Q4 2021 Syndax Pharmaceuticals Inc Earnings Call

Operator: Welcome to the Syndax First Quarter 2021 Earnings Conference Call. Today's call is being recorded.

Quarter 2021 earnings Conference call today's call is being recorded at this time I would like to turn the call over to making buyers of Argot partners. Please begin.

Thank you operator.

Megan Myers: 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 fourth quarter 2021 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 Nolte, Chief Accounting Officer.

Welcome and thank you to those of you joining us on the line and the webcast. This afternoon for a review of <unk> fourth quarter 2021 financial and operating results.

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 <unk>, Chief Accounting Officer.

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

And Dr. Angela Ganguly Chief business Officer.

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

Megan Myers: Also joining us on the call today for the question and answer session is Dr. Peter Ordutmik, Chief Scientific Officer, and Dr. Anjali Ganguli, 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. 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 Reform Act of 1995.

So 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 that are not historical are considered to be forward looking statements within the meaning of the private Securities Litigation Reform Act of 1095.

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

Megan Myers: Any forward-looking statements represent our views as of today, March 1st, 2022 only. A replay of this call will be available on the company's website, www.syndax.com, following this call. With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax. Thank you, Megan, and thank you to everyone joining us on today's call and webcast. Before we turn to the deck, let me start my comments by first welcoming Kate Madigan to Syndax as our new Chief Medical Officer.

Any forward looking statements represent our views as of today March one 2022 only.

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

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

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

Megan Myers: Kate completed her formal education and training at Dartmouth and USC and has had a distinguished professional career at some of America's most prestigious pharmaceutical, We are truly honored to have her joining our team, and you will hear more from her on future calls. I would also like to take this opportunity to thank Michael Meyers for his exceptional contributions to Syndax over the past seven years. Michael has flawlessly led the development of both of our programs into their registration.

Before we turn to the deck, let me start my comments by first welcoming Kate Madigan syntax as our new Chief Medical Officer.

K completed her formal education and training at Dartmouth and USC and has had a distinguished professional career at some of America's most prestigious pharmaceutical firms.

Truly honored to have her joining our team and you will hear more from her on future calls.

I would also like to take this opportunity to thank Michael Myers for his exceptional contributions to <unk> over the past seven years, Michael has flawlessly led the development of both of our programs into the registration trials. Michael is committed to seeing Sendek successfully transition into its next phase of growth and we are grateful that he will remain an active adviser to the company.

Michael Metzger: Michael is committed to seeing Syndax successfully transition into its next phase of growth, and we are grateful that he will remain an active advisor to the company. Now turning to slide three. 2021 was a truly transformational year for Syndax. We initiated registration trials for both of our lead programs, SNDX5613 and Axotilumab. We entered into a global partnership and collaboration with a world-class partner, Insight, on Axotilumab to expand the potential for this program.

Now turning to slide three 2021 was a truly transformational year for Sundar.

Michael Metzger: And we ended the year with an exceptionally strong balance sheet following $152 million upfront payment from our collaboration and $81.2 million in net proceeds from our December offering, following strong data disclosures for both of our lead programs at the 2021 American Society of Hematology Medical Conference. Especially given the current challenging market backdrop, we are starting 2022 with an extremely solid balance sheet position.

We initiated registration trials for both of our lead programs F&B X 56, <unk> and <unk>, we entered into a global.

Partnership in collaboration with a world class partner insight acetyl Nab to expand the potential for this program and.

And we ended the year with an exceptionally strong balance sheet following a $152 million upfront payment from our collaboration and $81 2 million in net proceeds from our December offerings. Following strong data disclosures for both of our lead programs at the 2021 American Society of Hematology Medical Conference.

Especially given the current the current challenging market backdrop, we're starting 2022 with an extremely solid balance sheet position. This gives us the resources to expand both of our assets into new indications and the flexibility to aggressively pursue business development opportunities to augment our.

Michael Metzger: This gives us the resources to expand both of our assets into new indications and the flexibility to aggressively pursue business development opportunities to augment our pipeline with potential best-in-class models. Slide 4 provides 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. The momentum is really building at Syndax.

With potential best in class molecules.

Slide four provides 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.

The momentum is really building its index.

Michael Metzger: Our three pivotal Phase II trials for SNDX5613, our highly selective menin inhibitor, which we call Augment 101 Cohorts 2A, 2B, and 2C is progressing very well and is actively enrolling patients. For axotilumab, our antibody against CSF1R, enrollment is ongoing in our pivotal Agave 201 trial, and we are now underway working closely with our new partner, Insight, to maximize the value of this important program. I want to emphasize that we now have two registrational programs ongoing for two first-in-class and potentially best-in-class medicines for two areas of important unmet medical need.

There are three pivotal phase II trials for SMB X 50, 613, our highly selective <unk> inhibitor.

Which we call augment 101 cohorts to a to B and C is progressing very well and is actively enrolling patients for.

<unk>, our antibody against CSF, one our enrollment is ongoing in our pivotal on <unk> 201 trial and we are now underway working closely with our new partner insight to maximize the value of this important program.

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

Michael Metzger: It is an enormously exciting time for the company as we anticipate filing potentially two NDAs in 2023 and are starting to expand the organization to support the commercial launch of both 5613 and Axotilumab in the United, Let's now turn to slide 5 and provide further details on where we are with S&DX5613. First, we have opened 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.

Is an enormously exciting time for the company as we anticipate filing potentially two NDA in 2023 and are starting to expand the organization to support the commercial launch of both 56, <unk> III and <unk> in the United States.

Let's now turn to slide five and provide further details on where we are with <unk> 603.

Michael Metzger: Augment 101 Cohort 2A will enroll patients with relapsed refractory MLR-ALL. Cohort 2B will enroll patients with relapsed refractory MLR-AML. And Cohort 2C will enroll patients with relapsed refractory NPM1-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 SNDX5613 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 all three, just depending on when they complete enrollment.

First we have opened 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.

101 cohort two will enroll patients with relapsed refractory all our ALLL cohort to be will enroll patients with relapsed refractory MLR AML and cohorts you see will enroll 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 additional regulatory approval for F&B X 50, 613 based on the results of any one of these trials should one trial enrolled faster than the others or we may see we may seek initial regulatory approval with any two or three just depending on when they complete in enrollment.

Michael Metzger: We are happy to report that additional site initiation and patient accrual across the cohorts is going extremely well. We are very optimistic that we will be able to complete enrollment in at least one of these cohorts this year. Given our current trajectory and our view of the landscape, we anticipate being the first company to achieve regulatory approval for amended inhibitors. Needless to say, we believe being first to market is extremely important and accretive to the long-term value of Syndax.

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

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

Michael Metzger: 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 CRH response, transfusion independence, overall survival, and safety. Importantly, the trial design allows patients to be treated with 5613 after bone marrow transplant, a design feature that allows us to, start to understand the role of 5613 in the post-transplant maintenance setting. We also have agreement with FDA on the statistical design of each trial, trial enrolls 64 patients and up to 10 pediatrics. Finally, we have agreement with FDA that 163 mg every 12 hours given with a strong CYP3A4 inhibitor is an appropriate phase 2 dose, and that is the dose we are using in each of these trials.

We have agreement with FDA.

For each trial the primary endpoint will be the percentage of patients achieving crs 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 $56 three after bone marrow transplants, a design feature that allows us to.

Start to understand the role of $56 three in the post transplant maintenance setting.

We also have agreement with FDA on the statistical design of each trial.

<unk> enrolled 64 patients at up to 10 pediatric patients.

Finally, we have agreement with FDA that a 163 milligrams every 12 hours given with a strong <unk> four inhibitor is an appropriate phase two dose and that is the dose we're using in each of these trials.

Michael Metzger: We know that the vast majority of eligible patients are on a strong CYP3A4 inhibitor, and in an effort to enroll the cohorts as quickly as possible, at least one cohort to complete this year, we have now prioritized the enrollment of these patients versus those not on a strong CYP3A4. Once one cohort closes to enrollment, we plan to increasingly focus on accumulating the data required for labeling, which includes the necessary dose adjustment, often referred to as the ArmA dose.

We know that the vast majority of eligible patients aren't as strong sip three or four inhibitor and in an effort to enroll the cohorts as quickly as possible at least one cohort to complete this year. We have now prioritize the enrollment of these patients versus those not on a strong set very four inhibitor <unk>.

Once one cohort closes to enrollment we plan to increasingly focus on accumulating the data required for labeling which includes the necessary dose adjustment often referred to as the RMA dose. Let me remind you that this claim farm data is not in any way limiting on our ability to enroll and complete the pivotal trial.

Michael Metzger: Let me remind you that this ClinPharm data is not in any way limiting on our ability to enroll and complete the Pivotal training. Beyond the Augment Pivotal Program in Relapse Refractory Disease, Slide 6 highlights some of the additional opportunities we are exploring with 5613, all of which build on the excellent safety and efficacy profile we have thus far seen with 5613. The panel on the left highlights the trial we are planning in collaboration with the Leukemia and Lymphoma Society, otherwise known as LLF.

Beyond the augment pivotal program in relapsed refractory disease slide six highlights some of the additional opportunities we're exploring with $56 three all of which build on the excellent safety and efficacy profile, we have thus far seen with $56 three.

The panel on the left highlights the trial, we are planning in collaboration with the leukemia and lymphoma society, otherwise known as LLS. They.

Michael Metzger: They have selected 5613 as the first mendenin inhibitor to be tested as a specific targeted therapy for patients with MLLR or MPM1 AML in their umbrella trial that they call BEAT AML. The collaboration we have agreed to with them will test 5613 in combination with venetoclax and ascitidine in newly diagnosed AML patients who are unfit for induction chemotherapy and will consist of a Phase I followed by a Phase II-III trial which could serve as the basis for a regulatory filing. Our scientists have generated preclinical data that supports the benefit of menin inhibition in combination with chemotherapy.

They have selected 56 three is the first menin inhibitor to be tested is specific targeted therapy for patients with MLR or NPM, one AML and their umbrella trial that they call beat AML.

The collaboration we have agreed to with them. We will test 50, 613 in combination with <unk> and <unk> in newly diagnosed AML patients who are unfit for induction chemotherapy and will consist of a phase one followed by a phase two three trial, which could serve as the basis for our regulatory filings.

Our scientists have generated preclinical data that supports the benefit of Menin inhibition in combination with chemotherapy and therefore, the middle panel of the slide highlights the trial to explore the use of 50 613 in combination with standard salvage chemo therapies used for pediatric patients with al or AML.

Michael Metzger: And therefore, the middle panel of the slide highlights a trial to explore the use of 5613 in combination with standard salvage chemotherapies used for pediatric patients with ALL or AML that we are calling Augment 102. And the panel on the right illustrates a third trial that explores the activity in 5613 in patients with AML who have MRD-positive disease. This trial is being conducted as part of the Intercept Master Clinical Trial being led by the Australian Leukemia and Lymphoma Group. The Intercept trial is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML.

We are calling augment 102.

In the panel on the right illustrates a third trial that explores the activity and 50 613 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 the.

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

Michael Metzger: The trial enrolled patients with measurable residual disease progression following initial treatment. A group of patients at very high risk will have three laps that represent an important unmet medical need. A general observation in the treatment of cancer is that the earlier in the patient's disease course that you treat, 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, I will also note that 5613 is the first menin inhibitor to be included in the Intercept AML Master Clinical Trial.

While all enrolled patients with measurable residual disease progression. Following initial treatment a group of patients at very high risk <unk>.

Relapsed that represent an important unmet medical need.

A general observation in the treatment of cancer is that the earlier in the patient's disease course that you treat the better patients do and the longer the patient stay on medicine the <unk>.

Intercept trial of <unk>.

<unk> creative approach to treating patients early in their disease course I'll also note that 50 613 is the first <unk> inhibitor to be included in the intercept AML Master clinical trial.

Michael Metzger: We believe the selection of 5613 for inclusion into two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with 5613. As mentioned on our last quarterly call, we are excited to expand the clinical opportunities for 5613 beyond the initial approval in relapsed refractory acute leukemia. Slide 7 highlights our goal as a company to be first to market in relapse refractory disease and then be first to garner additional value-enhancing indications by expanding the use of 5613 into newly diagnosed and maintenance settings in patients with MLLR and MPM1 mutant acute leukemia.

We believe the selection of $56 three for inclusion into two master clinical trial protocols.

Highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with 50 613.

As mentioned on our last quarterly call. We are excited to expand the clinical opportunities for $56 three beyond the initial approval in relapsed refractory acute leukemias slide seven highlights our goal as a company to be first in market to market in relapsed refractory disease, and then the first to garner additional value enhance.

Indications by expanding the use of $56 three into newly diagnosed and maintenance settings in patients with MLR and NPM one acute leukemias.

Michael Metzger: We see the opportunity to treat patients with these forms of mutant acute leukemia, which account for up to 40% of the eligible patient population, as early in their treatment journey as possible, and then drive them into remission and maintain them in that state for months, if not years. That emerging paradigm for men in inhibition is what will enable this to be one of the most important new franchises in heme malignancies and why we are so keen to invest in 5613 at this stage.

We see the opportunity to treat patients with these forms of mutant acute leukemia, which account for up to 40% of the eligible patient population as early in their treatment journey as possible and then drive them into remission and maintain them in that state for months if not years.

Emerging paradigm for Menin inhibition is what will enable this to be one of the most important new franchises in heme malignancies, and why we are so keen to invest and 50 613 at this stage.

Michael Metzger: Let me now turn to axotilamide, our potentially best-in-class monoclonal therapy, antibody therapy targeting CSF1 receptors. Slide 8 is our pivotal trial for Axotilamab and CGBHD. This trial is the Axotilamab for graft versus host disease trial called Agave 201. The trial is enrolling patients with CGBHD whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met overall entry criteria.

Let me now turn to exit telematics are potentially best in class monoclonal therapy antibody therapy targeting CSF one receptor.

Slide eight is our pivotal trial for <unk> and C. Gvhd. This trial is the <unk> for graft versus host disease trial called <unk> 201.

Trial is enrolling patients with CGP HD, whose disease has progressed after two prior therapies patients must be at least six 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 <unk> given either.

Michael Metzger: 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 overall 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 Symptom Scale.

Every two weeks or every four weeks.

The primary endpoint is overall response rate using the 2014 NIH consensus criteria for <unk> HD.

Secondary endpoints will include duration of response and validated quality of life assessments using the least symptom scale.

Michael Metzger: Enrollment to the study is going quite well, and we are on track to deliver top-line data in the first half of 2023. We were also delighted to announce during the quarter that Syndax and Insight closed our global collaboration that brings together two companies with a solid track record of innovation to accelerate and maximize the development of axotilamide. As you know, we presented our Phase 1-2 CGBHD data at ASH in December of last year, which received a very positive reaction and further underscored its best-in-class profile.

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

We were also delighted to announce during the quarter, that's index and insight closed our global collaboration that brings together two companies with a solid track record of innovation to accelerate and maximize the development of <unk>.

As you know we presented our phase <unk> data at Ash in December of last year, which received a very positive reaction and further underscored its best in class profile.

Michael Metzger: Through our collaboration, Syndax and Insight will pursue an expanded set of indications in CGBHD and other fibrotic diseases. The development plan calls for the partners to design novel combinations of axotilumab and Insite's JAK inhibitors with a goal of establishing axotilumab in earlier settings within CVHD and expanding its market opportunities. As we previously mentioned was our intention, Syndax will initiate a robust phase 2 trial in IPF in the fourth quarter of this year. The first expansion outside of establishing CGBHD as a beachhead into other fibrotic diseases where we believe axitilumab could have a significant impact.

Through our collaborations index and insight will pursue an expanded set of indications and see gvhd and other fibrotic diseases.

The development plan calls for partners to for the partners to design novel combinations with <unk> insights JAK inhibitors with a goal of establishing <unk> in earlier settings within CVA, gvhd and expanding its market opportunity.

We've previously mentioned was our intention to index will initiate a robust phase II trial in IPF in the fourth quarter of this year.

First expansion outside of establishing the gvhd as a beachhead into other fibrotic diseases, where we believe <unk> could serve as could have a significant impact <unk>.

Michael Metzger: Successful development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support to actinitilumab and other fibrotic driven diseases that the parties could explore over the course of the collaboration. Slide 9 highlights our view of the broad clinical and commercial opportunity for axotilamide. We believe chronic GVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from CGVHD in the U.S. today.

Successful development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support to exit until nab in other fibrotic driven diseases that the parties could explore over the course of the collaboration.

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

We believe chronic 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.

Michael Metzger: The recent approvals of Jacafi and Cadiman's Belmusadil will begin to delineate the commercial opportunity in CGVHD. Despite recent advancements in this area to our knowledge, Axotilamab is the only agent in clinical development that specifically targets the monocyte macrophage lineage.

The recent approvals of Jakafi and <unk>.

<unk> will begin to delineate the commercial opportunity in gvhd. 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 insight believed the data generated to date with Axa tell them that suggests it has the potential.

Michael Metzger: Both Syndax and Insight believe the data generated to date with axotilimab 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 jacafi and other JAK inhibitors within the Insight portfolio. 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.

<unk> to play an important role in the treatment of Gvhd, both as a monotherapy and given its safety profile in combination with complementary medicines, such as Jakob and other JAK inhibitors within the insight portfolio.

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

Michael Metzger: As we move Axotilumab into additional applications, starting with IPF, we really see Axotilumab contributing materially to the value of our company moving forward. Finally, slide 10 summarizes the transactions that led to the acquisition of 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. We anticipate in 2022 that we will be able to continue to expand our pipeline through product acquisitions or in licensing of quality differentiated assets. We expect to remain among preferred partners of such transactions.

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

Finally, slide 10 summarizes the transactions that led to the acquisition of MLR and <unk> 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 will be able to continue to expand our pipeline through product acquisitions or in licensing of <unk>.

Quality differentiated assets, we expect to remain among preferred partners of such transactions.

Alex Nolte: I would now like to turn the call over to Alex to review our financial report. Thank you, Michael. Let me now take a few minutes to discuss our financial results for the fourth quarter and the full year of 2021. The results of our operations for the fourth quarter of 2021 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 fourth quarter and full year report on Form 10-Q, 10-K, which will be filed today.

I would now like to 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 fourth quarter and the full year of 2021.

The results of our operations for the fourth quarter of 2021, 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 fourth quarter and full year report on Form 10-Q .

Which will be filed today.

Alex Nolte: I would like to point out that our net profit for the quarter was $96.2 million, or $1.81 per share, compared to our net loss of $20.4 million, or $0.44 per share, for the same period last year.

I would like to point out that our net profit for the quarter was $96 2 million.

$1 81 per share compared to a net loss of $20 4 million.

Or <unk> 44 per share for the same period last year.

Alex Nolte: This difference is primarily attributed to the change in license revenue generated from the collaboration agreement with Insight. Turning to slide 11. We ended our fourth quarter with $439.9 million in cash and cash equivalents, including net proceeds of approximately $81.2 million from our public offering completed in December 2021 and with 59 million shares and pre-funded warrants outstanding.

This difference is primarily attributed to the change in license revenue generated from the collaboration agreement with antibody.

Turning to slide 11.

Alex Nolte: This cash balance also includes $152 million in proceeds from the December closing of the collaboration agreement with Insight. Our current cash runway now extends into the second half of 2024 and supports our expanded development and early commercialization plans for both the Exotillamap and the Menem programs during this period and provides us flexibility for continued business development. Looking ahead, I'd like to provide financial guidance for the first quarter and full year of 2022.

We ended our fourth quarter reached $439 $9 million in cash and cash equivalents <unk>.

Including net proceeds of approximately $81 2 million.

From our public offering completed in December 2021.

And it's 59 million shares and pre funded warrants outstanding.

This cash balance also includes $152 million in proceeds from the December closing of the collaboration agreement with insight.

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 the extra telematics and the Magnum programs. During this period and provides us flexibility for continued business development.

Alex Nolte: For the first 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 $4 million of non-cash stock compensation. 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 of non-cash stock compensation.

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

For the first quarter of 2022, we expect R&D expense to be 30% to $35 million.

And total operating expense to be $38 million to $42 million, including $4 million of noncash stock compensation expense.

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

Alex Nolte: 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 Mannan into registration trials, expansion into new indications, and Initiation of Freelance Commercialization Activities. This guidance does not currently reflect any potential offset by the cost-sharing offset of Exeter Telemap operating expenses with our partner Insight, and we will continue to update guidance over the course of the year as we move forward with this collaboration. With that, let me now turn the call back over to my, Great.

The increase in R&D and operating expense in 2022 compared to the prior year periods is driven by the expansion of both <unk> and then into registration trials expansion into new indications and.

And initiation of pre launch commercialization activities.

This guidance does not currently reflect any potential offset by the cost sharing offset of exit settlement operating expenses with our partner insight.

And we will continue to update guidance over the course of the year as we move forward with this collaboration.

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

Great. Thanks, Alex.

Michael Metzger: Thanks, Alex. Let me close the call by again noting that this management team has been focused on obtaining regulatory approval for drugs that extend and improve the lives of people with cancer and other diseases, and we consider having two ongoing registration programs to be a major achievement. We are also really excited about the broad franchise opportunities for both programs beyond their initial registration. We believe SNDX5613 could have broad utility across a wide range of clinical settings in acute leukemia and possibly in a number of others as well.

Let me close the call by again, noting that this management team has been focused on obtaining regulatory approval for drugs that extend and improve the lives of people with cancer and other diseases and we consider having two ongoing registration programs to be a major achievement.

We're also really excited about the broad franchise opportunities for both programs beyond their initial registration indications.

We believe F&B X $56 three could have broad utility across a wide range of clinical settings, and acute leukemia, and possibly in a number of others as well.

Michael Metzger: Our immediate goal as a company is to be the first to market in relapse refractory disease and then to garner additional value-enhancing indications by expanding the use of 5613 into newly diagnosed and maintenance settings in patients with MLLR and MPM1 acute leukemia. And Axotilumab also holds the promise of a broad franchise opportunity in various lines of therapy in CGVHD and across a broad range of fibrotic diseases starting with IPF. We have a strong balance sheet to aggressively advance our programs and achieve key upcoming milestones.

Our immediate goal as a company is to be the first to market in relapsed refractory disease and to garner additional value enhancing indications by expanding the use of $56 three into newly diagnosed and maintenance settings in patients with MLR in MTM, one acute leukemias.

And <unk> also holds the promise of a broad franchise opportunity to unity in various lines of therapy in <unk> and across a broad range of fibrotic diseases, starting with Ips.

We have a strong balance sheet to aggressively advance our programs and achieve key upcoming milestones.

Michael Metzger: We remain optimistic in 2022 that we can continue 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.

We remain optimistic in 2022 that we can continue to identify and bring in novel molecules to deepen our portfolio. We have a proven track record of delivering on this pillar pillar of our corporate strategy and I believe this is a core strength of our company.

Operator: We could not accomplish all that we have without our wonderfully talented team here at Syndax, our collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical program. In addition, I would like to thank our committed long-term investors who are helping us build this great, With that, I would like to open the call for questions. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key.

We cannot accomplish all that we have 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 our committed long term investors, who are helping us build this great company.

With that I would like to open the call for questions.

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

Draw your question press the pound key please standby, while we compile our Q&A roster.

Operator: Please stand by while we compile our Q&A roster. Our first question comes from Phil Nadeau with Callan & Company. Please proceed. Good afternoon, thanks for taking my questions and congrats on a very productive year. First, a question on the 5613 no CYP3A4 dose. I want to make sure I understand the strategy. It sounds like you're saying, um... Patients who are not on a CYP3 or CYP4 probably won't be enrolled in the trial for some time. But that's okay because you just simply need to identify the do's.

Our first question comes from Phil Nadeau with Cowen and company. Please proceed.

Good afternoon, Thanks for taking my questions and congrats on a very productive year.

First a question on the 50 613, no <unk> four dose.

Sure I understand the strategy it sounds like you are saying.

Patients who are not on a trip through for everyone.

Probably won't be enrolled in the trial for some time.

But that's okay, because we simply need to identify the dose to.

Phil Nadeau: Pharmacokinetic Measures, and, Actually, having clinical data from patients who aren't on CYP3A4 inhibitors is less of a requirement for filing. Is that correct? Yeah, maybe I'll start and Brady can comment also, but Phil, thanks for the question.

Pharmacokinetic measures.

And.

Actually I haven't clinical data from patients who are on <unk> four inhibitors is less so.

Garment for filing.

Is that correct.

Yes, maybe I'll start and Briggs could comment offer but Phil thanks for the question. So.

Michael Metzger: So, look, I think the priority, as we've seen, most of the patients seem to be on strong CYP3A4 inhibitors, antifungals, and our priority is to get the trial enrolled, each of the cohorts enrolled as quickly as possible. And so as a result of the dynamics of what I just described, we're prioritizing getting it done versus collecting all the ClinPharm information in this trial. So we are seeing some patients that are not on a strong CYP3A4 inhibitor, but the cadence of that is we're not prioritizing putting them on the trial versus getting as many patients in as we can to complete it as early as we can. So I think, and what you said, it was correct.

So look I think the.

<unk> as we as we said most of the patients seem to be on strong <unk> four inhibitors.

Antifungals and our priority is to get the get the trial enrolled each of the cohorts enrolled as quickly as possible.

And so as a result of the dynamics of what I just described.

Prioritizing getting it done versus <unk>.

Collecting all the Quin farm information.

In this.

In this trial. So we are we are seeing some patients that have that are not on a strong set of <unk> four inhibitor.

But the cadence of that is not we're not prioritizing putting them on the trial versus getting as many patients as we can.

To completed as early as we can so.

And what you said was correct I think we want to get.

Michael Metzger: I think we want to get the information together, the ClinPharm information together in order to complete the trial, ultimately complete the trial for labeling purposes, but that's once we submit the NDA. But that's, you know, once we have one of the cohorts fully enrolled, we'll turn our attention to bringing more of those patients in. They're just harder.

The information together clean farm information together in order to.

Complete the trial ultimately complete the trial for labeling purposes, but thats.

Once we submit the NDA, but once we have one of the cohorts and fully enrolled we.

We will turn our attention to bringing more of those patients and they are just harder to find.

Michael Metzger: Got it, okay, and have you identified a dose yet, or are there complications in figuring out what dose? should be the dose that is ultimately submitted. No, no, there's been there's been no trouble identifying a dose.

Got it.

Have you identified the dose that or are there complications and figure out what dose.

Should be the dose that is.

Ultimately submitted.

Yes.

No no theres been theres been no trouble identifying a dose I think it's just a matter of acute.

Michael Metzger: I think it's just a matter of, you know, accumulating more patients. As you know, we have identified two doses that meet the RP2D as part of the phase one. So, you know, we've identified active doses. It's just a matter of, you know, putting on enough patients who are not on a strong-hit rate. And that's put enough patients on in order to figure out the dose that you want to register. What PK matches are RMB dose?

Accumulating more patients that's all.

Got it.

We have identified.

Two doses that meet the RP duty as part of the phase one so.

We've identified active doses, it's just a matter of.

On enough patients who are not on a strong set the rate for next year.

And thats, putting enough patients on in order to figure out the dose that you want to do you want to register.

Correct.

PK, what PK matches, our RMB dose.

Phil Nadeau: Perfect. Yep. Okay. That's very helpful.

Perfect. Okay, that's very helpful.

Phil Nadeau: Second question also on the pivotal trials. In terms of the pace of enrollment, I think in the past you've said MLR, AML patients, that group is likely to enroll more quickly because of the competing trials. Is that still your expectation?

Yes.

Second question also on the pivotal trials in terms of the pace of enrollment I think in the past you've said MLR.

AML patients or the voice.

<unk> group is likely to enroll more quickly because we are competing trials because thats still your expectation is that the cohort that we should expect to see data from first.

Michael Metzger: Is that the cohort that we should expect to see data from first? Yeah, I think we said, Phil, that, that the AML cohorts, we didn't differentiate between MLR and PM1, we just said that our expectation is the AML cohorts will enroll faster than ALL cohorts, and as I said in my remarks, we expect to enroll at least one, maybe two, hopefully fully this year, so we're not saying exactly which ones will enroll faster than the others, but that was the kind of guidance we had given, and we're sticking with that. Perfect. And then last question on ExcoMab, you referenced the two recent approvals, and the fact that those launches could inform you about the GVHD market. We're curious, what do you expect to learn most?

Yes, I think we said fill that.

That the AML cohorts.

Differentiate between MLR NPM, one we just said that our expectation is.

AML cohort will enroll faster than ALLL cohorts.

And as I said in my remarks, we expect to enroll at least one maybe two hopefully this fully this year so.

We're not we're not saying exactly what which ones will enroll faster than the others, but that was the kind of guidance, we have given them, we're sticking with that.

And then last question on <unk> do you referenced that two.

Two recent approvals.

And the fact that those launches can inform you about the gvhd market. We're curious.

What do you expect to earn most.

Phil Nadeau: from those launches, aside from the revenue trajectory, which we'll all see. But in terms of location of patients, access to reimbursement, desire to be treated, what do you think will be most informative about those launches as you contemplate exit till maps commercialization? Yeah, maybe I'll ask Anjali, our Chief Business Officer, to comment on that. Sure. Thanks, Michael.

From those launches aside from the revenue trajectory, which will we will see but in terms of like location of patients access to reimbursement.

Desire to be treated what do you think will be most most informative about those launches if you.

As you contemplate ex telematics commercialization.

Yes, maybe I'll ask annually.

Business officer to comment on that.

Anjali Ganguli: Thanks, Phil, for the question. I think, you know, a big part of the launches, too, is the awareness of new drugs in this space, because for so long it's been dominated by generic entry and the defining of a treatment algorithm for chronic GVHD, I think, is an ongoing and evolving event. And so that alone, I think, is really helpful for the space and for, you know, being able to position axotilumab within the treatment algorithm when it is approved in, we're hoping, the 2024 timeframe.

Thanks, Nicole and thanks, Phil for the question.

Thank you know a big part of the alliance is to is the awareness of new <unk>.

In the states because for so long it's been dominated by generic entry in.

The defining of the treatment algorithm.

Or panic.

<unk> TV HD I think is.

Im going in evolving.

Event, and so that alone I think is really helpful.

The state and for being able to position <unk> within the treatment algorithm when it is approved.

We're hoping that 2024 time frame.

Anjali Ganguli: So, you know, beyond the items that you mentioned, reimbursement, pricing, adoption, you know, understanding who are the physicians that are likely to be the decision makers or key influencers in this space and early adopters will also be very helpful, but I think even building awareness of these new drugs and agents and how they can help patients is also part of the process that we're watching. Perfect. Thanks for taking our questions and congrats again on the progress. Thanks, Phil.

So beyond the items that you mentioned.

Reimbursement pricing adoption.

Understanding who are the physicians that are likely to be the.

Decision makers and key Influencers in this space.

Early adopters will also be very helpful that I think even building awareness of these new drugs and agents and how they can help patients.

Is also part of the process that we're watching.

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

Thanks, Phil.

Phil Nadeau: Thank you. Our next question comes from Bert Haslett of BTIG. Please proceed. Hi, thank you.

Thank you. Our next question comes from Bert Hazlett of BPI. Please proceed.

Bert Haslett: And thanks for taking my question. Just with regard to 5613 and the expanded opportunities, in particular, the matched protocol trials, BEAT AML and Intercept, could you just give a little bit more granularity with regard to timing and when we might get a sense of initial data for really any of those studies, including Augment 102? Yeah, thanks, Bert.

Hi, Thanks.

Thank you for taking my question just with regard to 56, <unk> and the expanded opportunities in particular to the Master protocol trials beat AML and then its up could you just give a little bit more granularity.

With regard to timing and when we might get a sense of initial data for really any of those studies, including augment 102.

Michael Metzger: Thanks for the question. Maybe I'll ask Dr. Briggs Morrison to comment on this. Thanks for the question.

Yes. Thanks, Bert Thanks for the question, maybe I'll ask Briggs Dr. Briggs Morrison to comment on this as well.

Briggs Morrison: So, all three of those trials will be starting in the first half of this year. For each of them, for the first two, the LLS trial and the, Combination Chemotherapy Trial is for the Phase 1 portion to pick a dose, and the data that is used to support the dose, you know, could be available, let's say, for BAML early part of next year. Intercept is not a combination trial, it's just monotherapy, and so it's really a question of when we'll have some early data on converting MRT positive to MRT negative. Again, I would think perhaps by middle of next year that might be something.

Thanks for the question. So all three of those trials will be starting in the first half of this year.

Got it.

Again for each of them there for the first two the LLS trial and.

Combination chemotherapy trial, just sort of the phase one portion to pick a dose.

And the data that is used to support the dose could be available.

Let's say.

For beat AML.

Early early part of next year.

Potentially also for 700 to intercept is just not a combination trial its just mono therapy and so it's really a question of <unk>.

We will have some early data on converting <unk> positive <unk> negative again, I would think perhaps by middle of next year that might be something.

Bert Haslett: Okay, terrific. I'm just shifting gears to axotilumab for a question. With regard to the IPF study, could you provide any more granularity on the phase two effort there? I know it's early days, but would very much love to understand a little bit more of the scale and scope of the work there. Yeah, sure. Thanks, Bert. Maybe I'll ask Briggs to comment a little bit more on that as well. Yeah, so, Bert, we'll give a lot of details as we typically do once we have FDA endorsement on the trial and we're sort of opening the trial. I would say our general, the general approach that we've been advised by experts in the field is that if you're going to study IPF, you just have to study IPF.

Okay terrific.

Just shifting gears to.

<unk> four question.

Regarding the IPF study could you provide any more granularity on the phase III effort there.

It's early days, but would very much love to understand a little bit more of the scale and scope of the work there.

Yes sure Thanks, Brett.

Maybe I'll ask Briggs to comment a little bit more on that as well.

Yes, so we'll give a lot of details as we.

As we typically do once we have FDA endorsement on the trial and we're sort of opening the trial I would say our general the general approach that we have been advised by experts in the field is that.

If youre going to study Ips. So you just have to study Ips that you have to do.

Michael Metzger: And you have to do, you know, an FEC endpoint-driven trial that's about a year in duration. And so that's, you know, the sample size and some of the details we'll go through with you after we, you know, get endorsement and we're up and running the trial. But you should think of it as, you know, a, A year-long trial with FEC as the primary endpoint. We've looked at a talk with many experts about sort of surrogate biomarkers that you could use.

Endpoint efficacy endpoint driven trial.

That's about a year in duration.

And so that's.

The sample size and some of the details will go through with you after we.

Get endorsement and we're up and running the trial, but you should think of it as.

A year long trial with MPC as the primary endpoint we've looked.

<unk>.

Talk with many experts about.

Surrogate biomarkers that you could use.

Briggs Morrison: You know to sort of do an intermediate time point and the advice that we've gotten is that [inaudible] None of those have really been well validated, and they're maybe just as high a false positive as a false negative, and the best thing to do is if you really believe that you have an active agent, just go ahead and do the full one-year trial. So that's the current thinking, but we'll give you a lot more details once we open up the trial. Okay, great. And then just one big picture question.

To sort of do an intermediate time point and the advice that we've gotten is that.

None of those have really been well validated and there may be just as high a false positive false negative.

And the best thing to do if you really believe that you have an active agents. Just go ahead and do the full one year trial. So that's the current thinking but we'll give you a lot more details.

Once it.

We open up the trial okay great.

Then just one big picture question, you've had some intriguing success with licensing at 5600, <unk> X fill them up.

Bert Haslett: You've had some intriguing success with the licensing of 5613N-axetilumab. Is there a common theme here with regard to therapeutic area, oncology, fibrotic disease? You know, you've, again, had some unique experiences.

Is there a common theme here with regard to therapeutic areas oncology fibrotic disease.

Again had some unique.

Michael Metzger: Unique Success. How are you thinking about additional business development efforts more broadly? Yeah, thanks. Thanks for that question, too, Bert. You know, look, I think the theme for us has been identifying molecules that are sort of, we think, best in class differentiated molecules. And we have never sort of drawn a line saying that, you know, they're heme versus solid tumor or one modality versus the other.

Unique success, how are you thinking about additional business development efforts more broadly.

Yeah. Thanks, Thanks for that question Hubert.

Look I think.

Yes.

The theme for US has been identifying molecules that are sort of we think best in class differentiated molecules.

We have never sort of drawn a line.

Saying that their heme versus solid tumor or one modality versus the other I think where we are most interested in targeted therapy.

Michael Metzger: I think we're most interested in targeted therapy for oncology. Having said that, I think we are, you know, really looking for molecules at a time point in their development, generally on the earlier side, you know, late preclinical, early clinical, where, you know, we can use our expertise in terms of clinical development, translational medicine, in order to make a big difference with these molecules. And so I think the, you know, right now we are on the heme side of the equation in terms of what we're developing. And there is some synergy between call points between our molecules, which is great.

Our oncology, having said that I think.

<unk>.

Really looking for molecules at a at a time point in their development.

Generally on the earlier side late preclinical early clinical wear.

We can use our expertise in terms of clinical development translational medicine in order to make a big difference with these molecules and so.

I think the.

Right now we are on the heme side of the equation in terms of in terms of what we're developing.

And there are some synergy between call points between our our molecules, which is which is great.

But I wouldn't rule out a broader kind of opportunity set within oncology.

Maybe perhaps in solid tumors as well so as you know, it's a competitive field and it's hard enough to find molecules that debt.

Bert Haslett: But I wouldn't rule out a broader kind of opportunity set within oncology, you know, maybe perhaps in solid tumors as well. So as you know, it's a competitive field, and it's hard enough to find molecules that you feel are worthy of resources and the team's time. So we're hunting hard, and we expect we'll be able to identify hopefully one or more molecules this year and continue building the pipeline. Terrific.

You feel are worthy of resources and the team's time. So we're we're hunting hard and we expect we'll be able to identify.

Hopefully one or more molecules this year and continue building the pipeline.

Michael Metzger: Thanks for the call. I look forward to more progress. Thank you. Thank you, Bert.

Terrific. Thanks for the color and look forward to more progress. Thank you.

Thank you Bert.

Bert Haslett: Thank you. Our next question comes from Yigal Nochomovitz of Citi. Please proceed. Hi team, this is Ashiq Mubarack, I'm on for Yigal, and thanks for taking my question, and congrats on all the progress. I guess, can you talk a little bit about the ex-US opportunity for 5613, and do you think the expansion cohort data may be sufficient for a filing there as well, or perhaps you'll need another control study? And also just curious about how the BEAT AML cords might play.

Thank you. Our next question comes from Thomas <unk> of Citi. Please proceed.

Yigal Nochomovitz: Intuitive European Strategy, Yeah, maybe I'll ask Briggs to comment on our European strategy as well. And I took it to mean not necessarily a commercial opportunity, but you were thinking more in terms of trial and development, correct? Correct. Thanks, Ashiq. Great. Yeah, yeah, great.

Hi, Tim. This is also more borrower on for <unk>. Thanks for taking my question Congrats on all the progress.

I guess can you talk a little bit about the ex U S opportunity.

For us it's one three.

Do you think.

I think cohort data may be sufficient for filing there as well or perhaps with nida.

Another control study and also just curious about how the beat AML cohorts might play.

Until you can strategy. Thanks.

Yes, maybe I'll ask Briggs to comment on our European strategy as well.

And then I took the took it to me not a not necessarily a commercial opportunity, but you were thinking more in terms of trial and development correct.

Correct.

Thanks, Greg.

Great.

Briggs Morrison: Thanks so much for the question. Your instincts are quite right here that, you know, the regulatory environment in Europe is different. And so the single arm so-called palliative trial with CR-CRH and durability may not be enough, but it may. So we're in discussions with regulators about what it'll take to get the drug approved in the EU. I think your point about BDAML, since that is, as we move into the randomized phase two portion, that is a randomized trial with sort of standard of care as the control arm. So that could play into it. But I would say, you know, stay tuned for more information on the European strategy. It will be different from the U.S.

Yeah, Yeah, great. Thanks, so much for the question your instincts are quite right here that thank.

Regulatory environment.

In Europe is different and so the single arm.

So called palliative trial, with CRC RH and durability.

May not be enough.

It may.

So we're in discussions with regulators about what.

Will it take to get the drug approved.

The EU I think your point about <unk> since that is as we move into <unk>.

The randomized phase two portion of that is a randomized trial with.

Sort of standard of care at the control arm, so that could play into it but I would say.

Stay tuned for more information on the European strategy, it will be different from the U S.

Briggs Morrison: Okay, great. That makes a lot of sense. And I guess, could you, is there any color you can share on maybe the status of the acetylamide-jack inhibitor combo? Yeah, thanks for the question. As I said in my remarks, we're kicking off, we have kicked off our collaboration with Insight, and I think we're in the design phase of putting those trials together. And so we'll have more to say in future calls. But we hope one or more trials are initiated this year in combination with one or more of their JAK inhibitors. We haven't specified, they haven't specified as to which one. As of yet, but stay tuned.

Okay great.

That makes a lot of sense and I guess could you.

Is there any color you can share on maybe the status of the year.

Up until about a JAK inhibitor combo.

Yes, thanks for thanks for the question.

Yes, I think I said in my remarks, we're kicking off we have kicked off our collaboration with insight and I think we are in the.

In the design phase of putting those trials together and so we will have more to say on future calls.

But we hope.

One or more trials are initiated this year in combination with one or more of their their JAK.

JAK inhibitors, we haven't specified they havent specified as to which ones as of yet but stay tuned.

Okay, great. Thank you very much.

Thank you.

Yigal Nochomovitz: Okay, great. Thank you very much. Thank you. Thank you. Our next question comes from Justin Walsh of the Raleigh Securities. Please proceed. Hi, thanks for taking the questions. I know that BEAT AML has a pivotal portion, but I was wondering if you can provide some comments on how Augment 102 and Intercept could lead to label expansions.

Thank you. Our next question comes from Justin Walsh of B Riley Securities. Please proceed.

Justin Walsh: Specifically, do you think that the data for these trials could support an expansion on their own or, or maybe just inform the design of larger trials? Thanks for the question, Justin. I'll turn it to Briggs once again.

Hi, Thanks for taking my questions.

I know that beat AML has been pivotal portion, but I was wondering if you can provide some comments on how augment 101 O. Two an intercept could lead to label expansion. Specifically do you think that the data for these trials could support an expansion on their own or or maybe just inform the design of larger trials.

Yes. Thanks for the question, Justin I'll turn it to break us once again.

Briggs Morrison: Yeah, though, Justin, I think the second two are more to inform future trials, it's getting a dose for the combination with chemotherapy in the refractory setting. And I think intercept will give us a sense of what the MRD positive to MRD negative conversion rate is, which will allow us to sort of power a definitive trial. One more question for me.

Yeah, Justin I think.

Two or more to inform future trials, it's getting a dose.

Four.

The combination with chemotherapy in the refractory setting and I think intercept will give us a sense of what the MRV positive Mardi negative conversion rate is which will allow us to sort of power a definitive trial.

Justin Walsh: You mentioned potential benefits of being first to market with a novel drug. It's pretty obvious, but can you maybe provide some color on how you plan to lay the groundwork to take maximum advantage of this? And sort of related to that, any thoughts on any potential label differences between your asset and any fast follower menin MMLR inhibitors that could come to the market? Yeah, thanks, Justin. Great questions.

Got it thanks, one more question for me.

So you mentioned potential benefits of being first to market with a novel drug it's pretty obvious but can you maybe provide some color on how you plan to lay the groundwork to take maximum advantage of this and.

Sort of related to that any thoughts on any potential label differences between your asset in any fast follower men and MLR inhibitors that could come to the market.

Justin Walsh: In terms of label differences, I think it's a little early. I'll just take that question first. It's a little early to be speculating about label and how our molecule may be different than our competitors. I think at this stage, we're the only ones that have really shown much data in the clinical setting. And so I think we need to kind of wait and see what others show and how our drug continues to develop. But needless to say, I think we're in a very favorable position.

Yes, Thanks, Josh great questions.

In terms of label differences I think it's a little early I'll just take that question first it's a little early to be speculating about label.

And how are our molecule may be different than our competitors I think at this stage. We're the only ones that have really shown much data.

In the clinical setting and so I think we need to kind of wait and see what.

Michael Metzger: And in terms of seizing the opportunity to expand, I think we made comments, and then I think you've become accustomed to us hearing about the different trials we're doing in the frontline and the maintenance setting. I think strategy here is obviously to get the drug approved and relapse refractory disease, expand into the frontline setting in combinations. I think what's very nice about our molecule is that you can add our drug onto regimens.

What others show and how are and how our drug continues to develop but needless to say I think we're in a very favorable position and in terms of.

Seizing the opportunity to expand I think we made comments and then I think.

<unk> become accustomed to us hearing about the the different trials, we're doing in the frontline in the maintenance setting I think strategy here is obviously to get the drug approved in relapsed refractory disease.

Span into the frontline setting and combinations I think what's what's very nice about our molecules that you could add our drug onto regimen, and we hope to be able to add it onto regimens that already exist.

To be able to accommodate the MLR NPM one.

A mutation types and so.

Michael Metzger: We hope to be able to add it onto regimens that already exist to be able to accommodate the MLR or NPM1 mutation types. And so the opportunity to add in the frontline setting and then recapture patients in the maintenance setting and perhaps keep them on drug for a long period of time in order to keep their disease at bay, that's a vision we have for this molecule. And so we're going to continue to do those trials and look at combinations that position us both in the unfit frontline setting, maybe it's perhaps the fit as well, and then moving in parallel into the maintenance setting.

The opportunity to add to the frontline in the frontline setting and then recapture.

Patients in the maintenance setting and perhaps keep them on drug for.

A long period of time in order to keep their disease at Bay.

That's the vision, we have for this molecule and so we're going to continue to do those trials and look at combinations that position us both.

In the unfit front.

Frontline setting maybe it's perhaps the fit as well and then move in parallel into the into the maintenance setting I'll also note that.

Michael Metzger: I'll also note that one important feature of the Phase 2 pivotal trials that we're running now is that patients can go back on therapy after going through stem cell transplant, and that will be an opportunity to see how patients do in the, call it, maintenance setting, although we'll have to run, and I think we've said before, we'll be running additional maintenance trials. But it will give us an early look into how patients do post-transplant and perhaps give an indication of how long they can actually stay on treatment, which we expect to be, we hope, quite a long period of time. So that's just a general, I think that's a general landscape of how we'll be approaching this. Great, thanks for taking the questions. Thank you, Justin.

One important feature of the phase two pivotal trials that we're running now is that patients can go back on therapy after <unk>.

Going through stem cell transplant and that will be an opportunity to see.

How patients do in call it maintenance setting, although we will have to run and I think we've said before we will be running additional maintenance trials, but it will give us an early look into.

How patients do post transplant, and perhaps give an indication of how long they can actually stay on treatment, which we expect to be.

We hope quite quite a long period of time so.

That's just a general I think that the general landscape of how we'll be approaching.

Great. Thanks for taking the question.

Thank you Joseph.

Justin Walsh: Thank you. Our next question comes from Joel Beatty of Baird. Please proceed. Hi, thanks for taking the questions.

Thank you. Our next question comes from Joel Beatty of Baird. Please proceed.

Joel Beatty: First one is on the registrational trial of 5613. Just to clarify, what happens now when a patient screens for enrollment but is not on a CYP3A4? They're allowed to be admitted to the trial. Thanks, Joel, for the question. They're allowed to be admitted to the trial.

Hi, Thanks for taking the questions.

First one is on the Registrational trial of $56 13, just to clarify what happens now when a patient screening for enrollment but has not on a set three or four.

They're allowed to be admitted to the trial. Thanks Bill for the question.

Michael Metzger: I think there's no change to that. I think the point being that we're not holding spots for patients who are not on a strong CYP3A4 inhibitor. In fact, we're enrolling almost on a first-come, first-served basis. It just so happens that the vast majority of patients are on a strong CYP3A4 inhibitor. So I think the idea is that it might be a little bit slower to enroll patients who are not on a strong CYP3A4 inhibitor in the scheme of this trial. And that's what I meant by my remarks. We're not prioritizing them versus others who are on a strong CYP3A4 inhibitor. And there is in no way an impact on our ability to complete the trial.

They are allowed to be admitted to the trial I think.

I think there is no change to that I think the point being that we are we're not holding spots for patients who are not on a strong set three or four inhibitor in fact were enrolling.

Almost on a first come first serve basis for and it just so happens that the vast majority of patients are on a strong <unk> four inhibitor. So.

I think the idea is that it might be a little bit slower to enroll patients who are not on a strong Q3 <unk> four inhibitor in the scheme of this trial and Thats what I meant by my remarks, we're not we're not prioritizing them versus others.

Who are on a strong set three or four inhibitor.

There is no way and impact on our ability to complete the trial, it's more of a.

Michael Metzger: It's more of a submission issue and a labeling issue for dose adjustment that we're going to have to figure out in the course of the next while as the trial continues what those ClinPharm questions and answers are. So that's the kind of long-winded answer to your question. For Exotillumab, how much dose-finding work needs to be done for the IPF setting versus jumping right into a more robust study of efficacy? Yeah, that's a great question.

Submission issue than a labeling issue for dose adjustment that we're going to have to figure out in the course of the course of the next while as the trial continues.

Those Clinton farm questions and answers are so that's the that's the kind of long winded answer to your to your question.

Got it I appreciate it that makes sense.

For <unk>.

Dose finding work needs to be done for the IPF setting versus jumping right into <unk>.

More of a robust study of efficacy.

Yes, that's a great question, maybe I'll ask Briggs to comment there.

Briggs Morrison: Maybe I'll ask Bragg to comment there. Yeah, so thanks, Joel. The current thinking, which again, we'll have to validate with the FDA when we finalize the protocol, is that we would not do dose ranging in the IPF trial. We would take a dose that we think gives us maximal pharmacodynamic effect. So as you know, in Agave 201, there are three different arms, the 0.3, the 1, and then the 3 every four weeks.

So thanks.

Thanks, Joe.

The current thinking which again will have to validate with the FDA to finalize the protocol.

Is that we would not do dose ranging in the IPF trial, we would take a dose that we think gives us maximal pharmacodynamic effect.

So as you know and agave.

One there are three different arms to point to either one and then three every four weeks.

Briggs Morrison: So the one mg per kg, as you saw in our ASH data, looks like a very, very good dose. Gives us optimal PKPD, very good efficacy. So the current thinking is that we would not do dose ranging. We would just simply do a proof-of-concept trial at roughly that dose. So again, we'll say more about that once we have that finalized. But our view is that's a really good dose to be able to test the concept.

<unk> as you saw.

And our AST data it looks like a very very good dose gives us optimal PK PD very good efficacy. So what's the current thinking is that we would not do dose ranging we were just simply do a proof of concept trial.

At that roughly that dose.

Again, we'll say more about that once we have that finalized but our view is that's a really good dose to be able to test the concept and.

Briggs Morrison: And obviously, if the trial is positive, there may need to be similar to a GAVI-201, some additional, the regulators may want some dose ranging. But I think for us, it's a proof-of-concept trial where we would just take one dose. Great, thank you.

Obviously, if the trial's positive there may need to be similar to agave.

201, some additional to the regulators may want some dose regimen, but I think for us. It's a proof of concept trial, where it will just take one dose.

Great. Thank you.

Joel Beatty: Thank you, Joel. Thank you. Thank you. Our next question comes from Peter Lawson of Barclays. Please proceed. Thanks for taking the questions.

Thank you Joe.

Thank you. Our next question comes from Peter Lawson with Barclays.

Please proceed thanks.

Thanks for taking the questions.

Peter Lawson: Thanks for all the updates. Just around the CYP3A4 strong, weak arms, how many patients would you need that aren't on a strong CYP3A4 inhibitor for refining? Yeah, maybe I'll ask Briggs.

Thanks for the update.

Just around the Sip three four strong.

How many would you need.

How many patients would you need that.

On a strong <unk> inhibitor for a filing.

Briggs Morrison: Thank you for the question, Peter. Let me ask Briggs to answer that. Right, so so Peter, the question is, you know, how many patients worth of data at a dose that we feel comfortable saying that there's sufficient PK to, you know, label? We think it's probably in the, you know, let's call it 12 to 15 range of not on a strong CYP3A4 inhibitor, and then a separate group that's on a moderate, As Michael pointed out, the pivotal trial at this stage, they'll all be on a strong inhibitor. So it's a question of probably in the 12th to 15th should give us enough understanding of the PK to be able to inform the judgment. Okay, how is that, is that, how's that tracking?

Yes, maybe.

Ill ask Briggs. Thank you for the question, let me ask Briggs to answer that.

Right. So so Peter.

The question is how many patients worth of data at a dose that we feel.

Feel comfortable saying that there is sufficient PK too.

Label.

We think it's probably in the.

Let's call. It 12 to 15 range of not on a strong <unk> four inhibitor and then a separate group that's on a moderate.

As Michael pointed out the pivotal trial.

At this stage they will all be on a strong inhibitor.

So it's a question of probably in the 12 to 15 should give us enough understanding of the PK to be able to to inform the dose.

Okay.

Is that how is that tracking.

Briggs Morrison: So as Michael said, I think our decision was that we're prioritizing enrollment of the registration trial. The main reason to prioritize enrollment of the registration trial is so that we have good durability data, right? Because once we finish enrolling all of those patients, then it's six months after the last patient is when we do the data cut, and we'd like to have as much durability as possible for labeling purposes.

Is that significant right.

Yes, so as Michael said I think our decision was that.

Sure.

Prioritizing the enrollment of the registration trial and the main reason to prioritize enrollment or the registration trial is so that we have good durability data right because once we finish enrolling all of those patients.

And at six months after the last patient is when we do the data cut and we'd like to have as.

As much durability as possible for labeling purposes. So at this point the preference is put the focus is the decision is put people on who are honest shrontz hit harder and don't worry about the non or the moderates once that at least one cohort is fully enrolled then that patient population.

Briggs Morrison: So at this point, the preference is, the focus is, the decision is, put people on who are on a strong separated heart inhibitor, and don't worry about the non or the moderates. Once at least one cohort is fully enrolled, then that patient population where we've already fully enrolled, we will then enroll additional patients with the non or a non or a moderate. So I'm not sure if it's, to your question, if it's ahead or behind, but we've made a strategic decision that we're going to prioritize getting everybody in onto the pivotal trial because that'll allow us to get the durability that we need. Thank you. Would physicians have a problem as putting a patient on a strong CYP3A4 inhibitor, even if they didn't require it? So you kind of had a, almost like a label.

Where we are already fully enrolled we will then enroll additional patients with.

With the non or.

None or a moderate.

I'm not sure if it's to your question if it ahead or behind but we've.

Made a strategic decision that we're going to prioritize getting everybody in onto the pivotal trial, because that will allow us to get there.

The durability of that we need.

Thank you.

<unk> have a problem.

Putting a patient on a strong <unk> four inhibitor, even if they didn't require it. So you kind of had a almost like a later right that's right.

Right. So right now actually there are patients who come into the trial, who are not on a strong and they can then and in order to get onto the trial right now they need to be on a strong. So this isn't just switches, but it's actually not that many most of the patients whatever the bora all opposed to kind of call. It seemed to be the preferred agent anyhow. So most patients are.

On a strong Q4 inhibitor, but.

Every physician investigator.

Investigator on the trial has said they.

They need to be on a strong inhibitor to Golan I'll put them on a strong inhibitor not a problem.

Perfect. Thank you and then just kind of a final question around the strong weeks of trade.

Pete.

One or two in the intercept does that.

Have a requirement or will they have a requirement for strong <unk> four inhibitor.

Right so for <unk> and 702, right now again because of the dose that we have agreement with the FDA is.

With a strong inhibitor those patients will be on and again thats that standard of care in those populations.

Because they are similarly get put on an antifungal.

In the intercept trial.

It's not a requirement that they would be on a strong set three <unk> four inhibitor that these are patients who are in morphological remission.

And so they actually don't need necessarily new today is also that one.

Where there is an option to be on the trial with.

Without being on a strong inhibitor.

Great. Okay. Thanks, so much thanks for the details.

Thank you Peter.

Thank you I would now like to turn it back to Michael <unk> for closing remarks.

Great. Thank you. Thank you and thank you to everybody who participated on the call today.

We look forward to seeing many of you at the upcoming conferences in March I know there are a handful of those and.

And with that I wish you all a very very nice evening.

This concludes today's conference call. Thank you for participating and you may now disconnect.

Yes.

Okay.

Yes.

[music].

Okay.

Thanks.

Yes.

Okay.

Yes.

Okay.

Yes.

Yes.

Yes.

Yes.

Yes.

[music].

[music].

Peter Lawson: Right. That's right. That's right.

Good day, everyone and welcome to the <unk> first quarter 2021 earnings conference call. Today's call is being recorded at this time I would like to turn the call over to making Meyers of Argot partners. Please begin.

[music]. Thank you operator.

Briggs Morrison: So right now, actually, there are patients who come into the trial who are not on a strong, and in order to get onto the trial, right now, they need to be on a strong. So the physician just switches them. But it's actually not that many.

Welcome and thank you to those of you joining us on the line and the webcast. This afternoon for a review of <unk> fourth quarter 2021 financial and operating results.

I'm, making 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 <unk>, Chief Accounting Officer.

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

This call is being companies by 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.

Before we begin I would like.

To remind you that any statements made during this call that are not historical are considered to be forward looking statements within the meaning of the private Securities Litigation Reform Act of 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 those reports filed with the SEC.

Any forward looking statements represent our views as of today March 1st 2022 only.

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

Briggs Morrison: Most of the patients, whatever the boraconazole and posaconacol seem to be the preferred agents anyhow. So most patients are already on a strong CYP3A4 inhibitor, but every physician we've talked, every investigator on the trial has said, well, they need to be on a strong inhibitor to go on. I'll put them on a strong inhibitor. Not a problem. Perfect, thank you. And then just kind of a final question around the strong weak 634.

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

Yeah.

Peter Lawson: The beat, the augment 102 and the intercept, does that, Have a requirement or will I have a requirement for a strong CYP3A4 inhibitor? Right, so for BDAML and 702 right now, again, because the dose that we have agreement with the FDA is a with a strong inhibitor, those patients will be on and again, that's that standard of care in in those populations. Because they're, you know, similarly get put on on antifungal.

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

Briggs Morrison: In the intercept trial. It's not a requirement that they'd be on a strong 634 inhibitor that these are patients who are in morphologic remission. And so they actually don't need, necessarily need an azole.

Before we turn to the deck, let me start my comments by first welcoming Kate Madigan to syntax as our new Chief Medical Officer.

<unk> completed her formal education and training at Dartmouth and USC and has had a distinguished professional career at some of America's most prestigious pharmaceutical firms there.

Truly honored to have her joining our team.

You will hear more from her on future calls.

I would also like to take this opportunity to thank Michael Myers for his exceptional contributions to <unk> over the past seven years, Michael has flawlessly led the development of both of our programs into their registration Charles Michael is committed to seeing its index successfully transitioned into its next phase of growth and we are grateful that he will remain an active adviser to the company.

Briggs Morrison: So that one, you know, where there's an option to be on the trial without being on a strong inhibitor. Right. Okay. Thank you so much.

Now turning to slide three 2021 was a truly transformational year for Sundar.

Peter Lawson: Thanks for all the details. Thank you, Peter. Thank you. I would now like to turn it back to Michael Metzger for closing remarks. Great. Thank you, Dede.

We initiated registration trials for both of our lead programs SMB X 50, 613, and <unk>, we entered into a global partnership and collaboration with a world class partner insight actually telematics to expand the potential for this program.

And we ended the year with an exceptionally strong balance sheet following a $152 million upfront payment from our collaboration and $81 2 million in net proceeds from our December offering following strong data disclosures for both of our lead programs at the 2021 American Society of Hematology Medical Conference.

Especially given the current the current challenging market backdrop, we are starting 2022 with an extremely solid balance sheet position. This gives us the resources to expand both of our assets into new indications and the flexibility to aggressively pursue business development opportunities to augment our.

With potential best in class molecules.

Michael Metzger: Thank you. And thank you to everybody who participated on the call today. We look forward to seeing many of you at the upcoming conferences in March. I know there are a handful of those.

Slide four provides 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.

The momentum is really building its index.

Our three pivotal phase II trials for SMB X 50, 613, our highly selective <unk> inhibitor.

Which we call augment 101 cohorts to a to B and C is progressing very well and is actively enrolling patients for.

<unk>, our antibody against CSF, one our enrollment is ongoing in our pivotal AGA 201 trial and we are now underway working closely with our new partner insight to maximize the value of this important program.

Operator: And with that, I wish you all a very, very nice evening. This concludes today's conference call. Thank you for participating and you may now disconnect. [music] Good day, everyone, and welcome to the Syndax first quarter 2021 earnings conference call. Today's call is being recorded.

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

There is an enormously exciting time for the company as we anticipate filing potentially two NDA in 2023 and are starting to expand the organization to support the commercial launch of both 56, <unk> III and <unk> in the United States.

Let's now turn to slide five and provide further details on where we are with <unk> 603.

First we have opened 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.

101 cohort two will enroll patients with relapsed refractory MLR ALLL cohort to be will enroll patients with relapsed refractory MLR AML and cohorts you see will enroll 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.

Megan Myers: 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 fourth quarter 2021 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 Nolte, Chief Accounting Officer.

We may seek additional regulatory approval for F&B X 50, 613 based on the results of any one of these trials should one trial enrolled faster than the others or are we may or we may seek initial regulatory approval with any two or all three just depending on when they complete in enrollment.

Megan Myers: Also joining us on the call today for the question and answer session is Dr. Peter Ordundluk, Chief Scientific Officer, and Dr. Anjali Ganguli, 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. 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 Reform Act of 1995.

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

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

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

We have agreement with FDA.

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 $56 three after bone marrow transplants, a design feature that allows us to start to understand the role of $56 three in the post transplant maintenance setting.

We also have agreement with FDA on the statistical design of each trial each trials enrolled 64 patients at up to 10 pediatric patients.

Michael Metzger: Any forward-looking statements represent our views as of today, March 1st, 2022 only. A replay of this call will be available on the company's website, www.syndax.com, following this call. With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax. Thank you, Megan, and thank you to everyone joining us on today's call and webcast. Before we turn to the deck, let me start my comments by first welcoming Kate Madigan to Syndax as our new Chief Medical Officer.

Michael Metzger: Kate completed her formal education and training at Dartmouth and USC and has had a distinguished professional career at some of America's most prestigious pharmaceutical, We are truly honored to have her joining our team, and you will hear more from her on future calls. I would also like to take this opportunity to thank Michael Meyers for his exceptional contributions to Syndax over the past seven years. Michael has flawlessly led the development of both of our programs into their registration, Michael is committed to seeing Syndax successfully transition into its next phase of growth, and we are grateful that he will remain an active advisor to the company. Now turning to slide three. 2021 was a truly transformational year for Syndax.

Michael Metzger: We initiated registration trials for both of our lead programs, SMDX-5613 and X-Patilla Map. We entered into a global partnership in collaboration with a world-class partner in-site on the X-Patilla Map to expand the potential for this program. And we ended the year with an exceptionally strong balance sheet following $152 million upfront payment from our collaboration and $81.2 million in net proceeds from our December offering, following strong data disclosures for both of our lead programs at the 2021 American Society of Hematology Medical Conference. Especially given the current challenging market backdrop, we are starting 2022 with an extremely solid balance sheet position.

Michael Metzger: This gives us the resources to expand both of our assets into new indications and the flexibility to aggressively pursue business development opportunities to augment our pipeline with potential best-in-class models. Slide 4 provides 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. The momentum is really building at Syndax.

Michael Metzger: Our three pivotal Phase II trials for SNDX5613, our highly selective menin inhibitor, which we call Augment 101 Cohorts 2A, 2B, and 2C is progressing very well and is actively enrolling patients. For axotilumab, our antibody against CSF1R, enrollment is ongoing in our pivotal Agave 201 trial, and we are now underway working closely with our new partner, Insight, to maximize the value of this important program. I want to emphasize that we now have two registrational programs ongoing for two first-in-class and potentially best-in-class medicines for two areas of important unmet medical need.

Finally, we have agreement with FDA that a 163 milligrams every 12 hours given with a strong <unk> four inhibitor is an appropriate phase two dose and that is the dose we're using in each of these trials.

Michael Metzger: It is an enormously exciting time for the company as we anticipate filing potentially two NDAs in 2023 and are starting to expand the organization to support the commercial launch of both 5613 and Axotilumab in the United, Let's now turn to slide 5 and provide further details on where we are with S&DX5613. First, we have opened three single-arm phase 2 trials that FDA has agreed may each serve as a pivotal trial. Each of these single-arm phase 2 trials represent an independent path to a separate indication.

We know that the vast majority of eligible patients aren't as strong <unk> four inhibitor and in an effort to enroll the cohorts as quickly as possible at least one cohort to complete this year. We have now prioritize the enrollment of these patients versus those not on a strong set very four inhibitor once.

Michael Metzger: Augment 101 Cohort 2A will enroll patients with relapsed refractory MLR-ALL. Cohort 2B will enroll patients with relapsed refractory MLR-AML. And Cohort 2C will enroll patients with relapsed refractory NPM1-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 FNDX 5613 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 all three, just depending on when they complete enrollment.

Michael Metzger: We are happy to report that additional site initiation and patient accrual across the cohorts is going extremely well. We are very optimistic that we will be able to complete enrollment in at least one of these cohorts this year. Given our current trajectory and our view of the landscape, we anticipate being the first company to achieve regulatory approval for amended inhibitors. Needless to say, we believe being first-to-market is extremely important and accretive to the long-term value of Syndax.

Once one cohort closes to enrollment we plan to increasingly focus on accumulating the data required for labeling which includes the necessary dose adjustment often referred to as the RMA dose. Let me remind you that this claim farm data is not in any way limiting on our ability to enroll and complete the pivotal trial.

Michael Metzger: 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 CRH response, transfusion independence, overall survival, and safety. Importantly, the trial design allows patients to be treated with 5613 after bone marrow transplant, a design feature that allows us to, start to understand the role of 5613 in the post-transplant maintenance setting. We also have agreement with FDA on the statistical design of each trial.

Beyond the augment pivotal program in relapsed refractory disease slide six highlights some of the additional opportunities we're exploring with $56 three all of which build on the excellent safety and efficacy profile, we have thus far seen with $56 three.

Michael Metzger: Trial enrolls 64 patients and up to 10 pediatric, Finally, we have agreement with FDA that 163 milligrams every 12 hours given with a strong CYP3A4 inhibitor is an appropriate phase 2 dose, and that is the dose we are using in each of these trials. We know that the vast majority of eligible patients are on a strong CYP3A4 inhibitor, and in an effort to enroll the cohorts as quickly as possible, at least one cohort to complete this year, we have now prioritized the enrollment of these patients versus those not on a strong CYP3A4. Once one cohort closes to enrollment, we plan to increasingly focus on accumulating the data required for labeling, which includes the necessary dose adjustment, often referred to as the ArmA dose.

The panel on the left highlights the trial, we are planning in collaboration with the leukemia and lymphoma society, otherwise known as LLS. They.

Michael Metzger: Let me remind you that this ClinPharm data is not in any way limiting on our ability to enroll and complete the Pivotal training. Beyond the Augment Pivotal Program in relapsed refractory disease, Slide 6 highlights some of the additional opportunities we are exploring with 5613, all of which build on the excellent safety and efficacy profile we have thus far seen with 5613. The panel on the left highlights the trial we are planning in collaboration with the Leukemia and Lymphoma Society, otherwise known as LLF.

They have selected 50 613 as the first menin inhibitor to be tested as to specific targeted therapy for patients with MLR or NPM, one AML and their umbrella trial that they call beat AML. The collaboration we have agreed to with them will test 50, 613 in combination with <unk> and <unk> and <unk>.

Michael Metzger: They have selected 5613 as the first mendenin inhibitor to be tested as a specific targeted therapy for patients with MLLR or MPM1 AML in their umbrella trial that they call BEAT AML. The collaboration we have agreed to with them will test 5613 in combination with venetoclax and ascitidine in newly diagnosed AML patients who are unfit for induction chemotherapy and will consist of a phase 1 followed by a phase 2 free trial which could serve as the basis for a regulatory filing. Our scientists have generated preclinical data that supports the benefit of menin inhibition in combination with chemotherapy.

Diagnosed <unk> patients.

Our unfit for induction chemotherapy and will consist of a phase one followed by a phase two three trial, which could serve as the basis for our regulatory filings.

Our scientists have generated preclinical data that supports the benefit of Menin inhibition in combination with chemotherapy and therefore, the middle panel of the slide highlights the trial to explore the use of 50 613 in combination with standard salvage chemotherapy is used for pediatric patients with al or AML that we have.

Michael Metzger: And therefore, the middle panel of the slide highlights a trial to explore the use of 5613 in combination with standard salvage chemotherapies used for pediatric patients with ALL or AML that we are calling Augment 102. And the panel on the right illustrates a third trial that explores the activity in 5613 in patients with AML who have MRD-positive disease. This trial is being conducted as part of the Intercept Master Clinical Trial being led by the Australian Leukemia and Lymphoma Group. The Intercept Trial is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML.

Augment 102.

In the panel on the right illustrates a third trial that explores the activity and 50 613 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 Australia in leukemia and lymphoma group the.

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

Michael Metzger: The trial enrolled patients with measurable residual disease progression following initial treatment. A group of patients at very high risk will have three laps that represent an important unmet medical need. A general observation in the treatment of cancer is that the earlier in the patient's disease course that you treat, 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, I will also note that 5613 is the first menin inhibitor to be included in the Intercept AML Master Clinical Trial.

The trial will enroll patients with measurable residual disease progression following initial treatments.

<unk> patients at very high risk.

Relapsed that represent an important unmet medical need.

A general observation in the treatment of cancer is that the earlier in the patient's disease course that you treat 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 50 613 is the first menin inhibitor to be included in the intercept AML Master clinical trial.

Michael Metzger: We believe the selection of 5613 for inclusion into two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with 5613. As mentioned on our last quarterly call, we are excited to expand the clinical opportunities for 5613 beyond the initial approval in relapsed refractory acute leukemia. Slide 7 highlights our goal as a company to be first to market in relapse refractory disease and then be first to garner additional value-enhancing indications by expanding the use of 5613 into newly diagnosed and maintenance settings in patients with MLLR and MPM1 mutant acute leukemia.

We believe the selection of $56 three for inclusion into two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with 50 613.

As mentioned on our last quarterly call. We are excited to expand the clinical opportunities for $56 three beyond the initial approval in relapsed refractory acute leukemias slide seven highlights our goal as a company to be first in market to market and relapsed refractory disease and then the first to garner additional value enhance.

Indications by expanding the use of $56 three into newly diagnosed and maintenance settings in patients with MLR and NPM one acute leukemias.

Michael Metzger: We see the opportunity to treat patients with these forms of mutant acute leukemia, which account for up to 40% of the eligible patient population, as early in their treatment journey as possible, and then drive them into remission and maintain them in that state for months, if not years. That emerging paradigm for men in inhibition is what will enable this to be one of the most important new franchises in heme malignancies and why we are so keen to invest in 5613 at this stage.

We see the opportunity to treat patients with these forms of mutant acute leukemia, which account for up to 40% of the eligible patient population as early in their treatment journey as possible and then drive them into remission and maintain them in that state for months if not years.

Emerging paradigm for Menin inhibition is what will enable this to be one of the most important new franchises in heme malignancies, and why we are so keen to invest and 50 613 at this stage.

Michael Metzger: Let me now turn to axotilamide, our potentially best-in-class monoclonal therapy, antibody therapy targeting CSF1 receptors. Slide 8 is our pivotal trial for Axitilumab and CGBHD. This trial is the Axitilumab for graft versus host disease trial called AGAVE-201. The trial is enrolling patients with CGBHD whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met overall entry criteria.

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

Slide eight is our pivotal trial for <unk> and C. Gvhd. This trial is the <unk> for graft versus host disease trial called <unk>. The trial is enrolling patients with CGP HD, whose disease has progressed after two prior therapies patients must be at least six years of age and have met overall entry criteria.

Michael Metzger: 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 overall response rate using the 2014 NIH consensus criteria for CGBHD. Secondary endpoints will include duration of response and validated quality-of-life assessments using the Lee Symptom Scale.

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

The primary endpoint is overall response rate using the 2014 NIH consensus criteria for C. Gvhd.

Secondary endpoints will include duration of response and validated quality of life assessments using the leaf symptom scale.

Michael Metzger: Enrollment to the study is going quite well, and we are on track to deliver top-line data in the first half of 2023. We were also delighted to announce during the quarter that Syndax and Insight closed our global collaboration that brings together two companies with a solid track record of innovation to accelerate and maximize the development of axotilamide. As you know, we presented our Phase 1-2 CGBHD data at ASH in December of last year, which received a very positive reaction and further underscored its best-in-class profile.

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

We were also delighted to announce during the quarter Thats index and insight closed our global collaboration that brings together two companies with a solid track record of innovation to accelerate and maximize the development of <unk> until a map.

As you know we presented our phase <unk> data at Ash in December of last year, which received a very positive reaction and further underscored its best in class profile.

Michael Metzger: Through our collaboration, Syndax and Insight will pursue an expanded set of indications in CGBHD and other fibrotic diseases. The development plan calls for the partners to design novel combinations of axotilumab and Insite's JAK inhibitors with a goal of establishing axotilumab in earlier settings within CVHD and expanding its market opportunities. As we previously mentioned was our intention, Syndax will initiate a robust phase 2 trial in IPF in the fourth quarter of this year. The first expansion outside of establishing CGBHD as a beachhead into other fibrotic diseases where we believe axotilamide could have a significant impact.

Through our collaborations index and insight will pursue an expanded set of indications and see gvhd and other fibrotic diseases.

The development plan calls for partners to for the partners to design novel combinations with <unk> and insights JAK inhibitors with the goal of establishing <unk> in earlier settings within CVA, gvhd and expanding its market opportunity.

We've previously mentioned was our intention. So next we'll initiate a robust phase II trial in IPF in the fourth quarter of this year.

First expansion outside of establishing the gvhd as a beachhead into other fibrotic diseases, where we believe <unk> could serve as could have a significant impact.

Michael Metzger: Successful development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support to Actothelimab and other fibrotic-driven diseases that the parties could explore over the course of the collaboration. Slide 9 highlights our view of the broad clinical and commercial opportunity for axotilamide. We believe chronic GVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from CGVHD in the U.S. today.

Successful development in IPF could lead to an additional approval in a very important indication of considerable value and would provide support to exit until nab in other fibrotic driven diseases that the parties could explore over the course of the collaborations.

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

We believe chronic 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.

Michael Metzger: The recent approvals of Jakafi and Cadiman's Belmusadil will begin to delineate the commercial opportunity in CGVHD. Despite recent advancements in this area to our knowledge, Axotilamab is the only agent in clinical development that specifically targets the monocyte macrophage lineage.

The recent approvals of Jakafi and bad cabins, Bellevue, Sunil will begin 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 lineage Bolsa index insight believe the data.

Michael Metzger: Both Syndax and Insight believe the data generated to date with axotilimab suggest 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 jacafi and other JAK inhibitors within the Insight portfolio. 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.

Generated to date with Axa tell them that suggests it has the potential to play an important role in the treatment of C. Gvhd, both as a monotherapy and given its safety profile in combination with complementary medicines, such as Jack a fee and other JAK inhibitors within the insight portfolio.

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

Michael Metzger: As we move Axotilumab into additional applications, starting with IPF, we really see Axotilumab contributing materially to the value of our company moving forward. Finally, slide 10 summarizes the transactions that led to the acquisition of Menin MLR and Axitilumab programs.

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

Finally, slide 10 summarizes the transactions that led to the acquisition of MLR and <unk> programs.

Michael Metzger: 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 will be able to continue to expand our pipeline through product acquisitions or in licensing of quality differentiated assets. We expect to remain among preferred partners of such transactions.

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 will be able to continue to expand our pipeline through product acquisitions or in licensing of <unk>.

Quality differentiated assets, we expect to remain among preferred partners of such transactions.

Alex Nolte: I would now like to turn the call over to Alex to review our financial report. Thank you, Michael. Let me now take a few minutes to discuss our financial results for the fourth quarter and the full year of 2021. The results of our operations for the fourth quarter of 2021 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 fourth quarter and full year report on Form 10-Q, 10-K, which will be filed today.

I would now like to turn the call over to Alex to review our financial results Alex.

Alex Nolte: I would like to point out that our net profit for the quarter was $96.2 million, or $1.81 per share, compared to our net loss of $20.4 million, or $0.44 per share, for the same period last year.

Thank you Michael.

Let me now take a few minutes to discuss our financial results for the fourth quarter and the full year of 2021.

The results of our operations for the fourth quarter of 2021, 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 fourth quarter and full year report on Form 10-Q .

Which will be filed today.

I would like to point out that our net profit for the quarter was $96 2 million.

$1 81 per share compared to a net loss of $20 4 million.

Or <unk> 44 per share for the same period last year.

Alex Nolte: This difference is primarily attributed to the change in license revenue generated from the collaboration agreement with Insight. Turning to slide 11. We ended our fourth quarter with $439.9 million in cash and cash equivalents, including net proceeds of approximately $81.2 million from our public offering completed in December 2021 and with 59 million shares and pre-funded warrants outstanding.

This difference is primarily attributed to the change in license revenue generated from the collaboration agreements with and site.

Turning to slide 11.

Alex Nolte: This cash balance also includes $152 million in proceeds from the December closing of the collaboration agreement with Insight. Our current cash runway now extends into the second half of 2024 and supports our expanded development and early commercialization plans for both the Exetila map and the MENM programs during this period and provides us flexibility for continued business development. Looking ahead, I'd like to provide financial guidance for the first quarter and full year of 2022.

We ended our fourth quarter with $439 $9 million in cash and cash equivalents <unk>.

Including net proceeds of approximately $81 2 million.

From our public offering completed in December 2021.

And it's 59 million shares and pre funded warrants outstanding.

This cash balance also includes $152 million and proceeds from the December closing of the collaboration agreement with insight.

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 the extra telematics and the Menin programs. During this period and provides us flexibility for continued business development.

Alex Nolte: For the first 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 $4 million of non-cash stock compensation. 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 of non-cash stock compensation.

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

For the first quarter of 2022, we expect R&D expense to be $30 million to $35 million.

And total operating expense to be $38 million to $42 million, including $4 million of noncash stock compensation expense for.

For the full year 2022, we expect R&D expense to be $130 million to $140 million and total operating expense to be $160 million to $170 million.

<unk> approximately $14 million of noncash stock compensation expense.

Alex Nolte: 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 Mannan into registration trials, expansion into new indications, and Initiation of Freelance Commercialization Activity. This guidance does not currently reflect any potential offset by the cost-sharing offset of Exeter Telemap operating expenses with our partner Insight, and we will continue to update guidance over the course of the year as we move forward with this collaboration. With that, let me now turn the call back over to my... Great.

The increase in R&D and operating expense in 2022 compared to the prior year periods is driven by the expansion of both <unk> and then into registration trials.

Pension into new indications.

And initiation of pre launch commercialization activities.

This guidance does not currently reflect any potential offset by the cost sharing offset of exit settlement operating expenses with our partner insight.

And we will continue to update guidance over the course of the year as we move forward with this collaboration.

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

Michael Metzger: Thanks, Alex. Let me close the call by again noting that this management team has been focused on obtaining regulatory approval for drugs that extend and improve the lives of people with cancer and other diseases, and we consider having two ongoing registration programs to be a major achievement. We are also really excited about the broad franchise opportunities for both programs beyond their initial registration. We believe SNDX5613 could have broad utility across a wide range of clinical settings in acute leukemia and possibly in a number of others as well.

Great. Thanks, Alex.

Let me close the call by again, noting that this management team has been focused on obtaining regulatory approval for drugs that extend and improve the lives of people with cancer and other diseases and we consider having two ongoing registration programs to be a major achievement.

We're also really excited about the broad franchise opportunities for both programs beyond their initial registration indications we.

We believe <unk> hundred $56 three could have broad utility across a wide range of clinical settings, and acute leukemia, and possibly in a number of others as well.

Michael Metzger: Our immediate goal as a company is to be the first to market in relapse refractory disease and then to garner additional value-enhancing indications by expanding the use of 5613 into newly diagnosed and maintenance settings in patients with MLLR and MPM1 acute leukemia. And Axotilumab also holds the promise of a broad franchise opportunity in various lines of therapy in CGVHD and across a broad range of fibrotic diseases starting with IPF. We have a strong balance sheet to aggressively advance our programs and achieve key upcoming milestones.

Our immediate goal as a company is to be the first to market in relapsed refractory disease, and then to garner additional value enhancing indications by expanding the use of $56 three into newly diagnosed and maintenance settings in patients with MLR in MTM, one acute leukemias.

And <unk> also holds the promise of a broad franchise opportunity to unity in various lines of therapy in <unk> and across a broad range of fibrotic diseases, starting with Ips.

We have a strong balance sheet to aggressively advance our programs and achieve key upcoming milestones.

Michael Metzger: We remain optimistic in 2022 that we can continue 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. We could not accomplish all that we have without our wonderfully talented team here at Syndax, our collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical program.

We remain optimistic in 2022 that we can continue to identify and bring in novel molecules to deepen our portfolio. We have a proven track record of delivering on this pillar pillar of our corporate strategy and I believe this is a core strength of our company.

We could not accomplish all that we have 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 our committed long term investors, who are helping us build this great company.

Michael Metzger: In addition, I would like to thank our committed long-term investors who are helping us build this great, With that, I would like to open the call for questions. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key.

With that I would like to open the call for questions.

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

Draw your question press the pound key please standby, while we compile our Q&A roster.

Operator: Please stand by while we compile our Q&A roster. Our first question comes from Phil Nadeau with Callen & Company. Please proceed. Good afternoon, thanks for taking my questions and congrats on a very productive year. First, a question on the 5613 no CYP3A4 dose. I want to make sure I understand the strategy.

Our first question comes from Phil Nadeau with Cowen and company. Please proceed.

Good afternoon, Thanks for taking my questions and congrats on a very productive year.

First a question on the 50 613, no <unk> four dose.

Phil Nadeau: It sounds like you're saying, um... Patients who are not on a CYP3A4 probably won't be enrolled in the trial for some time. But that's okay because you just simply need to identify the do's.

Sure I understand the strategy it sounds like you are saying.

Patients who are not on a <unk> four inhibitor.

We won't be enrolled in the trial for some time.

But that's okay, because we simply need to identify the dose to.

Michael Metzger: Pharmacokinetic Measures, and, Actually, having clinical data from patients who aren't on CYP3A4 inhibitors is less of a requirement for filing. Is that correct? Yeah, maybe I'll start and Brady could comment also, but Phil, thanks for the question.

Pharmacokinetic measures.

And.

Actually I haven't clinical data from patients who are non <unk> <unk> four inhibitors.

Garment for filing is that is that correct.

Yes, maybe I'll start and Brady could comment also but Phil thanks for the question. So.

Michael Metzger: So, look, I think the priority, as we say, most of the patients seem to be on strong CYP3A4 inhibitors, antifungals, and our priority is to get the trial enrolled, each of the cohorts enrolled as quickly as possible. And so as a result of the dynamics of what I just described, we're prioritizing getting it done versus collecting all the ClinPharm information in this trial. So we are seeing some patients that are not on a strong CYP3A4 inhibitor, but the cadence of that is we're not prioritizing putting them on the trial versus getting as many patients in as we can to complete it as early as we can. So I think what you said was correct.

So look I think the priority as we as we said most of the patients seem to be on strong separate four inhibitors.

Antifungals and our priority is to get the get the trial enrolled each of the cohorts enrolled as quickly as possible.

And so as a result of of the dynamics of what I just described.

Prioritizing getting it done versus <unk>.

Collecting all the <unk> farm information.

In this.

In this trial. So we are we are seeing some patients that have that are <unk>.

Not on a strong set of <unk> four inhibitor.

But the cadence of that is not we're not prioritizing putting them on the trial versus getting as many patients as we can.

To completed as early as we can so.

And what you said was correct I think we want to get.

Phil Nadeau: I think we want to get the information together, the ClinPharm information together in order to complete the trial, ultimately complete the trial for labeling purposes, but that's once we submit the NDA. Once we have one of the cohorts fully enrolled, we'll turn our attention to bringing more of those patients in. They're just harder.

The information together clean farm information together in order to.

Complete the trial ultimately complete the trial for labeling purposes, but that.

Once we submit the NDA, but once we have one of the cohorts and fully enrolled.

We will turn our attention to bringing more of those patients and they are just harder to find.

Michael Metzger: Got it. Okay. And have you identified a dose yet? Or are there complications in figuring out what dose?

Got it.

Have you identified the dose fit or are there complications and figure out what dose.

Michael Metzger: should be the dose that is ultimately submitted. No, no, there's been there's been no trouble identifying a dose. I think it's just a matter of, you know, accumulating more patients. As you know, we have identified two doses that meet the RP2D as part of the phase one. So, you know, we've identified active doses. It's just a matter of, you know, putting on enough patients who are not on a strong-sip rate. And that's put enough patients on in order to figure out the dose that you want to register. What PK matches are R&B dose?

Should be the dose that is.

Ultimately submitted.

Yes.

No no theres been theres been no trouble identifying a dose I think it's just a matter of.

Accumulating more patients that's all.

Got it.

We have.

We have identified.

Two doses that meet the RP duty as part of the phase one so.

We've identified active doses and it's just a matter of.

Putting on enough patients who are not on a strong set of great work there.

Yes.

And thats, putting enough patients on in order to figure out the dose that you want to do you want to register.

Correct.

The PK, what PK matches, our RMB dose.

Phil Nadeau: Perfect. Yep. Okay. That's very helpful.

Okay, that's very helpful.

Michael Metzger: Second question, also on the pivotal trials. In terms of the pace of enrollment, I think in the past you've said MLR, AML patients, that group is likely to enroll more quickly because of the competing trials. Is that still your expectation?

Second question also on the pivotal trials in terms of the pace of enrollment I think in the past you've said MLR.

AML patients.

That group is likely to enroll more quickly because we are competing trials because thats still your expectation is that the cohort that we should expect to see data from first.

Phil Nadeau: Is that the cohort that we should expect to see data from first? Yeah, I think we said, Phil, that, that the AML cohorts, we didn't differentiate between MLR and PM1, we just said that our expectation is the AML cohorts will enroll faster than ALL cohorts, so, and as I said in my remarks, we expect to enroll at least one, maybe two, hopefully fully this year, so we're not saying exactly which ones will enroll faster than the others, but that was the kind of guidance we had given, and we're sticking with that. Perfect. And then last question on ExcoMap, you referenced the two recent approvals, and the fact that those launches could inform you about the GVHD market. We're curious, what do you expect to learn most?

Yes, I think we said fill that.

That the AML cohorts.

We didn't differentiate between MLR NPM one we just said that our expectation is the AML cohort will enroll faster than <unk> cohorts.

So and as I said in my remarks, we expect to enroll it.

One maybe to hopefully this fully this year so.

We're not we're not saying exactly what which ones will enroll faster than the others, but that was the kind of guidance, we have given them, we're sticking with that.

Perfect and then last question on <unk> you referenced the two.

Two recent approvals.

And the fact that it goes on to screen inform you about the gvhd market. We're curious.

What do you expect to learn most.

Phil Nadeau: from those launches, aside from the revenue trajectory, which we'll all see, but in terms of location of patients, access to reimbursement, desire to be treated, what do you think will be most informative about those launches as you contemplate Exit Hill Maps commercialization? Yeah, maybe I'll ask Anjali, our Chief Business Officer, to comment on that. Sure. Thanks, Michael.

From those launches aside from the revenue trajectory, which will we will see but in terms of like location of patients access to reimbursement.

Desire to be treated what do you think will be most most informative about those launches as you.

As you contemplate ex Tomas commercialization.

Yes, maybe I'll ask Angela <unk>, our chief business officer to comment on that.

Anjali Ganguli: Thanks, Phil, for the question. I think, you know, a big part of the launches, too, is the awareness of new drugs in this space, because for so long it's been dominated by generic entry and the defining of a treatment algorithm for chronic GVHD, I think, is an ongoing and evolving event. And so that alone, I think, is really helpful for the space and for, you know, being able to position axitilumab within the treatment algorithm when it is approved in, we're hoping, the 2024 timeframe.

Sure. Thanks, Thanks, Nick Thanks, Phil for the question.

Thank you know a big part of the logic two is the awareness of new <unk>.

<unk> in the states because for so long it's been dominated by generic entry.

The signing of a treatment algorithm.

Sure Patrick.

Chronic gvhd I think is an ongoing and evolving.

Event, and so that alone I think is really helpful.

For the state and for being able to position <unk> within the treatment algorithm when it is approved.

We're hoping that 2024 timeframe.

Anjali Ganguli: So, you know, beyond the items that you mentioned, reimbursement, pricing, adoption, you know, understanding who are the physicians that are likely to be the decision makers or key influencers in this space and early adopters will also be very helpful.

So beyond.

The items that you mentioned reimbursement pricing adoption.

Understanding who are the physicians that are likely to see that.

Decision makers and key Influencers in this space.

Early adopters will also be very helpful that I think even building awareness of these new drugs and agents and how they can help patients.

Phil Nadeau: And I think even building awareness of these new drugs and agents and how they can help patients is also part of the process that we're watching. Perfect. Thanks for taking our questions and congrats again on the progress. Thanks, Phil.

Is also part of the process that we're watching.

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

Thanks, Phil.

Bert Haslett: Thank you. Our next question comes from Bert Haslett of BTIG. Please proceed. Hi, thank you.

Thank you. Our next question comes from Bert Hazlett of BPI. Please proceed.

Michael Metzger: And thanks for taking my question. Just with regard to 5613 and the expanded opportunities, in particular, the mass protocol trials, BEAT-AML and Intercept, could you just give a little bit more granularity about, you know, with regard to timing and when we might get a sense of initial data for really any of those studies, including Augment 102? Yeah, thanks, Bert.

Hi, Thanks.

Thanks for taking my question, just with regard to $56 13, and the expanded opportunities in particular, the Master protocol trials beat AML and intercept could you just give a little bit more granularity.

With regard to timing and when we might get a sense of initial data for really any of those studies, including augment one or two.

Briggs Morrison: Thanks for the question. Maybe I'll ask Dr. Briggs-Morrison to comment on this. Thanks for the question. So, all three of those trials will be starting in the first half of this year. Again, for each of them, for the first two, the LLS trial and the...

Yes, Thanks, Brian Thanks for the question, maybe I'll ask Briggs, Dr. Briggs Morrison to comment on this as well.

Thanks for the question. So all three of those trials will be starting in the first half of this year.

Again for for each of them there for the first two the LLS trial.

Briggs Morrison: Combination Chemotherapy Trial is for the Phase 1 portion to pick a dose, and the data that is used to support the dose, you know, could be available, let's say, for BAML early part of next year. Intercept is not a combination trial, it's just monotherapy, and so it's really a question of when we'll have some early data on converting MRT positive to MRT negative. Again, I would think perhaps by middle of next year that might be something.

Combination of chemotherapy trial to sort of the phase one portion to pick a dose.

And the data that is used to support the dose could be available.

Let's say.

For beat AML.

Early part of next year.

Potentially also for 700 to intercept is just not a combination trial its just mono therapy and so it's really a question of <unk>.

We'll have some early data on converting <unk> positive <unk> negative again, I would think perhaps by middle of next year that might be something.

Bert Haslett: Okay, terrific. I'm just shifting gears to Axotilumab for a question. With regard to the IPF study, could you provide any more granularity on the phase two effort there? I know it's early days, but would very much love to understand a little bit more of the scale and scope of the work there.

Okay terrific.

Just shifting gears to.

<unk> for the question.

Regarding the IPF study could you provide any more granularity on the phase III effort there.

It's early days, but would very much love to understand a little bit more of the scale and scope of the work there.

Michael Metzger: Yeah, sure. Thanks, Bert. Maybe I'll ask Briggs to comment a little bit more on that as well. Yeah, so, Bert, we'll give a lot of details as we typically do once we have FDA endorsement on the trial and we're sort of opening the trial. I would say our general, the general approach that we've been advised by experts in the field is that if you're going to study IPF, you just have to study IPF.

Yes sure Thanks, Brett.

Maybe I'll ask Briggs to comment a little bit more on that as well.

Yes, so well.

We'll give a lot of details as we.

As we typically do once we have FDA endorsement on the trial and we're sort of opening the trial I would say our general the general approach that we have been advised by experts in the field is that.

If youre going to study Ips. So you just have to study Ips that you have to do.

Briggs Morrison: And you have to do, you know, an FEC endpoint-driven trial that's about a year in duration. And so that's, you know, the sample size and some of the details we'll go through with you after we, you know, get endorsement and we're up and running the trial. But you should think of it as, you know, a, A year-long trial with FEC as the primary endpoint. We've looked at a talk with many experts about sort of surrogate biomarkers that you could use.

Endpoint efficacy endpoint driven trial, that's about a year in duration.

And so that's.

The sample size and some of the details will go through with you after we.

Get endorsement and we're up and running the trial, but you should think of it as.

A year long trial with MPC as the primary endpoint we've looked.

<unk>.

Talk with many experts about.

Surrogate biomarkers that you could use.

Bert Haslett: You know, to sort of do an intermediate time point, and the advice that we've gotten is that… None of those have really been well validated, and they're maybe just as high a false positive as a false negative, and the best thing to do is if you really believe that you have an active agent, just go ahead and do the full one-year trial. So that's the current thinking, but we'll give you a lot more details once we open up the trial. Okay, great. And then just one big picture question.

Just to sort of do an intermediate time point and the advice that we've gotten is that.

None of those have really been well validated and there may be just as high a false positive false negative.

And the best thing to do if you really believe that you have an active agent to just go ahead and do the full one year trial. So that's the current thinking but we'll give you a lot more details.

Once it.

We opened up the trial okay great.

Then just one big picture question, you've had some intriguing success with the license I got 56000, <unk> X fill them up.

Michael Metzger: We've had some intriguing success with the licensing of 5613N, axosilamab. Is there a common theme here with regard to therapeutic area, oncology, fibrotic disease? You know, you've, again, had some unique...

Is there a common theme here with regard to therapeutic areas oncology fibrotic disease.

Again had some unique.

Michael Metzger: Unique Success. How are you thinking about additional business development efforts more broadly? Yeah, thanks. Thanks for that question, too, Bert. You know, look, I think the the theme for us has been identifying molecules that are sort of, we think, best in class differentiated molecules. And we have never sort of drawn a line saying that, you know, they're heme versus solid tumor, or one modality versus the other.

Unique success, how are you thinking about additional business development efforts more broadly.

Michael Metzger: I think we're, we're most interested in targeted therapy for oncology. Having said that, I think we are you know, really looking for molecules at a at a time point in their development, usually generally on the earlier side, you know, late preclinical, early clinical, where, you know, we can use our expertise in terms of clinical development, translational medicine, in order to make a big a big difference with these molecules. And so I think the, you know, right now we are on the heme side of the equation in terms of in terms of what we're developing. And there is some synergy between call points between our our molecules, which is which is great.

Yes. Thanks, Thanks for that question Hubert.

Look I think.

Yes.

The theme for US has been identifying molecules that are sort of we think best in class differentiated molecules.

We have never sort of drawn a line.

Saying that their heme versus solid tumor or one modality versus the other I think where we're most interested in targeted therapy.

Our oncology.

<unk> said that I think we are.

<unk>.

Really looking for molecules at a at a time point in their development.

Generally on the earlier side late preclinical early clinical wear.

We can use our expertise in terms of clinical development translational medicine in order to make a big difference with these molecules and so.

I think the.

Right now we are on the heme side of the equation in terms of in terms of what we're developing.

And there is some synergy between call points between our our molecules, which is which is great.

Michael Metzger: But I wouldn't rule out a broader kind of opportunity set within oncology, you know, maybe perhaps in solid tumors as well. So as you know, it's a competitive field, and it's hard enough to find molecules that that you feel are worthy of resources and the team's time. So we're we're hunting hard, and we expect we'll be able to identify hopefully one or more molecules this year and continue building the pipeline. Terrific. Thanks for the call. I look forward to more progress. Thank you. Thank you, Bert.

But I wouldn't rule out a broader kind of opportunity set within oncology.

Maybe perhaps in solid tumors as well so as you know, it's a competitive field and it's hard enough to find molecules that debt.

Do you feel are worthy of resources and.

Team's time, so we're we're hunting hard and we expect we'll be able to identify.

Hopefully one or more molecules this year and continue building the pipeline.

Terrific. Thanks for the color and look forward to more progress. Thank you.

Thank you Bert.

Bert Haslett: Thank you. Our next question comes from Yigal Nochomovitz of Citi. Please proceed. Hi team, this is Ashiq Mubarack, I'm on for Yigal, and thanks for taking my question, and congrats on all the progress. I guess, can you talk a little bit about the XUS opportunity for 5613, and do you think the expansion cohort data may be sufficient for a filing there as well, or perhaps you'll need another control study? And also just curious about how the BEAT AML codes might play, into a European strategy.

Thank you. Our next question comes from <unk> <unk> Tomo Vic of Citi. Please proceed.

Briggs Morrison: Yeah, maybe I'll ask Briggs to comment on our European strategy as well. And I took it to mean not necessarily a commercial opportunity, but you were thinking more in terms of trial and development, correct? Correct. Thanks, Ashiq. Great. Yeah, yeah, great.

Hi, Tim. This is also more bark on for Yigal. Thanks for taking my question Congrats on all the progress.

I guess can you talk a little bit about the ex U S.

For us it's one three.

We think the expansion cohort data may be sufficient for filing there as well or perhaps with nida.

Another control study and also just curious about how the beat AML cohorts might play.

Until your European strategy.

Yes, maybe I'll ask Bruce to comment on our European strategy as well.

And then I took the took it to me not a not necessarily a commercial opportunity, but you were thinking more in terms of trial and development correct.

Correct.

Thanks, Greg.

Great.

Ashiq Mubarack: Thanks so much for the question. Your instincts are quite right here that, you know, the regulatory environment in Europe is different. And so the single arm so-called palliative trial with CR-CRH and durability may not be enough, but it may. So we're in discussions with regulators about what it'll take to get the drug approved in the EU. I think your point about BDAML, since that is, as we move into the randomized phase two portion, that is a randomized trial with sort of standard of care as the control arm. So that could play into it. But I would say, you know, stay tuned for more information on the European strategy. It will be different from the U.S.

Yeah, Yeah, great. Thanks, so much for the question your instincts are quite right here that thank.

Regulatory environment in Europe is different and so the single arm.

So called palliative trial, with CRC RH and durability.

May not be enough.

It may.

So we're in discussions with regulators about what what what.

Will it take to get the drug approved.

The EU I think your point about <unk> since that is as we move into <unk>.

The randomized phase two portion of that is a randomized trial with.

Sort of standard of care as the control arm, so that could play into it but I would say.

Stay tuned for more information on the European strategy, it will be different from the U S.

Briggs Morrison: Okay, great. That makes a lot of sense. And I guess, could you, is there any color that you can share on maybe the status of the acetylamide-jack inhibitor combo? Yeah, thanks for the question. As I said in my remarks, we're kicking off, we have kicked off our collaboration with Insight, and I think we're in the design phase of putting those trials together. And so we'll have more to say in future calls. But we hope one or more trials are initiated this year in combination with one or more of their JAK inhibitors. We haven't specified, they haven't specified as to which one. As of yet, but stay tuned.

Okay great.

It makes a lot of sense and I guess could you.

Is there any color you can share on maybe the status of the acetyl amount of JAK inhibitor combo.

Yes, thanks for thanks for the question.

As I said in my remarks, we're kicking off we have kicked off our collaboration with insight and I think we are in the.

In the design phase of putting those trials together and so we will have more to say in future calls.

But we hope one or more trials are initiated this year in combination with one or more of their their JAK.

JAK inhibitors, we haven't specified they havent specified as to which ones are as of yet but stay tuned.

Okay, great. Thank you very much.

Thank you.

Yigal Nochomovitz: Okay, great. Thank you very much. Thank you. Thank you. Our next question comes from Justin Walsh of the Raleigh Securities. Please proceed. Hi, thanks for taking the questions. I know that BEAT AML has a pivotal portion, but I was wondering if you can provide some comments on how Augment 102 and Intercept could lead to label expansions.

Thank you. Our next question comes from Justin Walsh of B Riley Securities. Please proceed.

Hi, Thanks for taking my questions.

I know that beat AML has been pivotal portion, but I was wondering if you can provide some comments on how augment 100 102 in intercept could lead to label expansions specifically do you think that the data for these trials could support an expansion on their own or or maybe just inform the design of larger trials.

Justin Walsh: Specifically, do you think that the data for these trials could support an expansion on their own or maybe just inform the design of larger trials? Yeah, thanks for the question, Justin. I'll turn it to Briggs once again.

Yes. Thanks for the question, Justin I'll turn it to break us once again.

Briggs Morrison: Yeah, though, Justin, I think the second two are more to inform future trials, it's getting a dose for the combination with chemotherapy in the refractory setting. And I think intercept will give us a sense of what the MRD positive to MRD negative conversion rate is, which will allow us to sort of power a definitive trial. Got it.

Yeah, Justin I think.

Two or more to inform future trials, it's getting a dose.

For it.

The combination with chemotherapy in the refractory setting and I think intercept will give us a sense of what the <unk> positive to <unk> negative conversion rate is which will allow us to sort of power a definitive trial.

Justin Walsh: Thanks. One more question for me. You mentioned the potential benefits of being first to market with a novel drug. It's pretty obvious, but can you maybe provide some color on how you plan to lay the groundwork to take maximum advantage of this?

Got it thanks, one more question for me.

The you mentioned the potential benefits of being first to market with a novel drug it's pretty obvious but can you maybe provide some color on how you plan to lay the groundwork to take maximum advantage of this and.

Sort of related to that any thoughts on any potential label differences between your asset in any fast follower men and MLR inhibitors that could come to the market.

Justin Walsh: And sort of related to that, any thoughts on any potential label differences between your asset and any fast follower MEN and MMLR inhibitors that could come to the market? Yeah, thanks, Justin. Great questions.

Yes, Thanks, Josh great questions.

In terms of label differences I think it's a little early I will just take that question first it's a little early to be speculating about label.

And how our molecule may be different than our competitors I think at this stage. We're the only ones that have really shown much data.

In the clinical setting and so I think we need to kind of wait and see what.

Michael Metzger: In terms of label differences, I think it's a little early. I'll just take that question first. It's a little early to be speculating about label and how our molecule may be different than our competitors. I think at this stage, we're the only ones that have really shown much data in the clinical setting. And so I think we need to kind of wait and see what others show and how our drug continues to develop. But needless to say, I think we're in a very favorable position.

What others show and how are and how our drug continues to develop but needless to say I think we're in a very favorable position and in terms of.

Seizing the opportunity to expand I think we made comments and then I think.

<unk> become accustomed to us hearing about the the different trials, we're doing in the frontline in the maintenance setting I think strategy here is obviously to get the drug approved in relapsed refractory disease.

Michael Metzger: And in terms of seizing the opportunity to expand, I think we made comments, and then I think you've become accustomed to us hearing about the different trials we're doing in the frontline and the maintenance setting. I think strategy here is obviously to get the drug approved in relapsed refractory disease, expand into the frontline setting in combinations. I think what's very nice about our molecule is that you can add our drug onto regimens.

Span into the frontline setting and combinations I think what's what's very nice about our molecules that you could add our drug onto regimen, and we hope to be able to add it onto regimens that already exists.

To be able to accommodate the MLR NPM one.

A mutation types and so.

The opportunity to add to the frontline in the frontline setting and then recapture.

Patients in the maintenance setting and perhaps keep them on drug for.

A long period of time in order to keep their disease at Bay.

That's the vision, we have for this molecule and so we're going to continue to do those trials and look at combinations that position us both.

Michael Metzger: We hope to be able to add it onto regimens that already exist to be able to accommodate the MLR or NPM1 mutation types. And so the opportunity to add in the frontline setting and then recapture patients in the maintenance setting and perhaps keep them on drug for a long period of time in order to keep their disease at bay, that's a vision we have for this molecule. And so we're going to continue to do those trials and look at combinations that position us both in the unfit frontline setting is perhaps the fit as well, and then moving in parallel into the maintenance setting.

In the unfit front.

Frontline setting is perhaps the fit as well and then move in parallel into the maintenance setting I'll also note that.

Michael Metzger: I'll also note that one important feature of the phase two pivotal trials that we're running now is that patients can go back on therapy after going through stem cell transplant. And that will be an opportunity to see how patients do in the, call it, maintenance setting, although we'll have to run, and I think we said before, we'll be running additional maintenance trials. But it will give us an early look into how patients do post-transplant and perhaps give an indication of how long they can actually stay on treatment, which we expect to be, we hope, quite a long period of time. So that's just a general, I think, that's a general landscape of how we'll be approaching this. Great, thanks for taking the questions. Thank you, Justin.

One important feature of the phase two pivotal trials that we're running now is that patients can go back on therapy after <unk>.

Going through stem cell transplant and that will be an opportunity to see.

How patients do in call it maintenance setting, although we will have to run and I think we've said before we will be running additional maintenance trials, but it will give us an early look into.

How patients do post transplant, and perhaps give an indication of how long they can actually stay on treatment, which we expect to be.

We hope quite quite a long period of time so.

That's just a general I think the general landscape of how we'll be approaching.

Great. Thanks for taking the question.

Thank you Justin.

Justin Walsh: Thank you. Our next question comes from Joel Beatty of Baird. Please proceed. Hi, thanks for taking the questions.

Thank you. Our next question comes from Joel Beatty of Baird. Please proceed.

Joel Beatty: First one is on the registrational trial of 5613. Just to clarify, what happens now when a patient screens for enrollment but is not on a CYP3A4? They're allowed to be admitted to the trial. Thanks, Joel, for the question. They're allowed to be admitted to the trial.

Hi, Thanks for taking the questions.

First one is on the Registrational trial of $56 13, just to clarify what happens now when a patient screening for enrollment, but it is not on a set three or four.

They're allowed to be admitted to the trial. Thanks Joel for the question.

Michael Metzger: I think there's no change to that. I think the point being that we're not holding spots for patients who are not on a strong CYP3A4 inhibitor. In fact, we're enrolling almost on a first-come, first-served basis. It just so happens that the vast majority of patients are on a strong CYP3A4 inhibitor. So I think the idea is that it might be a little bit slower to enroll patients who are not on a strong CYP3A4 inhibitor in the scheme of this trial. And that's what I meant by my remarks. We're not prioritizing them versus others who are on a strong CYP3A4 inhibitor. And there is in no way an impact on our ability to complete the trial.

They are allowed to be admitted to the trial I think.

There is no change to that I think the point being that we are we're not holding spots for patients who are not on a strong set three or four inhibitor in fact were enrolling.

Almost on a first come first serve basis for and it just so happens that the vast majority of patients are on a strong set of <unk> four inhibitor. So.

I think the idea is that it might be a little bit slower to enroll patients who are not on a strong Q3 <unk> four inhibitor in the scheme of this trial and Thats what I meant by my remarks, we're not we're not prioritizing them versus others.

Who are on a strong set three or four inhibitor.

There is no way and impact on our ability to complete the trial, it's more of a.

Michael Metzger: It's more of a submission issue and a labeling issue for dose adjustment that we're going to have to figure out in the course of the next while as the trial continues what those ClinPharm questions and answers are. So that's the kind of long-winded answer to your question. For Exotillumab, how much dose finding work needs to be done for the IPF setting versus jumping right into a more robust study of efficacy? Yeah, that's a great question.

Submission issue than a labeling issue for dose adjustment that we're going to have to figure out in the course of the course of the next while as the trial continues.

What those clean pharm questions and answers are so that's the.

The kind of long winded answer to your to your question.

Got it I appreciate it that makes sense.

For <unk>.

Dose finding work needs to be done for the IPF setting versus jumping right into <unk>.

More of a robust study of efficacy.

Yes, that's a great question, maybe I'll ask Briggs to comment there.

Joel Beatty: Maybe I'll ask Bragg to comment there. Yeah, so thanks, Joel. The current thinking, which again, we'll have to validate with the FDA when we finalize the protocol, is that we would not do dose ranging in the IPF trial. We would take a dose that we think gives us maximal pharmacodynamic effect. So as you know, in Agave 201, there are three different arms, the point three, the one and then the three every four weeks.

So thanks.

Thanks, Joe.

The current thinking which again, we will have to validate with the FDA to finalize the protocol.

Is that we would not do dose ranging in the IPF trial, we would take a dose that we think gives us maximal pharmacodynamic effect.

So as you know.

One there are three different arms. The 0.3, the one and then the three every four weeks.

Briggs Morrison: So the 1 mg per kg, as you saw in our ass data, looks like a very, very good dose. It gives us optimal PKPD, very good efficacy. So the current thinking is that we would not do dose ranging. We would just simply do a proof-of-concept trial at roughly that dose. So, again, we'll say more about that once we have that finalized.

<unk> as you saw.

And our AST data it looks like a very very good dose gives us optimal PK PD very good efficacy. So the current thinking is that we would not do dose ranging we were just simply do a proof of concept trial.

At that roughly that dose.

Again, we'll say more about that once we have that finalized but our view is that's a really good dose to be able to test the concept and obviously if the trial's positive there may need to be similar to agave.

Briggs Morrison: But our view is that's a really good dose to be able to test the concept. And, obviously, if the trial is positive, there may need to be similar to a GAVI-201, some additional regulators may want some dose ranging. But I think for us it's a proof-of-concept trial where we would just take one dose. Great, thank you. Thank you, Joel.

200, <unk> some additional because regulators may want some dose regimen, but I think for us. It's a proof of concept trial, where we will just take one dose.

Great. Thank you.

Thank you Joe.

Joel Beatty: Thanks. Thank you. Our next question comes from Peter Lawson of Barclays.

Thank you. Our next question comes from Peter Lawson with Barclays.

Peter Lawson: Please proceed. Thanks for taking the questions. Thanks for all the updates. Just around the CYP3A4 strong, weak arms, how many patients would you need that aren't on a strong CYP3A4 inhibitor for refining? Yeah, maybe I'll ask Briggs.

Please proceed.

Thanks for taking the questions.

Thanks for the updates just just around the <unk> four strong.

How many would you need.

How many patients would you need.

On a strong situational inhibitor for a filing.

Briggs Morrison: Thank you for the question, Peter. Let me ask Briggs to answer that. Right, so, so Peter, the question is, you know, how many patients worth of data at a dose that we feel comfortable saying that there is sufficient PK to, you know, label? We think it's probably in the, you know, let's call it 12 to 15 range of not on a strong CYP3A4 inhibitor, and then a separate group that's on a moderate, As Michael pointed out, the pivotal trial at this stage, they'll all be on a strong inhibitor. So it's a question of probably in the 12th to 15th should give us enough understanding of the PK to be able to to inform the, Okay, how is that, is that, how's that tracking?

Yes, maybe I'll.

Ill ask Briggs. Thank you for the question, let me ask Briggs to answer that.

Right. So so Peter.

The question is how many patients worth of data at a dose that we feel.

If you're comfortable saying that there is sufficient PK too.

Label.

We think it's probably in the.

Let's call. It 12 to 15 range of not on a strong set three or four inhibitor and then a separate group that's on a moderate.

As Mike pointed out the pivotal trial.

At this stage they will all be on a strong inhibitor.

So it's a question of probably in the 12 to 15 should give us enough understanding of the PK to payable to inform the dose.

Okay.

Is that how is that tracking.

Briggs Morrison: As Michael said, I think our decision was that we're prioritizing enrollment of the registration trial. The main reason to prioritize enrollment of the registration trial is so that we have good durability data, right? Because once we finish enrolling all of those patients, then it's six months after the last patient is when we do the data cut, and we'd like to have as much durability as possible for labeling purposes. So, at this point, the preference is, the focus is, the decision is, put people on who are on a strong separative heart inhibitor, and don't worry about the non or the moderates. Once at least one cohort is fully enrolled, then that patient population where we've already fully enrolled, we will then enroll additional patients with the non or a non or a moderate.

Is that significant.

Right, Yes, so as Michael said I think our decision was that.

Sure.

Prioritizing the enrollment of the registration trial and the main reason to prioritize enrollment or the registration trial is so that we have good durability data right because once we finish enrolling all of those patients.

And at six months after the last patient is when we do the data cut and we'd like to have as.

As much durability as possible for labeling purposes. So at this point the preference is put it as a focus as the decision is put people on Orion Shrontz hit harder and don't worry about the non or the moderates once that at least one cohort is fully enrolled then that patient population.

Where we've already fully enrolled we will then enroll additional patients.

With the non core.

None or a moderate so I'm not sure if it's to your question if it ahead or behind but we've.

Briggs Morrison: So, I'm not sure if it's, to your question, if it's ahead or behind, but we've made a strategic decision that we're going to prioritize getting everybody in onto the pivotal trial because that will allow us to get the durability that we need. Thank you. Would physicians have a problem as putting a patient on a strong CYP3A4 inhibitor, even if they didn't require it? So you kind of had a, almost like a label.

<unk>.

Made a strategic decision that we're going to prioritize getting everybody in onto the pivotal trial.

That will allow us to get.

The durability of that we need.

Thank you.

<unk> have a problem.

Putting a patient on a strong <unk> four inhibitor, even if they didn't require so you kind of had a almost like a later right that's right.

Peter Lawson: That's right. That's right. So right now, actually, there are patients who come into the trial who are not on a strong, and in order to get onto the trial, right now, they need to be on a strong. So the physician just switches them. But it's actually not that many.

Right. So right now actually there are a lot of patients who come into the trial, who are not on a strong and they can then and in order to get onto the trial right now they need to be honest strong. So this isn't just switches.

Actually not that many most of the patients whatever the bora all opposed to kind of call. It seemed to be the preferred agents anyhow. So most patients are already on a strong four inhibitor, but.

Briggs Morrison: Most of the patients, whatever the boraconazole and posaconicol seem to be the preferred agents anyhow. So most patients are already on a strong CYP3A4 inhibitor. But every physician we've talked, every investigator on the trial has said, well, they need to be on a strong inhibitor to go on. I'll put them on a strong inhibitor.

Briggs Morrison: Not a problem. Perfect. Thank you. And then just kind of a final question around the strong weak 634.

Every physician we've talked every.

Investigator on the trial has said.

They need to be on a strong inhibitor to Golan I'll put them on a strong inhibitor not a problem.

Peter Lawson: The beat, the augment 102 and the intercept, does that, Have a requirement or will I have a requirement for a strong CYP3A4 inhibitor? Right, so for BDAML and 702 right now, again, because the dose that we have agreement with the FDA is a with a strong inhibitor, those patients will be on and again, that's that standard of care in in those populations. Because they're, you know, similarly get put on on antifungal.

Perfect. Thank you and then just kind of a final question around the strong weeks of straightforward.

Pete.

The augment one or two.

Intercept is debt.

Have a requirement or will they have a requirement for strong <unk> four inhibitor.

Briggs Morrison: In the intercept trial. It's not a requirement that they'd be on a strong CYP3A4 inhibitor that these are patients who are in morphologic remission. And so they actually don't need, necessarily need an azole.

Right so for <unk> and 702, right now again, because the dose that we have agreement with the FDA is with a strong inhibitor those patients will be on and again, that's that standard of care.

As populations.

Because they are similarly get put on an antifungal.

In the intercept trial.

It's not a requirement that they would be on a strong set three <unk> four inhibitor that these are patients who are in morphologic remission.

And so they actually don't need necessarily need today is also that one.

Briggs Morrison: So that one, you know, where there's an option to be on the trial without being on a strong inhibitor. Right. Okay. Thanks so much. Thanks for all the details.

Sure.

There is an option to be on the trial.

Without being on a strong inhibitor.

Great. Okay. Thanks, so much thanks for the details.

Peter Lawson: Thank you, Peter. Thank you. I would now like to turn it back to Michael Metzger for closing remarks. Great. Thank you, Dede. Thank you. And thank you to everybody who participated on the call today. We look forward to seeing many of you at the upcoming conferences in March. I know there are a handful of those.

Thank you Peter.

Thank you I would now like to turn it back to Michael <unk> for closing remarks.

Great. Thank you. Thank you and thank you to everybody who participated on the call today.

We look forward to seeing many of you at the upcoming conferences in March I know there are a handful of those and.

Michael Metzger: And with that, I wish you all a very, very nice evening. This concludes today's conference call. Thank you for participating and you may now disconnect.

And with that I wish you all a very very nice evening.

This concludes today's conference call. Thank you for participating and you may now disconnect.