Q2 2022 Syndax Pharmaceuticals Inc Earnings Call

Michael Meyers: We expect regulatory filings for both programs in 2023 and are laying the groundwork to support a strong launch of these first and potentially best-in-class products.

Expect regulatory filings for both programs in 2023 and are laying the groundwork to support a strong launch of these first and potentially best in class products. We are excited about the opportunities and important milestones ahead.

Michael Meyers: We are excited about the opportunities and important milestones ahead.

Michael Meyers: Turning to slide three, we provide a high-level summary of our current corporate priorities.

Turning to slide three we provide a high level summary of our current corporate priorities.

Michael Meyers: Starting with RevuMenid, previously referred to as SNDX5613, our highly selective menin inhibitor.

Starting with revenue minute previously referred to as <unk> 50, 613, our highly selective <unk> inhibitor.

Michael Meyers: Our pivotal Phase II Augment 101 trial evaluating RevuMenid in patients with relapsed refractory MPM1 mutant or MLR acute leukemia is enrolling well, and we continue to expect data from one of the three cohorts beginning in the first half of 2023.

Our pivotal phase III augment 101 trial evaluating <unk> in patients with relapsed refractory <unk> mutant or MLR acute leukemia is enrolling well and we continue to expect data from one of the three cohorts beginning in the first half of 2023.

Michael Meyers: Data from the Phase I portion of this trial continues to mature, and we are looking forward to announcing updated data in the fourth quarter of this year.

Data from the phase one portion of this trial continues to mature and we are looking forward to announcing updated data in the fourth quarter of this year.

Michael Meyers: Beyond the Augment 101 trial in relapsed refractory disease, RevuMenid is the focus of several ongoing and planned trials that present important expansion opportunities. The ongoing BEAT AML and Augment 102 trials will provide data on safety and initial efficacy of RevuMenid in combination with approved agents.

Beyond the augment 101 trial in relapsed refractory disease <unk> is the focus of several ongoing and planned trials that present important expansion opportunities.

The ongoing beat AML and augment 102 trials will provide data on safety and initial efficacy of <unk> in combination with approved agents.

Michael Meyers: Additionally, we expect the Australasian leukemia and lymphoma group to initiate the intercept trial in the fourth quarter of 2022. This trial explores the activity of RevuMenid in patients with AML who have MRD-positive disease.

Additionally, we expect the Austral Asian leukemia, and lymphoma group to initiate the intercept trial in the fourth quarter of 2022.

This trial explores the activity of revenue minute in patients with AML, who have <unk> positive disease.

Michael Meyers: Beyond acute leukemia, we have also identified solid tumor indications that could benefit from RevuMenid, and we are preparing to initiate a proof-of-concept trial in colorectal cancer in the fourth quarter of this year.

Beyond acute leukemia, we have also identified solid tumor indications that could benefit from <unk> minute and we are preparing to initiate a proof of concept trial in colorectal cancer in the fourth quarter of this year.

Michael Meyers: Moving to axotilumab, our antibody against CSF1R. Our pivotal Phase II Agave 201 trial, evaluating axotilumab in patients with chronic graft-versus-host disease, or CGBHD, is enrolling well, and we continue to expect data in the first half of 2023.

Moving to <unk>, our antibody against the CSF Oner.

Our pivotal phase III <unk> to a one trial evaluating <unk> in patients with chronic graft versus host disease or CGP HD is enrolling well and we continue to expect data in the first half of 2023.

Michael Meyers: We are actively working with our partner, Insight, to maximize the value of the axotilumab program, and this includes planning additional trials of axotilumab in earlier lines of CGBHD. We anticipate that Insight will initiate a trial of axotilumab in combination with Jakafi in the fourth quarter of this year.

Activity working with our partner insight to maximize the value of the exits on that program and this includes planning additional trials of <unk> earlier and earlier lines of CGP HD.

We anticipate that insight, we will initiate a trial of <unk> in combination with Jakafi in the fourth quarter of this year.

Michael Meyers: Beyond CGBHD, we expect to begin a Phase II trial of axotilumab in idiopathic pulmonary fibrosis, or IPF, in the fourth quarter of this year.

Beyond <unk> Gvhd, we expect to begin a phase II trial of <unk> in idiopathic pulmonary fibrosis or Ips in the fourth quarter of this year brings.

Briggs: Briggs will speak to our strategy in IPFs, including the trial design, later in his remarks.

Briggs will speak to our strategy and Ips, including the trial design later in his remarks.

Michael Meyers: We also continue to assess business development opportunities to complement our existing pipeline.

We also continue to assess business development opportunities to complement our existing pipeline.

Michael Meyers: While our bar is high for in-licensing drug candidates, given the strength of our pipeline, we continue to evaluate potential opportunities to in-license earlier-stage targeted oncology compounds that we believe could become high-value differentiated assets.

While our bar is high for in licensing drug candidates given the strength of our pipeline, we continue to evaluate potential opportunities to in license earlier stage targeted oncology compounds that we believe could become high value differentiated assets.

Michael Meyers: Let's now turn to slide four, and I'll provide further details on the Revumentin program.

Let's now turn to slide four and I'll provide further details on the recommended recommended program.

Michael Meyers: First, 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 represents an independent path to a separate indication, and will serve as the basis for a full regulatory filing in the U.S. 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 NPM1 mutant AML.

First we are conducting three single arm phase II trials that FDA has agreed they each serve as a pivotal trial.

Each of these single arm phase II trials represented independent path to a separate indication and will serve as the basis for a full regulatory filing in the U S.

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

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

Each trial is open to patients aged one month or older.

And each trial will enroll independent of the other two.

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 CRC RH response transfusion independence overall survival and safety importantly, the trial design allows patients to be treated with <unk>.

Michael Meyers: Importantly, the trial design allows patients to be treated with Revumentib after bone marrow transplant, a design feature that allows us to start to understand the role of Revumentib in the post-transplant maintenance setting. We also have agreement with FDA on the statistical design of each trial.

After bone marrow transplant, a design feature that allows us to start to understand the role of revenue minute in the post transplant maintenance setting.

Michael Meyers: Each trial will enroll approximately 64 adult patients and up to 10 pediatric patients.

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

Patient accrual across the individual trials is going well and we remain optimistic that we can fleet enrollment in one of these trials this year.

Michael Meyers: Patient accrual across the individual trials is going well, and we remain optimistic that we can complete enrollment in one of these trials this year.

Michael Meyers: As we look at the competitive landscape and engage with experts in the field, we believe Revumentib's compelling clinical profile, as demonstrated in the robust Phase I experience in 59 patients that we presented at ASH in 2001, positions Revumentib to not only be the first in class, but also a potentially best-in-class treatment.

As we look at the competitive landscape and engage with experts in the field, we believe revenue minutes compelling clinical profile as demonstrated in the robust phase one experience in 59 patients that we presented at Ash in 2001 positions revenue method to not only be the first in class, but also a potentially best in class treatment.

Michael Meyers: Importantly, we have decided to provide updated data from the Phase I portion of the Augment 101 trial in the fourth quarter. We are seeing improvements in key metrics of the data since last year's ASH presentation, and we believe this update will further strengthen our leadership position and confidence in the outcome of the pivotal trial.

Importantly, we have decided to provide updated data from the phase one portion of the augment 101 trial in the fourth quarter. We are seeing improvements in key metrics of the data since last year's Ash presentation, and we believe this update will further strengthen our leadership position and confidence in the outcome of the pivotal trial.

Michael Meyers: Beyond the Augment 101 pivotal program in relapsed refractory disease, Slide 5 highlights some of the additional opportunities that we are exploring with Revumentib, all of which build on Revumentib's excellent safety and efficacy profile that lends well to the treatment across all settings and in combination with currently approved agents.

Beyond the augment 101 pivotal program and relapsed refractory disease slide five highlights some of the additional opportunities that we're exploring with every minute.

All of which build on <unk> excellent safety and efficacy profile that lends well to the treatment across all settings and in combination with currently approved agents.

Michael Meyers: The Phase I BEAT AML umbrella trial is currently enrolling patients. As part of our collaboration with the Leukemia and Lymphoma Society, Revumentib, the first menin inhibitor to be included in this trial, is being combined with venetoclax and asositidine in newly diagnosed AML patients who are unfit for induction chemotherapy. This trial will assess safety as well as initial efficacy.

The phase one beat AML umbrella trial is currently enrolling patients as part of our collaboration with the leukemia and lymphoma Society recommended the first <unk> inhibitor to be included in this trial is being combined with <unk> in newly diagnosed AML patients who are unfit for induction chemotherapy.

RFP.

This trial will assess safety as well as initial efficacy.

Michael Meyers: We expect initial data from this trial to be available in 2023.

We expect initial data from this trial to be available in 2023.

Michael Meyers: Longer term, we expect that positive BEAT AML trial results would lead to a Phase II-III trial, which could serve as the basis for a regulatory final.

Longer term, we expect that positive beat AML trial results would lead to a phase III trial, which could serve as the basis for regulatory filings.

Michael Meyers: Our other combination trial that is currently enrolling patients, the Augment 102 trial, is designed to assess Revumentib in combination with standard salvage chemotherapies for patients with acute leukemias. 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.

Our other combination trial that is currently enrolling patients. The augment 102 trial is designed to assess <unk> in combination with standard salvage chemotherapy for patients with acute leukemias.

Both the augment 102 and beat AML trials are supported by preclinical data, which demonstrate the potential benefit of amended inhibitor used in combination regimens in these settings.

Michael Meyers: Further, Revumentum is suitable for use in combination based on its safety profile as seen in the Phase 1 portion of the Augment 101 trial.

Other revenue Menon is suitable for combination.

We're using combination based on its safety profile as seen in the phase one portion of the augment 101 trial.

Michael Meyers: The Intercept trial is focused on investigating novel therapies to target early relapse and clonal evolution as a preemptive therapy in AML and is being conducted as part of the Intercept Master Clinical Trial led by the Australasian Leukemia and Lymphoma Group. The trial is designed to explore the activity of Revumentum as monotherapy in patients with AML who have MRD-positive disease following initial treatment, a group of patients at very high risk of relapse.

The intercept trial is focused on investigating novel therapies to target early relapse and clonal evolution as a preemptive therapy in AML and is being conducted as part of the intercept master clinical trial led by the Australia Asian leukemia, and lymphoma group. The trial is designed to explore the activity of <unk>.

<unk> as monotherapy in patients with AML.

Who have <unk> positive disease. Following initial treatment a group of patients at very high risk of relapse.

Michael Meyers: Of note is that Revumentum is the first menin inhibitor to be included in the Intercept AML Master Clinical Trial.

Of note is that revenue method as a first met inhibitor to be included in the intercept AML Master clinical trial the.

Michael Meyers: The Intercept trial is a very creative approach to treating patients early in their disease course, which is important because the general tenet in oncology is that the earlier you treat the patient's disease, the better patients do and the longer patients stay on medicine.

The intercept trial is a very creative approach to treating patients early in their disease course, which is important because the general tenant in oncology is that the earlier you treat the patients disease, the better patients do and the longer patients stay on medicine.

Michael Meyers: We currently expect the Australasian Leukemia and Lymphoma Group to initiate dosing in the fourth quarter of this year.

We currently expect expect the Australia Asian leukemia.

Lymphoma group to initiate dosing in the fourth quarter of this year.

Michael Meyers: Turning now to slide six, our goal is to unlock the full potential of Revumentum beyond the relapse-refractory acute leukemia setting.

Turning now to slide six.

Our goal is to unlock the full potential of <unk> beyond the relapsed refractory acute leukemia setting.

Michael Meyers: In acute leukemia, we plan to engage patients early in their treatment journey, get them into remission, and hopefully maintain them in that state for months, if not years.

In acute leukemia, we plan to engage patients early in their treatment journey get them into remission and hopefully maintain them in that state for months if not years.

Michael Meyers: With these expansion opportunities, we see the potential to address upwards of 12,000 NPM1 mutant and MLR acute leukemia patients across various settings. These two forms of acute leukemia together 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.

With these expansion opportunities, we see the potential to address upwards of 12000, <unk> mutant and MLR acute leukemia patients across various settings.

These two forms of acute leukemia, together 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.

Michael Meyers: Beyond the acute leukemia opportunity, we believe there is a significant value in expanding to solid tumors where Revumentum could address areas of unmet need. As we mentioned on our first quarter call, we plan to start an initial proof-of-concept clinical trial in colorectal cancer in the fourth quarter of this year. The phase one trial is designed as a signal-seeking trial in 20 to 30 patients with refractory colorectal cancer to look for responses or disease stabilization. We are excited about this opportunity, given the compelling preclinical science supporting the role of MNN-MLL1 interaction in beta-catenin-driven tumors such as colorectal cancer.

Beyond the acute leukemia opportunity. We believe there is significant value there is significant value in expanding to solid tumors, where revenue could address areas of unmet need.

As we mentioned on our first quarter call. We plan to start an initial proof of concept clinical trial in colorectal cancer in the fourth quarter of this year.

As one trial is designed as a signal seeking trial in 20 to 30 patients with refractory colorectal cancer to look for responses or disease stabilization.

We are excited about this opportunity given the compelling preclinical science supporting the role of Menon, MLR, one interaction and beta <unk> driven tumors, such as colorectal cancer.

Michael Meyers: We anticipate that Revumentum could be one of the most important new franchises in hematology, along with the added potential in solid tumors.

We anticipate that <unk> could be one of the most important new franchise franchises in hematology along with the added potential in solid tumors. We are laying the groundwork for potential launches. So that we are well prepared to get medicine quickly to patients quickly to physicians and the patients they treat and take advantage of our leading position.

Michael Meyers: We are laying the groundwork for potential launches so that we are well prepared to get medicine quickly to physicians and the patients they treat and take advantage of our leading physician.

Michael Meyers: We are educating and building mindshare with oncologists as they utilize and gain comfort with the drug while it's in clinical trials.

We are educating and building mind share with oncologists as they utilize and gain comfort with the drug while it's in clinical trials.

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

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

Michael Meyers: Slide 7 outlines our pivotal Agave 201 trial evaluating axotilumab in patients with CGBHD. The trial is enrolling patients whose disease has progressed after two prior therapies.

Slide seven outlines our pivotal agave 201 trial evaluating <unk> in patients with Gvhd.

The trial is enrolling patients whose disease has progressed after two prior therapies.

Michael Meyers: Patients must be at least two years of age and have met overall entry criteria.

<unk> must be at least two years of age and have met overall entry criteria.

Michael Meyers: This is a pivotal dose-ranging trial in which 210 patients will be randomized to one of three treatment groups, each investigating a distinct dose of acutelamide given every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for CGBHD, while secondary endpoints include duration of response and validated quality-of-life assessments using the Lee Symptom Scale.

This is a pivotal dose ranging trial in which 210 patients will be randomized to one of three treatment groups. Each investigating a distinct dose of <unk> given every two weeks or every four weeks.

Primary endpoint is overall response rate using the 2014 NIH consensus consensus criteria for CG BHG, while secondary endpoints include duration of response and validated quality of life assessments using the least symptom scale.

Michael Meyers: Enrollment of the study is going well, and we are on track to complete enrollment by the end of this year, and deliver top-line data in the first half of 2023. This trial is supported by positive Phase I-II data in 40 CGBHD patients we presented at ASH in 2021, where the overall response rate was 68%, and the median time on treatment was over six months. Along with an excellent safety profile, these results were well-received among thought leaders, who recognized acutelamide as having a clinical profile that would be beneficial in the treatment of these heavily pretreated patients.

Enrollment of this study is going well and we are on track to complete enrollment by the end of this year and deliver topline data in the first half of 2023.

This trial is supported by positive phase one two data and 40 C. Gvhd patients we presented at Ash in 2021 for the overall response rate was 68% and the median time on treatment was over six months.

Along with an excellent safety profile. These results were well received among thought leaders, who recognized <unk> as having a clinical profile that would be beneficial in the treatment of these heavily pretreated patients.

Michael Meyers: In collaboration with our partner, Insight, we are eager to expand the acutelamide program, to include combination therapy as well as to assess its use in other fibrotic diseases, including IPS.

In collaboration with our partner insight, we are eager to expand the <unk> program to include combination therapy as well as to assess its use in other fibrotic diseases, including IPF.

Michael Meyers: The collaboration has brought together two companies with solid track records of innovation, and we are benefiting from Insight's expertise in CGBHD.

The collaboration has brought together two companies with solid track records of innovation and we are benefiting from insights expertise and gvhd.

Michael Meyers: We are currently planning to assess a novel combination of acutelamide and Jakafi, with the goal of establishing acutelamide in earlier settings within CGBHD and expanding its market opportunity. We anticipate this combination trial could begin in the fourth quarter of 2022.

We are currently planning to assess a novel combination of Axa <unk> jackup fee with the goal of establishing <unk> in earlier settings within CGP, HD and expanding its market opportunity.

We anticipate this combination trial could begin in the fourth quarter of 2022.

Michael Meyers: 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 previously mentioned was our intention we plan to initiate a robust phase II trial in IPF in the fourth quarter of this year.

Michael Meyers: IPF is the first expansion opportunity that we have committed to pursuing beyond CGBHD, and we believe acutelamide could have a significant impact in this disease.

IPF is the first expansion opportunity that we have committed to pursuing beyond CGP HD and we believe <unk> could have a significant impact in this disease.

I'll now ask Briggs to walk through the biologic rationale development strategy and market opportunity for <unk> and IPF.

Briggs: I will now ask Briggs to walk through the biologic rationale, development strategy, and market opportunity for acutelamide in IPF.

Operator: Briggs?

Briggs: Thanks very much, Michael.

Thanks, very much Michael turning to slide eight.

Briggs: Turning to slide eight, acutelamide, you may recall, is an IgG4 monoclonal antibody, that binds to the CSF1 receptor and blocks the interaction with its two ligands, CSF1 and IL34, thereby decreasing the proliferation and function of CSF1R-dependent monocytes and macrophages.

<unk> you may recall IGT for monoclonal antibody that binds to the CSF, one receptor and blocks the interaction with its two ligand CSF, one and IL 34, thereby decreasing the proliferation and function of CSF, one are dependent monocytes macrophages.

Briggs: Preclinical data has indicated that bone marrow-derived monocytes, which are dependent on CSF1, could mediate the inflammatory and fibrotic components of a number of diseases.

Great clinical data has indicated that bone marrow derived monocytes, which dependent on CSF, one could mediate the inflammatory and fibrotic components of a number of diseases.

Briggs: As I've noted before, our work with experts in the field of fibrotic diseases points to a strong consensus, that the scientific basis for the efficacy of acutelamide in chronic graft-versus-host disease is likely to extend to a wide variety of other fibrotic diseases, including IPF. We've established that acutelamide is active in chronic graft-versus-host disease, and we're excited about the opportunity to expand acutelamide into other fibrotic diseases where the monocyte-macrophage lineage plays a key role.

As I have noted before our work with experts in the field of fibrotic diseases points to a strong consensus that the scientific basis for the efficacy of <unk> in chronic graft versus host disease.

Likely to extend to a wide variety of other fibrotic diseases, including IPF.

We've established that <unk>.

<unk> is active in chronic graft versus host disease, and we're excited about the opportunity to expand <unk> into other fibrotic diseases, where the monocyte macrophages lineage plays a key role and today, we will focus on our development on that.

Briggs: And today we'll focus on our development on it.

Briggs: IPF is a chronic fibrosing lung disease for which there are currently very limited treatment, options. Only two drugs have been approved and both have only been shown to slow, but not stop, or reverse disease progression. The only opportunity for a cure is a lung transplant, which is limited to less than, 5% of patients.

So IPF is a chronic fibrosis lung disease for which there are currently very limited treatment options.

These two drugs have been approved and both have only been shown to slow, but not stop or reverse disease progression.

The only opportunity for cure in the lung transplant, which is limited to less than 5% of patients.

Briggs: With the estimated U.S. prevalence of IPF growing to over 180,000 by 2026, we think, there is an increasing need for new and safe, effective medications.

With the estimated U S prevalence of IPF growing to over 180000 by 2026, we think there is an increasing need for new and safe effective medications.

There are several reasons why we are excited to pursue.

Briggs: There are several reasons why we are excited to pursue fibrotic disease outside of GVHD, and why we have confidence that axopilimab can have a meaningful benefit in IPF. There is a wealth of emerging preclinical and clinical data indicating that the CSF-1, signaling pathway appears to play a significant role in the development of pulmonary fibrosis.

<unk> disease outside of Gvhd, and why we have confidence that <unk> can have a meaningful benefit in IPF.

There's a wealth of emerging preclinical and clinical data, indicating that the CSF oner signaling pathway appears to play a significant role in the development of pulmonary fibrosis and.

Briggs: And there's a growing understanding of the important role that macrophages play as a, master regulator of the fibrotic process.

And there is a growing understanding of the important role that macrophages play as a master regulator of the fibrotic process.

Preclinical data, which I'll review in a minute supports our planned clinical program.

Briggs: Preclinical data, which I'll review in a minute, supports our planned clinical program.

Perhaps of greatest relevance is the data we've generated in patients with pulmonary manifestations of chronic graft versus host disease, we have observed clinically important improvements in lung function.

Briggs: Perhaps of greatest relevance is the data we've generated in patients with pulmonary, manifestations of chronic graft-versus-host disease, where we have observed clinically important improvements in lung function. For example, within our Phase I-II data that we presented at ASH in 2021 in heavily pre-treated, patients, we saw lung-specific response rate in 5 of 15 patients.

For example, within our phase one two data that we presented at Ash in 2021 in heavily pretreated patients. We saw lung specific response rate and five of 15 patients.

Briggs: Furthermore, axopilimab has shown good safety and tolerability profile in this Phase I-II, trial at the doses that we've identified to use in our IPF trial. Slide 9 briefly summarizes some of the data that supports our entry into this proof of, concept trial.

Furthermore, <unk> has shown good safety and Tolerability profile in this phase one two trial at the doses that we've identified to us and our IPF trial.

Slide nine briefly summarizes some of the data that supports our entry into this proof of concept trial.

Briggs: In the panel on the left, we show data from an experiment in which bleomycin is instilled, into the lungs of mice, which is known to induce pulmonary fibrosis. In this case, bleomycin was instilled, and nine days later, the animals were treated, with an anti-CSF-1R antibody or a saline control.

Panel on the left we show data from an experiment in which bleomycin is instilled into the lungs of mice, which is known to induce pulmonary fibrosis.

In this case bleomycin was instilled in nine days later, the animals are treated with an anti CSF, one antibody or a salient control.

Briggs: The histologic section on the top left shows a normal lung with extensive white airspace.

A logic section on the top left shows the normal lung with extensive like aerospace.

Briggs: Conversely, the bleomycin lung has extensive fibrosis, the dark-colored material in the, slide.

Conversely, the bleomycin lung has extensive fibrosis, the dark colored material in the spine.

Briggs: Strikingly, the lung treated with bleomycin and then therapeutically treated with an anti-CSF-1R, antibody on day 9 has significantly less fibrosis and markedly preserved white airspace.

Strikingly the lung treated with bleomycin, and then therapeutically treated with an anti CSF oner antibody on day nine has significantly less fibrosis and markedly preserved white aerospace.

Briggs: A semi-quantitative analysis of these histologic sections yields what's known as an Ashcroft, score, and you can see a statistically improved Ashcroft score in the bar graph on the bottom left with administration of the anti-CSF-1R antibody.

Semi quantitative analysis of these histologic sections yields is what's known as the Ashcroft score and you can see a statistically improved ash cross score in the bar graph on the bottom left with the administration of the anti CSF Oner antibody.

And dependent on the right. We show data from Comet investigators comment is a trial that haynes to correlate outcomes.

Briggs: In the panel on the right, we show data from Comet investigators. Comet is a trial that aims to correlate outcomes with biochemical markers to estimate time, to progression in IPF. The patients were assessed at baseline and then followed over time, and the primary endpoint, of the trial was progression-free survival as determined by the time until any one of the following. Death, acute exacerbation of IPF, lung transplant, or decrease of 10% in FEC or 15% in DLC.

With biochemical markers to estimate time to progression in IPF.

The patients were assessed at baseline and then followed over time and the primary endpoint of the trial with progression free survival as determined by the time until any one of the following death acute exacerbation of IPF lung transplant or decrease of 10% in FEC or 15% in DLC.

Briggs: The investigators conducted a screen from biomarkers that would predict IPF progression. The data in the figure on the right shows that patients who have high levels of specific, monocytes have a much worse prognosis than patients without these high levels of these monocytes.

And the investigators conducted a screen for biomarkers that would predict IPF progression.

The data in the figure on the right shows that patients who have high levels of specific monocytes have a much worse prognosis in patients without these high levels of these mines.

Briggs: In the table below the graph is a reminder that axotilamide has been shown to specifically, deplete the non-classical and intermediate monocytes, the cell type that's correlated with more rapid disease progression in IPF. As we review this data with experts, they are particularly excited about the prospect, of axotilamide not simply targeting a specific pathway, but instead targeting and depleting a specific inflammatory cell, thus leaving very little room for redundancy or resistant mechanisms.

Table below the graph is a reminder, that <unk> has been shown to specifically deplete the nonclassical intermediate monocytes the cell type that's correlated with more rapid disease progression in IPF.

As we reviewed this data with experts they are particularly excited about the prospect of ACA till about not simply targeting specific pathway, but instead targeting and depleting our specific inflammatory cell, thus, leaving very little room for redundancy of resistant mechanisms.

Briggs: On slide 10, we've laid out the design of our Phase IIb trial in IPF. This is a multinational trial that will enroll 170 patients with IPF randomized one-to-one, to receive 75 milligrams of axotilamide every two weeks or placebo over a 52-week double-blind treatment period.

On slide 10, we've laid out the design of our phase <unk> trial in IPF.

This is a multinational trial that will enroll 170 patients with IPF randomized one to one to receive 75 milligrams of <unk> every two weeks or placebo over a 52 week double blind treatment period.

Briggs: We've leveraged the data from the ongoing chronic graft-versus-host disease program, to select an optimal dose that we believe is well-suited to the IPF patients, considering an expectation that approximately 80% will be on background medications.

Leveraging the data from the ongoing chronic graft versus host disease program to select an optimal dose that we believe is well suited to the IPF patients considering an expectation that approximately 80% will be on back background medications.

Briggs: In order to maximize the probability of success in the trial, we've worked with experts to, design a study that essentially mirrors a pivotal Phase III trial. Primary endpoint will measure change from baseline and FEC, which is a current registrational, endpoint in IPF.

Order to maximize the probability of success in the trial, we have worked with experts to design a study that essentially mirrors, a pivotal phase III trial.

Primary endpoint will measure change from baseline in FEC, which has a current registrational endpoint in IPF.

Briggs: These secondary endpoints include disease progression, St. George's respiratory question, which is a quality-of-life instrument designed for patients with obstructive airway disease, a six-minute walk test, and diffusing capacity for carbon monoxide.

These secondary endpoints include disease progression.

George's respiratory question, which is a quality of life instrument designed for patients with obstructive airway disease or <unk>.

Six minute walk test and diffusing capacity for carbon monoxide.

We anticipate enrollment in the IPF trial to initiate in the fourth quarter of this year.

Briggs: We anticipate enrollment in the IPF trial to initiate in the fourth quarter of this, year.

Briggs: And if successful, we believe this trial, along with perhaps one additional Phase III, trial, could potentially form the basis for FDA approval in IPF.

And if successful we believe this trial along with perhaps one additional phase III trial could potentially have formed the basis for FDA approval in IPF.

Michael Meyers: Let me now turn the call back over to Michael.

Let me now turn the call back over to Michael.

Michael Meyers: Great.

Great. Thank you Briggs.

Michael Meyers: Thank you, Briggs.

Michael Meyers: I'd like to highlight that successful development in IPF would allow us to unlock a very important, indication of considerable value.

I'd like to highlight that successful development in IPF would allow us to unlock a very important indication of considerable value.

Michael Meyers: Thus, we're very eager to get this trial up and running and anticipate doing so in, the fourth quarter of this year.

Thus, we are very eager to get this trial up and running and anticipate doing so in the fourth quarter of this year.

Michael Meyers: Slide 11 highlights the broad clinical and commercial opportunity for axotilamide.

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

Michael Meyers: 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.

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.

Successful commercial launches of insights jackup fee and incentive fees reservoir rock are encouraging.

Michael Meyers: Successful commercial launches of Insight's Jacopi and Sanofi's Resiroc are encouraging, both posting meaningful early revenues that begin to speak to the commercial opportunity in CGBHD.

Posting meaningful early revenues that begin to speak to the commercial opportunity in CGP HD.

Despite recent advances in this area to our knowledge <unk> is the only agent in clinical development that specifically targets the monocyte macrophage lineage.

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

Michael Meyers: We and Insight believe that data generated to date with axotilamide 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 medicine.

And insight believe that data generated to date with <unk> suggested has the potential to play an important role in the treatment of gvhd, both as a monotherapy and given its safety profile in combination with complementary medicines through.

Michael Meyers: Through combinations in the frontline setting, as well as the opportunity to expand to ex-U.S. markets, 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 to ex U S markets, we envision the C gvhd opportunity more than doubling as shown on this slide.

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

Keith Goldan: I will now turn the call over to Keith to review our financial results.

Thank you Michael Let me now take a few minutes to discuss our financial results for the second quarter of 2022.

Turning to slide 12.

The results of our operations for the second quarter of 2022, and the comparison to the prior year's quarter are included in our press release.

Don't repeat them in these remarks.

<unk> financial details are available in our second quarter report, which was filed earlier today on Form 10-Q.

Like to point out that our net loss for the quarter was $37 6 million or <unk> 62 per share.

<unk> to a net loss of $22 9 million or <unk> 44 per share for the same period last year.

This difference is primarily attributed to an increase in research and development expense driven by the expansion of both revenue and <unk> into registration trials expansion into new potential indications and increased manufacturing activities.

We ended the second quarter with $378 $9 million in cash equivalents and marketable securities and.

$60 4 million shares and pre funded warrants outstanding and we continue to forecast the cash runway into the second half of 2024.

Our current cash on hand supports our development and pre commercialization plans.

The revenue met Ed and <unk> programs. During this period and it provides us flexibility should we decide to engage in business development.

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

For the third quarter of 2022, we expect R&D expense to be $25 million to $30 million and total operating expense to be $35 million to $40 million.

For the full year 2022 <unk>.

Consistent with previous guidance, we expect R&D expense to be $130 million to $140 million.

And total operating expense to be $160 million to $170 million, including approximately $15 million of noncash stock compensation expense.

Keith Goldan: Thank you, Michael.

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

Keith Goldan: Let me now take a few minutes to discuss our financial results for the second quarter of 2022.

Thank you Keith.

Keith Goldan: Turning to slide 12, the results of our operations for the second quarter of 2022 as a comparison to the prior year's quarter are included in our press release, so I won't repeat them in these remarks.

As you can see we continue to make significant progress executing against the ambitious goals and milestones that we set forth at the beginning of this year.

Keith Goldan: We ended the second quarter with $378.9 million in cash equivalents and marketable securities and 60.4 million shares and pre-funded warrants outstanding, and we continue to forecast a cash runway into the second half of 2024. Our current cash on hand supports our development and pre-commercialization plans for both the RevuMetap and Exitilumetap programs during this period, and it provides us flexibility should we decide to engage in business development.

Keith Goldan: Looking ahead, I'd like to provide financial guidance for the third quarter and full year of 2022. For the third quarter of 2022, we expect R&D expense to be $25 to $30 million and total operating expense to be $35 to $40 million.

The index has always been focused on delivering new medicines that extend and improve the lives of people with cancer and today with two ongoing registration programs. A notable achievement in its own right. We stand on the precipice of realizing this goal.

Keith Goldan: For the full year of 2022, consistent with previous guidance, we expect R&D expense to be $130 to $140 million and total operating expense to be $160 to $170 million, including approximately $15 million of non-cash stock compensation expense.

And the potential of these programs extends well beyond their initial registration indications with both offering broad franchise opportunities that we believe are achievable given their compelling clinical profiles.

We believe <unk> could have utility across a wide range of clinical settings in acute leukemia, as well as potentially in 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 mutant and MLR acute leukemia.

Same franchise potential holds for <unk> that were broad broad opportunity exists both in various lines of therapy in <unk> HD and across a broad range of fibrotic diseases, starting with IPF.

We are in a strong financial position with a balance sheet that allows us to deliver on key near term milestones.

We're confident in our ability to identify and bring in novel molecules to deepen our portfolio. 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.

Lastly, we are thankful to our index team collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs for helping us to execute on our mission of realizing a future in which people with cancer live longer and better than ever before.

Further thank you to our committed long term investors, who share our vision and support us in building syntax.

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

That I would like to open the call for questions.

Michael Meyers: Thank you, Keith.

At this time, if you would like to ask a question.

One on your telephone.

If you wish to remove yourself from the queue. Please press star two.

We will take our first question Scott.

Baidu Kumar with Goldman Sachs. Please go ahead.

Yeah.

Hi, this is omar or for module.

So far first question you'd like to know what should we be looking for in the updated augment 101 data in <unk>.

What will be the focus durability of response or other disease features.

And then second question.

How many of the three cohorts from the phase two.

Cohort will be expected to complete enrollment by year end and should we expect an NDA so wait for multiple cohorts.

Great. Thank you Mark So let me take your first question related to the update on <unk>.

Michael Meyers: As you can see, we continue to make significant progress executing against the ambitious goals and milestones that we set forth in the beginning of this year.

At the end of the year for revenue manner I think.

Michael Meyers: Syndex has always been focused on delivering new medicines that extend and improve the lives of people with cancer, and today, with two ongoing registration programs, a notable achievement in its own right, we stand on the precipice of realizing this goal. The potential of these programs extends well beyond their initial registration indications, with both offering broad franchise opportunities that we believe are achievable, given their compelling clinical profiles.

The plan we had.

<unk> talked about this as a possibility of the plan is to update the dataset.

At.

At an opportunity in the fourth quarter.

Michael Meyers: We believe RevuManif could have utility across a wide range of clinical settings in acute leukemia, as well as potentially in solid tumors.

Michael Meyers: 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 MPM1 mutant and MLR acute leukemia.

<unk>.

We have presented a fulsome data set as you know as of Ash at last at last year's meeting.

The plan is to present a comprehensive updated.

Similar detail as to what was presented at that meeting so.

We're not going to comment specifically on the data what will be shown but I think you should assume that it'll be a similar level of detail.

And that presentation as well.

And then in terms of your second question.

Remind me sorry, just remind me that question.

Yes, how many of the three cohorts from the phase II regulator court, which we expect.

To be complete enrollment by year end, and then should we expect NBA to wait for North American multiple cohorts.

Alright, so the guidance that we've given is that we will have at least.

One one cohort we hope to have at the end of the year by the end of the year enrolled.

And that we will not necessarily wait.

To file to get all three cohorts together, but we'll soon as we have the data together for one cohort at least one cohort we will we will look to file that with the FDA. So.

It could be it could mean, an ongoing submission of data for additional cohorts beyond beyond the initial.

Alright, thanks for taking our questions.

Yes.

Okay.

So nadeau with Cowen and company. Please go ahead.

Good afternoon. Thanks for taking my questions first a follow on to the last question in the prepared remarks, there was a triggering teaser saying that some of the measures that were disclosed at ash last year have improved over time.

Michael Meyers: The same franchise potential holds for Axotilimat, where broad opportunity exists both in various lines of therapy in CGVHD and across a broad range of fibrotic diseases, starting with IPF.

Michael Meyers: We are in a strong financial position with a balance sheet that allows us to deliver on key near-term milestones.

Michael Meyers: We remain competent in our ability to identify and bring in novel molecules to deepen our portfolio. 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.

Michael Meyers: Lastly, we are thankful to our Syndax team, collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs for helping us to execute on our mission of realizing a future in which people with cancer live longer and better than ever before.

Michael Meyers: Further, thank you to our committed long-term investors who share in our vision and support us in building Syndax.

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

Operator: At this time, if you would like to ask a question, please press star 1 on your telephone keypad.

<unk>, whether you'd be willing to disclose which of those measures.

Operator: If you wish to remove yourself from the queue, please press star 2.

Proof.

Okay.

Operator: We'll take our first question from Madhu Kumar with Goldman Sachs.

Yes, thanks for the question Phil.

No, we're not going to we're not going to get into the detail there I think.

Omari: Please go ahead.

<unk>.

There are lots of detail that was provided in the ash in the ash presentation.

Omari: Hi, this is Omari from Madhu.

Last year, some some of it may be a.

A bit more important to certain investors and others than not but I'd say that it'll be a comprehensive update and we're looking forward to presenting all the detail which should.

Omari: So, for our first question, we'd like to know what you will be looking for in the updated Augmented 101 data in 4Q.

Omari: What will be the focus, durability of response, and other disease features?

I think further strengthen our position.

Build confidence in the outcome of the pivotal trials as well.

Omari: And then, second question, how many of the three cohorts from the Phase II Revumentib cohort will be expected to complete enrollment by year end, and should we expect an NDA to wait for multiple cohorts?

That's that's understand a couple of questions on the earlier stage pipeline in terms of colorectal cancer what level of response would you need to see from every minute to move forward in that indication.

Michael Meyers: Great.

Yes. Thanks for the question again, maybe I'll ask breaks to address that please.

Michael Meyers: Thank you, Omari.

Michael Meyers: So, let me take your first question related to the update at the end of the year for Revumentib. I think the plan, and we had talked about this as a possibility, the plan is to update the data set at an opportunity in the fourth quarter. We had presented a fulsome data set, as you know, as of ASH at last year's meeting. The plan is to present a comprehensive update in similar detail as to what was presented at that meeting.

So Phil you May remember, we set the tray.

Trial up as a.

We can win on one of either a response rate or disease.

Disease control rate and as you may recall the standard of care for this refractory population of patients has a very low less than 5% response rate.

So I don't want go into all the details of statistics, but if the lower bound exceeds that that historical 5% then that would it be intriguing to us and then the disease control rate again for standard of care at six months is probably no greater than 15%. So if we saw a disease control rate.

Exceeding that that would also capture our attention and I think what we've outlined is that if.

If we were to see responses, we could potentially advanced more rapidly given that the drugs, giving responses. If we saw a disease control rate or <unk>.

The protocol is set up to immediately go into a small randomized phase III to try to confirm that because.

I think our single arm disease control rate is low a little more challenging to interpret could get us excited to do the randomized portion. So that's the way the trial setup.

That's very helpful. And then last question kind of a similar question on IPF, what FCC change is the <unk>.

Trial powered to detect.

Youre welcome.

Yes, no I don't think we are at Liberty to talk about that I mean, I think what we have.

Yes.

Looked at the regulatory precedents for the other two drugs that are approved and try to power for a degree of.

The change from baseline in efficacy that would be clinically meaningful.

Got it.

Thanks for taking my questions and congrats on the progress.

Thank you Phil.

And thanks to <unk> with B Riley Securities. Please go ahead.

Yeah.

Yeah, Hey, good afternoon, and thanks for taking the questions.

For <unk> you have.

Ongoing efforts to explore their drug in an earlier line setting I guess.

How are you thinking about your strategy for advancing the drug with the seven plus <unk> combo in AML would that be a potential future development opportunity.

Yeah. Thanks for the question.

I'd say, absolutely I think there are number of combinations that we're looking at and then as Youre pointing out seven plus three is the fit population and certainly our drug could be used in that setting.

We're looking at designing trials to address that as well so thats in the planning process.

Okay.

And then diving a little more into the planned updated phase one data from augment 101.

I'm not sure if you'll comment but should we expect maybe a breakdown of CRC RH rates based on that dose and an underlying patient characteristics for example.

Which patients progressed on when either class and then received a CR of CRH.

Yes. Thanks for the question I think you should expect to see a similar level of details of what we provided at.

Michael Meyers: So, we're not going to comment specifically on the data, what will be shown, but I think you should assume that it will be a similar level of detail in that presentation as well.

At Ash in 2021.

Whether or not we're going to provide further breakdown on any subsets and things of that nature.

Wait to see for the update.

In the fourth quarter.

Okay.

And then one last question for the Gvhd trial. The Jackup fee is there going to be a comparator arm or has that not been decided for the trial.

Yes, I mean, we're again, we haven't disclosed the details of that trial as of yet, but stay tuned and that will be forthcoming.

Okay fantastic. Thank you very much for taking my question.

Thank you.

Michael Meyers: And then, in terms of your second question, remind me, sorry, just remind me of that question.

We'll go next to E.

<unk> with Citi.

Please go ahead.

Omari: Yeah, how many of the three cohorts from the Phase II Revumentib cohort should we expect to be complete enrollment by year end, and then should we expect an NDA to wait for, or to wait for multiple cohorts?

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

Michael Meyers: Right, so the guidance that we've given is that we'll have at least, we'll have one cohort we hope to have at the end of the year, by the end of the year enrolled.

A couple on the competitive landscape.

The competitive landscape.

Michael Meyers: And that we will not necessarily wait to file, to get all three cohorts together, but we'll, as soon as we have the data together for one cohort, at least one cohort, we will look to file that with the FDA.

How are you thinking about data from one of your key competitors or the minute Menin inhibitor, which is expected later this year.

Michael Meyers: So, it could be, it could mean an ongoing submission of data for additional cohorts beyond the end of the year.

Michael Meyers: All right.

And ultimately do you think the NPM on MLR leukemia spaces.

Specifically related to men as a winner take all situation or do you think it's a little more nuanced than that.

Maybe how are you thinking about the first mover advantage part and stickiness with prescribers and so on.

Omari: Thanks for taking our questions.

Yeah. Thanks, Ashwin I think look I think first to market advantage is important.

Michael Meyers: Thank you.

Operator: And we'll move next to Phil Nadeau with Cowan & Company.

We feel very.

Good about our current position we've presented.

Philip Nadeau: Please go ahead.

Philip Nadeau: Good afternoon.

<unk> data at Ash last year, and I think the clinical profile is quite compelling as I think you would agree.

Philip Nadeau: Thanks for taking our questions.

And so I think it positions us very nicely and we'll have an update at the end of this year.

Philip Nadeau: First, a follow-on to the last question.

We're enrolling our trials very well and I think we will have.

<unk> to have one enrolled this year and then.

Data next year, So I think we're well set up for success.

And then in terms of NPM, one MLR winter take off that's a tough one to comment on I think I think we have a what we think is a very compelling compound an opportunity for us to exploit and.

Philip Nadeau: In the prepared remarks, there was an intriguing teaser saying that some of the measures that were disclosed at ASH last year have improved over time.

Philip Nadeau: We're curious whether you'd be willing to disclose which of those measures did improve today.

We will do that to the greatest extent, we can whether or not there are other competitors in the space time will tell as of now where we're really the only ones to present any any.

Meaningful data. So I think we will we'll have to see but we like our position, we like our chances and I think we're well positioned to do that.

Okay, Great and then maybe if I can ask one more on the competitive space.

What are your thoughts generally on the strategy of covalent.

Inhibition.

Correct me, if I'm wrong, but my understanding is that.

Inhibition of results from the <unk> protein turning over pretty rapidly. So I'm. Just wondering if you think there is even an advantage to us.

Covalent inhibition or even a longer half life. Thanks.

Yeah no. Thanks for the question, so maybe I'll ask Briggs to comment on that as well.

Yes, no I think you've captured it correctly the protein does turnover, so youre going to need drug onboard two.

To inhibit newly synthesized protein and again I think our our view is we can safely and adequately completely cover the target.

We've shown IC nineties at trough exposures that trough that exceed the IC 90, so it's.

It's not clear to Westwood covalent will do.

That would exceed what we can do already with our molecule.

Okay, great. Thank you so much for all the color.

Thanks, guys.

And next to Joe <unk> with Baird. Please go ahead.

Michael Meyers: Yeah.

Hi, Thanks for taking the questions. The first one is on revenue and the opportunity in first line unfit patients.

Sure a pretty large opportunity.

And.

Increasing the number of eligible patients.

Could you could you describe the characteristics of the patients.

Patients could make them.

Good Mark.

Again for Brexit.

Second question.

IPF.

On the preclinical data you've had so far.

Policies on how the drug can work.

On top of one of the two approved drugs versus the monotherapy.

Michael Meyers: Thanks for the question, Phil.

Yeah, great. Thank you Joe for the question, maybe I'll ask.

Michael Meyers: We're not going to get into the detail there.

Our chief business Officer, Angela Ganguly to address the first related to market opportunity in the unfit patient population for revenue.

Michael Meyers: I think there are lots of detail that was provided in the ASH presentation last year.

Michael Meyers: Some of it may be a bit more important to certain investors and others than not.

Michael Meyers: But I'd say that it would be a comprehensive update, and we're looking forward to presenting all the detail, which should, I think, further strengthen our position and build confidence in the outcome of the pivotal trials as well.

Philip Nadeau: That's understandable.

Yes, Thanks, Mike.

Yes.

Sure.

In the frontline.

You commented that the.

Philip Nadeau: A couple of questions on the earlier stage pipeline.

The two populations and I think there is an understanding that.

Philip Nadeau: In terms of colorectal cancer, what level of response would you need to see from every medic to move forward in that indication?

Philip Nadeau: Yeah.

Michael Meyers: Thanks for the question again.

Almost evenly split.

Advantaged to the population.

It is treated.

More and more wins.

And Eva and I think our combination.

<unk> could allow us.

To justify moving forward.

Trying to get our labor in that population those patients could potentially.

Key long duration.

Treatment with <unk> with revenue minute in that setting as they see patients.

Tolerate the drug really well and so.

The cluster.

Year therapy, I think on average.

<unk> is.

Is over 11 months.

And.

Okay.

If you imagine 2000 21000 patients a year.

AML.

15%.

And then sorry.

And for the population.

We're targeting can.

It can be up to 40% of AML.

It's actually a pretty sizable opportunity.

And then the fifth.

It really depends on how they will keep them on therapy beyond induction and consolidation.

We are seeing.

Treatments.

Our next trial in <unk> patients.

In treated up to three years.

So that can also get to a very large population.

Great. Thanks, Thanks, Angela and maybe Briggs can I ask you to weigh in on the IPF question. Please.

Briggs: Maybe I'll ask Briggs to address that, please.

Briggs: Right.

Yeah sure. Thanks, so much Joe so.

Briggs: So, Phil, you may remember we set the trial up as a – we could win on one of either a response rate or a disease control rate. And as you may recall, the standard of care for this refractory population of patients has a very low, less than 5 percent response rate.

Briggs: So I don't want to go into all the details of the statistics, but if the lower bound exceeds that historical 5 percent, then that would be intriguing to us.

Briggs: And I think what we've outlined is that if we were to see responses, we could potentially advance more rapidly, given that the drug is giving responses.

Briggs: And then the disease control rate, again, for standard of care at six months is probably no greater than 15 percent.

Briggs: If we saw a disease control rate, the protocol is set up to immediately go into a small, randomized phase two to try to confirm that because I think a single-armed disease control rate is a little more challenging to interpret.

Briggs: So if we saw a disease control rate exceeding that, that would also capture our attention.

Briggs: It could get us excited to do the randomized portion.

Again.

Philip Nadeau: So that's the way the trial is set up.

Noted in our comments and it's very similar to the observations we've made in gvhd. It's the only mechanism that is actually depleting what are potentially the driver sells for the fibrosis, which are these pro inflammatory macrophages.

Philip Nadeau: That's very helpful.

Philip Nadeau: And then last question, kind of a similar question on IPF.

Philip Nadeau: What FVC change is the trial powered to detect, if you want to say?

<unk> and <unk>.

Work sort of downstream on a specific pathway that are believed to be involved.

The fiberglass level of laying down collagen this is acting more proximal and.

Completely takes out these inflammatory monocytes and macrophages, which probably as best we can tell from the preclinical work impacts a much broader set of processes and just.

The.

The pathways that are impacted by the two approved drugs.

And that's why we're continuing we're doing the trial as an addition to those two approved drugs.

Got it.

To test that hypothesis.

Alright, thank you.

Thank you Joel.

Briggs: Yeah, no, I don't think we're at liberty to talk about that.

We'll take our last question Peter.

Peter Lawson with Barclays. Please go ahead.

Philip Nadeau: I mean, I think what we looked at, the regulatory precedence for the other two drugs that are approved, and try to power for a degree of a change from baseline in FVC, that would be clinically meaningful.

Hey, Thanks for taking my questions just.

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

Mike on the improvement in key.

Key metrics should we assume that that's around efficacy.

What you've seen.

Philip Nadeau: Thank you, Phil.

Yes. Thanks, Thanks for the question Peter I think.

Operator: And we'll move next to Kalpit Patel with B. Reilly Security.

I think where we're pointing out that we've seen the data set improve.

And obviously key metrics or are things that you are I would say youre, most paying attention to and so.

Among others and so we're excited to present the data in the fourth quarter.

Kalpit Patel: Please go ahead.

Probably not going to say any more than that at this point, but youll have to just tune in in the fourth quarter.

Kalpit Patel: Yeah, hey, good afternoon, and thanks for taking the question.

Got you appreciate that thank you.

Kalpit Patel: For Revumented, you have ongoing efforts to explore the drug in an earlier-life setting.

And then the first.

You think we could see combination data submitted when do you think that could happen.

Yeah. Thanks, Peter So as I mentioned in my remarks, we have two combination trials ongoing now augment 102 and the beat AML trial, I think we expect data to start to accumulate.

Kalpit Patel: I guess, how are you thinking about your strategy for advancing the drug with a 7 plus 3 combo in AML?

Michael Meyers: Would that be a potential future development opportunity?

Kalpit Patel: Yeah, thanks for the question.

In 2023 and that will most likely.

Come from the beat AML trial first and so we don't have specific timing for that just yet, but we'll update as we get a little bit closer how that's materializing.

Michael Meyers: I'd say absolutely.

Michael Meyers: I think there are a number of combinations that we're looking at, and as you're pointing out, 7 plus 3 is the fit population, and certainly our drug could be used in that setting.

Michael Meyers: We're looking at designing trials to address that as well, so that's in the planning process.

Kalpit Patel: Okay, and then diving a little more into the planned updated Phase I data from Augment 101,

Kalpit Patel: I'm not sure if you'll comment, but should we expect maybe a breakdown of CR, CRH rates based on the dose and on the underlying patient characteristics, for example, which patients progressed on when either Clax and then received a CR or CRH?

Michael Meyers: Yeah, thanks for the question.

Michael Meyers: I think you should expect to see a similar level of detail as what we provided at ASH in 2021.

Kalpit Patel: Whether or not we're going to provide further breakdown on any subsets and things of that nature, we'll just have to wait to see for the update in the fourth quarter.

Thank you.

I guess the gist.

Final question the decision to have the year end data was that.

Kalpit Patel: Okay, and then one last question for the CGBHD trial at Jacofi.

Kalpit Patel: Is there going to be a comparator arm, or has that not been decided for this trial?

Driven by the improvement in the key metrics that you were seeing.

Michael Meyers: Yeah, I mean, again, we haven't disclosed the details of that trial as of yet, but stay tuned.

Kalpit Patel: That will be forthcoming.

Look I think we.

Michael Meyers: Okay, fantastic.

Kalpit Patel: Thank you very much for taking the question.

Michael Meyers: Thank you.

We.

Had said early on and repeatedly was that our focus has been to.

To enroll our trials and really operationally to get to.

To get done what we needed to get done and if we had the opportunity to to.

Update the dataset sometime at the end of the year that we may choose to do that I think we are encouraged quite encouraged about what we're seeing.

And it really gives us the opportunity more so to engage with physicians at.

Operator: And we'll move next to Yigal Nokomovic with CITI.

At Ash, we plan to have a presence there and so this is a really I think a really good way to get in front of physicians and.

And then relate to what we're doing in AML. So I think thats those are some of the factors.

But we are quite excited about.

About about the data and what we can what we'll be able to say at the end of the year.

And then just finally, just since I've got the kind.

The last set of questions.

Business development, just your thoughts around.

Of assets asset pricing.

Okay.

Tangible signs that youre kind of potentially looking to.

Yes, as you know Peter we are completely focused on building value for <unk> shareholders and in building this portfolio as part of that strategy.

Business development has always been a part of what we do we have a high bar as I've said, many many times to bring in.

High quality assets Theyre hard hard to find.

And we tend to focus on the earlier stage assets, because I think that we have the opportunity to bring.

Differentiated assets in sits index at that stage and really exploit the.

The expertise we have to develop them. So that is that is our focus on business development, it's earlier stage assets.

Targeted oncology and that has continued to be the case for quite some time.

And hopefully we can add to the portfolio in the future.

It's general the general strategy.

Great. Thanks, so much.

Yes.

At this time there are no more questions from the audience I will now hand, it back to these indexes.

Operator: Please go ahead.

Ashik Mubarak: Hi, team.

Great. Thank you operator, and thank you all for joining us on the call today, we look forward to seeing many of you. This week at the industry conferences and I wish you all a gray.

Ashik Mubarak: This is Ashik Mubarak on for Yigal.

Ashik Mubarak: Thanks for taking my questions.

Ashik Mubarak: I just had a couple on the competitive landscape, the MNIN competitive landscape.

Ashik Mubarak: How are you thinking about data from one of your key competitors with the MNIN inhibitor, which is expected later this year?

Ashik Mubarak: And ultimately, do you think the NPM1 and MLR leukemia spaces, specifically related to MNIN, is a winner-take-all situation, or do you think it's a little more nuanced than that?

Ashik Mubarak: And maybe how are you thinking about the first-mover advantage part, and sticking this with prescribers and so on?

Michael Meyers: industry conferences.

Michael Meyers: Thanks.

Michael Meyers: And I wish you all a great end to the summer and a very pleasant evening.

Michael Meyers: Yeah, thanks, Buster.

Operator: Thank you again.

Michael Meyers: I think, look, I think first-to-market advantage is important.

Michael Meyers: You know, we feel very good about our current position.

Michael Meyers: We presented a lot of data at ASH last year, and I think the clinical profile is quite compelling, as I think you'd agree.

And to the summer and a very pleasant evening. Thank you again.

Michael Meyers: And so I think it positions us very nicely, and we'll have an update at the end of this year.

Michael Meyers: We're enrolling our trials very well, and I think we'll have a position to have one enrolled this year and then data next year.

Operator: This does conclude today's program.

Michael Meyers: So I think we're well set up for success.

Operator: Thank you for your participation.

Michael Meyers: And then in terms of NPM1, MLR winner-take-all, that's a tough one to comment on.

Operator: You may disconnect at any time.

Michael Meyers: I think we have what we think is a very compelling compound, and opportunity for us to exploit.

A. Malinowski: Have a wonderful afternoon.

This does conclude today's program. Thank you for your participation you may disconnect at any time and have a wonderful afternoon.

Michael Meyers: And we'll do that to the greatest extent we can.

Michael Meyers: Whether or not there are other competitors in the space, time will tell.

Michael Meyers: As of now, we're really the only ones to present any meaningful data.

Michael Meyers: So I think we'll have to see.

Michael Meyers: But we like our position, we like our chances, and I think we're well-positioned.

Unknown Speaker: Unknown Speaker Okay, great.

Unknown Speaker: And maybe if I can ask one

Unknown Speaker: more on the competitive space.

Unknown Speaker: What are your thoughts generally on strategy of covalent

[music] amendments.

Unknown Speaker: menin inhibition? Please correct me if I'm wrong, but my understanding is that menin inhibition results in the menin protein turning over pretty rapidly.

Ashik Mubarak: So I'm just wondering if you think there's even an advantage to covalent inhibition or even a longer half-life?

Ashik Mubarak: Thanks.

Michael Meyers: Yeah, no, thanks for the question.

Michael Meyers: So maybe I'll ask Briggs to comment on that, as well.

Briggs: Yeah, no, I think you captured it correctly.

Briggs: The protein does turn over.

Briggs: So you're going to need drug on board to inhibit newly synthesized protein.

Briggs: And again, I think our view is we can safely and adequately completely cover the target.

Briggs: You know, we've shown IC90s atrophs, I mean, exposures atrophs that exceed the IC90s.

Briggs: So it's not clear to us what, covalent will do that would exceed what we can do already with our molecule.

Ashik Mubarak: Okay, great.

Yes.

Ashik Mubarak: Thank you so much for all the color.

Operator: And we'll move next to Joel Beattie with Baird.

Joel Beatty: Please go ahead.

Joel Beatty: Hi, thanks for taking the questions.

Joel Beatty: The first one is on Revumenib and the opportunity

Joel Beatty: in the first line, unfit patients.

Joel Beatty: The slides show a pretty large opportunity and increase in number of eligible patients.

Joel Beatty: Could you describe the characteristics of the unfit patients that could make them a good market, a good target for Revumenib?

Joel Beatty: And then the second question is on IPF.

Joel Beatty: Based on the preclinical data you've had so far, any hypotheses on how the drug could work on top of one of the two approved drugs versus as a monotherapy?

Michael Meyers: Yeah, great.

Michael Meyers: Thank you, Joel, for the questions.

Michael Meyers: Maybe I'll ask our Chief Business Officer, Anjali Ganguly, to address the first related to market opportunity in the unfit patient population for Revumenib.

Anjali Ganguli: Sure, thanks, Michael.

Anjali Ganguli: Yeah, in the front line, as you commented, there are, you know, there's two populations.

Anjali Ganguli: I think there's an understanding that they're almost evenly split, maybe slight advantage to the fit population.

Anjali Ganguli: And the unfit is treated more and more with Vanazza.

Okay.

Anjali Ganguli: And I think our combination in BAML could allow us to justify moving forward into, a phase three to get a label in that population. Those patients could potentially see long duration of treatment with Revumenib in that setting, as we've seen patients tolerate the drug really well.

Anjali Ganguli: And so, you know, it could be close to, you know, a year of therapy, I think on average, the Venn estimate is over 11 months.

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Anjali Ganguli: And so,

Anjali Ganguli: If you imagine 20-21,000 patients a year with incident AML, 50% in the unfit and then 12 months duration for the population that we're targeting, that could be up to 40% of AML.

Anjali Ganguli: So it starts to be a pretty sizable opportunity.

Anjali Ganguli: And then the fit, you know, it really depends on how long you can keep them on therapy beyond induction consolidation.

Anjali Ganguli: But we are seeing treatments, like with the Closartem trial where they're seeing patients being treated up to three years.

Anjali Ganguli: So that could also get to a very large population.

Anjali Ganguli: Great.

Michael Meyers: Thanks, Anjali.

Briggs: And maybe, Briggs, can I ask you to weigh in on the IPF question, please?

Briggs: Yeah, sure.

Briggs: Thanks so much, Joel.

Briggs: So, you know, again, what I noted in our comments, and it's very similar to the observations we've made in GVHD, it's the only mechanism that is actually depleting what are potentially the driver cells for the fibrosis, which are these pro-inflammatory macrophages.

Briggs: So the profenadone and tetanib work sort of downstream on a specific pathway that are believed to be involved at the fibroblast level of laying down collagen.

Briggs: This is acting more proximal and completely takes out these inflammatory monocytes and macrophages, which probably, as best we can tell from the preclinical work, impacts a much broader set of processes than just the pathways that are impacted by the two approved drugs.

Briggs: So we're doing the trial as an addition to those two approved drugs to test that hypothesis.

Briggs: Great, thank you.

Joel Beatty: Thank you, Joel.

Operator: We'll take our last question from Peter Lawson with Barclays.

Peter Lawson: Please go ahead.

Peter Lawson: Hey, thanks for taking the questions.

Peter Lawson: Mike, on the improvement in key metrics, should we assume that that's around efficacy that you're seeing?

Michael Meyers: Yeah, no, thanks for the question, Peter.

Okay.

Michael Meyers: I think we're pointing out that we've seen the data set improve, and obviously key metrics are things that I would say you're most paying attention to, among others.

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Michael Meyers: And so we're excited to present the data in the fourth quarter, and probably not going to say any more than that at this point, but you'll have to just tune in in the fourth quarter.

Peter Lawson: Gotcha.

Michael Meyers: Appreciate that.

Peter Lawson: Thank you.

Peter Lawson: And then the first time that you think we could see combination data for the menin inhibitor, when do you think that could happen?

Peter Lawson: Yeah, thanks, Peter.

Michael Meyers: So as I mentioned in my remarks, we have two combination trials ongoing now, Augment 102 and the BEAT AML trial.

Michael Meyers: I think we expect data to start to accumulate in 2023, and that will most likely come from the BEAT AML trial first.

Michael Meyers: And so we don't have specific timing for that just yet, but we'll update as we get a little bit closer how that's materialized.

Peter Lawson: Thank you.

Michael Meyers: And I guess just a final question, the decision to have that year-end data, was, that driven by the improvement in the key metrics that you were seeing?

Peter Lawson: Look, I think we had said early on and repeatedly was that our focus has been to enroll our, trials and really operationally to get done what we needed to get done.

Michael Meyers: And if we had the opportunity to update the data set sometime at the end of the year, that we may choose to do that.

Michael Meyers: I think we are encouraged, quite encouraged about what we're seeing.

Michael Meyers: And, you know, it really gives us the opportunity more so to engage with physicians at ASH.

Michael Meyers: We plan to have a presence there. And so this is a really, I think, a really good way to get in front of physicians, and, you know, have them relate to what we're doing in AML.

Michael Meyers: So I think that's, those are some of the factors.

Peter Lawson: But we are quite excited about the data and what we can, what we'll be able to say at the end of the year.

Michael Meyers: And just finally, just since I've got the last set of questions, business development, just your thoughts around kind of, assets, asset pricing, and potential size that you're kind of potentially looking to?

Peter Lawson: Yeah, as you know, Peter, we're completely focused on building value for Syndex shareholders and building this portfolio is, part of that strategy.

Directed by A. Malinowski

Michael Meyers: Business development has always been a part of what we do.

Michael Meyers: We have a high bar, as I've said, many, many times to bring in, you know, high quality assets. They're hard, hard to find.

Michael Meyers: And we tend to focus on the earlier stage assets, because I think that we have the opportunity to bring, you know, I think differentiated assets into Syndex at that stage and really exploit the expertise we have to develop them.

Michael Meyers: So that is our focus on business development, it's earlier stage assets, targeted oncology, and that has continued to be the case for quite some time.

Michael Meyers: And hopefully we can add to the portfolio in the future.

Michael Meyers: That's the general, you know, strategy we have.

Peter Lawson: Great, thanks so much.

Michael Meyers: Thank you.

Operator: At this time, there are no more questions from the audience.

Michael Meyers: I will now hand it back to the Syndex team.

Michael Meyers: Great.

Michael Meyers: Thank you, Operator.

Michael Meyers: And thank you all for joining us on the call today.

Michael Meyers: We look forward to seeing many of you this week at the