Q3 2021 Syndax Pharmaceuticals Inc Earnings Call

November 15, 2021

Good day and thank you for standing by welcome to just index third quarter 2021 conference call.

Operator: Thank you for standing by. Welcome to the Syndax 3rd Quarter 2021 conference call.

Operator: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. If you require any further assistance, please press star zero. I would now like to hand the conference over to your first speaker today, Melissa Forst, with Argo Partners. Thank you, and please go ahead.

At this time all participants are in a listen only mode.

After the speaker presentation, there will be a question and answer session basket question. During the session you will need to press star one on your telephone.

If you require any further assistance please press star zero.

I would now like to hand, the conference over to your first speaker today, Melissa Forst with Argot partners. Thank you. Please go ahead.

Melissa Forst: 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 third quarter 2021 financial and operating results. With me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer, and Michael Metzger, President and Chief Operating Officer. Also joining us on the call today for the question and answer session are Dr. Michael Myers, Chief Medical Officer, Dr. Peter Ordentlich, Chief Scientific Officer, and Dr. Anjali Ganguli, Chief Business Officer.

Thank you operator, welcome and thank you to those of you joining us on the line and the webcast. This afternoon for the list index at third quarter, 'twenty, 'twenty, one financial and operating results.

With me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer, and Michael Metzger, President and Chief operating Officer.

Also joining us on the call today for the question answer session is Dr. Michael Meyers, Chief Medical Officer, Dr. Peter <unk>, Chief Scientific Officer, and Dr. Enjoy couldn't gulli Chief business Officer.

Melissa Forst: This call is being accompanied by a slide deck that has been posted on the company's website, so I would ask that you please turn to the 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 Security Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors.

This call is being accompanied by a slide deck, but it's been posted on the company's website.

I ask that you. Please turn to the 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. This includes those discussed in the risk factors section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC.

Melissa Forst: This includes those discussed in the risk factors section of the company's most recent quarterly reports on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements represent the company's views as of today, November 15, 2021, only. A replay of this call will be available on the company's website following the call. And with that, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer.

Any forward looking statements represent the company's views as of today November 15th 2021, hopefully.

This call will be available on the company's website following the call and with that I'm pleased to turn the call over to Dr. Briggs Morrison Chief Executive Officer.

Dr. Briggs Morrison: Great, thank you very much Melissa, and thank you to everyone who's joining us on today's call and the webcast. Slide 3 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. Our prepared comments are a bit more extensive today than some of our prior calls, and that is because this has really been a breakout quarter for us, and we'd like to ensure investors have a full view of our progress. We can really feel the momentum building in our country.

Okay. Thank you very much Melissa and thank you to everyone who is joining us on today's call and the webcast.

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

Our prepared comments are a bit more extensive today than some of our prior calls and that is because this has really been a breakout quarter for us we'd like to ensure investors have a full review of our progress we can really feel the momentum building in our company.

Dr. Briggs Morrison: We continue to advance both of our clinical programs, and both were selected for oral presentations at ASH this year. Augment 101, our Phase 1-2 trial of SNDX5613, our selective menin inhibitor, has progressed as anticipated. We're pleased to announce today that our three pivotal Phase II trials for SMDX5613, which we call Augment 101 Cohorts 2A, 2B, and 2C, are now open and enrolling patients after we obtained important agreements from FDA. Notably, we were the first to demonstrate clinical validation of targeting menin for acute leukemias, and now ours is the first program to advance to registration-oriented trials.

We continue to advance both of our clinical programs and both were selected for oral presentations at Ash This year.

Augment 101, our phase one two trial of S. N D X 50, 613, our selective <unk> inhibitor has progressed as anticipated.

We're pleased to announce today that our three pivotal phase III trials for F&B X 56000 team, which we call augment 101 cohort to a to B to C are now open and enrolling patients. After we obtained important agreement from FDA.

Notably we were the first to demonstrate clinical validation of targeting menin for acute leukemias and now ours is the first program to advance to registration oriented trials.

Dr. Briggs Morrison: For Axitilumab, our antibody against CSF-1R, enrollment is ongoing in our pivotal Agave 2-in-1 trial, and we are immensely gratified that we have Insight as a fabulous partner to maximize the value of this important program. We therefore now have two registrational programs ongoing for two first-in-class, potentially best-in-class medicines for two areas of important unmet medical needs. Thanks to the support of our many committed investors, we are well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline. Let's now turn to slide 4 and update you on where we are with SNDX5613.

For <unk>, our antibody against CSF, one our enrollment is ongoing in our pivotal agave to a one trial and we are immensely gratified that we have inside is a fabulous partner to maximize the value of this important program.

We therefore now have two registrational programs ongoing for two first in class potentially best in class medicines for two areas an important unmet medical need.

Thanks to the support of our many committed investors we are well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline.

Let's now turn to slide four and update you on where we are with S&P X 50 613.

Dr. Briggs Morrison: We have completed the Phase 1 portion of Arm B of Augment 101 and have agreement from FDA on key aspects of our go-forward clinical development plan. First, we have now opened three single-arm Phase II trials that FDA has agreed may each serve as a pivotal trial. Each of these single-arm phase 2 trials represents an independent path to a separate indication. Augment 101 Cohort 2A will enroll patients with relapsed refractory MLLR-

We have completed the phase one portion of RMB of augment 101 and have agreement from FDA on key aspects of our go forward clinical development plan.

First we have now opened three single arm phase two trials that FDA has agreed may each serve as a pivotal trial.

Each of these single arm phase II trial represents an independent path to a separate indication.

101 cohort two will enroll patients with relapsed refractory MLR a L L.

Dr. Briggs Morrison: Cohort 2B will enroll patients with relapsed refractory MLAML, and cohort 2C will enroll patients with relapsed refractory NPM1AML. Each trial is open to patients aged one month or older, and each trial will enroll independent of the other two.

Cohort two b will enroll patients with relapsed refractory AML or AML and to see will enroll patients with relapsed refractory N P. M. One AML.

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

Dr. Briggs Morrison: 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 other, or we may seek initial regulatory approval for any two or all three, just depending on when they complete enrollment. Needless to say, we are thrilled to have advanced the program into these initial pivotal trials. We anticipate being the first company to achieve regulatory approval for a menin inhibitor, and today's announcement regarding the advancement of the program increases our confidence that we will do so. We have agreement with FDA that for each trial, the primary endpoint will be the percentage of patients achieving CR plus CRH, with secondary endpoints including durability of CR-CRH responses, Transfusion Independence, Overall survival, and tolerability.

We may seek initial regulatory approval for <unk> Dx 50, 613 based on the results of any one of these trials should one trial enrolled faster than the others.

Or we may seek initial regulatory approval for any two or all three just depending on when they complete enrollment.

Needless to say, we are thrilled to advance have advanced the program into these initial pivotal trials.

We anticipate being the first company to achieve regulatory approval for amended inhibitor and today's announcement regarding the advancement of the program increases our confidence that we will do so.

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

Overall survival and Tolerability.

Importantly, the trial design allows patients to be treated.

Yeah.

With S N D X 50, 613th after a bone marrow transplant.

Dr. Briggs Morrison: And most importantly, the trial design allows patients to be treated with SNDX5613 after a bone marrow transplant. The Design Feature that allows us to start to understand the role of 5613 in the post-transplant setting. We also have agreement with FDA on the statistical design of each trial.

Design feature that allows us.

To start to understand the role of 50 613.

In the post transplant setting.

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

Each trial will enroll 64 adult patients in up to 10 pediatric patients.

Finally, we have agreement with FDA that our recommended phase II dose of 163 milligrams every 12 hours given with any strong Sip through 84 inhibitor is inappropriate phase two dose and that is the dose we're taking forward in each trial.

Dr. Briggs Morrison: Each trial will enroll 64 adult patients and up to 10 pediatric patients. Finally, we have agreement with FDA that our recommended phase 2 dose of 163 mg PO every 12 hours, given with any strong CYP3A4 inhibitor, is an appropriate phase 2 dose, and that is the dose we are taking forward in each trial. We know that the majority of eligible patients are on a strong 5th or A4 inhibitor. We'll be finalizing our phase two arm A dose over the next few months and anticipate being able to enroll patients who are not on a strong CYF3A4 inhibitor as our three pivotal trials proceed.

We know that the majority of eligible patients are on a strong 54 inhibitor.

Be finalizing our phase two arm a dose over the next few months and anticipate being able to enroll patients who are not on a strong set three <unk> four inhibitor. That's our pivotal three pivotal trials proceed.

I want to again reinforce that we are incredibly excited about what we have seen in our phase one program on November 4th Ash released an abstract that summarized our data as of June 29 of this year, which we briefly summarized on slide five.

Let me first remind everyone that this is a phase one trial.

Dr. Briggs Morrison: I want to again reinforce that we are incredibly excited about what we have seen in our Phase 1 program. On November 4th, ASH released an abstract that summarized our data as of June 29th of this year, which we briefly summarize on slide 5.

Since had received on average three prior therapies and about 40% had relapsed after bone marrow transplant very negative prognostic sign and almost 60% had previously received a frenetic class.

Very difficult to treat patients and we were delighted to report in the abstract a 44% overall response rate of 22% CR Cri rate and 70% of the responses were M. R D negative, meaning using the most sensitive assays available.

Dr. Briggs Morrison: Let me first remind everyone that this is a phase one trial. Patients had received, on average, three prior therapies, and about 40% had relapsed after a bone marrow transplant, a very negative prognostic sign, and almost 60% had previously received a phonetic therapy. These are very difficult to treat patients, and we were delighted to report in the abstract a 44% overall response rate, a 22% CR-CRH rate, and 70% of the responses were MRD negatives, meaning using the most sensitive assays available.

There was no detectable leukemia after treatment with ethane person Dx 50 613.

Despite having only a median of 3.2 months of follow up the initial estimate of durability of the CR CRH responses was five two months and that did not include any patients who had gone on to transplant.

We are finalizing our ash presentation, which represents an additional approximately three months of follow up and.

And we remain excited about breaking out the efficacy data by mutational status and to present, the updated durability of CRH CR CRH responses with patients who went on to transplant. Additional details will presented presented by Dr. <unk> Stein and his oral presentation on Monday December 13th.

Dr. Briggs Morrison: There was no detectable leukemia after treatment with SNDX5613. Despite having only a median of 3.2 months of follow-up, the initial estimate of durability of the CR-CRH responses was 5.2 months, and that did not include patients who had gone on to transplant.

Beyond the augment pivotal program in relapsed or refractory disease slide six highlights some of the additional opportunities. We are exploring with F. N. D X 50, 613, all of which build on the excellent safety and efficacy profile, we have thus far seen with the molecule.

The panel on the left highlights the trial, we are planning in collaboration with the leukemia and lymphoma society, otherwise known as L. L. S. They have selected S. N. D. X 50, 613 is the first menin inhibitor to be tested as a specific targeted therapy for patients with MLR in N. P. M on AML in their umbrella trial that they called beat.

Dr. Briggs Morrison: We are finalizing our ASH presentation, which represents an additional approximately three months of follow-up, and we remain excited about breaking out the efficacy data by mutational status and presenting the updated durability of CR-CRH responses in the patients who went on to transplant. Additional details will be presented by Dr. Eytan Stein in his oral presentation on Monday, December 13. Beyond the Augment Pivotal Program in Relapse or Refractory Disease, slide six highlights some of the additional opportunities we are exploring with SNDX5613, all of which build on the excellent safety and efficacy profile we have thus far seen with the model.

To pay them out.

The collaboration that we have agreed to with them will test 50, 613 in combination with Panetta Klaxoning decided in newly diagnosed AML patients that 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 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 a trial to explore the use of 50 613 in combination with standard salvage chemotherapy is used for pediatric patients with a L. L. R. A M L that we're calling <unk>.

One O two.

Dr. Briggs Morrison: The panel on the left highlights a trial we are planning in collaboration with the Leukemia and Lymphoma Society, otherwise known as LLS. They have selected SNDX5613 as the first menin inhibitor to be tested as a specific targeted therapy for patients with MLLR and NPM1 AML in their umbrella trial that they call BEAT-AML. The collaboration we have agreed to with them will test 5613 in combination with benetoclax and nasacitidine in newly diagnosed AML patients that 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 regulatory dossiers. Our scientists have generated preclinical data that supports the benefit of menin inhibition in combination with chemotherapy.

And the panel on the right illustrates a new trial that explores the activity of 50 613 in patients with AML, who have M. R. D positive disease. This trial is being conducted as part of the intercept master clinical trial being led by the Australian leukemia and lymphoma group in.

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

The trial will enroll patients with measurable measurable residual disease progression. Following their initial treatment group of patients who are at very high risk of relapse and represents an important unmet medical need.

I think I have mentioned previously 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 therapy intercept trial as an innovative approach to treating patients early in their disease course, I will also note that S&P X 56000.

This is the first met inhibitor to be included in the intercept a master clinical trial. We believe in the selection of 50 613 for inclusion in two master clinical trial protocols highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with our compound.

Dr. Briggs Morrison: 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 new trial that explores the activity of 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. Intercept is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML.

We anticipate announcing additional trials over the next six to 12 months that will further build out that 50, 613 franchise and as I mentioned earlier the registration cohorts of augment 101 will allow for patients to be dosed post transplant, providing an early look and setting the stage for future trials in the maintenance setting.

As I mentioned on our second quarter earnings call. This past August we are excited to expand the clinical opportunities for 50 613 beyond the initial approval in relapsed or refractory leukemias slide seven highlights our goal as a company to be first to market in relapsed refractory disease, and then to be first to garner additional.

Our value driving indications by expanding the use of 56 or team into newly diagnosed patients and into the maintenance setting in patients with both MLR and N. P. M. One acute leukemia.

Dr. Briggs Morrison: The trial will enroll patients with measurable residual disease progression following their initial treatment, a group of patients who are at very high risk of relapse and represents an important unmet medical need. As I think I have mentioned previously, 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 patients stay on therapy.

We are taking our first steps towards building out the franchise through the collaborations with LLS to explore in newly diagnosed patients.

And with.

Australia leukemia group of patients with AML, who have M already positive disease. Despite their initial standard of care treatment.

Let me now turn to slide eight and I can tell him at our potentially best in class monoclonal antibody therapy targeting the CSF one receptor.

Dr. Briggs Morrison: The Intercept trial is an innovative approach to treating patients early in their disease; I will also note that SNDX5613 is the first meta-inhibitor to be included in the Intercept Master Clinical Trial. We believe the selection of SNDX5613 for inclusion in two Master Clinical Trial Protocols highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with our campaign. We anticipate announcing additional trials over the next 6 to 12 months that will further build out the 5613 framework.

We were delighted to announce that syntax insights have entered into a broad long term global collaboration that brings together two companies with a solid track record of innovation to accelerate and maximize the development of acts to tell them that.

As you know we presented our phase <unk> Gvhd data last year at Ash in December the reaction to our data was extremely positive and given our belief in the broad clinical potential of actually tell them that we initiated a process to look for a global partner to collaborate with us on further development of this exciting molecule.

To briefly recap the agreement the deal provides $152 million upfront $117 million in cash and notably $35 million of equity at a 30% premium which we believe is a strong endorsement of our company and its overall value proposition.

Dr. Briggs Morrison: And, as I mentioned earlier, the registration cohorts of Augment 101 will allow patients to be dosed post-transplant, providing an early look and setting the stage for future trials in the main. As I mentioned on our second quarter earnings call this past August, we are excited to expand the clinical opportunities for 5613 beyond the initial approval and relapse-refractory leukemia. Slide 7 highlights our goal as a company to be first to market in relapsed refractory disease and then to garner additional value-driving indications by expanding the use of 5613 into newly diagnosed patients and into the maintenance setting in patients with both MLLR and NPM1 acute leukemia.

The 50 50 profit split in the U S enables us to retain significant upside and actively participate long term in the franchise build out the $45 55 per cent cost sharing mechanism limits, our downside and extends our cash for.

So the opportunity for co commercialization in the U S will allow us to participate in the launch of an important product alongside a strong commercial partner.

Side the U S. We will rely on insight to develop and launch the product in all the major markets to maximize its full potential as a global brand.

The economics to send out over the course of the collaboration are enhanced with key regulatory and sales milestones covering multiple indications throughout the world the payments totaling an additional $450 million and syntax receive double digit royalties ex U S.

Also important to highlight just a development plan, which calls for the partners to design novel combinations with Axa tell them at and insights JAK inhibitors with the goal of establishing half the telematic earlier settings within chronic graft versus host disease and expanding its market opportunity.

Dr. Briggs Morrison: We are taking our first steps towards building out the franchise through the collaborations with LLF to explore in newly diagnosed patients, and with the Australian Leukemia Group in patients with AML who have MRD-positive disease despite their initial standard of care. Let me now turn to slide 8, enacted pilumab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor. We are delighted to announce that Syndax Insight has entered into a broad, long-term 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 I GVHD data last year at ASH in December.

As we previously mentioned was our attention its index will initiate a POC trial in interstitial pulmonary fibrosis. The first expansion outside of establishing chronic graft versus host disease, that's a beachhead into other fibrotic diseases.

I'll be back to tell them that could have a significant impact.

Significant successful development of IPF can lead to an additional approval in a very important indication of considerable value and would provide support for <unk> until I'm, having other fibrotic diseases.

Marty could explore over the course of the collaboration.

As you know our ash abstract for ash to tell them that also recently published and slide nine is a brief summary of that data.

Dr. Briggs Morrison: The reaction to our data was extremely positive, and given our belief in the broad clinical potential of Axopilimab, we initiated a process to look for a global partner to collaborate with us on further development of this exciting molecule. To briefly recap the agreement, the deal provides $152 million upfront, $117 million in cash, and notably $35 million in equity at a 30% premium, which we believe is a strong endorsement of our company and its overall value proposition.

We're 40 patients enrolled who had received a median of four prior therapies at the one milligram per kilogram dose given every two weeks, which we anticipate will be a labeled dose the drug was well tolerated and we saw an overall response rate of 75%.

We believe this is a kind of a material dataset that significantly de risks our ongoing registration trial.

Additional details will be presented by doctors definitely and her oral presentation on Saturday December 11th.

Slide 10 is our pivotal trial for acetyl I'm, having chronic graft versus host disease. This is this trial at the telematics for chronic versus host disease trial called the agave to own one.

Dr. Briggs Morrison: The 50-50 profit split in the U.S. enables us to retain significant upside and actively participate long-term in the franchise build-out. The 45-55% cost-sharing mechanism limits our downsides and extends our reach. And the opportunity for co-commercialization in the U.S. will allow us to participate in the launch of an important product alongside a strong commercial partner. Outside the U.S., we rely on Insight to develop and launch the product in all the major markets to maximize its full potential as a global brand.

The trial is enrolling patients with chronic graft versus host disease, 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 the pivotal dose ranging trial in which patients will be randomized to one of three treatment groups. Each investigating a distinct dose back to tell them and give them either.

Every two weeks or every four weeks.

The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft versus host disease.

Dr. Briggs Morrison: The economics of Syndax over the course of the collaboration are enhanced with key regulatory and sales milestones covering multiple indications throughout the world. The payments total an additional $450 million, and Syndax receives double-digit royalties excugated. Also important to highlight is the development plan, which calls for the partners to design novel combinations with axopilimab and Insight's JAK inhibitors with the goal of establishing axopilimab at earlier settings within chronic RAF or SOAS disease and expanding its market opportunities.

Secondary endpoints will include duration of response and validated quality of life assessments using deadly symptoms scale.

Enrollment to the study is underway and we are on track to deliver top line data in 2023.

Slide 11 highlights our view of the broad clinical and commercial opportunity for <unk> to tell them that we believe chronic graft versus host disease represents a high unmet medical need and an important commercial opportunity with approximately 14000 patients suffering from chronic graft versus host disease in the U S. Today.

Recent approvals of insights Jakafi and cadman, probably most of the deal will begin to delineate the commercial opportunity in this disease.

Dr. Briggs Morrison: As we previously mentioned was our intention, Syndax will initiate a POC trial in interstitial pulmonary fibrosis, the first expansion outside of establishing chronic graft-versus-host disease as a beachhead into other fibrotic diseases where we believe axitilumab could have a significant impact. Significant successful development in IPS could lead to an additional approval and a very important indication of considerable value and would provide support for axotilumab and other fibrotic-driven diseases that the parties could explore over the course of the collaboration. As you know, our Ash Abstract for Acetylamide was also recently published, and slide 9 is a brief summary of that data.

Despite recent advances in this area to our knowledge ex tell them that is the only agent in some of the development that specifically targets. The monocyte macrophage lineage, both sendak and insight believes the debt data generated to date with actually tell them that suggests it has the potential to play an important role in the treatment of chronic graft versus host disease, both as monotherapy.

And given its safety profile in combination with other mechanisms.

As you move out to tell them that into additional indications starting with IPF, We really see act to tell them that contributing materially to the value of our company going forward.

Finally, slide 12 summarizes the transactions that led to the acquisition of both the men in and tell them that programs.

Dr. Briggs Morrison: There were 40 patients enrolled who had received a median of four prior therapies. At the one milligram per kilogram dose given every two weeks, which we anticipate will be our label dose, the drug was well tolerated, and we saw an overall response rate of 75%. We believe this is a material data set that significantly de-risks our ongoing registration trial. Additional details will be presented by Dr. Stephanie Lee in her oral presentation on Saturday, December 11th.

Believe these transactions underscore our robust capabilities to evaluate and identify high value differentiated assets as well as the clinical development expertise to bring these compounds through key value inflection points.

We anticipate we will be able to continue to expand our pipeline through product acquisitions or in licensing of quality differentiated assets.

Spec to remain among preferred partners of such transactions.

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

Thank you Briggs.

The results of our operations for the third quarter of 2021, and the comparison to the prior year quarter are included in our press release, So I won't repeat these remarks these them in our remarks.

Dr. Briggs Morrison: Slide 10 is our pivotal trial for axopilimab in chronic graft-versus-host disease. This trial is the basis for a chronic-versus-host disease trial called Agave 201. The trial is enrolling patients with chronic graft-versus-host disease whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met overall entry criteria.

Additional financial details are available in the third quarter report on Form 10-Q, which was filed earlier today.

I would like to point out that our net loss for the quarter was $20 6 million or 40 cents, a share compared to $24 million or <unk> 46 per share for the same period last year.

Turning to slide 13, we ended the third quarter with $229 $7 million in cash and cash equivalents and $52 2 million shares and pre funded warrants outstanding.

Dr. Briggs Morrison: 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 acetilumab given either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft-versus-hospitalization. Secondary endpoints will include duration of response and validated quality of life assessments using the least. Enrollment of the study is underway, and we are on track to deliver top-line data in 2023.

Cash balance does not include any proceeds related to the recently announced collaboration agreement with insight, we anticipate those payments would extend our cash runway into 2024 and support our expanded development plans for both the <unk> and <unk> programs. During this period looks.

Looking ahead.

I'd like to provide financial guidance for the full year of 2021 full year 2021 guidance remains unchanged and we continue to expect R&D expense to be $90 million to $100 million in total operating expense to be $110 million to $120 million. This includes approximately $13 million in noncash stock compensation.

Dr. Briggs Morrison: Slide 11 highlights our view of the broad clinical and commercial opportunity for accessibility. We believe chronic graft-versus-host disease represents a high unmet medical need and an important commercial opportunity, with approximately 14,000 patients suffering from chronic graft-versus-host disease in the U.S. today. The recent approvals of Insight's Jackify and Cadman's Velimosadil will begin to define the commercial opportunity in this disease. However, despite recent advances in this area, to our knowledge, Axitilumab is the only agent in clinical development that specifically targets the monocyte macrophage lineage.

That I would like to turn the call back over to Briggs.

Thank you very much Michael.

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 as a major achievement.

So very excited about the broad franchise opportunities for both programs beyond their initial registrational indications.

We believe 50 613 could have broad utility across a wide range of clinical settings acute leukemia.

Our goal as a company is to be the first to market in relapsed refractory disease, and then it would be first to garner additional value driving indications by expanding the use of 50 613 into newly diagnosed patients and at the maintenance settings.

Dr. Briggs Morrison: Both Syndax and Insight believe the data generated to date with axotilamide suggests it has the potential to play an important role in the treatment of chronic graft-versus-host disease, both as monotherapy and, given its safety profile, in combination with other mechanisms. As we move axotilamide into additional indications, starting with IPF, we really see axotilamide contributing materially to the value Finally, slide 12 summarizes the transactions that led to the acquisition of both the Mennon and Acetelimab programs.

Since both with MLR N P M. One.

Acute leukemias.

Fred and I have to tell them that also holds the promise of a broad franchise opportunity both in various lines of therapy in gvhd and across a broad range of fibrotic diseases, starting with Ips.

We're comfortable given our cash on hand that we have the financial resources to aggressively advance our programs and achieve upcoming milestones we will.

Remain optimistic that we can continue to identify and bring in novel molecules to deepen our portfolio.

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.

Dr. Briggs Morrison: We believe these transactions underscore our robust capabilities to evaluate and identify high-value differentiated assets, as well as our clinical development expertise to bring these compounds through key value inflections. We anticipate 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 in such transactions. I'll now turn the call over to Michael to review our financial results. Thank you, Briggs.

As always I would like to thank the 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 to build this great company.

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

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

Again, if he would like to ask a question. Please press Star then the number one on your telephone keypad.

Michael A. Metzger: The results of our operations for the third quarter of 2021 and the comparison to the prior year quarter are included in our press release, so I won't repeat them in our remarks. Additional financial details are available in the third quarter report on Form 10-Q, which was filed earlier today. I would like to point out that our net loss for the quarter was $20.6 million, or $0.40 a share, compared to $20.4 million, or $0.46 per share, for the same period last year.

Let me draw your question. Please press the pound key.

Standby well compile the Q&A roster.

Our first question comes from the line of sales not do of Cowen and co. Your line is now open.

Congrats on the progress and thanks for taking our questions just a couple from us. So first on the pivotal cohorts can you go into a little bit more detail why the non.

It has not been defined yet what else do you need to.

Could do to defend that dose is there additional patient experience, where you're expecting or feedback from FDA kind of what's the what's the rate limiting step and Tamara diameters.

I hope you all thanks very much for your question.

Michael A. Metzger: Turning to slide 13, we ended the third quarter with $229.7 million in cash and cash equivalents and 52.2 million shares and pre-funded warrants outstanding. The cash balance does not include any proceeds related to the recently announced collaboration agreement with Insight.

So I wont I cant emphasize that we are 163.

With any strong Sip three or four inhibitor is that an acceptable recommended phase two dose that we agreed to with FDA and that's the dose that's going forward.

We have two very good doses in arm, a $2 26, and $2 76, and what we think we need is a little bit more PK data on a few more patients to pick between those two to see which one most closely matches. The PK of the of the 163 with any strong set three or four inhibitor.

Michael A. Metzger: We anticipate those payments will extend our cash runway into 2024 and support our expanded development plans for both the Axa-Tilamab and the Mennon programs during this period. Looking ahead, I'd like to provide financial guidance for the full year of 2021. Full year 2021 guidance remains unchanged, and we continue to expect R&D expense to be $90 to $100 million and total operating expense to be $110 to $120 million. This includes approximately $13 million in non-cash stock compensation.

Perfect. That's very helpful and then second.

I'm not sure it can be willing to answer this question, but we're all curious in the ash presentation.

We have certainly we've all reviewed how many more patients will there be.

And in particular I think we're all focused on N. P. M on Fischer Barclays should give us some sense of how many.

Patients who are likely to be presented at ash.

I'm not sure I know off the top of my head how many additional patients there are compared to the abstract I don't know if Michael Myers do you know that.

It gets about five additional patients Briggs.

Michael A. Metzger: And with that, I would like to turn the call back over to you. Thank you very much, Michael. 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 as a major achievement. We're also very excited about the broad franchise opportunities for both programs beyond their initial registrational indication.

<unk>.

Okay, great. Thank you.

And the total number of NPM, one patient's Michael that'll be in the presentation.

That is in the presentation, yes.

No I think Phil it's asking how many total patients.

It'll N P M one patients whether it would be.

Alright, thank it's about 13 patients in it.

The in the presentation itself.

Great. Thank you.

Perfect. Your question Phil Yeah, that's very helpful. Thanks, so much for taking our questions.

Okay.

Yeah.

Our next question comes from the line of V go not some of it of Citi. Your line is now open.

Michael A. Metzger: We believe 5613 could have broad utility across a wide range of clinical settings in acute leukemia. Our goal as a company is to be the first to market in relapsed refractory disease, and then to garner additional value-driving indications by expanding the use of 5613 into newly diagnosed patients and into maintenance settings, patients both with MLLR and NPM1 acute leukemia. Frit, and Axotilumab also holds the promise of a broad franchise opportunity, both in various lines of therapy in GVHD and across a broad range of fibrotic diseases, starting with IPF.

Pardon me. This is the Oxford Mubarak going pretty girl. Thanks for taking my questions and congrats on all the progress I just wanted to ask about the.

Post trends post transplant durability.

Can you kind of help put into context, how post transplant durability might be assessment interpreted and maybe the dynamics. There is it and it will be durability of CR CRC.

So you are see our H or the most recent CR or something else.

Can you walk me through the dynamics and I have a follow up.

Sure.

First let me just say that for all the durability infer.

Information that we have in the abstract and that will present at.

The oral presentation, it's it's durability of CR CRH. So if you look at the labels of drift targeted agents that had been approved in AML.

Dr. Briggs Morrison: We are comfortable, given our cash on hand, that we have the financial resources to aggressively advance our programs and achieve upcoming milestones. We remain optimistic 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. As always, I would like to thank the wonderful talented team here at Syndax, our collaborators, and, most importantly, the patients, trial sites, and investigators involved in our clinical program. In addition, I would like to thank our committed long-term investors who are helping us to build this great company. With that, I'd like to open the call to questions.

We'll see the CR CRH rate and the durability of those responses.

In the approved labels. The durability is is from the time of first obtaining a CR or a CRH until relapse, including the time post bone marrow transplant. So if a patient had at CRH.

That lasted three or four months. They were then able to go out to bone marrow transplant and that complete remission continued postmill postponed marrow transplant, that's what's counted as the durability of their response and that's the way.

The data is for example in the guilty written in cable if you look at their median duration of response. It includes the time after transplant. So what we had in our ash abstract does not include time post transplant for any of the patients well, we will present at the oral presentation as we now have data.

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. Again, if you would like to ask a question, please press star, then the number one on your telephone keypad. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Phil Nadeau of Cohen & Co. Your line is now open.

On those patients post bone marrow transplant, so it'll be from the time of their first C. R. R. CRH.

Until we lap if they've relaxed.

Okay.

Okay. Thank you.

I guess I just had one other question.

Phase one meeting where there any other takeaways you might be able to share.

Operator: Good afternoon, congratulations on the progress, and thanks for taking our questions. Just a couple from us.

Especially I'm, especially curious about the inclusion of the Doe at some point was that something you were expecting and.

Philip M. Nadeau: So first, on the pivotal cohorts, can you go into a little bit more detail why the non-CYPDOS has not been defined yet? What else do you need to do to define that dose? Is there additional patient experience that you're expecting or feedback from the FDA? What's the rate-limiting step to nailing that?

Maybe what do you think the OSP bar could be how should we think about that.

Yeah, again, I would say that the primary endpoint is the percentage of patients who have either a CR or a C. R. H the durability of those responses.

Transfusion independent OS is an exploratory endpoint in the trial.

As you know the agency.

Dr. Briggs Morrison: I want to emphasize that 163 with any strong CYP3A4 inhibitor is an acceptable recommended phase 2 dose that we agreed to with FDA, and that's the dose that's going forward. We have two very good doses in ARMA, 226 and 276, and what we think we need is a little bit more PK data on a few more patients to pick between those two to see which one most closely matches the PK of the 163 with any strong CYP3A4 inhibitor.

I find it difficult to interpret uncontrolled PFS or OS data so its descriptive but it's.

I don't think Theres, a bar there because there really isn't a control group.

Okay that makes a lot of sense, thanks very much.

Yeah.

Our next question comes from the line of Justin Walsh of B Riley Securities. Your line is now open.

Hi, Thanks for taking my question.

Based on what you saw in the phase one portion of the augment 101 do you have any expectations with respect to enrollment rates for the three populations.

Philip M. Nadeau: Perfect. That's very helpful.

Yes, I guess the only thing that we would say is are the AML cohort may enroll a bit faster than the a L. L cohorts simply because of the.

Philip M. Nadeau: And then second, I'm not sure you're going to be willing to answer this question, but we're all curious about how many more patients there will be in the ASH presentation versus the abstract that we've all reviewed. And in particular, I think we're all focused on the NPM1 patient population. Give us some sense of how many NPM1 patients are likely to be presented at Ashiq.

The competition for patients there is a fair amount of them.

Innovation, that's being tested in patients with a L. L.

A little less in the AML space. So I think the AML cohorts may enroll a bit faster, but again, it's in it.

We'll just have to see as we as we open up the trial.

Dr. Briggs Morrison: I'm not sure I know off the top of my head how many additional patients there are compared to the abstract. I don't know if Michael Myers, do you know that?

Got it and then maybe one more for me.

Maybe you guys can remind us of the unmet need and an opportunity in IPF and if you have any thoughts on what other fibrotic diseases, you think could be a bit perhaps yourself on that that would be that'd be great.

Michael Werner Schmidt: I think it's about five additional patients.

Michael Werner Schmidt: And the total number of NPM1 patients, Michael, that'll be in the presentation. That is in the presentation. No, I think Philip's asking how many total patients, total NPM1 patients there are.

Yeah.

Yeah, maybe I'll.

Let Angela talk a little bit about the patient numbers, but I would just say that from a clinical point of view. There are two agents approved for the treatment of IPF they've been shown to slow the progression of the disease, but they don't reverse the progression of the disease.

And unfortunately, he does continue really.

Philip M. Nadeau: I think it's about 13 patients and... in the presentation itself. Great, thank you. Perfect. Yeah, that's very helpful. Thanks so much for taking our questions.

That deteriorate. So I think there's lots of from a clinical point of view, what we've heard from physicians, who treat these patients.

A big big need for additional agents to either further slow the progression of the disease or potentially at some point reverse that progression, but Angela you may want to speak a little bit about.

Operator: Our next question comes from the line of Yigal Nochomovitz of Citi. Your line is now open.

Operator: Hi team, this is Ashiq Mubarack going for Yigal. Thanks for taking my questions and congrats on all the progress. I just wanted to ask about post-transplant durability. Can you kind of help put it in the context of how post-transplant durability might...

The numbers of patients.

Yeah, I think saying happy to I think in the in the current estimates for prevalent mm for the U S. It's upwards of 150000 patients. So it's still considered an orphan indication, but it's.

You know a few fold larger than what the prevalence of chronic gvhd is today and it's very similar across.

URL Placeholder: https://www.kenhub.com

Dr. Briggs Morrison: Sure. So first, let me just say that for all the durability information that we have in the abstract and that we'll present in the oral presentation, it's the durability of CR-CRA. So if you look at the labels of targeted agents that have been approved in AML, you will see the CR-CRH rate and the durability of those responses. In the approved labels, the durability is from the time of first obtaining a CR or a CRH response until relapse, including the time post bone marrow transplant.

Uh huh.

You know EU size, if you will and then Japan is a little bit smaller so I guess, it's a you know what.

Worldwide or seven major markets. He estimated you know closer to.

Q2, 275000 patients today.

Yeah.

Got it thanks for taking the question.

Yeah.

Our next question comes from the line of Joel Beatty of Baird. Your line is now open.

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

My first one is on 56 their team.

Correct the debt is not broken out.

Ncr's CRH for N P M one and.

Population, but we do have that data.

CRC rate and it seems like it's trending a little bit more favorable.

For MLR compared to M. P. M. One I'm just curious on your thoughts of what may be behind that if it could be that a drug a chance or other considerations.

Dr. Briggs Morrison: If you look at their median duration of response, it includes the time after transplant. So what we have in our abstract does not include time post transplant for any of the patients. What we will present at the oral presentation is we now have data on those patients after bone marrow transplant. So it'll be from the time of their first CR or CRH until relapse, if they've relapsed.

Yeah look Joe.

I said in my prepared remarks, I think we're quite excited to be able to break out more details on the <unk>.

The response rate in N P M one versus MLR in the oral presentation.

As you know when we entered the clinic based upon all of the preclinical data we thought that the efficacy would be roughly comparable in the two populations. We felt very very good efficacy in preclinical models for both diseases. So we think that at the sample size increases and we get a better.

Dr. Briggs Morrison: Okay, thank you. And

The point estimate.

Ashiq Alim Mubarack: I guess I just had one other question about your end-of-phase one meeting. Were there any other takeaways you might be able to share? I'm just especially curious about the inclusion of the OS endpoint. Was that something you were expecting? And maybe what do you think the OS bar should be?

We're feeling.

Or are still excited that the that potentially the two will have fairly similar.

Efficacy perf.

Performance.

Yeah.

Thank you appreciate that.

And then maybe one other question on the.

101 Registrational trials.

What endpoints would be important from a competitive landscape perspective.

Ashiq Alim Mubarack: Should be. How should we think about that?

Dr. Briggs Morrison: Yeah, again, I'd say that the primary endpoint is the percentage of patients who have either a CR or a CRH, the durability of those responses, transfusion independence, and OS is an exploratory endpoint in the trial. As you know, the agency finds it difficult to interpret uncontrolled PFS or OS data, so it's descriptive, but it's Um, I don't think there's a bar there because there really Okay, that makes a lot sense...

Would it be the same crs.

Each rate that's important the regulators or are there other focuses.

Well, so it's quite interesting and obviously from a regulatory point of view as you can see our CRA tree.

As we've talked about previously the from a from a clinical point of view the other.

Excitement that we've gotten from investigators participating in trial as the high <unk> negative rate so there.

We do have patients in the trial and this goes to the earlier question about durability, who had M. A C. R. P. Their platelets hadn't fully recovered yet they were negative and they immediately went to bone marrow transplant.

Ashiq Alim Mubarack: Okay, that makes a lot of sense. Thanks very much.

Operator: Our next question comes from the line of Justin Walsh of V. Riley Securities. Your line is now open.

Operator: Hi, thanks for taking the question. Based on what you saw in the Phase 1 portion of Augment 101, do you have any expectations with respect to enrollment rates for the three populations? Yeah, I guess the only thing that we would say is the AML cohorts may enroll a bit faster than the ALL cohort, simply because of the competition for patients. There's a fair amount of innovation that's being tested in patients with ALL, little less in the AML space. So I think the AML cohorts may enroll a bit faster, but again, you will just have to see as we open up the trial. I got it.

Those patients won't get counted in the CR cri rate.

And so in terms of your C RCRA trade and durability of CR CRH, those crp's, who go to bone marrow transplant don't get counted.

The regulatory rules, that's okay, but from a clinical point of view, that's a very very important result for the patient. So the the total number of MRV negative CR patients who can go on to bone marrow transplant is something that we've heard a lot of excitement about from our investigators.

Yes.

Terrific. Thank you.

Yeah.

Our next question comes from the line of Peter Lawson of Barclays. Your line is now open.

Hey, thanks for the update pretty.

Pretty much I appreciate it.

Thanks for taking the questions.

Justin Walsh: Maybe one more for me. Maybe you guys can remind us of the unmet need and opportunity in IPF, and if you have any thoughts on what other fibrotic diseases you think could be a fit for axophilimab, that would be great. Yeah, maybe I'll let Anjali talk a little bit about the patient numbers, but I would just say that from a clinical point of view, there are two agents approved for the treatment of IPF.

Just one.

I guess as patients move on to transplant.

The S and.

The X.

The team how quickly do they move on to transform and Ya study.

Yeah. It's a good question Peter I don't have that data right at the tip of my fingers of how long it takes from when they start treatment to go on to transplant I think the one other thing to remember and I mentioned this in my prepared remarks about the design of our pivotal trial and the pivotal trials once they go on to transplant.

Justin Walsh: They've been shown to slow the progression of the disease, but they don't reverse the progression of the disease, and unfortunately, the disease does continually deteriorate. So I think there's lots of, from a clinical point of view, what we've heard from physicians who treat these patients, a big, big need for additional agents to either further slow the progression of the disease or potentially at some point reverse that progression. But Anjali, you may wanna speak a little bit about the numbers of patients.

They are eligible to go back on 50, 613, Wednesday, and graft and that again has been a.

A frequent request from the treating physicians they they look at their patient and they say I had nothing to offer this patient your drug got them to an <unk> negative CR.

Great took on the transplant I'd love to put them back on your drug and maintain that that CR postpone marrow transplant and in the phase one trial. The trial wasn't really set up to do that but in the pivotal trial, we will be able to do that so I think we'll start to learn a bit about how the drug.

Dr. Briggs Morrison: I think the current estimates for prevalence in the U.S. are upwards of 150,000 patients, so it's still considered an orphan indication, but it's, you know, a few fold larger than what the prevalence of chronic GVHD is today, and it's very similar across, you know, the EU5, if you will, and then Japan is a little bit smaller. So, I guess it's worldwide, or in seven major markets; the estimate is, you know, closer to 275,000 patients today.

Performs in the post transplant setting.

Got you. Thank you and then when do you expect to start the.

I don't have the strokes.

<unk> three <unk> four inhibitor.

Yeah, we think it will just be a couple of months as I mentioned in a response to Phil's question, we do want to get a little bit more PK data to decide between the $2 26 in the $2 76.

Anjali Ganguli: Got it. Thanks for taking the question.

So it'll be a couple of months to enroll some additional patients and make that final decision.

Operator: Our next question comes from the line of Joel Beatty of Baird. Your line is now open.

Thank you and then just.

Is there anything that precludes NPM one patients do you think from reach in CRH.

Operator: Hi, congrats on the progress, and thanks for taking the time.

No.

Perfect.

Okay.

Joel Lawrence Beatty: Thank you for taking the questions. My first one is on 5613. In the AASHA abstract, the data is not broken out on CRH for MPM1 and Mennon.

Thank you.

Sure thing.

There are no questions coming in at this time.

Now turning to call back the Doctor Morrison.

Thank you.

Thank you very much operator, and thank you everybody again for joining us on the call today as I said, we felt like this was really a very.

Dr. Briggs Morrison: But we do have that data in the CRC rate, and it seems like it's trending a little bit more favorably.

Joel Lawrence Beatty: I'm just curious about your thoughts of what may be behind that, if it could be due to drugs or chance or other considerations.

Very important breakout quarter for us we now have an.

FDA buy in to take our amendment program into pivotal trials.

Dr. Briggs Morrison: Yeah, look, Joel, as I said in my prepared remarks, I think we're quite excited to be able to break out more details on the response rate in NPM1 versus MLLR during the oral presentation. As you know, when we entered the clinic, based on all the preclinical data, we thought that the efficacy would be roughly comparable in the two populations. We saw very, very good efficacy in preclinical models for both diseases. So we think that as the sample size increases and we get a better point estimate, we're feeling, you know, still excited that potentially the two will have fairly similar efficacy performance.

Finally, the agreement with insight and really feel a tremendous sense of momentum building in the company. So we look forward to sharing additional updates on both programs at Ash and thank you for your time.

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

Yes.

[music].

Okay.

[music].

Joel Lawrence Beatty: Thanks, I appreciate that. And then one other question about the Augment 101 registrational trials: what endpoints would be important from a competitive landscape perspective, you know, with

Joel Lawrence Beatty: Well, so it's quite interesting.

Dr. Briggs Morrison: Well, so it's quite interesting. Obviously, from a regulatory point of view, it's the CRCRH. As we've talked about previously, from a clinical point of view, the other excitement that we've gotten from investigators participating in the trial is the high MRD negative rate. So we do have patients in the trial, and this goes to the earlier question about durability, who had a CRP, their platelets hadn't fully recovered yet, they were MRD negative, and they immediately went to bone marrow transfer.

Okay.

[music].

Dr. Briggs Morrison: Those patients won't get counted in the CRCRA. And so in terms of your CR-CRH rate and durability of CR-CRH, those CRPs who go to bone marrow transplant don't get counted, that's the regulatory rules that's okay but from a clinical point of view that's a very very important result for the patient so the the total number of MRD negative CR patients who can go on to bone marrow transplant is something that we've heard a lot of excitement about from our investigators.

Operator: Our next question comes from the line of Peter Lawson of Barclays. Your line is now open. Hey, thanks for the update. I very much appreciate it.

Operator: They very much appreciate it. Thank you for taking the questions. Just on, I guess, as patients move on to transplantation on the FNDX. How quickly do they move on to transplant in your studies? Yeah, it's a good question, Peter.

Peter Richard Lawson: I don't have that data right at the tip of my fingers about how long it takes from when they start treatment to go on to transplant. I think the one other thing to remember, and I mentioned this in my prepared remarks about the design of our pivotal trial, in the pivotal trials, once they go on to transplant, they are eligible to go back on 5613 once they engraft. And that, again, has been a frequent request from the treating physicians. They look at their patient, and they say, I have nothing to offer this patient.

Dr. Briggs Morrison: Your drug got them to an MRD negative CR. Great, I took him to transplant. I'd love to put him back on your drug and maintain that CR post bone marrow transplant. And in the phase one trial, the trial wasn't really set up to do that, but in the pivotal trial, we will be able to do that. So I think we'll start to learn a bit about how the drug performs in the post-transplant setting. Thank you.

Peter Richard Lawson: When do you expect to start the arm where patients don't have the strong CYP3A4? Yeah, we think it'll just be a couple of months. As I mentioned in the response to Phil's question, we do want to get a little bit more PK data to decide between the 226 and the 276. So it'll be a couple of months before we enroll some additional patients and make that final decision. Is there anything that precludes NPM1 patients from reaching CRH?

Operator: There are no questions coming in at this time. I'm now turning the call back to Dr. Morrison.

Dr. Briggs Morrison: Thank you very much. Thank you everybody again for joining us on the call today. As I said, we feel like this was really a very important breakout quarter for us. We now have FDA buy-in to take our Menden program into pivotal trials. We've finalized the agreement with Insight, and we really feel a tremendous sense of momentum building in the company. So we look forward to sharing additional updates on both programs at ASH, and thank you for your time.

Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.

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Operator: Good day, and thank you for standing by. Welcome to the Syndax third quarter 2021 conference call.

Operator: At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. If you require any further assistance, please press star zero. I would now like to hand the conference over to your first speaker today, Melissa Forst, with Argo Partners. Thank you, and please go ahead.

Melissa Forst: 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 3rd Quarter 2021 Financial and Operating Results. With me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer, and Michael Metzger, President and Chief Operating Officer. Also joining us on the call today for the question and answer session are Dr. Michael Myers, Chief Medical Officer, Dr. Peter Ordentlich, Chief Scientific Officer, and Dr. Anjali Ganguli, Chief Business Officer.

[music].

Melissa Forst: This includes those discussed in the risk factors section of the company's most recent quarterly reports on Form 10-Q, as well as other reports filed with the FCC. Any forward-looking statements represent the company's views as of today, November 15, 2021, only. A replay of this call will be available on the company's website following the call. And with that, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer.

Dr. Briggs Morrison: We continue to advance both of our clinical programs, and both were selected for oral presentations at ASH this year. Augment 101, our Phase 1-2 trial of SNDX5613, our selective menin inhibitor, has progressed as anticipated. We're pleased to announce today that our three pivotal Phase 2 trials for SNDX5613, which we call Augment 101 Cohorts 2A, 2B, and 2C, are now open and enrolling patients after we obtained important agreements from FDA. Notably, we were the first to demonstrate clinical validation of targeting menin for acute leukemias, and now ours is the first program to advance to registration-oriented trials.

Dr. Briggs Morrison: For Axitilumab, our antibody against CSF-1R, enrollment is ongoing in our pivotal Agave-201 trial, and we are immensely gratified that we have Insight as a fabulous partner to maximize the value of this important program. We therefore now have two registrational programs ongoing for two first-in-class, potentially best-in-class medicines for two areas of important unmet medical needs. Thanks to the support of our many committed investors, we are well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline. Let's now turn to slide 4 and update you on where we are with SNDX5613.

Dr. Briggs Morrison: We have completed the Phase 1 portion of RMB for Augment 101 and have agreement from FDA on key aspects of our go-forward clinical development plan. First, we have now opened three single-arm Phase II trials that FDA has agreed may each serve as a pivotal trial. Each of these single-arm phase 2 trials represents an independent path to a separate indication. Augment 101 Cohort 2A will enroll patients with relapsed refractory MLLR-ALL. Cohort 2B will enroll patients with relapsed refractory MLR-AML, and 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.

[music].

Good day, and thank you for standing by and welcome to this index third quarter 2021 conference call.

This time, all participants are in a listen only mode.

After the speaker presentation, there will be a question and answer session. That's good question. During the session you will need to press star one on your telephone.

If you require any further assistance please press star zero.

I would now like to hand, the conference over to your first speaker today, Melissa Forst with Argot partners. Thank you. Please go ahead.

Thank you operator, welcome and thank you to those of you joining us on the line and the webcast. This afternoon for the OS indexes third quarter, 2021 financial and operating results.

Dr. Briggs Morrison: 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 other, or we may seek initial regulatory approval for any two or all three, just depending on when they complete enrollment. Needless to say, we are thrilled to have advanced the program into these initial pivotal trials. We anticipate being the first company to achieve regulatory approval for a menin inhibitor, and today's announcement regarding the advancement of the program increases our confidence that we will do so. We have agreement with FDA that for each trial, the primary endpoint will be the percentage of patients achieving CR plus CRH, with secondary endpoints including durability of CR-CRH responses Transfusion Independent, Overall survival, and tolerability.

Also joining us on the call today for the question answer session with Dr. Michael Meyers, Chief Medical Officer, Dr. Peter <unk>, Chief Scientific Officer, and Dr enjoy getting gulli Chief business Officer.

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

I ask that you. Please turn to the forward looking statements on slide two.

Dr. Briggs Morrison: And most importantly, the trial design allows patients to be treated with SNDX5613 after a bone marrow transplant, a design feature that allows us to start to understand the role of 5613 in the post-transplant setting. We also have agreement with FDA on the statistical design of each trial.

Well its other reports filed with the SEC.

Any forward looking statements represent the companys team as of today November 15th 2021 only.

This call will be available on the company's website following the call and with that I'm pleased to turn the call over to you Dr. Briggs Morrison Chief Executive Officer.

Dr. Briggs Morrison: Each trial will enroll 64 adult patients and up to 10 pediatric patients. Finally, we have agreement with FDA that our recommended phase 2 dose of 163 mg PO every 12 hours, given with any strong CYP3A4 inhibitor, is an appropriate phase 2 dose, and that is the dose we are taking forward in each trial. We know that the majority of eligible patients are on a strong 5th or A4 inhibitor. We'll be finalizing our phase two arm A dose over the next few months and anticipate being able to enroll patients who are not on a strong CYP3A4 inhibitor as our three pivotal trials proceed.

Great. Thank you very much Melissa and thank you to everyone who is joining us on today's call and the webcast.

Slide three 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.

We continue to advance both of our clinical programs and those were selected for oral presentations at ash This year.

Augment 101, our phase one two trial of F&D X 50, 613, our selective <unk> inhibitor has progressed as anticipated. We're pleased to announce today that our three pivotal phase III trials for F&D X 50, 613, which we call augment 101 cohort two a two b two.

Dr. Briggs Morrison: Let me first remind everyone that this is a phase one trial. Patients had received, on average, three prior therapies, and about 40% had relapsed after a bone marrow transplant, a very negative prognostic sign, and almost 60% had previously received chemotherapy phonetically. These are very difficult to treat patients, and we were delighted to report in the abstract a 44% overall response rate, a 22% CR-CRH rate, and 70% of the responses were MRD negatives, meaning using the most sensitive assays available.

C are now open and enrolling patients after we obtained important agreements from FDA.

Notably we were the first to demonstrate clinical validation of targeting menin for acute leukemias and now ours is the first program to advance to registration oriented trials.

We therefore now have two registrational programs ongoing for two first in class potentially best in class medicines for two areas an important unmet medical need.

So the support of our many committed investors we are well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline.

Let's now turn to slide four and update you on where we are with S&P X 50 613.

We have completed the phase one portion of RMB of augment 101 and have agreement from FDA on key aspects of our go forward clinical development plan.

First we have now 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 represents an independent path to a separate indication.

Dr. Briggs Morrison: Beyond the Augment Pivotal Program in Relapse or Refractory Disease, slide six highlights some of the additional opportunities we are exploring with SNDX5613, all of which build on the excellent safety and efficacy profile we have thus far seen with the model. The panel on the left highlights a trial we are planning in collaboration with the Leukemia and Lymphoma Society, otherwise known as LLS. They have selected SNDX5613 as the first menin inhibitor to be tested as a specific targeted therapy for patients with MLLR and NPM1AML in their umbrella trial that they call BEATAML.

Augment 101 cohort two.

We will enroll patients with relapsed refractory MLR a L L.

Cohort two b will enroll patients with relapsed refractory MLR AML and to see will enroll patients with relapsed refractory N P. M. One each.

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

We may seek initial regulatory approval for <unk> Dx 50, 613 based on the results of any one of these trials should one trial enrolled faster than the others.

Or we may seek initial regulatory approval for any two or all three just depending on when they complete enrollment.

Needless to say, we are thrilled to advance have advanced the program into these initial pivotal trials.

Dr. Briggs Morrison: The collaboration we have agreed to with them will test 5613 in combination with benetoclax and nasacitidine in newly diagnosed AML patients that 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 regulatory dossiers. Our scientists have generated preclinical data that supports the benefit of menin inhibition in combination with chemotherapy.

We have agreement with FDA that for each trial. The primary endpoint will be the percentage of patients achieving CR plus CRH with secondary endpoints, including durability of CR CRH responses.

<unk> fusion independence.

Overall survival and Tolerability.

Importantly, the trial design allows patients to be treated.

Yes.

With F&B X 50, 613, after a bone marrow transplant.

<unk> feature that allows us.

Just trying to understand the role of 50 613 in the post transplant setting.

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

Each trial will enroll 64 adult patients in up to 10 pediatric patients.

Finally, we have agreement with FDA that our recommended phase two dose of 163 milligrams every 12 hours given with any strong Sip through 84 inhibitor is inappropriate phase two dose and that is the dose we're taking forward in each trial.

Dr. Briggs Morrison: The Intercept trial is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML. The trial will enroll patients with measurable residual disease progression following their initial treatment, a group of patients who are at very high risk of relapse and represent an important unmet medical need. I think I have mentioned previously 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 patients stay on therapy.

We know that the majority of eligible patients are on a strong set three four inhibitor, we will be finalizing our phase two or a dose over the next few months and anticipate being able to enroll patients who are not on a strong set of <unk> four inhibitor as our pivotal three pivotal trials proceed.

Dr. Briggs Morrison: The Intercept Trial is an innovative approach to treating patients early in their disease; I will also note that SNDX5613 is the first meta-inhibitor to be included in the Intercept Master Clinical Trial. We believe the selection of SNDX5613 for inclusion in two Master Clinical Trial protocols highlights the enthusiasm that investigators have shown for treating patients with acute leukemias with our campaign. We anticipate announcing additional trials over the next 6 to 12 months that will further build out the 5613 framework.

First remind everyone. It is a.

Phase one trial pace.

Patients had received on average three prior therapies and about 40% had relapsed after bone marrow transplant, a very negative prognostic sign and almost 60% had previously received panetta class.

They're very difficult to treat patients and we were delighted to report in the abstract a 44% overall response rate of 22% CR cri rate and 70% of the responses, where MRV negative meaning using the most sensitive assays available.

With no detectable leukemia after treatment with Aetna, passing the X 50 613.

Dr. Briggs Morrison: And, as I mentioned earlier, the registration cohorts of Augment 101 will allow patients to be dosed post-transplant, providing an early look and setting the stage for future trials in maintenance. As I mentioned on our second quarter earnings call this past August, we are excited to expand the clinical opportunities for 5613 beyond the initial approval and relapse-refractory leukemia. Slide 7 highlights our goal as a company to be first to market in relapsed or fractured disease and then to be first to garner additional value-driven indications by expanding the use of 5613 into newly diagnosed patients and into the maintenance setting in patients with both MLLR and NPM1 acute leukemia.

We are finalizing our ash presentation, which represents an additional approximately three months of follow up.

And we remain excited about breaking out the efficacy data by mutational status and to present, the updated durability of CRH CR CRH responses with patients who went on to transplant.

Additional details will presented he presented by Dr. <unk> Stein and his oral presentation on Monday December 13th.

Beyond the augment pivotal program in relapsed or refractory disease slide six highlights some of the additional opportunities. We are exploring with S. N D X 50, 613, all of which build on the excellent safety and efficacy profile, we have thus far seen with the molecule.

On the left highlights the trial, we are planning in collaboration with the leukemia and lymphoma society, otherwise known as L. L. S. They have selected S. N. D. X 50, 613 is the first menin inhibitor to be tested as a specific targeted therapy for patients with MLR in N. P. M. One ml in their umbrella trial that they call <unk> a M.

Dr. Briggs Morrison: We are taking our first steps towards building out the franchise through the collaborations with LLS to explore and treat newly diagnosed patients, and with the Australian Leukemia Group in patients with AML who have MRD-positive disease despite their initial standard of care. Let me now turn to slide 8, connective tilamab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor. We were delighted to announce that Syndax Insight has entered into a broad, long-term 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 I GVHD data last year at ASH in December.

The collaboration we have agreed to with them will test 50, 613 in combination with vanilla klaxon, they've decided in newly diagnosed AML patients that 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 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 this slide highlights a trial to explore the use of 50 613 in combination with standard salvage chemotherapy is used for pediatric patients with a L. L. R. AML that we're calling.

One O two.

And the panel on the right illustrates a new trial that explores the activity of 50 613 in patients with AML, who have Mardi positive disease. This trial is being conducted as part of the intercept master clinical trial being led by the Australian leukemia and lymphoma group.

Dr. Briggs Morrison: The reaction to our data was extremely positive, and given our belief in the broad clinical potential of axitilumab, we initiated a process to look for a global partner to collaborate with us on further development of this exciting molecule. To briefly recap the agreement, the deal provides $152 million up front, $117 million in cash, and notably $35 million in equity at a 30% premium, which we believe is a strong endorsement of our company and its overall value proposition.

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

The trial will enroll patients with measurable measurable residual disease progression. Following their initial treatment a group of patients who are at very high risk of relapse and represents an important unmet medical need.

That's the first met inhibitor to be included in the intercept a master clinical trial, we believe in the selection of 50 613 for inclusion in two master clinical trial protocols highlights the enthusiasm investigators have shown for treating patients with acute leukemias with our count that.

Dr. Briggs Morrison: The economics of Syndax over the course of the collaboration are enhanced with key regulatory and sales milestones covering multiple indications throughout the world. The payments total an additional $450 million, and Syndax receives double-digit royalties extra. Also important to highlight is the development plan, which calls for the partners to design novel combinations with axotilumab and Insite's JAK inhibitors with the goal of establishing axotilumab in earlier settings within chronic graft-versus-host disease and expanding its market opportunities.

Value driving indications by expanding the use of 56% or team into newly diagnosed patients and into the maintenance setting in patients with both MLR and N. P. M. One acute leukemia.

We are taking our first steps towards building out the franchise through the collaborations with LLS to explore in newly diagnosed patients.

Dr. Briggs Morrison: As we previously mentioned was our intention, Syndax will initiate a POC trial in interstitial pulmonary fibrosis, the first expansion outside of establishing chronic graft-versus-host disease as a beachhead into other fibrotic diseases where we believe axitilumab could have a significant impact. Significant successful development in IPS could lead to an additional approval and a very important indication of considerable value and would provide support for axopilumab and other fibrotic-driven diseases that the parties could explore over the course of the collaboration. As you know, our Ash Abstract for Acetylamide was also recently published, and slide 9 is a brief summary of that data.

And with the Australia.

Australia leukemia group of patients, where they are now who have M already positive disease. Despite their initial standard of care treatment.

Let me now turn to slide eight and I have to tell them at our potentially best in class monoclonal antibody therapy targeting the CSF one receptor.

As you know we presented our phase <unk> Gvhd data last year at Ash in December the reaction to our data was extremely positive and given our belief in the broad clinical potential of that to tell them that we initiated a process to look for a global partner to collaborate with us on further development of this exciting molecule.

Dr. Briggs Morrison: There were 40 patients enrolled who had received a median of four prior therapies. At the one milligram per kilogram dose given every two weeks, which we anticipate will be our label dose, the drug was well-tolerated, and we saw an overall response rate of 75%. We believe this is a material data set that significantly de-risks our ongoing registration trial, and additional details will be presented by Dr. Stephanie Lee in her oral presentation on Saturday, December 11.

The 50 50 profit split in the U S enables us to retain significant upside and actively participate long term in the franchise to build out the 45, 55% cost sharing mechanism limits, our downside and extends our cash in.

Dr. Briggs Morrison: Slide 10 is our pivotal trial for axitilumab in chronic graft-versus-host disease. This trial is the axitilumab for chronic graft-versus-host disease trial called Agave 201. The trial is enrolling patients with chronic graft-versus-host disease whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met overall entry criteria.

And the opportunity for full commercialization in the U S will allow us to participate in the launch of an important product alongside a strong commercial partner.

Aside the U S. We will rely on insight to develop and launch the product in all the major markets to maximize its full potential as a global brand.

The.

Economics to send backs over the course of the collaboration are enhanced with key regulatory and sales milestones covering multiple indications throughout the world the payments totaling an additional $450 million and syntax receive double digit royalties ex U S.

Dr. Briggs Morrison: 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 acetilumab given either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronographers. Secondary endpoints will include duration of response and validated quality of life assessments using the least. Enrollment of the study is underway, and we are on track to deliver top-line data in 2023.

Also important to highlight the development plan, which calls for the partners to design novel combinations with axis tell them at and insights JAK inhibitors with the goal of establishing half the telematic earlier settings within chronic graft versus host disease and expanding its market opportunity.

As we previously mentioned was our attention its index will initiate a POC trial interstitial pulmonary fibrosis. The first expansion outside of establishing chronic graft versus host disease is a beachhead into other fibrotic diseases, where it.

Dr. Briggs Morrison: Slide 11 highlights our view of the broad clinical and commercial opportunity for Axopilumab. We believe chronic graft-versus-host disease represents a high unmet medical need and an important commercial opportunity, with approximately 14,000 patients suffering from chronic graft-versus-host disease in the U.S. today. The recent approvals of Insight's Jackify and Cadman's Vellumosadil will begin to define the commercial opportunity in this disease. However, despite recent advances in this area, to our knowledge, Axitilumab is the only agent in clinical development that specifically targets the monocyte macrophage lineage.

And believe <unk> could have a significant impact significant successful development of IPF can lead to an additional approval in a very important indication of considerable value and would provide support for that to tell them that in other fibrotic diseases.

Heartiest could explore over the course of the collaboration.

As you know our ash abstract for ash to tell them that also recently published and slide nine is a brief summary of that data.

There were 40 patients enrolled who had received a median of four prior therapies at the one milligram per kilogram dose given every two weeks, which we anticipate will be a labeled dose the drug was well tolerated and we saw an overall response rate of 75%.

We believe this is a material dataset that significantly de risks our ongoing registration trial.

Dr. Briggs Morrison: Both Syndax and Insight believe the data generated to date with Axotilamab suggests it has the potential to play an important role in the treatment of chronic graft-versus-host disease, both as monotherapy and, given its safety profile, in combination with other mechanisms. As we move Axotilumab into additional indications, starting with IPF, we really see Axotilumab contributing materially Finally, slide 12 summarizes the transactions that led to the acquisition of both the Menin and Acetelimab programs.

And additional details will be presented by doctors definitely and her oral presentation on Saturday December 11th.

Slide 10 is our pivotal trial for actually telematic chronic graft versus host disease. This is this trial at the till that for a chronic versus host disease trial called Agave 201.

Every two weeks or every four weeks.

Dr. Briggs Morrison: We believe these transactions underscore our robust capabilities to evaluate and identify high-value differentiated assets, as well as our clinical development expertise to bring these compounds through key value inflection points. We anticipate 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 in such transactions. I'll now turn the call over to Michael to review our financial report. Thank you, Briggs.

The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft versus host disease.

Secondary endpoints will include duration of response and validated quality of life assessments using deadly symptoms scale.

Enrollment to the study is underway and we are on track to deliver top line data in 2023.

Our recent approvals of insights Jakafi and cadman value most of the deal will begin to delineate the commercial opportunity in this disease. Despite.

Despite recent advances in this area to our knowledge actually tell them that is the only agent in clinical development that specifically targets. The monocyte macrophage lineage, both syntax and insight believe the debt data generated to date with actually tell them that suggests it has the potential to play an important role in the treatment of chronic graft versus host disease, both as monotherapy.

And given its safety profile in combination with other mechanisms.

As you move <unk> into additional indications starting with IPF, We really see act until I mab contributing materially to the value of our company going forward.

Finally, slide 12 summarizes the transactions that led to the acquisition of both the men in and tell them that programs. We believe these transactions underscore our robust capabilities to evaluate and identify high value differentiated assets as well as the clinical development expertise to bring these compounds through key.

Value inflection points.

Michael A. Metzger: We anticipate those payments will extend our cash runway into 2024 and support our expanded development plans for both the ACTLA-TILIMEB and the MENM programs during this period. Looking ahead, I'd like to provide financial guidance for the full year of 2021. Full year 2021 guidance remains unchanged, and we continue to expect R&D expense to be $90 to $100 million and total operating expense to be $110 to $120 million. This includes approximately $13 million in non-cash stock compensation.

Anticipate 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.

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

Thank you Briggs the results of our operations for the third quarter of 2021, and the comparison to the prior year quarter are included in our press release, So I won't repeat these remark these them in our remarks.

Additional financial details are available.

In the third quarter report on Form 10-Q, which was filed earlier today.

I would like to point out that our net loss for the quarter was $26 million or 40 cents, a share compared to $24 million or <unk> 46 per share for the same period last year.

Turning to slide 13, we ended the third quarter with $229 $7 million in cash and cash equivalents and $52 2 million shares and pre funded warrants outstanding.

Dr. Briggs Morrison: And with that, I would like to turn the call back over to you. Thank you very much, Michael. 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 as a major achievement. We're also very excited about the broad franchise opportunities for both programs beyond their initial registrational indication.

Looking ahead.

Dr. Briggs Morrison: We believe 5613 could have broad utility across a wide range of clinical settings in acute leukemia. Our goal as a company is to be the first to market in relapsed refractory disease, and then to garner additional value-driving indications by expanding the use of 5613 into newly diagnosed patients and into maintenance settings, patients both with MLLR and NPM1 acute leukemia. And Axotilamab also holds the promise of a broad franchise opportunity, both in various lines of therapy for GVHD and across a broad range of fibrotic diseases, starting with IPF.

That I would like to turn the call back over to Briggs.

Thank you very much Michael.

And we consider having two ongoing registration programs as a major achievement we're all.

So very excited about the broad franchise opportunities for both programs beyond their initial registrational indications.

We believe 50 613 could have broad utility across a wide range of clinical settings in acute leukemia. Our goal as a company is to be the first to market in relapsed refractory disease, and then there'll be first to garner additional value driving indications by expanding the use of 50 613 into newly diagnosed patients and that's it.

Maintenance settings.

Since both with MLR N P M. One.

Acute leukemias.

Fred and I can tell them that also holds the promise of a broad franchise opportunity both in various lines of therapy in gvhd and across a broad range of fibrotic diseases, starting with Ips.

We are comfortable with given our cash on hand that we have the financial resources to aggressively advance our programs and achieve upcoming milestones. We remain optimistic 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 strengths of our company.

As always I would like to thank 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 to build this great company.

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

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. Again, if you would like to ask a question, please press star and then the number 1 on your telephone keypad. To withdraw your question, please press the pound sign. Please stand by while we compile the Q&A list. Our first question comes from the line of Phil Nadeau of Cohen & Co. Your line is now open. Good afternoon,

As a reminder to ask a question you will need the best firewall on your telephone.

Again, if he would like to ask a question. Please press Star then the number one on your telephone keypad.

Your question. Please press the pound key.

Nissan dialogue compile the Q&A roster.

Our first question comes from the line of failing to do of Cowen and co. Your line is now open.

Philip M. Nadeau: Good afternoon, congratulations on the progress, and thanks for taking our questions. Just a couple from us.

Good afternoon, Congrats on progress and thanks for taking our questions. Just a couple from us. So first on the pivotal cohorts can you go into a little bit more detail why the non.

Philip M. Nadeau: So first, on the pivotal cohorts, can you go into a little bit more detail why the non-SIP dose has not been defined yet? What else do you need to do to define that dose? Is there additional patient experience that you're expecting or feedback from the FDA? Kind of what's the rate-limiting step to nailing it?

This has not been defined yet what else do you need to.

To do to defend that dose is there additional patient experience, where you're expecting or feedback from FDA kind of what's the.

What's the rate limiting step and Tamara diameters.

Thanks very much for your question.

Dr. Briggs Morrison: I want to emphasize that 163 with any strong 6384 inhibitor is an acceptable recommended phase 2 dose that we agreed to with FDA, and that's the dose that's going forward. We have two very good doses in ARMA, 226 and 276, and what we think we need is a little bit more PK data on a few more patients to pick between those two to see which one most closely matches the PK of the 163 with any strong 6384 inhibitor.

So I don't I cant emphasize that we are 163.

With any strong Sip three or four inhibitor is that an acceptable recommended phase two dose and we agreed to with FDA and that's the dose that's going forward.

We have two very good doses in arm, a 226 and $2 76, and what we think we need is a little bit more PK data on a few more patients to pick between those two to see which one most closely matches. The PK of the of the 163 with any strong set three or four inhibitor.

Philip M. Nadeau: Perfect. That's very helpful.

Perfect. That's very helpful and then second I'm.

I'm not sure you'd be willing to answer this question, but we're all curious in the ash presentation versus we have certainly we won't reviewed how many more patients will there be.

And in particular I think we're all focused on N. P. N. One push Barclays should give us some sense of harmony N. P. M on patients who are likely to be presented at ash.

Michael Werner Schmidt: I'm not sure I know off the top of my head how many additional patients there are compared to the abstract. I don't know if Michael Myers, do you know that?

I'm not sure I know off the top of my head how many additional patients there are compared to the abstract I don't know if Michael Myers do you know that.

Yeah.

It gets about five additional patients Briggs.

Michael Werner Schmidt: I think it's about five additional patients, for example. Okay, great, thank you, and the total number of NPM1 patients. Michael, that'll be in the presentation. That is in the presentation. No, I think Philip's asking how many total patients, total NPM1 patients there are. I think it's about 13 patients.

Okay, great. Thank you.

And the total number of N P M. One patient's Michael that'll be in the presentation.

That is in the presentation, yes.

No I think Phil it's asking how many total patients.

Total N P M one patients whether it would be.

Alright, thank you.

<unk> 13 patients.

Philip M. Nadeau: About 13 patients, the number in the presentation itself. Great. Thank you. Perfect. Yeah, that's very helpful. Thanks so much for taking our question.

They are in the presentation itself.

Great. Thank you.

So to your question Phil Yeah, that's very helpful. Thanks, so much for taking our questions.

Operator: Our next question comes from the line of Yigal Nochomovitz of Citi. Your line is now open.

Okay.

Our next question comes from the line of V go much I'll move it of Citi. Your line is now open.

Operator: Hi, this is Ashiq Mubarack going for you guys.

Hi, This is akshay Mubarak gone pretty girl, thanks for taking my.

Ashiq Alim Mubarack: Thanks for taking my questions and congrats on all the progress. I just wanted to ask about post-trance.

And congrats on all the progress I just wanted to ask about the post trends post transplant durability can you kind of help put into context, how post transplant durability might be assessment interpreted and maybe the dynamics. There is it and it will be durability of CRC.

Ashiq Alim Mubarack: Post-transplant durability, can you kind of help put into context how post-transplant durability might be assessed and interpreted, and maybe the dynamics there, is it, you know, will it be durability of CR, CRH, or the most recent CR, or something else? Yeah, could you walk me through the dynamics, and I have a follow-up. Sure.

CRH or the most recent CCAR or something else.

Can you walk me through the dynamics and I have a follow up.

Dr. Briggs Morrison: So first, let me just say that for all the durability information that we have in the abstract and that we'll present at the oral presentation, it's the durability of CR-CRA. So if you look at the labels of targeted agents that have been approved in AML, you will see the CR-CRH rate and the durability of those responses. In the approved labels, the durability is from the time of first obtaining a CR or a CRH until relapse, including the time post-bone marrow transplant.

Sure.

First let me just say that for all the durability.

Information that we are having the abstract and that will present at the oral.

Presentation, it's it's durability of CR CRH. So if you look at the labels of targeted agents that have been approved in AML.

We'll see the CR CRH rate and the durability of those responses.

In the approved labels. The durability is is from the time of first obtaining a CR or a CRH until relapse, including the time post bone marrow transplant. So if a patient had to CRH.

Dr. Briggs Morrison: So if a patient had a CRH that lasted three or four months, they were then able to go on to bone marrow transplant, and that complete remission continued post-bone marrow transplant, that's what's counted as the durability of their response, and that's the way the data is, for example, in the GILTSA written label. If you look at their median duration of response, it includes So what we have in our abstract does not include time post transplant for any of the patients. What we will present at the oral presentation is that we now have data on those patients post bone marrow transplant. So it'll be from the time of their first CR or CRH until relapse, if they've relapsed.

That lasted three or four months. They were then able to go onto a bone marrow transplant and that complete remission continued plus now postponed marrow transplant, that's what's counted as the durability of their response and that's the way. The data is for example in the Delta written labels. If you look at their median duration of response at <unk>.

The time after transplant. So what we have in our ash abstract does not include time post transplant for any of the patients while we will present at the oral presentation as we now have data.

And those patients postpone their transplant, so it'll be from the time of their first C. R. CRH.

Until we lap if they've relaxed.

Okay.

Ashiq Alim Mubarack: Okay, thank you. And

Okay. Thank you.

Ashiq Alim Mubarack: I guess I just had one other question about your end of phase one meeting. Were there any other takeaways you might be able to share? Especially, I'm just especially curious about the inclusion of the OS endpoint. Was that something you were expecting? And maybe what do you think the OS bar should be? How should we think about that?

I guess I just had one other question on your end of Phase one meeting where there any other takeaways you might be able to share.

Especially I'm, especially curious about the inclusion of deal at some point was that something you were expecting and maybe what do you think the OSP bar should be how should we think about that.

Dr. Briggs Morrison: Yeah, again, I'd say that the primary endpoint is the percentage of patients who have either a CR or a CRH, the durability of those responses, and transfusion independence. OS is an exploratory endpoint in the trial. As you know, the agency finds it difficult to interpret uncontrolled PFS or OS data, so it's descriptive, but it's um, I don't think there's a bar there because there really isn't any control Okay, that makes sense.

Yeah, again, I'd say that the primary endpoint is the percentage of patients who have either a C or a C. R. H the durability of those responses.

Transfusion independence OS is an exploratory endpoint in the trial.

As you know the agency.

I find it difficult to interpret uncontrolled PFS or OS data so its descriptive but it's.

I don't think Theres, a bar there because there really isn't a control group.

Ashiq Alim Mubarack: Okay, that makes a lot of sense. Thanks very much.

Okay that makes a lot of sense, thanks very much.

Operator: Our next question comes from the line of Justin Walsh of V. Riley Securities. Your line is now open.

Yeah.

Our next question comes from the line of Justin Walsh of B Riley Securities. Your line is now open.

Operator: Hi, thanks for taking the question. Based on what you saw in the Phase 1 portion of Augment 101, do you have any expectations with respect to enrollment rates for the three populations? Yeah, I guess the only thing that we would say is the AML cohorts may enroll a bit faster than the ALL cohort simply because of the competition for patients. There's a fair amount of innovation that's being tested in patients with ALL, little less in the AML space. So I think the AML cohorts may enroll a bit faster. But again, it's, you will just have to see as we open up the trial. I got it.

Hi, Thanks for taking my question.

Based on what you saw in the phase one portion of the augment 101 do you have any expectations with respect to enrollment rates for the three populations.

Yes, I guess the only thing that we would say is are the AML cohorts may enroll a bit faster than the ALLL cohorts simply because of the.

The competition for patients, there's a fair amount of.

Innovation, that's being tested in patients with a L. L.

Little less in the AML space. So I think the AML cohorts may enroll a bit faster, but again it's.

We'll just have to see as we as we open up the trial.

Got it and then maybe one more for me.

Maybe you guys can remind us of the unmet need and an opportunity in IPF and if you have any thoughts on what other fibrotic diseases, you think could be a fit for us with on that that would be that'd be great.

Yeah.

Yeah, maybe I'll.

Let Andrew talk a little bit about the patient numbers, but I would just say that from a clinical point of view. There are two agents approved for the treatment of IPF they've been shown to slow the progression of the disease, but they don't reverse the progression of the disease.

Justin Walsh: They've been shown to slow the progression of the disease, but they don't reverse the progression of the disease, and unfortunately, the disease does continually deteriorate. So I think there's lots of, from a clinical point of view, what we've heard from physicians who treat these patients, a big, big need for additional agents to either further slow the progression of the disease or potentially at some point reverse that progression. But Anjali, you may want to speak a little bit about the numbers of patients.

And forest.

And the disease does continue really.

Deteriorate. So I think there's lots of from a clinical point of view, what we've heard from physicians, who treat these patients.

Big Big need for additional agents to either further slow the progression of the disease or potentially at some point reverse that progression, but Angela you may want to speak a little bit about.

The numbers of patients.

Yeah, I think saying happy to I think in the in the current estimates for prevalent mm for the U S. It's upwards of 150000 patients. So it's still considered an orphan indication, but it's.

Dr. Briggs Morrison: In the current estimates for prevalence in the US, it's upwards of 150,000 patients, so it's still considered an orphan indication, but it's, you know, a few fold larger than what the prevalence of chronic GVHD is today, and it's very similar across, you know, EU5, if you will, and then Japan is a little bit smaller. So, I guess it's worldwide, or in seven major markets; the estimate is, you know, closer to 275,000 patients today.

You know a few fold larger than what the prevalence of chronic gvhd is today and it's very similar across.

<unk>.

You know EU five if you will and then Japan is a little bit smaller so I guess at the you know what.

Worldwide that are served.

Major market. He estimated you know closer to.

Q2, 275000 patients today.

Anjali Ganguli: Got it. Thanks for taking the question.

Yeah.

Got it thanks for taking the question.

Operator: Our next question comes from the line of Joel Beatty of Baird. Your line is now open.

Yep.

Okay.

Our next question comes from the line of Joel Beatty of Baird. Your line is now open.

Operator: Hi, congrats on the progress. And thanks for taking the questions. My first one is on 5613.

Hi, Congrats on the progress and thanks for taking the question.

My first one is on 56 third team.

Joel Lawrence Beatty: Data is not broken out on NCRH or NPM-1.

Correct.

That is not broken it out.

CRH for N P M, one and the mining.

Joel Lawrence Beatty: Populations, but we do not

Populations, but we do have the data.

Joel Lawrence Beatty: I do have that data on the CRC rate, and it seems like it's trending a little bit more.

And the CRC rate and it seems like it's trending a little bit more favorable.

For MLR compared to MTN, one I'm just curious on your thoughts.

Dr. Briggs Morrison: I'm just curious about your thoughts of what may be behind that, if it could be due to drugs or chance or other considerations.

May be behind that or if it could be that a drug a chance or other considerations.

Joel Lawrence Beatty: Yeah, look, Joel, as I said in my prepared remarks, I think we're quite excited to be able to break out more details on the response rate in NPM1 versus MLLR during the oral presentation. As you know, when we entered the clinic, based on all the preclinical data, we thought that the efficacy would be roughly comparable in the two populations. We saw very, very good efficacy in preclinical models for both diseases. So we think that as the sample size increases and we get a better point estimate, we're feeling, you know, still excited that potentially the two will have fairly similar efficacy performance.

Yeah look Joe as I as I said in my prepared remarks, I think we're quite.

Excited to be able to break out more details on the.

The response rate and NPM, one versus MLR in the oral presentation.

As you know when we entered the clinic based upon all the preclinical data we thought that the efficacy would be roughly comparable in the two populations. We felt very very good efficacy in preclinical models for both diseases. So we think that as the sample size increases and we get a better a point estimate.

We're feeling or are still excited that that potentially the two will have fairly similar.

Joel Lawrence Beatty: Thanks, I appreciate that. And then there is one other question.

<unk>.

<unk> efficacy.

Performance.

Joel Lawrence Beatty: and Augment 101 Registrational Trials. What endpoints would be important from a competitive lens?

Okay.

Thanks.

And then maybe one other question on the.

One O one registrational trials.

And points will be important from a competitive landscape perspective.

Joel Lawrence Beatty: And from a competitive landscape perspective, you know, with clinicians, would it be that same CRCRH rate that's important to regulators, or are there other focuses? Well, so it's quite interesting.

Missions would it be the same crs.

That's important to regulators or are there other focuses.

Dr. Briggs Morrison: Well, so it's quite interesting. Obviously, from a regulatory point of view, it's the CR-CRH. As we've talked about previously, from a clinical point of view, the other excitement that we've gotten from investigators participating in the trial is the high MRD negative rate. So we do have patients in the trial, and this goes to the earlier question about durability, who had a CRP, their platelets hadn't fully recovered yet, they were MRD negative, and they immediately went for a bone marrow transplant.

Well, so it's quite interesting and obviously from a regulatory point of view as you can see our share a tree.

As we've talked about previously the from a clinical point of view the other.

Excitement that we've gotten from investigators participating in trial as the high margin negative rate. So there.

We do have patients in the trial and this goes to the earlier question about durability, who had M. A C. R. P. Their platelets hasn't fully recovered yet they were negative and they immediately went to bone marrow transplant.

Dr. Briggs Morrison: Those patients won't get counted in the CRCRA. And so, in terms of your CR-CRH rate and durability of CR-CRH, those CRPs who go to bone marrow transplantation don't get counted. The regulatory rules, that's okay, but from a clinical point of view, that's a very, very important result for the patient. So, the total number of MRD negative CR patients who can go on to bone marrow transplant is something that we've heard a lot of excitement about from our investigators.

Those patients would get counted in the CR cri rate.

And so in terms of your CRC, our HOA and durability of CR CRH, those crp's, who go to bone marrow transplant don't get counted.

That regulatory rules, that's okay, but from a clinical point of view, that's a very very important.

<unk> for the patient so the total number of MRV negative CR patients who can go on to bone marrow transplant is something that we've heard a lot of excitement about it from our investigators.

Operator: Our next question comes from the line of Peter Lawson of Barclays. Your line is now open. Hey, thanks.

Terrific. Thank you.

Yeah.

Our next question comes from the line of Peter Lawson of Barclays. Your line is now open.

Operator: Thanks for the update; I very much appreciate it. Thank you for taking the questions.

Thanks for the update.

Very much appreciate it.

Thanks for taking the questions just.

Peter Richard Lawson: Just on, I guess, as patients move on to transplantation on the FNDX. How quickly do they move on to transplant in your studies? Yeah, it's a good question, Peter.

All of them.

I guess as patients move on to transplant.

If in the X.

It's the team how quickly do they move on to transport them and you.

<unk> studies.

Dr. Briggs Morrison: I don't have that data right at the tip of my fingers about how long it takes from when they start treatment to go on to transplant. I think the one other thing to remember, and I mentioned this in my prepared remarks about the design of our pivotal trial, in the pivotal trials, once they go on to transplant, they are eligible to go back on 5613 once they engraft. And that, again, has been a frequent request from the treating physicians. They look at their patient, and they say, I have nothing to offer this patient.

They are eligible to go back on 50, 613, Wednesday, and graft and that again has been a.

A frequent request from the treating physicians they they look at their patient and they say I had nothing to offer this patient your drug got them to an <unk> negative CR.

Peter Richard Lawson: Your drug got him to an MRD negative CR. Great, I took him to transplant. I'd love to put him back on your drug and maintain that CR post bone marrow transplant. And in the phase one trial, the trial wasn't really set up to do that, but in the pivotal trial, we will be able to do that. So I think we'll start to learn a bit about how the drug performs in the post-transplant setting.

Great took on the transplant I'd love to put them back on your drug and maintain that that C or postpone their transplant and in the phase one trial. The trial wasn't really set up to do that but in a pivotal trial, we will be able to do that so I think we'll start to learn a bit about how the drug.

Ah performs in the post transplant setting.

Perfect. Thank you and then when do you expect to start the <unk>.

Peter Richard Lawson: Thank you. When do you expect to start the arm where patients don't have the strong CYP3A4? Yeah, we think it'll just be a couple of months. As I mentioned in the response to Phil's question, we do want to get a little bit more PK data to decide between the 226 and the 276. So it'll be a couple of months to enroll some additional patients and make that final decision. Thank you. And just finally, is there anything that precludes NPM1 patients, do you think, from reaching CRH?

Patients don't have the stroke.

<unk> three <unk> four inhibitor.

Yeah, we think it will just be a couple of months as I mentioned in a response to Phil's question, we do want to get a little bit more PK data to decide between the $2 26 in the $2 76.

So it'll be a couple of months to enroll some additional patients and make that final decision.

Thank you and then just finally is there anything that precludes NPM one patients do you think from reaching CRH.

Operator: There are no questions coming in at this time. I'm now turning the call back to Dr. Morrison.

No.

Perfect.

Okay.

Thank you.

Sure thing.

There are no questions coming in at this time I'm now turning the call back to Dr. Morrison.

Dr. Briggs Morrison: Thank you everybody again for joining us on the call today. As I said, we feel like this was really a very important breakout quarter for us.

Thank you.

So much operator, and thank you everybody again for joining us on the call today as I said, we felt like this was really a very important breakout quarter for us we now have.

Dr. Briggs Morrison: We now have FDA buy-in to take our lending program into pivotal trials. We've finalized the agreement with Insight, and we really feel a tremendous sense of momentum building in the company. So we look forward to sharing additional updates on both programs at ASH, and thank you for your time.

FDA buy in to take our amendment program into pivotal trials.

We've.

Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.

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

Q3 2021 Syndax Pharmaceuticals Inc Earnings Call

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