mentioned in my remarks, 64 patients enrolled in each of the trials individual trials and up to 10 pediatric patients so that sort of.

The statistics are set around the 64 patients.

<unk>.

As of today there is no we don't see any reason why that would move.

And that obviously is driven all the powering is done after the lower bounds. So.

While we haven't disclosed what that is we feel like it the statistics hold and we have agreement with FDA on the design so.

We don't see any reason why we change.

Okay, Great and then a question on business development.

You mentioned, how there could be a bigger focus for this year.

How does the recent biotech downturn affected the outlook for that.

Yes, thanks for the question Joel.

Yes, I think I mentioned that obviously, we're in a tough environment.

And I don't think.

Many companies are immune to that but I do think that.

Our business model is to in license or acquire other assets. We've generally focused on early stage assets call. It.

Lead stage preclinical through phase one. So these these are assets that allow us to do some very good development work.

Not spend as much on.

On development at the early stages until we get to a point of value inflection.

And so I think that's the area that we tend to focus on and I think those are the assets that perhaps are not getting as much attention in the down market and so we.

We continue to be encouraged by some of the things that we're seeing and we're being very selective.

On the types of assets and what we're bringing what we could potentially bring into <unk> and so it's.

And that way I think we're feeling we're feeling good about our goals for the future and building our pipeline.

Great. Thank you.

Thanks, Phil.

Thanks.

Final question comes from the line of Peter Lawson.

Barclays. Your line is now open.

Great. Thanks for taking my questions.

I guess first one was just around whether we'd see any.

<unk> phase one data.

Men and emphasis.

This year or early next.

Yes, Thank you Peter for the.

For the question.

In our mind.

We're pretty much focused on enrolling and doing all the work that's required.

Now in the phase III to get they get the drug.

Get the drug ultimately approved and so that's where our focus is.

I guess the.

Only real question and there are some questions that I'm sure people have but the question that.

It's something we could potentially talk about.

Coming out of the phase one is maybe just an update on the.

On the durability of the endpoint of CRC, our H, which we reported on at Ash as of now we don't have specific plans.

To update the market on that again, because our focus has turned to the phase III.

But if that were to change obviously, we'd let people know.

You shouldnt be an expectation necessarily that we would do that so.

Other than that I don't think theres much to say about the phase one at any particular time this year, but again if that were to change we'll certainly let people know.

With the durability kind of help with the enrollment for the <unk>.

Once that in any way you think to help.

Investigators get.

And this greater comfort around the durability of these drugs.

Yes, thanks for that question too I do think that.

More data helps wherever the data is if it's positive about your program.

And people are interested in your program they tend to notice.

<unk>.

The data that you put out.

And so.

Could that help I would imagine there could be some positive some benefit to that.

I would also offer that physicians are extremely excited today about what we've what we've put out.

The phase one and we did that at ash and the the follow through has been tremendous in our trials are enrolling well. So I think we feel very encouraged by.

The interest of physicians and investigators and so that's.

Just where we are today, but additional data never hurts as long as it is supportive of your program.

Thank you and then the function to solid tumor indications.

Curious if you see any preclinical data for CRC or other indications do you think there's any preclinical evidence that they can.

Look better with the.

CSC mutations such as the <unk>.

Maybe I'll, let I'll, let <unk> take that question.

Yes.

Yes, so Peter we can send us.

Okay.

Come out.

Okay.

Have you given us a lot of confidence in this mechanism.

Yes.

Again, as I mentioned earlier, I think combinations with other agents in colorectal cancer.

Thank you Bob.

Okay.

Yes.

Okay.

Perfect.

Is there anything coming out from your own work.

We could potentially see this year pre clinically.

Potentially potentially yes.

I wouldn't say, there's an expectation, but the team is.

Doing some additional work to validate some of the things that we've seen in the literature.

I don't know when that will be ready.

Perfect. Thank you so much thanks for taking the question.

Thank you Peter.

This concludes the Q&A portion of the call I will now turn the call back of it.

Oh, right.

So, if you look at…we actually…we've been thinking through this on the beta-catenin pathway and CRC and whether we should be taking a biomarker-selected population, but the vast majority of colorectal cancers have either…have an activation…necessarily have an activation of the beta-catenin pathway. So, we think it's actually the majority…the vast majority of patients have this pathway activated.

Michael Metzger, who will make a few closing remarks.

Okay, maybe one last one for me.

Great. Thank you operator, and thank you for joining us on the call. This afternoon, we look forward to seeing many of you at the upcoming conferences this spring and as well as on any future calls.

How do you expect revumentib to behave in solid tumors versus leukemia?

And maybe, do you think you would need to dose with a CYP304 based on your prior work with…in leukemia?

Thanks.

Yeah, so the dosing should be…can I take that, Michael?

Thank you, Operator, and thank you for joining us on the call this afternoon.

Yes, please.

We look forward to seeing many of you at the upcoming conferences this spring, as well as on any future calls.

Go ahead.

Yeah, so the dosing should be the same.

Again, you're just blocking the interaction of menin with MLL, just as we do with NPM1, where the dosing is the same.

So, the dose…whether you see responses or whether you see differentiation, as we see in AML, is one that will be very interesting.

Preclinically, you actually see a very similar differentiation with AML.

Okay, and maybe the last point on using a CYP304?

Again, have a great evening, and thanks for joining us.

No, again, so…just to clarify, it's not that you need a CYP…that you give.

Again have have a great evening and thanks for joining us.

It depends on whether they're also taking a CYP304 inhibitor.

So, we think that that…the exposure response should be the same in…leukemia.

So, again, we don't need a CYP304 inhibitor.

We just need to know what the dose is, with or without.

Good night.

Correct.

And that should be the same in colorectal cancer.

Okay, sorry.

I think the connection isn't great, but I appreciate the answers, Briggs.

Yeah, thanks, Ezra.

This concludes today's conference call.

This concludes today's conference call. Thank you all for you.

We can follow up afterwards if need be.

Next question is from Joe Beatty with Baird.

Your line is now open.

Thank you all for your participation.

Hi, congrats on the progress, and thanks for taking the questions.

You may now disconnect, www.mytrendyphone.co.uk , Good day and welcome to the Syndex First Quarter 2022 Earnings Conference Call.

Your participation you may now disconnect.

The first one is on AUGMA 101.

Today's call is being recorded.

You may now disconnect.

And with a lower bound that has to be ruled out when you submit the data to FDA, do you see any potential for the enrollment size in any of the three arms to change?

At this time, I would like to turn the call over to Megan Myers of Argot Partners.

Based on early data and how it looks.

Please begin.

Joel, thank you for the question.

Thank you, Operator.

As you know, this is a pivotal trial, so we're not looking at the data.

Welcome, and thank you to those of you joining us on the line and the webcast this afternoon, for a review of Syndex's First Quarter 2022 Financial and Operating Results.

I think the concept is that we have, and I think I mentioned in my remarks, 64 patients enrolled in each of the trials, individual trials, and up to 10 pediatric patients.

I'm Megan Myers with Argot Partners, and with me this afternoon to discuss the results, and provide an update on the company's progress are Michael Metzger, Chief Executive Officer, Dr. Briggs Morrison, President and Head of R&D, and Alex Milti, Chief Accounting Officer.

So that sort of, the statistics are set around the 64 patients, and as of today, there's no, we don't see any reason why that would move.

Also joining us on the call today for the question and answer session is Dr. Peter O'Dutleck, Chief Scientific Officer, and Dr. Anjali Ganguly, Chief Business Officer.

And that obviously is driven, you know, all the powering is done off of the lower bound.

This call is being accompanied by a slide deck that has been posted on the company's website, so I would ask you to please turn to our forward-looking statements on slide two.

So while we haven't disclosed what that is, we feel like it, you know, the statistics hold, and we have agreed with FDA on the design.

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 and Reform Act of 1995.

So in our mind, we don't see any reason why it would change.

Actual results may differ materially from those indicated by these statements as a result, of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC.

Okay, great.

Any forward-looking statements represent our views as of today, May 9, 2022, only.

And then a question on business development.

A replay of this call will be available on the company's website, www.syndax.com, following this call.

You know, you mentioned how that could be a bigger focus for this year.

With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of SYNDAX.

How has the recent biotech downturn affected the outlook for that?

Thank you, Megan, and thank you to everyone joining us on today's call and webcast.

Yeah, thanks for the question, Joel.

On the heels of a transformational 2021, we're off to a strong start for 2022, and I look, forward to sharing with you today our recent progress and several key developments.

Yeah, I think I mentioned that obviously we're in a tough environment, and I don't think many companies are immune to that.

I'm especially excited to report that Syndax is now on pace to deliver two U.S. applications, for potential drug approvals in 2023, a distant and aspirational goal for most biotech companies, and yet a near-term and highly achievable one for Syndax.

But I do think that, you know, our business model is to in-license or acquire other assets.

Despite the challenging market backdrop, we currently find ourselves with a solid balance, sheet and the support of a strong pharmaceutical partner to advance the development of one of our lead molecules.

We've generally focused on early-stage assets, call it lead-stage preclinical through Phase I. So these are assets that allow us to do some very good development work and not spend as much on development at the early stages until we get to a point of value inflection.

We are well-positioned to expand both of our lead assets into new indications and to build, out a commercial organization to support the potential launch of these first and potentially best-in-class products.

And so I think that's the area that we tend to focus on, and I think those are the assets that perhaps are not getting as much attention in the down market.

We also have the flexibility to selectively pursue business development opportunities, to augment our pipeline with additional promising molecules to complement the ones we have.

And so we continue to be encouraged by some of the things that we're seeing, and we're being very selective on the types of assets and what we could potentially bring into Cinex.

The momentum is building at Syndax, and it is indeed a very exciting time for the company.

And so in that way, I think we're feeling good about our goals for the future and building our pipeline.

Now turning to slide three, we provide a high-level summary of our current corporate priorities, as we strive to realize a future in which people with cancers live longer and better than ever before.

Great, thank you.

Starting with RevuMenib, our official generic name for SNDX5613, our highly selective menin-inhibitor.

Thanks, Joel.

Enrollment in our three pivotal Phase II trials in patients with relapsed refractory MPM1, or MLR acute leukemia, which we call Augment 101, 2A, 2B, and 2C, remains on track.

Final question comes from the line of Peter Lawson with Barclays.

We're also pleased to announce that we have enrolled our first patients in the BEAT AML, and Augment 102 trials, which represent important expansion opportunities to the franchise in combination with other approved agents and begin to move us into newly diagnosed patients.

Your line is now open.

Beyond acute leukemia, we will be initiating a proof-of-concept trial later this year in, colorectal cancer, to our knowledge, represents the first assessment of a menin-inhibitor in patients with solid tumors.

Great.

This is an exciting development, and Briggs will discuss this effort further in a few, minutes.

Thanks for taking my questions.

Moving to axotilumab, our antibody against CSF1R, enrollment is ongoing in our pivotal, Agave 201 trial in patients with chronic RAF-versus-host disease, with top-line data expected in 2023.

I guess the first one is just around whether we'd see any updated Phase I data for the menin inhibitor this year or early next.

In addition, we are excited to announce today that we recently received Fast-Track designation, for axotilumab for the treatment of CGBHD.

Yeah, thank you, Peter, for the question.

We are currently making progress, working closely with our partner, Insight, to maximize, the value of this important program and expect to begin trials to move axotilumab into earlier lines of CGBHD later this year.

I think in our mind, we're pretty much focused on enrolling and doing all the work that's required now in the Phase II to get the drug ultimately approved.

And beyond RAF-versus-host disease, we remain on track to commence a Phase II proof-of-concept, trial of axotilumab in idiopathic pulmonary fibrosis, or IPF, in the fourth quarter of this year.

And so that's where our focus is.

Again, I want to emphasize that we now have two registrational programs ongoing for two, first-in-class and potentially best-in-class medicines in two areas of unmet medical need.

I guess the only real question, and there are some questions that I'm sure people have, but the question that something we could potentially talk about coming out of the Phase I is maybe just an update on the durability of the endpoint of CRCRH, which we reported on at ASH.

With filings for both programs expected in 2023, we are starting to expand the, organization to support the potential commercial launch of both molecules in the U.S. Later this year we expect to hire the company's first chief commercial officer to lead the additional build-out of our commercial organization.

As of now, we don't have specific plans to update the market on that, again, because our focus has turned to the Phase II.

Let's now turn to slide four and provide further details on where we are with Revumenit.

But if that were to change, obviously, we'd let people know, and there shouldn't be an expectation necessarily that we would do that.

First, we are conducting three single-arm phase two trials that FDA has agreed may each serve as a pivotal trial. Each of these single-arm phase two trials represent an independent path to a separate indication. The Augment 101-2A trial is enrolling patients with relapsed refractory MLLR-ALL, 2B is enrolling patients with relapsed refractory MLLR-AML, and 2C is enrolling patients with relapsed refractory MPM-1-AML. Each trial is open to patients aged one month or older and each trial will enroll independent of the other two.

So other than that, I don't think there's much to say about the Phase I at any particular time this year.

We may seek initial regulatory approval for Revumenit based on the results of any one of these trials should one trial enroll faster than the others, or we may seek initial regulatory approval with any two or three depending on when they complete enrollment.

But again, if that were to change, we'll certainly let people know.

Would the durability kind of help with the enrollment for the Augment study in any way, you think, to help investigators get, I guess, greater comfort around the durability of these drugs?

Given our current trajectory and our view of the competitive landscape, we anticipate being the first company to achieve regulatory approval for amended inhibitor. Needless to say, we believe this is, we believe being first to market is important and accretive to the long-term value of SYNDAX.

Yeah, look, thanks for that question, too.

We have agreement with FDA that for each trial the primary endpoint will be the percentage of patients achieving CR-CRH with secondary endpoints including durability of CR-CRH response, transfusion independence, overall survival, and safety.

I do think that more data helps.

Importantly, the trial design allows patients to be treated with Revumenib after bone marrow transplant, a design feature that allows us to start to understand the role of Revumenib in the post-transplant maintenance setting.

Whatever the data is, if it's positive about your program and people are interested in your program, they tend to notice the data that you put out.

We also have, agreement with FDA on the statistical design of each trial. Each trial will enroll 64 adult patients and up to 10 pediatric patients.

And so, could that help?

Beyond the Augment pivotal program in relapse refractory disease, slide 5 highlights some of the additional opportunities we are exploring with Revumenib, all of which build on the excellent safety and efficacy profile we have seen thus far with Revumenib.

I would imagine there could be some benefit to that.

As I mentioned at the start of today's remarks, we are excited to share that enrollment is now underway in both the BEAT AML and Augment 102 trials.

I would also offer that physicians are extremely excited today about what we've put out from the phase one, and we did that at ASH, and the follow-through has been tremendous, and our trials are enrolling well.

The Phase 1 BEAT AML umbrella trial is a collaboration with Leukemia and Lymphoma Society.

So, I think we feel very encouraged by the interest of physicians and investigators, and so that's just where we are today.

As part of the collaboration, Revumenib, the first mending inhibitor to be included in the trial, will be combined with Venetoclax and the asocytidine in newly diagnosed AML patients who are unfit for induction chemotherapy. This trial will assess safety as well as initial efficacy with top-line data expected next year.

But additional data never hurts, as long as it is supportive of your program.

We expect a Phase 2-3 trial which could serve as the basis for a regulatory filing to follow soon after completion of the Phase 1 trial.

Great.

The middle panel of the slide highlights our Augment 102 trial which is designed to assess Revumenib in combination with standard salvage chemotherapies used for pediatric patients with ALL or AML. I am pleased to report that patients have begun accruing in this trial as, well.

Thank you.

Both the AUGMENT 102 and BEAT AML trials are supported by preclinical data, which demonstrate the potential benefit of a menin inhibitor used in combination regimens in these settings, and we are excited to see how these data translate in the clinic.

And then the branch into solid tumor indications.

The third panel on the right illustrates the INTERCEPT trial, which is designed to explore the activity of revumenib in patients with AML who have MRD-positive disease.

I'm just curious if we see any preclinical data for CRC or other indications, and do you think there's any preclinical evidence that they could work better with the CRC mutations, such as the G12C?

This trial is being conducted as part of the INTERCEPT master clinical trial being led by the Australian Leukemia and Lymphoma Group, and we expect patients to begin enrolling into that trial later this quarter.

Yeah, maybe I'll let Briggs take that question.

The INTERCEPT trial is focused on investigating novel therapies to target early relapse and clonal evolution as a preemptive therapy in AML. The trial will enroll patients with measurable residual disease progression following initial treatment, a group of patients at very high risk of relapse that represents an important unmet medical need. The general tenet in cancer treatment is that the earlier you treat the patient's disease, the better patients do and the longer the patients stay on medicine. The INTERCEPT trial is a very creative approach to treating patients early in their disease course.

Yeah.

I'll also note that revumenib is the first menin inhibitor to be included in the INTERCEPT AML master clinical trial. We believe the selection of revumenib for inclusion in two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with revumenib.

So, Peter, we can send you some data that's come out that have given us a lot of confidence in this mechanism.

As we have previously communicated, we are committed to unlocking the full potential of revumenib beyond the relapse-refractory acute leukemia setting.

Again, as I mentioned earlier, I think combinations with other agents and colorectal can't speak about.

Slide six highlights our goals as a company to be the first to market in the relapse-refractory disease setting.

But, yeah.

Beyond that, we intend to pursue approval in additional value-enhancing indications in patients with MLR and MPM1 mutant acute leukemias, including the newly diagnosed and maintenance settings. As we continue to develop revumenib for use beyond treatment of relapse-refractory patients and into the first-line treatment setting, we see the opportunity to treat up to 12,500 patients identified each year with these two forms of mutant acute leukemia. MPM1 and MLR represent up to 40% of the overall AML population, which, to our knowledge, will be the largest subpopulation of AML to be addressed by a new targeted therapy.

Okay.

Our goal is to engage patients early in their treatment journey, get them into remission, and maintain them in that state for months, if not years.

Perfect.

That emerging potential for revumenib is why we believe it could be one of the most important new franchises and largest market opportunities in hematology and certainly worthy of significant investment.

But is there anything coming out from your own work that we could potentially see this year, preclinically?

As I mentioned earlier, we are also preparing to start an initial proof-of-concept trial in solid tumors, yet another exciting new area of exploration for revumenib.

Potentially, yes.

I will now turn the call over to Briggs, who will walk through the biologic rationale, development strategy, and market opportunity for revumenib in colorectal cancer.

I wouldn't set an expectation, but the team is doing some additional work to validate some of the things that we've seen in the literature.

Briggs?

So, don't know when that will be ready.

Thanks very much, Michael.

Perfect.

Given that we have already established that our drug is active both in MPM1 and MLR leukemias and have initiated a series of trials to explore the use of revumenib in earlier lines of leukemia therapy, we believe now is the time to turn our attention to exploring the utility of mending inhibition in diseases beyond leukemia.

Thank you so much.

As we have continued to assess the emerging science across a range of opportunities, we have decided that our initial clinical program, advanced colorectal cancer. On slide seven, we note that colorectal cancer is the third most frequently diagnosed cancer and is the second leading cause of cancer death in the U.S, significant unmet medical need, most notably in patients with metastatic disease.

Thanks for taking the question.

It's well established that the beta-catenin pathway is a key driver of essentially all, final common pathway being beta-catenin transcriptional activation of several transforming genes.

Thank you, Peter.

What has become increasingly clear is that this model is required for beta-catenin biotransferable cancer, and that molecules like revumenib, which disrupt the binding of MLL1 to menin, displace MLL1 from transcriptional start sites, transforming genes.

This concludes the Q&A portion of the call.

What's really quite remarkable is that when MLL1 is displaced from the beta-catenin complex, the colon cancer cells differentiate into normal colonic cells and lose their ability to proliferate.

I will now turn the call back with Michael Metzger, who will make a few closing remarks.

This differentiation is highly reminiscent of what we see both pre-clinically and clinically, with reference to intercell differentiation.

Great.

Psilate is a diagrammatic illustration of what we believe is happening in colorectal cancer cells.

In the panel on the left, MLL1 is a component of the beta-catenin transcriptional genes like MYC, and cyclins that drive cell division.

In the panel on the right, in the presence of revumenib, we see disruption of the beta-catenin complex, which leads to a loss of expression and cell differentiation.

Using this emerging science, slide 9 shows our development strategy for revumenib in colorectal cancer.

Our initial study will be a signal-seeking trial in patients with...

Given what has been described pre-clinically, we think we might see tumor responses, actual tumor shrinkage, but given the differentiation that I mentioned earlier, it's also possible that we will not see actual responses, but rather we'll see a lack of progression as the cancer cells differentiate and lose their ability to proliferate. We've therefore designed a signal-seeking portion of the trial to look for either responses, or disease stabilization. Responses are assessed using the well-known resist assessments, and disease stabilization is assessed by the disease control rate at six months.

I should note that the standard of care in this population of patients provides a very low response rate, about 5%, and the disease control rate at six months is only about 15%.

If we start to see responses, we believe there could be a very rapid path to accelerated regulatory approval, based upon ORR and duration of response. That's illustrated as one option coming out of our proof-of-concept trial.

If we don't see a significant response rate but do see... As assessed by the disease control rate, the other option is to proceed to a small, randomized trial to confirm the clinical activity using PFS.

We are currently finalizing the protocol for this trial and expect to start enrolling patients in the fourth quarter of this year, with possible data anticipated by the end of 2023. I want to emphasize that the preclinical science supporting the role of menin-MLL1 interaction in beta-catenin-driven tumors such as colorectal cancer is quite compelling, and we are eager to translate this science to the clinic.

Nonetheless, we are taking a staged approach to studying this in the clinic, starting with what we believe is a modest investment in a signal-seeking trial.

Let me turn the call back over to Michael.

Yeah, thanks, Briggs.

Before we move on, let me further emphasize that seeing disease control rates above standard of care, even seeing a few responses in these metastatic colorectal patients, will indeed be a very exciting result. As you may know, this is an area of high medical need where current therapies are not particularly effective.

If we are right and the science translates in the clinic, this discovery would enable Syndex to meaningfully expand the market opportunity for menin inhibition beyond heme malignancies.

Let me now turn to axotilumab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor.

Slide 10 is our pivotal trial for axotilumab in CGVHD. This trial is the axotilumab for graft-versus-host disease trial called Agave 201. The trial is enrolling patients with CGVHD whose disease has progressed after two prior therapies.

Patients must be at least two years of age and have met overall entry criteria. This is a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axotilumab given either every two weeks or every four weeks. The primary endpoint is response rate using the 2014 NIH consensus criteria for CGVHD. Secondary endpoints will include duration of response and validated quality-of-life assessments using the Lee-Simpson scale.

Enrollment of the study is going well, and we are on track to deliver top-line data in the first half of 2023.

Our Phase I-II CGVHD data presented at ASH in December of last year received very positive feedback, from the investigator community and further underscores its best-in-class profile.

Through our collaboration, Syndax and Insight will pursue an expanded set of indications in CGVHD, and other fibrotic diseases. Together, we plan to assess novel combinations of axotilumab and Insight's JAK inhibitors, with the goal of establishing axotilumab in earlier settings within CGVHD and expanding its market opportunity.

As we previously mentioned was our intention, we plan to initiate a robust Phase II trial in IPF in the fourth quarter of this year.

The first expansion outside of establishing CGVHD is a beachhead into other fibrotic diseases, where we believe axotilumab could have a significant impact.

Successful development in IPF could lead to an additional approval, and a very important indication of considerable value and would provide support for axotilumab and other fibrotic-driven diseases that Syndax and Insight could explore over the course of the collaboration.

Slide 11 highlights our view of the broad clinical and commercial opportunity for aspartilumab.

We believe CGBHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from CGBHD in the U.S. today.

The recent approvals and early successful commercial launches of Insite's Gacafi and Sanofi's Resiroc have begun to delineate the commercial opportunity in CGBHD.

Despite recent advancements in this area, to our knowledge, aspartilumab is the only Asian in clinical development that specifically targets the monocyte macrophage lineage.

Both Syndax and Insite believe the data generated to date with aspartilumab suggests it has the potential to play an important role in the treatment of CGBHD, both as a monotherapy and, given its safety profile, in combination with complementary medicines such as Gacafi or other GAC inhibitors within the Insite portfolio.

With new combinations in the frontline setting, as well as the opportunity to expand ex-U.S., we envision the CGBHD opportunity more than doubling as shown on this slide.

As we move aspartilumab into additional indications, starting with IPF, we really see aspartilumab contributing materially to the value of our company moving forward.

Finally, on slide 12, this summarizes the transactions that led to the acquisition of the Menin MLR and aspartilumab programs.

We believe these transactions underscore our robust capabilities to identify and evaluate high-value differentiated assets, as well as the clinical development expertise to bring these compounds through key value inflection points.

We anticipate in 2022 that we'll be able to continue to expand our pipeline through in-licensing of earlier quality differentiated assets.

We expect to remain among preferred partners of such transactions.

I'm going to now turn the call over to Alex to review our financial results.

Alex?

Thank you, Michael.

Let me now take a few minutes to discuss our financial results for the first quarter of 2022.

The results of our operations for the first quarter of 2022 in comparison to the prior year quarter are included in our press release, so I won't repeat them in these remarks.

Turning to slide 13, we ended the first quarter with $397.9 million in cash-in-cash equivalents and 59 million shares in pre-funded warrants outstanding. Our current cash runway now extends into the second half of 2024 and supports our expanded development and early commercialization plans for both the Exeter TeleMAT and the Mennon programs during this period and provides us flexibility for continued business development.

Looking ahead, I'd like to provide financial guidance for the second quarter and full year, of 2022. For the second quarter of 2022, we expect R&D expense to be $30 to $35 million and total operating expense to be $38 to $42 million, including approximately $4 million of non-cash stock compensation expense.

For the full year 2022, we expect R&D expense to be $130 to $140 million and total operating expense to be $160 to $170 million, including approximately $40 million in non-cash stock compensation expense for the full year of 2022. The increase in R&D and operating expense in 2022 compared to the prior year period, is driven by the expansion of both Exetil and MNN into registration trials, expansion into new indications, and initiation of prelaunch commercialization activities.

With that, let me now turn the call back over to Michael.

Thank you, Alex.

Let me close the call by again emphasizing the tremendous progress we have made as a company.

Syndex has always been focused on delivering new medicines that extend and improve the lives of people with cancer and other serious diseases. And today, with two high-value, ongoing registration programs, a notable achievement in its own right, we stand on the precipice of realizing this goal.

And the potential of these programs extends well beyond their initial registration indications, with both offering broad franchise opportunities.

We believe RevuMenib could have utility across a wide range of clinical settings in acute leukemia, as well as potentially in some solid tumors.

The same franchise potential holds for Exetilimab, where a broad opportunity exists both in the, various lines of therapy in CGVHD and across a broad range of fibrotic diseases, starting with IPS.

Underpinning all of these efforts, we have the balance sheet to aggressively advance our programs through key near-term milestones.

We have a proven track record of delivering on this pillar of our corporate strategy, and I believe this is a core strength of our company and management team.

We could not accomplish what we have and what we hope to achieve without our wonderfully talented team here at Syndex, our collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs.

In addition, I would like to thank the many committed long-term investors who continue to help us in building this great company.

And with that, I'd like to open the call for questions.

As a reminder, to ask a question, you will need to press star followed by 1 on your telephone, keypad.

If your question has been answered or you wish to withdraw your question, press the pound key.

Again, it's at star 1.

Your first question comes from the line of Madhu Kumar from Goldman Sachs, your line, is now open.

Hey everyone, thanks for taking our questions, I guess our first one relates to the cadence, of recruitment into the phase 2 arms of the Augment 101 trial, so you mentioned you could either disclose one cohort or several cohorts in the first half of 2023, given the kind of recruitment cadence you've seen so far, do you expect to report one versus multiple in one go, how are you thinking about that today?

Yeah, Madhu, thanks for the question, look I think what we were referring to was actual, enrollment in the trial and how the cadence kind of rolls forward from there, so we have three independent, as you pointed out, we have three independent trials that are enrolling, we haven't given guidance as to whether one is enrolling more quickly than the other, I think we had said that the AML cohorts would probably finish earlier than the ALL cohorts, but we haven't given any guidance as to whether MLLR or MPM1 will be first or second, and so I think the concept of having one or more of the individual trials finish enrollment this year is still operative, and certainly what follows from that is additional follow-up and a filing or two perhaps in the 2023 timeframe, but we do think that we'll have top-line data starting in the first half of 2023.

Okay, and one follow-up question, you mentioned that you have agreement with the FDA on a, statistical plan for these three Augment 101 cohorts, can you give us some details on how to think about that in terms of like, is there an effective CRCRA trade that needs to be seen, is there a durability that you're kind of looking at, like how should we think about those kind of parameters for evaluating Augment 101 based on your interactions with the regulators so far?

Great, maybe I'll ask Briggs to address that question.

Yeah, so maybe for some of the opposites, I guess my line is breaking up a little bit, but there is a statistical hypothesis, as you can imagine, that we've agreed to for sort of a lower bound that has to be ruled out, that's the primary endpoint.

There is no pre-specified requirement for durability, as we've talked about with you, previously, you know, there's regulatory precedent for both CRCRH rates and durability from other targeted agents in AML, and that's sort of what we've been thinking about.

Okay, great, thanks very much, everybody.

Thanks, Madhu.

Next question comes from Phil Nadeau with Cowen and Company, your line is now open.

Phil Nadeau with Cowen and Company, your line is now open.

Operator, maybe we'll put him back in the queue, and we'll circle back.

Phil Nadeau, are you online?

Your line is now open.

Hi, can you hear me now?

Yes.

Great.

Sorry about that, I don't know what happened there.

So I guess just a follow-up first on Madhu's question.

In terms of the durability that you need to file in for approval, one, can you remind us what that is?

And then second, what's your data disclosure strategy?

Will you wait until you have the full duration of durability that's necessary, or will you give us a preliminary look on the data from Augment 101 before it's fully mature?

Right.

Again, I guess maybe I'll ask Briggs to follow up.

Thanks for the question, Phil.

Right.

So, Phil, there is no durability that's required for filing.

I think if you look at the precedents for some of the other targeted agents, a median duration of response of at least four to six months has been acceptable in the past.

So I think that's sort of the lower bound of what people would see.

As you will recall, the data we showed at ASH, the Kaplan-Meier estimate for durability of response, even at six months, was greater than around 70%.

So if the data for our filing holds up similar to what we presented at ASH, I think we're in very, very good shape from a regulatory point of view.

So that's approximately when we, as investors, should expect to see the data, about six months after you get the last patient for each cohort?

Exactly.

Got it.

Okay.

And then second question is on the intercept trial, how is MRD negativity being assessed for the different genotypes?

There is regulatory precedent for MRD negativity for an NPM1 AML patient established by Cronos, but I don't believe the FDA has ever said how you assess MRD negativity for MLR.

How is the intercept trial doing that?

So maybe if Peter is on the line, Peter or Dan, maybe you want to comment on that one.

Yeah, hi, this is Peter.

For the MLR, the MRD is a little tricky, as you note, just because of the individualized nature of the different infusions that can occur.

I believe it's by flow cytometry predominantly for the MLR patients.

Great.

That's very helpful.

And then last question, we saw that the SAVE trial is on clinicaltrials.gov now.

Can you remind us what the rationale is for looking at combinations with ASTX727?

Why choose that as one of the agents that you're first moving into combo studies with?

Yeah, Phil, first of all, it's an investigator-sponsored trial, so that's part of the equation here.

But maybe I'll ask Briggs or Peter to comment on the rationale.

The logic is the same as Venasa, essentially the SX molecule is essentially an oral ASA.

So I think the MD Anderson team, as Michael said, it's an investigator sponsored trial, they were quite interested in being able to potentially develop an oral regimen without having to give parenteral ASA cytidine.

So the scientific rationale for the combo is the same as for the Venasa.

Why that molecule specifically, I think they're quite interested in an oral regimen.

Perfect.

Thanks for taking our questions and congrats on the progress.

Thank you, Phil.

Next question comes from Bert Hazlitt with BDIG, your line is now open.

Thanks.

Thank you for taking the questions.

I have a couple on 5613, forgive me for not, excuse me.

Could you just maybe provide benchmarks, I think you may have done this previously, but, for the BEAT AML trial with regard to frontline Venasa, the combination with frontline Venasa in specifically in NPM1 or MLLR patients, what should be the benchmarks we're considering for meaningful activity in that patient group, frontline?

Greg, do you want to take that one?

Yeah.

So, Bert, we can send you the Viala A trial, which was the Venasa versus ASA first-line, trial.

The overall response rate, I think, if I remember correctly, was sort of in the mid-60s.

The actual CR rate was lower than that. There are some subsequent publications where they break it out by mutational status, but, as you can imagine, the number of patients in each one of those is smaller.

So, I think in an early look at the data, looking at an MRD negative rate, then looking, at the CR or CRI rate, but we'll send you the Viala A paper and all the supporting information.

Okay.

That's helpful.

Then, one kind of strategically, given the effort into solid tumors here with CRC, is, this foreshadowing some additional combination therapy or potential combinations or licensing potential with Revumenib and other molecules that focus on the Wnt beta-container pathway?

Or is this moving into CRC?

Or how should we think about what this initial step means strategically for the development, of Revumenib?

Yeah.

Thanks for the question, Bert.

I'll just say overall strategy here is we think we're following good science into particular, form of solid tumor biology, and I think that's where we find we think that this will be something to explore.

It is a signal-seeking phase one trial, limited investment, as Briggs pointed out in his remarks.

So, market opportunity is quite significant. There's a lot of unmet medical need in this area of colorectal cancer, and we think the, mechanism has very strong rationale.

We'll find out, essentially, if it works.

But in terms of a larger strategy in solid tumors, I think we're being strategic and, surgical about how we go into certain other areas outside of hematology and leukemia, I should say.

So, I think this is one such opportunity.

There may be others, but again, we're very much focused on the biology at hand and where, it takes us with, of course, our first focus being very much in the leukemia space.

So, I don't know.

Briggs, do you want to add anything to that?

No, no, I think that's right.

I mean, it's, I wouldn't necessarily think about novel, we want to just sort of see is this, does the preclinical data, the clinic, there obviously is, there are additional opportunities if it does work in the beta-catenin pathway beyond colorectal cancer.

Fair enough.

And then just one more kind of big picture in the, in this class in general.

How do you see, you're clearly in the lead with a number of these indications and certainly the move into, you know, colorectal and the other space.

How do you see the competitive landscape evolving in these menin interaction inhibitor space?

Thanks.

Yeah, thanks, Bert.

Look, I think you pointed to us, you point out what we believe to be true, which is that we're in the lead in terms of developing our drug and becoming the first menin inhibitor approved potentially.

And that's our, that's the thrust of our effort.

And in terms of looking at other indications, frontline, maintenance, what have you, that's, you know, those are areas that we'll go into as well.

And then we've talked about today, we talked about colorectal cancer.

There may be other areas to exploit, as Briggs just pointed out, around in solid tumors.

But, you know, essentially, I think we feel like we are, you know, able to leverage our first mover advantage, exploit the attributes of our agent, which we think are pronounced, and we'll have a good opportunity to show that in the market.

Others have to put up data, and we'll look forward to seeing what they have when they actually, you know, produce the data and present it at conferences.

All right, thank you.

Thanks, Bert.

Next question comes from the line of Egal Nachamovitz from CD Group.

Your line is now open.

Hi, team.

This is Ashok Mubarak on for EGAL.

Thanks for taking my questions.

A bit of a basic one, but regarding your new plant study in colorectal cancer, does there need to be an MLL rearrangement to support, I guess, aberrant activation of the Wnt beta-catenin pathway, or is it all just wild type?

And maybe what proportion of the CRT population do you think is addressable with menin?

Yeah, it's more akin to the NPM1 story.

It's not – there's not a fusion protein.

It's more akin to NPM1 where the NPM1-driven transformation is dependent upon the – for beta-catenin, it's similar to it.

Okay, and what proportion do you think is addressable with menin inhibition?

Oh, right. So, if you look at – we actually – we've been thinking through this on the beta-catenin pathway and CRC and whether we should be taking a biomarker-selected population, but the vast majority of colorectal cancers have either – have an activation – necessarily would have an activation of the beta-catenin pathway, so we think it's actually the majority – the vast majority of patients have this pathway activated.

How do you expect revumentib to behave in solid tumors vs. leukemia and do you think you would need to dose with a CYP304 based on your prior work in leukemia?

Yes, so the dosing should be the same.

Again, you are just blocking the interaction of menin with MLL just as we do with NPM1 where the dosing is the same.

So the dose of whether you see responses or whether you see differentiation as we see in AML is one that will be very interesting.

Preclinically, you actually see a very similar differentiation with AML.

Okay, and maybe the last point on using a CYP304?

No, again, so just to clarify, it's not that you need a CYP304, it's that you give.

It depends on whether they're also taking a CYP304 inhibitor.

So we think that the exposure response should be the same in leukemia.

So, again, we don't need a CYP304 inhibitor, we just need to know what the dose is with or without.

And that should be the same in colorectal cancer.

Okay, sorry, I think the connection isn't great, but I appreciate the answers, Greg.

Yeah, thanks, Ezra.

We can follow up afterwards if need be.

Next question is from Joe Beatty with Baird.

Your line is now open.

Hi, congrats on the progress and thanks for taking the questions.

The first one is on AUGMA 101.

With a lower bound that has to be ruled out when you submit the data to FDA, do you see any potential for the enrollment size and any of the three arms to change based on early data and how it looks?

Yeah, Joel, thank you for the question.

Well, as you know, this is a pivotal trial, so we're not looking at the data.

I think the concept is that we have, and I think I mentioned in my remarks, 64 patients enrolled in each of the trials, individual trials, and up to 10 pediatric patients.

So that sort of, the statistics are set around the 64 patients, and as of today, there's no, we don't see any reason why that would move.

And that, obviously, is driven, you know, all the powering is done off of the lower bound.

So while we haven't disclosed what that is, we feel like it, you know, the statistics hold and we have agreed with FDA on the design.

So in our mind, we don't see any reason why it would change.

Okay, great.

And then a question on business development.

You know, you mentioned how that could be a bigger focus for this year.

How has the recent biotech downturn affected the outlook for that?

Yeah, thanks for the question, Joel.

Yeah, I think I mentioned that, obviously, we're in a tough environment, and I don't think many companies are immune to that, but I do think that, you know, our business model is to in-license or acquire other assets.

We've generally focused on early stage assets, call it lead stage preclinical through phase one. So these are assets that allow us to do some very good development work and not spend as much on development at the early stages until we get to a point of value inflection.

And so I think that's the area that we tend to focus on.

And I think those are the assets that, perhaps are not getting as much attention in the down market.

And so we continue to be encouraged by some of the things that we're, we're seeing, and we're being very selective on the types of assets and what we're bringing, what we could potentially bring into Synax.

And so it's, in that way, I think we're, we're feeling, we're feeling good about our goals for the future and building our pipeline.

Great.

Thank you.

Thanks, Joe.

Final question comes from the line of Peter Lawson with Barclays.

Your line is now open.

Great.

Thanks for taking my questions.

I guess the first one is just around whether we'd see any, updated phase one data for the menin inhibitor this year or early next.

Yeah, thank you, Peter, for the, for the question.

I think, you know, in our mind, we're, you know, pretty much focused on enrolling and, and doing all the work that's required now in the phase two to get the, get the drug, get, get the drug ultimately approved.

And so that's where our focus is.

I guess the only real question, and there are some questions that I'm sure people have, but the question that something we could potentially talk about coming out of the phase one is maybe just an update on the, on the durability of the endpoint of CRCRH, which we reported on at ASH.

As of now, we don't have specific plans to update the market on that, again, because our focus has turned to the phase two.

But if that were to change, obviously, we'd let people know.

And there shouldn't be an expectation, necessarily that we would do that.

So other than that, I don't think there's, there's much to, to say about the phase one at any particular time this year.

But again, if that were to change, we'll certainly let people know.

Gotcha.

Would the durability kind of help with the enrollment for the Augment study in any way, you think, to help investigators get, I guess, greater comfort around the durability of these drugs?

Yeah, look, thanks for that question, too.

I, I do think that more data helps.

Whatever the data is, if it's, if it's positive about your program, and people are interested in your program, they tend to notice the, you know, the, the data that you put out.

And so could that help?

I would imagine there could be some positive, you know, some benefit to that.

I would also offer that physicians are extremely excited today about what we've, what we've put out from the phase one.

And we did that at ASH, and the follow through has been tremendous, and our trials are enrolling well.

So I think we feel very encouraged by the interest of physicians and investigators.

And so that's, you know, just where, where we are today.

But additional data never hurts as long as it is supportive.

The branching to solid tumor indications, I'm just curious if we see any preclinical, data for CRC or other indications and do you think there's any preclinical evidence that they could work better with the CRC mutations such as the G12C?

Maybe I'll let Briggs take that question.

Yeah, so Peter, we can send you some data that have come out that have given us a lot, of confidence in this mechanism.

Again, as I mentioned earlier, I think combinations with other agents in colorectal can't speak, about, but yeah.

Okay, perfect.

Is there anything coming out from your own work that we could potentially see this year, preclinically?

Potentially, yes.

I wouldn't set an expectation, but the team is doing some additional work to validate, some of the things that we've seen in the literature, so don't know when that will be ready.

Perfect.

Thank you so much.

Thanks for taking the question.

Thank you, Peter.

This concludes the Q&A portion of the call.

I will now turn the call back with Michael Metzger, who will make a few closing remarks.

Great.

Thank you, operator, and thank you for joining us on the call this afternoon.

We look forward to seeing many of you at the upcoming conferences this spring as well as, on any future calls.

Again, have a great evening and thanks for joining us.

Good night.

This concludes today's conference call.

Thank you all for your participation.

Q1 2022 Syndax Pharmaceuticals Inc Earnings Call

Request a DemoDemo

SNDX

Syndax Pharmaceuticals

Earnings