Q2 2021 Syndax Pharmaceuticals Inc Earnings Call

August 9, 2021

[music].

Thank you for standing by and welcome to this index second quarter 2021 financial results conference call.

Operator: Thank you for standing by, and welcome to the next second quarter of 2021.

Operator: 2021 Financial Results conference call. At this time, all which is on a list in only mode.

At this time, all participants on a listen only mode.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question at that time, please press star than one on your touchtone telephone. As we are today, today's conference call is being recorded. I would now turn the conference over to your host, Melissa Forrest, with Oracle Partners. You may begin.

After the Speakers' presentation, there'll be a question and answer session.

To ask a question at that time. Please press Star then 1 when you touch tone telephone.

As for them on today's call. This call is being recorded.

I will now turn the conference over to your host Melissa Forst with Oracle partners you may begin.

Thank you Valerie welcome and thank you for those of you joining us on the line and the webcast. This afternoon for a review of Sinton, Texas second quarter, 2021 financial and operating results.

Melissa Forrest: Thank you, Valerie. Welcome, and thank you to those of you joining us on the line and the webcast this afternoon for a view of Syndax's second 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 Daphne Corridis, Chief Financial Officer. Also joining us on the call for the question-and-answer session is Michael Mesker, President and Chief Operating Officer, Dr. Michael Myers, Chief Medical Officer, and Dr. Michael Myers, Chief Medical Officer, and Dr. Peter Ordentlick, Chief Scientific Officer.

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 Daphne Curtis Chief Financial Officer also joining us on the call for the question answer session is Michael Metzger, President and Chief Operating Officer, Dr. Michael Meyers Chief Medical Officer.

Dr Peter or test like Chief Scientific Officer.

This call is being accompanied by a slide deck that has been posted on the company's website. So I'd ask that you. Please turn to the forward looking statements on slide 2.

Melissa Forrest: This call is being accompanied by a slide deck that has been posted on the company's website. So I'd 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. However, actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factors section of the company's most recent quarterly report on Form 10Q, as well as other reports filed with the SEC.

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

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

Melissa Forrest: Any forward-looking statements represent the company's views as of today, August 9th, 2021, only. A replay of the call will be available on the company's website at the conclusion of the call. And with that, I'm pleased to turn the call over to you, Dr. Briggs-Morson, Chief Executive Officer of Sindh.

Any forward looking statements represent the company's views as of today August 9.2021 only.

A replay of the call will be available on the company's website at the conclusion of the call and with that I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer Index.

Thanks, very much Melissa and thank you to everyone joining us on today's call and the webcast.

Dr. Briggs Morrison: Thanks very much, and thank you to everyone 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. We've continued to make great progress in both of our clinical programs during the second quarter of this year. Augment 101, our phase one-two trial of S&DX 5613, our selective MEN inhibitor, is progressing as anticipated with a meaningful FTA meeting coming up this quarter.

Slide 3 provides a high level summary of our current corporate priorities as we strive to realize on future, which people with cancer live longer and better than ever before with <unk>.

Continue to make great progress on both of our clinical programs during the second quarter of this year augment 101, our phase 1.2 trial of S. Index 50, 613 are selected Menin inhibitor is progressing as anticipated with meaningful FTA BD coming up this quarter.

Dr. Briggs Morrison: Today we are announcing that we are initiating two trials that capitalize on the favorable combinability profile of 5613, and importantly, one of the trials represents our first opportunity to move into the frontline therapy of AMS. For Acetylomab, our antibody against CSF-R, enrollment is ongoing in our pivotal Agave 201 trial. We therefore remain on track to have two registrational programs ongoing this year for two first-in-class and potentially best-in-class medicines for two areas of important unmet medical needs.

Today, we are announcing that we are initiating 2 trials that capitalized on the favorable compatibility profile of 56, <unk> and <unk>.

Fortunately 1 of the trials represents our first opportunity to move into the frontline therapy of email.

For <unk>, our antibody against yourself on our enrollment is ongoing in our pivotal agave to a 1 trial.

We therefore remain on track to have 2 registrational programs ongoing this year for 2 first in class and potentially best in class medicines for 2 areas important unmet medical need.

Dr. Briggs Morrison: 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. Now, let's now turn to slide four in our recent data disclosure from the Phase 1 portion of the Augment 101 trial of SNDX 5613 for the treatment of leukemia. As we noted in our recent data disclosure, in our phase one trial, 5613 has been well tolerated over multiple cycles, with no patient discontinuing due to a drug-related adverse event.

Thanks to the support of our many committed investors, we are well financed and 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 our recent data disclosure from the phase 1 portion of the augment 1 on 1 trial of S. N D. Ex 56, <unk> for the treatment of leukemia.

As we noted in our recent data disclosure in our phase 1 trial 50, 613 had been well tolerated over multiple cycles with no patients discontinuing for drug related adverse event.

Dr. Briggs Morrison: We were, of course, excited to have also observed clear evidence of monotherapy activity in this population of patients, relapse or refractory acute leukemia with either MLLR or NPMia with either MLLR or NPM 1C mutation, with most responders achieving MRD negative status.

We were of course excited to have also the clear evidence of monotherapy activity in this population of patients with relapsed or refractory acute leukemia with either MLR or N. P. M..1 see mutations with most responders achieving <unk> negative status.

Our pharmacodynamic data confirm the mechanism of action and perhaps most importantly, we had had identified candidate recommended phase 2 dose that met all of our pre specified criteria.

Dr. Briggs Morrison: Our pharmacodynamic data confirmed the mechanism of action, and perhaps most importantly, we had identified a candidate recommended phase two dose that met all of our pre-specified criteria. We also previously communicated that we were exploring intermediate doses that represented an increase in dose over the candidate recommended phase-through dose. Since our last call, we have now completed our review of initial results from the intermediate dose, which is 276 milligrams twice a day in arm A and 163 milligrams twice a day in arm B.

We also previously communicated that we were exploring intermediate doses that represent an increase in dose over the candidate recommended phase 2 dose.

Since our last call. We have now completed our review of the initial results from the intermediate doses, which are 276 milligrams twice a day and army.

Hundred and 63 milligrams twice a day in RMB.

These intermediate doses have also met all of our pre specified criteria for our recommended phase 2 dose and therefore, we have updated our recommended phase 2 dose selection.

On slide 5 we include the DRP results and the dose selection portion of the trial.

And arm as you see we have moved from 113 to 226 to $3.39, and finally to $2.76 with no DLT observed at these intermediate dose level of $2.76.

Dr. Briggs Morrison: These intermediate doses have also met all of our pre-specified criteria for a recommended phase two dose, and therefore, we have updated our recommended phase two dose selection. On slide 5, we include the DLP results in the dose selection portion of the trial. In arm A, you can see we have moved from 113 to 226 to 339 and finally to 276.

In RMB, we moved from $1.13 to $2.26, and finally to 163 with again no D. L tease out the intermediate 163 milligram dose level.

Both $2.76 in arm, a and 163 and RMB had been well tolerated and now represent are nominated recommended phase 2 dose.

As you may recall, the only D. L. T. We have seen with 50.613 is grade 3 Q T C prolongation and we did not see that in.

Dr. Briggs Morrison: No DLTs were observed at the intermediate dose level of 276. In R&B, we moved from 113 to 226 and finally to 163, with, again, no DLTs at the intermediate 163 milligram dose. Both 276 in Arm A and 163 in RB have been well tolerated and now represent our nominated recommended phase 2. As you may recall, the only DLT we have seen with 5613 is Grade 3 QTC prolongation, and we did not see that in the 276 Arm A or the 163 Arm B cohort.

The $2.76 on 8 or the $1.63 arm B cohorts.

We attribute this to efforts we have made with our investigative sites to implement simple clinical measures to minimize the incidence of Qt prolongation.

I did want to reinforce why we are so excited about what we're seeing in our phase 1 program.

First remind everyone that this is a phase 1 trial patients had received on average 3 prior therapies about 40% of patients had relapsed after a bone marrow transplant, but he's a very negative prognostic sign and almost 60 per cent had previously received the net o'clock.

These are very difficult to treat patients and we were delighted to see a 48% overall response rate or <unk>.

Dr. Briggs Morrison: We attribute this to efforts we have made with our investigative sites to implement simple clinical measures to minimize the incidence of QT prolongation. I again want to reinforce why we are so excited about what we are seeing in our Phase 1 program. Let me first remind everyone that this is a phase one trial, and patients had received on average three prior therapies. About 40% of patients had relapsed after a bone marrow transplant, which is a very negative prognostic sign, and almost 60% had previously received chemotherapy phonetically.

23%, CR CRH rate and 67 per cent of the responses achieving MLD negative staff.

Every physician currently treating acute leukemia, who has reviewed this data with US has been excited by the efficacy we are seeing.

We are aware of the regulatory precedent for the approval of novel targeted therapies for patients with relapsed refractory acute leukemia.

And while there are no guidelines on a specific rate that is required for approval. We have previously pointed out the rates that were reported for recently approved flip III and IV H inhibitors that suggests that a C. R. CRH rate above 20% has been acceptable to FDA.

Dr. Briggs Morrison: These are very difficult to treat patients, and we were delighted to see a 48% overall response rate, a 23% CRCRH rate, and 67% of the responses achieved an MRD negative status. Every physician currently treating acute leukemia who has reviewed this data with us has been excited by the efficacy We are aware of the regulatory precedents for the approval of novel targeted therapies for patients with relaps, refractory, and acute leuk And while there are no guidelines on a specific rate that is required for approval, we have previously pointed out the rates that were reported for recently approved flip 3 and IDH inhibitors that suggest that a CRCRH rate above 20% has been acceptable to FDA.

The phase 1 data we have generated from around 50 patients treated in our ongoing augment 1 on 1 trial gives us confidence that 56 her team will achieve that level of efficacy or better in our phase 2 trial.

Slide 6 shows our go forward plans for 50, 613th.

We had the option to initiate the phase 2 portion of augment 1 on ones as previously communicated we have our updated recommended phase 2 dose.

However, our clinical and regulatory team decided not to start the phase 2 portion at risk and instead decided to first garner endorsement from FDA regarding our recommended phase 2 dose selection.

This decision was in keeping with the excellent working relationship we've established with the agency and are being awarded fast track designation.

Dr. Briggs Morrison: Phase 1 data we have generated from around 50 patients treated in our ongoing Augment 101 trial gives us confidence that 5613 will achieve that level of efficacy or better in our Phase 2 trial. Slide 6 shows our Go Forward Plans for 5613.

The end of Phase 1 meeting is anticipated to occur this quarter as we have previously communicated with the phase II portion to open soon thereafter.

While we have not officially started the phase 2 expansion portion of the trial, we are continuing to enroll additional patients at our proposed recommended phase 2 dose and have FDA agreement that these newly enrolled patients may be included in our phase 2 expansion cohorts pending of course their approval of our recommended phase 2 dose.

Dr. Briggs Morrison: We had the option to initiate the phase two portion of Augment 101, as previously communicated. We have our updated recommended phase two dose. However, our clinical and regulatory team decided not to start the phase two portion at risk and instead decided to first garner endorsement from FDA regarding our recommended phase two dose selection. This decision was in keeping with the excellent working relationship we've established with the agency and will be awarded Fast Track designation.

We anticipate presenting a full and substantive update of augment in 1 on 1 at a medical conference at the end of this year.

We have treated over 40 patients with either MLR or N P M mutations and anticipate having a relatively mature dataset.

To date, we've only shown the CR CRH rate for our phase 1 population as a whole, but we are excited that at the end of the year given this larger and more mature dataset that we will be able to break out the C. RCRA trade for MLR versus N. P. M line.

Dr. Briggs Morrison: The end of phase one meeting is anticipated to occur this quarter, as we have previously communicated, with the phase two portions to open soon there. While we have not officially started the phase two expansion portion of the trial, we are continuing to enroll additional patients at our proposed recommended phase two dose and have FDA agreement that these newly enrolled patients may be included in our phase two expansion cohorts pending, of course, their approval of our recommended phase two.

We will also present a promising first look at the durability of the C. R series responses, which is an important aspect on the efficacy of 50.613.

We believe these updates at a medical conference at the end of the year will be important and could meaningfully address key aspects of the 50.613 profile.

As I've mentioned previously the phase 2 portion of the trial will enroll 3 distinct expansion cohorts patients with MLR, a O L patients with MLR AML and patients with N P M on mute CML.

Dr. Briggs Morrison: We anticipate presenting a full and substantive update of Augment 101 at a medical conference at the end of this year, when we will have treated over 40 patients with either MLLR or NPM mutations and anticipate having relatively mature data. To date, we've only shown the CRCR rate for our phase one population as a whole, but we are excited that at the end of the year, given this larger and more mature data set, we'll be We will also present a promising first look at the durability of the CRCR responses, which is an important aspect of the efficacy of 5630.

The phase 2 portion will enroll both pediatric and adult patients, thereby providing us the potential path to regulatory approval with a broad label, including both adults and pediatrics.

I should note that the results are positive. This phase 2 portion of augment 1 on 1 could potentially support a regulatory filing given existing regulatory precedence.

We look forward to soon finalizing the details on the trial with the FDA and believe we could potentially have topline data for 1 or more of a cohorts sometimes sometime next year.

Over the last period, we have also been conducting extensive research into the broad landscape of clinical opportunities for 50.613 beyond the initial approval in relapsed refractory acute leukemias as illustrated on slide 7.

Our goal as a company is to be first to market in relapsed refractory disease, and then be first to garner additional value driving indication.

Dr. Briggs Morrison: We believe these updates at a medical conference at the end of the year will be important and could meaningfully address key aspects of the 5613 profile. As I've mentioned previously, the phase two portion of the trial will enroll three distinct expansion cohorts, patients with MLR, ALL, patients with MLR AML, and patients with MPM1 mutant AML. The phase two portion will enroll both pediatric and adult patients, thereby providing us a potential path to regulatory approval with a broad label including both adults and children. I should note that the results are positive.

Today, we are announcing our first steps towards building out the 50.613 franchise.

Our scientists in collaboration with scientists at M. D. Anderson have recently published preclinical data supporting the use of our Menin inhibitor in combination with Vanadic lacks the references provided on the slide.

The leukemia and lymphoma society, otherwise known as L. L. S is sponsoring an umbrella trial the day called beat AML.

Yes.

They had been assessing potential menin inhibitors to include in the trial and based on the strength of our data have selected 50.613 is the first menin inhibitor to be tested as a specific targeted therapy for patients with MLR or N P. M on AML.

The collaboration we have agreed to with them flow test 50, 613th in combination with the net of class and as decided in newly diagnosed AML patients that are unfit for induction chemotherapy and will consist of a phase 1 and a phase 2.3 trial, which potentially could serve as the basis for our regulatory filings.

Dr. Briggs Morrison: This phase two portion of Augment 101 could potentially support a regulatory filing given existing regulatory precedent. We look forward to soon finalizing the details of the trial with FDA and believe we could potentially have top-line data for one or more of the cohorts sometime next. Over the last period, we have also been conducting extensive research into the broad landscape of clinical opportunities for 5613 beyond the initial approval in relapse refractory acute leukemias, as illustrated on slide 7. Our goal as a company is to be first to market in relapse refractory diseases, and then be first to garner additional value-driving indications. Today we are announcing our first steps towards building out the 5613 franchise.

Our scientists have also generated preclinical data that supports the use of our menin inhibitor in combination with chemotherapy.

As a result, we are also initiating a second phase 1 trial exploring 50, 613, which will be called augment 1 or 2 in combination with standard salvage chemotherapy is used for pediatric patients with either <unk> or AML.

We anticipate announcing additional trials over the remainder of the year that will further build out there.

The 50.613 franchise.

I mean, now turn to slide 8 and axis filling up our potentially best in class monoclonal antibody therapy targeting the CSF 1 receptor.

As you know we presented our phase 1 chronic graft versus host disease data at Ash in December of last year.

Dr. Briggs Morrison: Our scientists, in collaboration with scientists at MD Anderson, have recently published preclinical data supported the use of our Menden Inhibitor in combination with Benetoclast, the reference is provided on the slide. The Leukemia and Lymphoma Society, otherwise known as LLS, is sponsoring an umbrella trial that they call Beat AML. They have been assessing potential meninhibitors to include in the trial, and based on the strength of our data, have selected 5613 as the first menin inhibitor to be tested as a specific targeted therapy for patients with MLLR or NPM1 AML, collaboration we agreed to with them will test 5613 in combination with Benetoclax and Aesicidine in newly diagnosed A&L patients that are unfit for induction chemotherapy, and will consist of a phase one and a phase two three trial, which potentially could serve as a basis for regulatory file.

You may recall that we had open day phase 2 expansion cohort at the 1 milligram per kilogram dose.

And as previously announced that cohort has now been fully enrolled.

Later this year, we anticipate presenting a full updated data from both the 17 patients from the phase 1 portion of the trial as well as the 23 patients enrolled in the phase 2 expansion cohort at the 1 day protect us.

I should emphasize that our base case assumption is that this 1 big per ticket dose will be our label dose and hence the phase 2 expansion cohort data is quite relevant as a derisking event to the eventual outcome of our pivotal trial.

Slide 9 is our pivotal trial for ex until I'm, having chronic graft versus host disease. This trial is the act of telematics for graft versus host disease trial called the debate on 1.

The trial is enrolling patients with chronic graft versus host disease, whose disease has progressed after 2 prior therapies.

Patients must be at least 6 years of age and have met overall entry criteria.

Dr. Briggs Morrison: Our scientists have also generated preclinical data that supports the use of an mRNA inhibitor in combination with chemotherapy. As a result, we are initiating a second phase one trial exploring 5613, which will be called Augment 102, in combination with standard salvage chemotherapy used for pediatric patients with either ALL or AMI. We anticipate announcing additional trials over the remainder of the year that will further build out the 5613 framework. I may now turn to slide 8 and axiolam is potentially the best in class monocon antibody therapy targeting the CSF1. As you know, we presented our Phase 1 chronic graph versus host disease data at Ash in December of last year. And we may recall that we had opened a phase-expansion cohort at the one milligram per kilogram dose

It's a pivotal dose ranging trial in which patients will be randomized to 1 of 3 treatment groups. Each investigating a distinct dose abaxis telematics given either every 2 weeks or every 4 weeks.

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

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

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

We believe the chronic gvhd 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.

With the most recent pivotal results from both inside Jakafi and cabinets value most of the deal and the recent approval of value. Most of the deal. We will soon see commercial launches that will begin to delineate the commercial opportunities in chronic graft versus host disease.

Despite recent advancements in this area to our knowledge ex told that was the only agent in clinical development that specifically targets the monocyte macrophage lineage.

Dr. Briggs Morrison: And as previously announced, that cohort has now been fully enrolled. Later this year, we anticipate presenting the full updated data from both the 17 patients from the phase one portion of the trial, as well as the 23 patients enrolled in the phase two expansion cohort at the one-mig meeting. I should emphasize that our base case assumption is that this one-mig-pig dose will be our label dose, and hence the phase two expansion cohort data is quite relevant as a derisking event for the eventual outcome of our pivotal trial.

We believe the data generated to date with ex until a mab 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 complementary medicines.

We've also been working extensively with experts in the field on fibrotic diseases and half on a strong consensus that the scientific rationale for the ex efficacy backs until on that chronic graft versus host disease supports its potential in a wide variety of for fibrotic diseases, such as idiopathic pulmonary fibrosis instead of on.

Dr. Briggs Morrison: Slide 9 is our pivotal trial for axiomab in chronic graph versus host disease. This trial is the basis for a graph versus host disease trial called agavecone 1. The trial is open to patients with chronic graph 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.

Burma or.

We're actively evaluating options by which to build out the telematic ex till that franchise beyond chronic graft versus host disease and to take advantage of book, we believe our significant set of opportunities that could materialize enhance shareholder value.

As we have previously communicated we obtained orphan drug designation from FDA for the use of ex until the mab in IPF.

Dr. Briggs Morrison: It's a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axiomab given either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria per chronic graph versus host. Secondary endpoints will include duration of response and validated quality of life assessments using the least. Enrollment in the study is underway, We believe that chronic DVHD 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.

And finally on slide 10, we summarize the transactions that led to the acquisition of the 50, 613th and acts and tell him out program.

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.

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 the preferred partners for such transactions.

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

Thank you Fred the results of operations for the second quarter of 2021.

And the comparison to the prior year quarter are included in our press release, So I won't repeat them on these remarks additional financial details are available on our first 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 $22.9 million or 44 cents per share compare.

Dr. Briggs Morrison: With the most recent pivotal results from both Insights, Jackify, and Cadmonds' Bellum-Mosidil, and the recent approval of ValuMosidil, we will soon see commercial launches that will begin to delineate the commercial opportunities in chronic grapher's social, Despite recent advancements in this area, to our knowledge, Aptilamad is the only agent in clinical development that specifically targets the monocyte macrophage, You believe the data generated to date with acetylomab suggests it has the potential to play an important role in the treatment of chronic graph versus host of these, both as monotherapy and given its safety profile in combination with complementary models. We've also been working extensively with experts in the field of fibrodic diseases and have found a strong consensus that the scientific rationale for the efficacy of axiomab and chronic graft versus host disease supports its potential in a wide variety of fibroic diseases such as idiopathic pulmonary fibrosis and stederm, actively evaluating options by which to build out the Acetylamm franchise beyond chronic graft versus host disease and to take advantage of what we believe are significant set of opportunities that can materially enhance shareholder value.

To the $17.1 million or 42 cents per share for the same period last year.

Net loss for the second quarter was below the guidance of $35 million to $40 million on total operating expenses for the quarter due primarily to the shifting of timing for some CMC activity, which shifted into the second half of this year.

Turning to slide 11, we ended the second quarter with $253.1 million in cash and cash equivalents and 51.9 million shares and pre funded warrants warrants outstanding. This cash balance provides us cash runway into 2023, and importantly covers the development cost.

For both our lead programs to achieve our corporate objectives and milestones during the period.

Looking ahead I'd like to provide financial guidance for the third quarter of 2021 for the third quarter, we expect R&D expenses to be $25 million to $30 million and total operating expenses to be $30 million to $35 million, including approximately 2 and a half million of noncash stock compensation.

Expense.

A year 2021 guidance remains unchanged and we continue to expect R&D expenses to be $90 million to $100 million and total operating expenses to be $110 million to $120 million, including approximately 2 and a half million dollars of noncash stock compensation.

Dr. Briggs Morrison: As we have previously communicated, we obtained orphan drug designation from FDA for the use of acetylamab in IP. And finally, on slide 10, we summarized the transactions that led to the acquisition of the 5613 and HACTAL amount 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 stages, and We anticipate we will be able to continue to expand our pipeline through product acquisitions or in-licensing, quality differentiated assets, and we expect to remain among the preferred partners for such transactions. I now turn the call over to Daphne to review our financial response. Thank you, Brid.

And per quarter with that I would like now to turn the call back over to Brad.

Great. Thank you so much Daphne let me close the call by again, noting that we have begun the registrational trial for ex until a map in chronic graft versus host disease and are on track to start the Registrational program for SMB ex 50.613 shortly.

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 2 ongoing registration programs is a major achievement.

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

Daphne Corridis: Thank you, Briggs. The results of our operations for the second quarter of 2021 and the comparison to the prior year quarter are included in our press release, so I won't repeat them in these remarks. Additional financial details are available in our first quarter report on Form 10Q, which was filed earlier today. I would like to point out that our net loss for the quarter was $22.9 million, or 44 cents per share, compared to $17.1 million, or 42 cents per share, for the same period last year.

We believe 50.613 could have broad utility across a wide range of clinical settings in acute leukemia.

We're excited to be announcing our next steps in building out the F&B ex 50.613 franchise.

I could tell him out also holds the promise of a broad franchise opportunity both in chronic graft versus host disease and across a broad range of fibrotic disease.

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

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

Proven track record of delivering on this pillar of our corporate strategy and I believe this is a core strength of our company.

Daphne Corridis: This net loss for the second quarter was below the guidance of $35 to $40 million of total operating expenses for the quarter due primarily to the shifting of timing for some CMC activities, which shifted into the second half of this year.

As always I'd like to thank the wonderfully talented team here at index, our collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs.

Daphne Corridis: Turning to slide 11, we ended the second quarter with $253.1 million in cash and cash equivalents and 51.9 million shares and pre-funded warrants outstanding. This cash balance provides this cash runway into 2023 and importantly covers the development cost for both our lead programs to achieve our corporate objectives and milestones during this period. Looking ahead, I'd like to provide financial guidance for the third quarter of 2021. For this third quarter, we expect R&D expenses to be $25 to $30 to $30 to $30 to $35 million, including approximately $2.5 million of non-cash stock compensation expense.

In addition, I'd like to thank our committed long term investors, who are helping us build this great company.

With that I'll open the call for questions.

Thank you again, ladies and gentlemen, if you like to ask a question. Please press Star then 1 on your Touchstone telephone again back a question. Please press Star then 1 on them on Macquarie first question.

Our first question comes from Phil Nadeau of Cowen and company. Your line is open.

Thanks for taking my questions a few from US just first would you be willing to disclose what do you see your time above the ICU 94, the recommended phase 2 doses.

Second were the updated data you rented crude goes first.

This initial experience from the recommended phase 2 doses and then third we're quicker to do you hope to get from you after the meeting.

So Phil I think your first question if I heard it correctly you wanted to know the AUC in time above IC 94, the intermediate doses.

If you'd be willing to disclose that.

Yeah, I think we'd be willing to I, just don't know that off the top of my head. So let me, let me dig into that and we can get back to you on that.

Daphne Corridis: Full year 2021 guidance remains unchanged, and we continue to expect R&D expenses to be $90 to $100 million and total operating expenses to be $110 to $120 million, including approximately $2.5 million of non-cash stock compensation expense per quarter. With that, I would like to turn the call back over to Briggs.

Your second question was at the year end, we also have data from the intermediate doses yeah. That's about.

That rate debt financing that is yes, okay, perfect and then the F. D. A meeting there's there's sort of 4 things that we'd like to.

Get some agreement on number 1 of course is the recommended phase II dose.

Number 2 are the endpoints were pretty clear that it's CR CRH are complemented by information on transfusion independence or infections or other palliative endpoints.

Dr. Briggs Morrison: Great, thank you so much, Stephanie. Let me close the call by again noting that we have begun the registrational trial for axiomab in chronic graft versus host disease and are on track to start the registrational program for SNDX 5613 soon. 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.

Our net number 3 is the sample size, how many patients do we need to enroll in.

Number 4 is some endorsement that if the data is positive that these are phase 2 expansion cohorts.

It could be registrational. So those are the some of the things that we want to get in our conversation with them.

That's perfect.

Thanks for taking our questions.

Thank you.

Our next comes from golf, it's Pamela.

Your line is open.

Oh I assume this is awesome would work on a pretty girl congrats on all the progress and thanks for taking my questions.

Dr. Briggs Morrison: We are also very excited about the broad franchise opportunities for both programs beyond their initial registration indications. We believe 5613 could have broad utility across a wide range of clinical settings and acute leukemia, and we are excited to be announcing our next steps in building out the S&DX 5613 franchise. Axitellamount also holds the promise of a broad franchise opportunity, both in chronic graph versus host disease and across a broad range of fibronic diseases. We are comfortable, given our cash on hand, that we have the financial resources to aggressively advance our program and achieve key upcoming models.

I guess my first 1 would be on the the another clocks combo.

Is it correct to think that there maybe exposure or PK extension.

Benefit for 615613.

Given that the other classes of sort of 3 or 4 inhibitor.

And maybe how does that affect the need for 2 different doses, depending on sort of 3 or 4 usage and I guess, how are you thinking about the dosing strategy with the net o'clock generally.

Yeah.

Right. So just to clarify venetic lacks actually is not a flip through a 4 inhibitor.

Net of classes metabolized by for 3 or 4 so if you look at the Vanilla class label, what you'll see is debt if you'd give a net of clocks in combination with another drug that inhibits hippurate for it there's a dose adjustment for venetic class just as there. We anticipate there is 450.613, so the net of class.

<unk> should not inhibit the metabolism of 50, 613, and 50.613 should not affect the metabolism of genetic Max So we're pretty optimistic that the combination of a 50.630, plus you know the class A's decided inc.

Dr. Briggs Morrison: 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'd like to thank the wonderful talented team here at Syndax, our collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical program. In addition, I'd like to thank our committed long-term investors who are helping us build this great company. Now, I'd open the call to questions.

We should be able given the safety profile of 50.613 to be able to get full doses.

Both our drug and then either in the triplet.

Oh, Okay. Thank you for clarifying on I guess my second question would be on I can tell him up and maybe how you're thinking about the evolving landscape, especially with the recent approval of the on most of the deal.

The recent Paducah extension for Rux wasn't it.

Dr. Briggs Morrison: Thank you. Again, ladies and gentlemen, if you would like to ask a question, please press star and then one on your touch tone telephone. Again, to ask the question, please press star and then one. One moment for our first question.

It sounds like the FDA is being cautious with the Jack So I'm just kind of wondering how you and maybe physicians for gvhd or excuse me on that thanks.

Yeah, I mean, the initial data that we presented at Ash last year, we were quite encouraged to see efficacy for a Max of telematics in patients who had previously received rux or had previously received the most.

Operator: Good afternoon, thanks for taking our questions. A few from us.

Phil: Just first, would you be willing to disclose the AUC or time above the IC90 for the recommended phase two doses? Second, will the updated data at ERAN include those phases, the initial experience from the recommended phase two doses? And then third, what clarity do you hope to get from the FDA meeting? Thank you.

So we think there is an evolving now sort of approval landscape toward drugs in chronic graft versus host disease, and we think that ex until a mab will provide a complementary mechanism.

Dr. Briggs Morrison: So, Phil, I think your first question, if I heard it correctly, you wanted to know the AUC and Time Above IC90 for the intermediate doses. Yeah, if you'd be willing to disclose it.

That again, either as monotherapy in patients who have received other therapies or in combination with some of these emerging therapies. We think offers a very promising opportunity for those patients.

Dr. Briggs Morrison: Yeah, I think we're going to, I just don't know that off the top of my head, so let me dig into that, and we can get back to you on that. Your second question was, at year end, would we also have data from the intermediate doses? Yeah, that's right? Yep. And the answer to that is yes.

Okay. Thank you very much.

Thank you. Our next question comes from Joel Beatty of Baird. Your line is open.

Hi, congrats on the progress.

It's great to see Theres no dose limiting toxicities are great.

And the ex.

Expansion.

On the print.

Paired remarks too much in debt.

Dr. Briggs Morrison: Yep, and then at the FDA meeting, there are sort of four things that we'd like to get some agreement on. Number one, of course, is the recommended phase two dose. Number two are the endpoints. We are pretty clear that it's CRCRH, complemented by information on transfusion independence or infections or other palliative outcomes. Number three is the sample size, how many patients do we need to enroll, and number four is some endorsement that if the data is positive, these phase two expansion cohorts could be registrational. So those are some of the things that we want to get in our conversation. That's perfect. Thanks for taking our questions.

Maybe attributed upwards that clinical sites on pick the minimized those could you talk more about those efforts.

Yeah sure Joel so.

On the observation that had been made by some of our investigators and our clinical staff that I'm, a little more I should say aggressive correction of electrolyte.

Which again is a squirrel supplementation, that's not very complicated it's a very straightforward thing, but rather than having patients who have their electric lights in the normal range that on.

<unk> some have made as if she can keep patients on the high normal range you tend to see less.

Qt prolongation from any agent that is known to.

Phil: That's perfect. Thanks for taking our question.

To to cost per location. So we've been working with the sites to help them with that and educate them on that it seems to be paying off again, it's pretty straightforward. It's just oral supplementation of their electric lights, but once we get them into the right range. They do seem to be kind of small number they do seem to be seeing less qt prolongation.

Operator: Tomlin, a city group, your line is open.

Ashiq Alim Mubarack: Hi, this is Asha Mubarak, Andreagal. Congratulations on all the progress, and thanks for taking the time to answer my questions. I guess my first one will be on the Venetoplax combo. Is it correct to think that there may be an exposure or PK extension benefit for 61513, given that Benadiplax is a 530-4 inhibitor? And maybe how does that affect the need for two different doses depending on 5-4 usage? And I guess, how are you thinking about the dosing strategy with Venetoclax generally?

Great and then maybe 1 more question on the.

<unk> AML.

Trial that was announced today.

Could you talk a little bit more about the trial design.

Sounds like there may be multiple phases to it I guess I'm curious.

Is there a point in time, where there'd be maybe on a go no go decision that may be made.

So I'd, rather the growth continues or not and if so what would cause that decision be based on.

Yeah, so they're so it's on it.

Dr. Briggs Morrison: Right, so just to clarify, Venetaclax is not actually a Sip-3-A-4 inhibitor, although it is metabolized by Sip-3-A-4. So if you look at the Venetaclax label, what you'll see is that if you give Venetaclax in combination with another drug that inhibits Cip-3-A-4, there's a dose adjustment for Venetaclax, just as we anticipate there will be for 56-13. So Venetaclax should not inhibit the metabolism of 5613 and 506. 613 should not affect the metabolism of Venetoclact, and so we're pretty optimistic that the combination of 5613 plus metacicicidine we should be able, given the safety profile of 5613, to be able to get full doses of both our drug and Benaza in the triple.

It's a program that essentially we have collaborated with the beat AML team. The first part of course is just it is a phase 1.2 assets earlier question of <unk>.

Can you get what is the right dose of the triplet for each of the agents and the triplet. So that's the phase 1 portion.

Once we have confirmed that the 56th or team we have.

The right dose to give them venues that it goes into randomized Ah Ah trial of than is ever since my days at plus 50, 613, and we'll say more in the future Joel about exactly what those that don't know goes are from phase 2 to phase III.

But it is sort of setup beds.

Certainly.

Initial thought is it would be a seamless phase II 3 and there will be a go no go which we'll say more about in the future.

Great. Thank you.

Thank you on next question comes from Peter Lawson of Barclays. Your line is open.

Ashiq Alim Mubarack: Oh, okay, thank you for clarifying that. I guess my second question would be about axitlamab, and maybe how you are thinking about the evolving landscape, especially with the recent approval of Bill and Mostadil and the recent Padufa extension for ruxlitnib. Sounds like the FDA is being cautious with the jack, so I'm just kind of wondering how you and maybe physicians for GVHD are perceiving that. Thanks. Yeah, I mean, the initial data.

Thanks for taking my question, thanks for the updates as well.

On <unk> as we think about patients rolling over to the <unk>.

Phase III pivotal.

Your line and if so how many patients do you think you could have.

As the phase 2 pivotal studies.

Yeah.

Yeah. So again, Peter remember, we had said we could potentially add agency has said as you know the as.

As you continue to backfill.

Our cohorts, where you've already seen efficacy.

Dr. Briggs Morrison: Yeah, I mean, the initial data that we presented at Ash last year, you know, we were quite encouraged to see efficacy from acetylamab in patients who had previously received rucks or had previously received amosidil. So we think there is an evolving landscape now for drugs in chronic graft or soce disease, and we think that Axitilamab will provide a complementary mechanism that, again, either as monotherapy, in patients who have received other therapies or in combination with some of these emerging therapies, we think offers a very promising opportunity for those patients.

You know those could count we.

We haven't really said yet how many patients those are but it just gives you a little bit of.

Head start as we head into the phase II.

But again, we don't know the final number of patients to be enrolled in the phase 2 so hard to say exactly what you know what what.

Percentage of the total phase III population that represents.

Got you Okay. Thank you and then on.

Augment 1 them too or chemotherapies that you're looking to combine with.

Yeah, Michael mirrors are you on can you just say more about that.

Yeah.

Yes.

I don't know if Michael's go on.

Yeah.

Yes.

Okay, sorry, I had trouble getting myself book, so yeah, Peter what we were going to complying with would be 2 different regimens that are typically used in relapsed refractory AML 1 being a.

Ashiq Alim Mubarack: Okay, thank you very much. Thank you. Our next question comes from Joel Beatier Barrett. Your line is open.

Operator: Hi, congrats on the progress. It's great to see.

Joel Lawrence Beatty: to see that there are no those limiting toxicities or great

Joel Lawrence Beatty: three QTCs in the expansion or intermediate doses. And I think on the prepared remarks you mentioned, that may be attributed to efforts.

On a flag based regimen for AML and then the other would be a 4 drug regimen typically use.

A O L.

Okay.

Joel Lawrence Beatty: efforts at clinical sites to minimize those risks could tell us more about those efforts.

Thank you and then I guess the.

The final question would just be about other frontline trials that youre growth put their own suit.

Dr. Briggs Morrison: Yeah, sure, so the observation has been made by some of our investigators and our clinical staff that a little more, I should say, aggressive correction of electrolytes, which, again, is this oral supplementation. It's not very complicated. It's a very straightforward thing. But rather than having patients who have their electrolytes in the normal range, the observations some have made is that if you can keep patients in the high normal range, you tend to see less.

Either.

Good day.

The 1 that's about to start.

But on the other ones you want to run frontline and would that go through academic firmer or non for profit or going on.

Okay.

Yeah. So we I think as we've talked about before we've been doing quite a bit of work trying to understand what are the debt.

The various development opportunities, obviously, a combination with venues that we think is.

On a timely unimportant given its increasing use of standard of care in patients who are not candidates for induction chemotherapy.

Dr. Briggs Morrison: QD prolongation from any agent that is known to cross-tukes. So we've been working with the sites to help them with that and educate them on that, and it seems Again, it's pretty straightforward. It's a floral supplementation of their electrolytes, but once we get them into the right range, we do seem to be, again, a small number; we do seem to have less QT prolongation. Great, and then maybe one more question. It's on the Beat AML trial that was announced today. Can you tell us a little bit more about the trial design? It sounds like there

A binding with so called 7 plus 3 in patients who are candidates for induction chemotherapy.

Also makes sense and then there are there are other other aspects of the program that we'll be saying more about progressive.

Okay. Thank you so much.

Thank you. Our next question comes from Justin <unk> with B Riley Securities. Your line is open.

Hi, Thanks for taking my questions I have a couple on the beat trial.

So I guess the first is is there a possibility of that competitor menin inhibitors could get added to that or is it most likely 1 drug from a single class and then the other question related to beat is on.

Joel Lawrence Beatty: There may be multiple phases to it. I guess I'm curious, you know; is there a point in time where there might be maybe a go-no-go decision that may be made?

Are you guys actually running the trial yourselves and how much control do you have over those data releases.

Yeah. So the first question you know I think we probably have to defer to the LLS team.

Joel Lawrence Beatty: be made to decide whether the drug should continue or not, and if so, on what basis that decision should be based? Yeah, so it's

I don't believe in the in the arrangement, we have with them that they can't.

Dr. Briggs Morrison: Yeah, so it's a program that essentially, we have collaborated with the BDML team. The first part, of course, is just a phase one to ask this earlier question of, you know, can you get, what is the right dose of the triplet for each of the agents in the triplet? So that's the phase one portion. Once we have confirmed that 5613, you know, we have, we know the right dose to give in Venetia, that it goes into a randomized trial. of Vanazza versus Vanneza plus 5613.

Include another met inhibitor, if they wish to.

Hum.

I don't see that that's about all I can say I don't know if they wish to.

And then the second question is part of the reason of working with the beat AML team is.

Because these trials are already up and running and the sites are all up and running and the beat AML team is a sort of ready to go.

We will let them run the trial.

They've proven that they can do this quite efficiently and effectively we think the trial actually will start faster.

Dr. Briggs Morrison: And we'll say more in the future, Joel, about exactly what those go-no-goes are from phase two to phase three. But it is sort of set up as... sort of a, the initial thought is there will be a seamless phase two, and three, and there will be a go-no-go, which we'll say more about the Great, thank you. Thank you. The next question comes from Peter Lawson-Barclaid. Thanks for taking the questions.

Because you already have all their sites opened this is just another part of adding into the trial.

We've worked closely with them on the on data disclosures.

You know I think there is excited to present data as we are.

Got it thanks for the question that's all for me.

Thank you and our next question comes from David Lebowitz of Morgan Stanley. Your line is open.

Thank you very much for taking my question.

Operator: the updates as well. Just on, as we think about patients rolling over to phase two pivotal, for your men, and inhibiting. How many patients do you think you will have

When you look at the men on data to date, thus far.

Could you I guess elaborate on the efficacy across the doses are.

Peter Richard Lawson: I think you could have it as the

And how that plays into the ultimate dose selection.

Peter Richard Lawson: as the phase two pivotal starts.

Dr. Briggs Morrison: Yeah, so again, Peter, remember we said we could potentially, what the agency has said is, you know, as you continue to backfill cohorts where you've already seen efficacy, those could count. We haven't really said yet how many patients those are, but it just gives you a little bit of a head start as we head into phase two. But again, we don't know the final number of patients to be enrolled in phase two, so it's hard to say exactly what, you know, what percent of the total phase two population they represent.

Yeah.

Yeah, So again, David the dose selection and the recommended phase 2 dose selection is not based on efficacy the dose selection, it's based upon safety Tolerability and PK.

What we have said.

<unk> said previously is that.

When we were looking at the 113 RMB 226 RMA.

Africa C in that population is.

Roughly the same as it is in the overall population, which is really the way that we presented the data.

And obviously, we'll have a lot more to say about efficacy.

By dose by arm and by Mutational status.

Dr. Briggs Morrison: Okay, thank you. And then on Augment.

At the end of the year on a medical conference and as I said on my prepared remarks will also we're excited to be able to show with the initial durability of the C. R CRH responses as well.

Peter Richard Lawson: augment 102 or chemo.

Peter Richard Lawson: What chemotherapy is you looking to combine Yeah, Michael Myers, are you on? Can you say more?

Michael Werner Schmidt: Yeah, Michael Myers. Are you on? Can you say more about that?

Thank you for that and with respect to the Qt elongation.

Michael Werner Schmidt: Sorry, I had trouble getting myself off the mute.

Michael Werner Schmidt: getting myself off the mute. So, yeah, Peter, what we were going to combine with would be two different regimens that are typically used in relapse refractory AML, one being a flag-based regimen for AML, and then the other would be a four drug regimen typically used in ALL.

I guess yeah.

You you spoke about.

How practices, we're handling I guess, the newer patients on the different doses differently.

Is there any way you could elaborate on on how that changed and why those 2 doses seem to have no Q2 on the elongation, whereas lower doses did it.

Peter Richard Lawson: And then I guess the final question would just be about other frontline trials that you'd want to run.

And the prior release.

Yeah. So again, if you look at 1.6 debt 113, RMB and the $2.26 arm a there wasn't 1 day L. T in each of those and again in RMB, a relatively large number of patients.

Peter Richard Lawson: So nice to see the

Peter Richard Lawson: The one that is about to start. Are there other ones you want to run on the front line, and would that go through academic, farmer, or non-for-profit organizations?

As I said with the.

Helping sites to make sure that there there are adequately or supplement the electrolyte seems to be helping.

Dr. Briggs Morrison: Yeah, I think as we've talked about before, we've been doing quite a bit of work trying to understand what the various development opportunities are, obviously, a combination with Veniz that we think is timely and important given its increasing use as the standard of care in patients who are not candidates for induction chemotherapy. Combining with the so-called 7 plus 3 in patients who are candidates for induction chemotherapy also makes sense. And then there are other aspects of the program that we will be saying more about as the year progresses.

Helping on those intermediate doses.

But.

Well start to see how that plays out as we enroll more patients I think what we had said at the last when we presented the data in April is that at the recommended phase II dose, we were seeing somewhere around 8 or 9% re III Qt prolongation.

It is possible with this.

And interaction with the sites and people getting more comfortable with what needs to be done that that rate could come down.

As we enroll more patients.

Thank you for taking my questions.

Thank you.

Peter Richard Lawson: Okay, thank you so much.

I'm showing no further questions at this time on I'm trying to call back over to Doctor Morrison for any closing remarks.

Operator: Thank you. Our next question comes from Justin Walsh with D. Rowley Security. Hi, thanks for taking the questions. I have a couple on the Beat trial.

Thanks, so much operator, and thanks, everybody for joining us on the call again, we think it was a very productive quarter.

We're excited about the data that we'll be updating at the end of the year at a medical conference and we're excited to be able to start our first first line trial.

Justin Walsh: So I guess the first question is, is there a possibility that competitor meta-inhibitors could get added to that, or is it most likely one drug from a single class? And then the other question related to Beat is, are you guys actually running the trial yourselves, and how much control do you have over the data related to that? Yeah, so the first question, you know, I think we probably have to defer to the LLS team. I don't believe in the arrangement we have with them that they can't include another male inhibitor if they wish to. That's about all I can say.

And as Daphne pointed out I think we're well financed to be able to get through a lot of this work. So thank you all for your attention and your questions anything else you can do please get in touch with us.

Thank you ladies and gentlemen, this does conclude today's conference. Thank you all participating you may all disconnect have a great day.

[music].

Dr. Briggs Morrison: I don't know if they wish to. And then the second question is, part of the reason for working with the BMA team is that because this trial's already up and running, and the sites are all up and running, and the BID AML team is sort of ready to go, we will let them run the trial. They've proven that they can do this quite efficiently and effectively. We think the trial will actually start faster because you already have all their sites open. This is just another arm added to the trial, and we've worked closely with them on data disclosures. I think they're as excited to present the data as we are.

Dr. Briggs Morrison: Got it. Thanks for the question that's been offered. Thank you. And our next question comes from David Levelwood of Morgan Stanley. Your line is open.

Operator: Thank you very much for taking

David Levelwood: My question.

David Levelwood: I will look at the metan data to date thus far. Could you, I guess, elaborate on the efficacy across the doses and how that plays into the ultimate dose selection?

Dr. Briggs Morrison: Yeah, so again, David, the dose selection, the recommended phase to dose selection is not based on efficacy. The dose selection is based upon safety, tolerability, and PK. What we have said previously is that when we were looking at the 113RMB, 226 arm A, efficacy in that population was roughly the same as it is in the overall population, which is really the way that we presented the data. And obviously, we'll have a lot more to say about efficacy by dose, arm, and by mutational status at the end of the year at a medical conference.

Dr. Briggs Morrison: And as I said in my prepared remarks, we're excited to be able to show the initial durability of the CRH responses as well. Thank you. With respect to the QT elongation, I think you spoke about how practices were handling the newer patients.

[music].

David Levelwood: the newer patients on the different doses differently. Is there any way you could elaborate on how that changed and why those two doses seem to have no QT longation, whereas lower doses did in the prior release?

Dr. Briggs Morrison: Yeah, so again, if you look at 113 arms B and 226 arms A, there was one DLT in each of those. And again, in Arm B, a relatively large number of patients. As I said, helping sites to make sure that they're adequately or supplementing electrolytes seems to be helping on those intermediate doses. But we'll sort of see how that plays out as we get more patients. I think what we had said at the last when we presented the data in April was that at the recommended phase two dose, we were seeing somewhere around 8 or 9% rate 3 QTC prolongation. It's possible with this, you know, closer interaction with the sites and people getting more comfortable with what needs to be done, that that rate could come down as we enroll more patients.

Operator: Thank you for taking my questions. I'm showing no further questions at this time. I was trying to call back over to Dr. Morrison for any closing remarks. Thanks so much, and thanks everybody for joining us on the call. Again, we think it was a very productive quarter. We're excited about the data that we'll be updating at a medical conference at the end of the year, and we're excited to be able to start our first, first-line trial. And, as Daphne pointed out, I think we're well financed to be able to get through a lot of this work.

Dr. Briggs Morrison: So thank you all for your attention and your questions. Anything else you can do, please again, touch me. Thank you. Ladies and gentlemen, this does include today's conference. Thank you all for participating. You may all just connect. Have a great day. Theeerner

Operator: I'm gonna be able to be, and and and and and and You Thank Bhopi, Bres. Thank you. Thank you. Thank you. Thank you. I. Thank you, and and Thank you, Thee.

Operator: Thank you. Thank you. Thank you. Thank you.

Operator: call. At this time, all of which is been on a listen-only mode. After the speaker's presentations, there will be a question-and-answer session. To ask a question at that time, please press star than one on your touchtone telephone, as we are on today's conference call is being recorded. I would now turn the office over to your host, Melissa Forst, with Oracle Partners. You may begin.

Melissa Forrest: Thank you, Valerie. Welcome, and thank you to those of you joining us on the line and the webcast this afternoon for a view of Syndax's second 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 Daphne Corridis, Chief Financial Officer. Also joining us on the call for the question and answer session is Michael Mesker, President and Chief Operating Officer, Dr. Michael Myers, Chief Medical Officer, Dr. Michael Myers, Chief Medical Officer, and Dr. Peter Ordentlick, Chief Scientific Officer.

Dr. Briggs Morrison: Thanks very much, and thank you to everyone 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. We've continued to make great progress in both of our clinical programs during the second quarter of this year. Augment 101, our phase one-two trial of S&DX 5613, our selective men inhibitor, is progressing as anticipated with a meaningful FDA meeting coming up this quarter.

[music].

Dr. Briggs Morrison: Today we are announcing that we are initiating two trials that capitalize on the favorable combinability profile of 5613, and importantly, one of the trials represents our first opportunity to move into the frontline therapy of A&L. For Acetylamab, our antibody against CSF-R, enrollment is ongoing in our pivotal Agave 201 trial. We therefore remain on track to have two registrational programs ongoing this year for two first-in-class and potentially best-in-class medicines for two areas of important unmet medical needs.

Thank you for standing by and welcome to the second quarter 2021 Financial result conference call.

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

The speaker's presentation, there will be a question and answer session baskets.

To ask a question at that time. Please press Star then 1 on your Touchtone telephone.

On today's call. This call is being recorded.

I would now I'll turn the conference over to your host Melissa Forst with Argot partners you may begin.

Thank you Valerie welcome and thank you for those of you joining us on the line and the webcast. This afternoon for a review of some taxes second quarter 2021 financial and operating results.

Dr. Briggs Morrison: Our pharmacodynamic data confirmed the mechanism of action, and perhaps most importantly, we had identified a candidate recommended phase two dose that met all of our pre-specified criteria. We also previously communicated that we were exploring intermediate doses that represented an increase in dose over the candidate recommended phase-through dose. Since our last call, we have now completed our review of the initial results from the intermediate dose, which is 276 milligrams twice a day in arm A and 163 milligrams twice a day in arm B.

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 Daphne <unk> Chief Financial Officer.

Also joining us on the call for the question answer session is Michael Metzger, President and Chief Operating Officer, Dr. Michael Meyers, Chief Medical Officer, and Dr. Peter <unk>, Chief Scientific Officer.

This call is being accompanied by a slide deck that has been posted on the company's website. So I'd ask you. Please turn to the forward looking statements on slide 2.

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

Dr. Briggs Morrison: No DLTs were observed at the intermediate dose level of 276. In R&B, we moved from 113 to 226 and finally to 163, with again no DLTs at the intermediate 163 milligram dose. Both 276 in RMA and 163 in RB have been well tolerated and now represent our nominated recommended phase 2. As you may recall, the only DLT we have seen so far is 5613, Grade 3 QTC prolongation, and we did not see that in the 276 arm A or the 163 Arm B cohort.

Any forward looking statements represent the company's views as of today August 9th 2021 on like a replay of the call will be available on the company's website at the conclusion of the call and with that I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer Index.

Thanks, very much Melissa and thank you to everyone joining us on today's call and webcast.

Slide 3 provides a high level summary of our current corporate priorities as we strive to realize on future, which people with cancer live longer and better than ever before.

Continue to make great progress on both of our clinical programs during the second quarter of this year, albeit 1 on 1 our phase 1.2 trial of <unk> ex 50, 613 are selected Menin inhibitor is progressing as anticipated with a meaningful FTA BD coming up this quarter.

Today, we are announcing that we are initiating 2 trials that capitalize on the favorable compatibility profile of 56 <unk>.

Accordingly, 1 of the trials represents our first opportunity to move into the frontline therapy. There you go.

Perhaps you tell them on our antibody against yourself on our enrollment is ongoing in our pivotal agave to a 1 trial.

We therefore remain on track to have 2 registrational programs ongoing this year for 2 first in class and potentially best in class medicines for 2 areas important unmet medical need.

Dr. Briggs Morrison: These are very difficult to treat patients, and we were delighted to see a 48% overall response rate, a 23% CRCRRH rate, and 67% of the responses achieved an MRD negative status. Every physician currently treating acute leukemia who has reviewed this data with us has been excited by the efficacy we are achieving. We are aware of the regulatory precedents for the approval of novel targeted therapies for patients with relapsing, refractory, acute leukemia.

Thanks for the support of our many committed investors, we are well financed and vigorously pursued 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 our recent data disclosure from the phase 1 portion of the augment 101 trial of S&P ex 56, <unk> for the treatment of leukemia.

As we noted in our recent data disclosure in our phase 1 trial 50, 613 has been well tolerated over multiple cycles with no patients discontinuing for drug related adverse event.

Dr. Briggs Morrison: And while there are no guidelines on a specific rate that is required for approval, we have previously pointed out the rates that were reported for recently approved flip-3 and IDH inhibitors that suggest that a CRCRH rate above 20% has been acceptable to FDA. The phase 1 data we have generated from around 50 patients treated in our ongoing Augment 101 trial gives us confidence that 5613 will achieve that level of efficacy or better in our Phase 2 trial. Slide 6 shows our Go Forward Plans for 5613.

We were of course excited to have also observed a clear evidence of monotherapy activity in this population of patients with relapsed or refractory acute leukemia with either MLR on N. P. M..1 see mutations with most responders achieving <unk> negative status.

On a pharmacodynamic data confirm the mechanism of action and perhaps most importantly, we had had identified candidate recommended phase 2 dose that met all of our pre specified criteria.

We also previously communicated that we were exploring intermediate doses that represents an increase in dose over the candidate recommended phase 2 dose.

Dr. Briggs Morrison: We had the option to initiate the phase two portion of Augment 101, as previously communicated. Additionally, we have our updated recommended phase two dose. However, our clinical and regulatory team decided not to start the phase two portion at risk and instead decided to first garner endorsement from FDA regarding our recommended phase two dose selection. This decision was in keeping with the excellent working relationship we've established with the agency and will be awarded Fast Track designation.

Since our last call. We have now completed our review of the initial results from the intermediate doses, which are 276 milligrams twice a day and army.

Hundred and 63 milligrams twice a day in RMB.

Are these intermediate doses have also met all of our pre specified criteria for our recommended phase 2 dose and therefore, we have updated our recommended phase 2 dose selection.

On slide 5 we include the D. L. P results and the dose selection portion of the trial.

Dr. Briggs Morrison: The end of phase one meeting is anticipated to occur this quarter, as we have previously communicated, with the phase two portions to open soon thereafter. While we have not officially started the phase two expansion portion of the trial, we are continuing to enroll additional patients at our proposed recommended phase two dose and have FDA agreement that these newly enrolled patients may be included in our phase two expansion cohorts pending, of course, their approval of our recommended phase two, We anticipate presenting a full and substantive update of Augment 101 at a medical conference at the end of this year, who will have treated over 40 patients with either MLLR or NPM mutations and anticipate having a relatively mature data, To date, we've only shown the CRCR rate for our phase one population as a whole, but we are excited that at the end of the year, given this larger and more mature data set, that we'll be able to break out the CRCRH rate for MLR versus NPM.

And on a U C. We have moved from 113 to $2.26 to 339, and finally to $2.76 with no DLT observed at the intermediate dose level of $2.76.

And on B, we moved from 113 to $2.26, and finally to 163 with again no DLP is at the intermediate 163 milligram dose level.

Both $2.76 in arm, a and $1.63, and RMB had been well tolerated and now represent are nominated recommended phase 2 dose.

As you may recall, the only D. L. T. We have seen with 50.613. This grade III Qt prolongation, and we did not see that Inc.

The 276 or 8 or the $1.63 on B cohort.

We attribute this to efforts we have made with our investigator sites to implement simple clinical measures to minimize the incidence of Qt prolongation.

Dr. Briggs Morrison: We will also present a promising first look at the durability of the CRCR responses, which is an important aspect of the efficacy of 5630. We believe these updates at a medical conference at the end of the year will be important and could meaningfully address key aspects of the 5613 profile. As I've mentioned previously, the phase two portion of the trial will enroll three distinct expansion cohorts, patients with MLR-A-L, patients with MLR AML, and patients with MPM-1 mutant AML. The phase two portion will enroll both pediatric and adult patients, thereby providing us a potential path to regulatory approval with a broad label including both adults and pediatric patients. I should note that the results are positive.

I again want to reinforce why we are so excited about what we're seeing in our phase 1 program.

First remind everyone that he was a phase 1 trial patients had received on average 3 prior therapies about 40 per cent of patients had relapsed after a bone marrow transplant, if he'd been very negative prognostic sign and almost 60 per cent had previously received phonetically.

These are very difficult to treat patients and we were delighted to see a 48% overall response rate.

23%, CR CRH rate and 67 per cent of the responses achieving MLD negative status.

On every physician currently treating acute leukemia, who has reviewed this data with US has been excited by the efficacy we are seeing.

We are aware of the regulatory precedent for the approval of novel targeted therapies for patients with relapsed refractory acute leukemia and while there are no guidelines on a specific rate that is required for approval. We have previously pointed out the rates that were reported for recently approved flit 3 in Ath inhibitors that suggests.

Dr. Briggs Morrison: This phase two portion of Augment 101 could potentially support a regulatory filing given existing regulatory precedent. We look forward to soon finalizing the details of the trial with FDA and believe we could potentially have top-line data for one or more of the cohorts sometime next year. Over the last period, we have also been conducting extensive research into the broad landscape of clinical opportunities for 5613 beyond the initial approval in relapse-refractory acute leukemias, as illustrated on slide 7. Our goal as a company is to be first to market in relapse refractory disease and then be first to garner additional value-driving indications. Today we are announcing our first steps towards building out the 5613 franchise.

See our CRH rate above 20 per cent has been acceptable to FDA.

The phase 1 data we have generated from around 50 patients treated in our ongoing augment 1 on 1 trial gives us confidence that 50, 613, well achieve that level of efficacy or better in our phase 2 trial.

Slide 6 shows our go forward plans for 50, 613th we had the option to initiate the phase 2 portion of augment 1 on 1 as previously communicated we have our updated recommended phase 2 dose.

However, on a clinical and regulatory team decided not to start the phase 2 portion at risk and instead decided to first garner endorsement from FDA regarding our recommended phase 2 dose selection.

Dr. Briggs Morrison: Our scientists, in collaboration with scientists at MD Anderson, have recently published preclinical data supported the use of our Mending Inhibitor in combination with Benetoclass, the reference is provided on the slide. The Leukemia and Lomoma Society, otherwise known as LLS, is sponsoring an umbrella trial that they call Beat AML. They have been assessing potential meninhibitors to include in the trial, and based on the strength of our data, have selected 5613 as the first menin inhibitor to be tested as a specific targeted therapy for patients with MLLR or NPM 1 AML, collaboration we have agreed to with them will test 5613 in combination with Venetac's and Asa Cidididine in newly diagnosed AML patients that are unfit for induction chemotherapy, and will consist of a phase one and a phase two three trial, which potentially could serve as a basis for regulatory file.

This decision was in keeping with the excellent working relationship we've established with the agency and are being awarded fast track designation.

The end of Phase 1 meeting is anticipated to occur this quarter as we have previously communicated with the phase 2 portion to open soon thereafter.

Well, we have not officially started the phase II expansion portion of the trial, we are continuing to enroll additional patients at our proposed recommended phase 2 dose and have FDA agreement that these newly enrolled patients may be included in our phase 2 expansion cohorts pending of course their approval of a recommended phase 2 dose.

We anticipate presenting a full and substantive update of augment 1 on 1 at a medical conference at the end of this year.

We have treated over 40 patients with either another la or N. P M mutations and anticipate having a relatively mature dataset.

Dr. Briggs Morrison: Our scientists have also generated preclinical data that supports the use of an inhibitor in combination with chemotherapy. As a result, we are initiating a second phase one trial exploring 5613, which will be called Augment 102, in combination with standard salvaged chemotherapies used for pediatric patients with either ALL or AMB. We anticipate announcing additional trials over the remainder of the year that will further build out the 5613 framework. I may now turn to slide 8. Axiomab and axiomab are potentially best-in-class monocon antibody therapy targeting the CSF-1. As you know, we presented our Phase 1 chronic graph versus host disease data at Ash in December of last year. We may recall that we opened a phase to expansion cohort at the one milligram per kilogram dose.

We will also present, a promising first look at the durability of CR CRH responses, which is an important aspect on the efficacy of 50.613.

We believe these updates at a medical conference at the end of the year will be important and could meaningfully address key aspects of the 50.613 profile.

As I've mentioned previously the phase 2 portion of the trial will enroll 3 distinct expansion cohorts patients with MLR a L. L patients with MLR AML and patients with N P M on mute AML.

The phase 2 portion will enroll both pediatric and adult patients, thereby providing us a potential path to regulatory approval with a broad label, including both adults and pediatrics.

I should note that the results are positive this phase II portion of augment 1 on 1 could potentially support a regulatory filing given existing regulatory pressures.

We look forward to soon finalizing the details on the trial with the FDA and believe we could potentially have topline data for 1 or more of a cohorts sometimes sometime next year.

Dr. Briggs Morrison: And as previously announced, that cohort has now been fully enrolled. Later this year, we anticipate presenting the full updated data from both the 17 patients from the phase one portion of the trial, as well as the 23 patients involved in the phase to expansion cohort at the 1-mig per kign. I should emphasize that our base case assumption is that this one-mig-per-kig dose will be our label dose, and hence the phase two expansion cohort data is quite relevant as a derisking event for the eventual outcome of our pivotal trial.

Our goal as a company is to be first to market in relapsed refractory disease, and then be first to garner additional value driving indication.

Today, we are announcing our first steps towards building out the 50.613 franchise.

Our scientists in collaboration with scientists at M D Anderson.

Actually published preclinical data supporting the use of our many inhibitor in combination with Benetti class references provided on the slide there.

Dr. Briggs Morrison: Slide 9 is our pivotal trial for axiomab in chronic graph versus host disease. This trial is the arm for a graph versus host disease trial called Agave-211. The trial is open to patients with chronic graph 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.

The leukemia and lymphoma society, otherwise known as LLS is sponsoring an umbrella trial the day called beat AML.

The collaboration we have agreed to with them go past 50.613 in combination with the net of class and as decided in newly diagnosed AML patients that are unfit for induction chemotherapy and will consist of a phase 1 and a phase 2.3 trial, which potentially could serve as the basis for our regulatory filings.

Dr. Briggs Morrison: It's a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axiolam given either every two weeks or every four. The primary endpoint is overall response rate using the 2014 NIH consensus criteria per chronic graph versus hose. Secondary endpoints will include duration of response and validated quality of life assessments using the least. Enrollment in the study is underway, and we are on track to deliver top-line data in 2020.

Our scientists have also generated preclinical data that supports the use of our menin inhibitor in combination with chemotherapy.

As a result, we're also initiating a second phase 1 trial exploring 50, 613, which will be called augment 1 O..2 in combination with standard salvage chemotherapy is used for pediatric patients with either a L. L. R. A M L.

We anticipate announcing additional trials over the remainder of the year that will further build out there.

Dr. Briggs Morrison: We believe that chronic GVHD 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. With the most recent pivotal results from both Insights of Jacify and Cadmines-Val and the recent approval of Valu-Mosidil, we will soon see commercial launches that will begin to delineate the commercial opportunity in chronic grapher's social, Despite recent advancements in this area, to our knowledge, Axtelamad is the only agent in clinical development that specifically targets the monocyte macrophage, You believe the data generated to date with acetylamab suggests it has the potential to play an important role in the treatment of chronic graph versus host disease, both as monotherapy and given its safety profile in combination with complementary models.

The 50.613 franchise.

Let me now turn to slide 8 and actually tell them at a potentially best in class monoclonal antibody therapy targeting the CSF 1 receptor.

As you know we presented our phase 1 chronic graft versus host disease data at Ash in December of last year.

You may recall that we had open day phase 2 expansion cohort at the 1 milligram per kilogram dose.

And as previously announced that cohort has now been fully enrolled.

I should emphasize that our base case assumption is that this 1 big per tank dose will be our label dose and hence the phase 2 expansion cohort data is quite relevant as a derisking event to the eventual outcome of our pivotal trial.

Slide 9 is our pivotal trial for ex until I'm, having chronic graft versus host disease. This trial is the active till them up for a graft versus host disease trial called the agave till 1.

Dr. Briggs Morrison: We've also been working extensively with experts in the field of fibrodic diseases and have on a strong consensus that the scientific rationale for the efficacy of acetylamab and chronic graft versus host disease supports its potential in a wide variety of fibroic fibroic diseases such as idiopathic pulmonary fibrosis and scleroderm, actively evaluating options by which to build out the Acetylamm franchise beyond chronic graft versus host disease and to take advantage of what we believe are significant set of opportunities that can materially enhance shareholder value. As we have previously communicated, we obtained orphan drug designation from FDA for the use of acetylamab in IP.

The trial is enrolling patients with chronic graft versus host disease, whose disease has progressed after 2 prior therapies.

Patients must be at least 6 years of age and have met overall entry criteria.

It's a pivotal dose ranging trial in which patients will be randomized to 1 of 3 treatment groups. Each investigating a distinct dose that's telematics given either every 2 weeks or every 4 weeks.

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 the least symptom scale.

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

Dr. Briggs Morrison: And finally, on slide 10, we summarized the transactions that led to the acquisition of the 5613 and HACTELAMAP 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 and flex. We anticipate we will be able to continue to expand our pipeline through product acquisitions or in-licensing of quality differentiated assets, and we expect to remain among the preferred partners for such transactions. I now turn the call over to Daphne to review our financials. Thank you, Bri

Despite recent advancements in this area to our knowledge that's still on that would be only agents in clinical development that specifically targets the monocyte macrophage lineage.

We've also been working extensively with experts in the field on fibrotic diseases and half on a strong consensus that the scientific rationale for the ex efficacy back to tell them that chronic graft versus host disease supports its potential in a wide variety of for fibrotic diseases, such as idiopathic pulmonary fibrosis instead of on.

Daphne Corridis: The results of our operations for the second quarter of 2021 and the comparison to the prior year quarter are included in our press release, so I won't repeat them in these remarks. Additional financial details are available in our first quarter report on Form 10Q, which was filed earlier today. I would like to point out that our net loss for the quarter was $22.9 million, or 44 cents per share, compared to $17.1 million, or 42 cents per share, for the same period last year.

Burma or.

We're actively evaluating options by which to build out the telematic ex until that franchise beyond chronic graft versus host disease and to take advantage of book, we believe our significant set of opportunities that can materially enhance shareholder value.

As we have previously communicated we obtained orphan drug designation from FDA for the use of ex until on that and IPF.

And finally on slide 10, we summarize the transactions that led to the acquisition of the 50, 613th and acts and tell them that progress.

We anticipate we will be able to continue to expand our pipeline through product acquisitions or in licensing of quality differentiated assets and we expect to remain among the preferred partners for such transactions.

Daphne Corridis: Turning to slide 11, we ended the second quarter with $253.1 million in cash and cash equivalents and 51.9 million shares and pre-funded warrants outstanding. This cash balance provides this cash runway into 2023 and importantly covers the development cost for both our lead programs to achieve our corporate objectives and milestones during this period. Looking ahead, I'd like to provide financial guidance for this third quarter of 2021. For this third quarter, we expect R&D expenses to be $25 to $30 million, and total operating expenses to be $30 to $35 million, including approximately $2.5 million of non-cash stock compensation expense.

I'll now turn the call over to Daphne to review our financial itself.

Thank you Fred.

All of our operations for the second quarter of 2021.

And the comparison to the prior year quarter are included in our press release, So I won't repeat on the need for marks additional financial details are available in our first 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 $22.9 million or 44 cents per share compare.

The $17.1 million or 42 cents per share for the same period last year.

Net loss for the second quarter was below the guidance of $35 million to $40 million on total operating expenses for the quarter due primarily to the shifting of timing for some CMC activities, which shifted into the second half of this year.

Turning to slide 11, we ended the second quarter with $253.1 million on cash and cash equivalents and 51.9 million shares and pre funded warrants warrants outstanding debt cash balance provides us cash runway into 2023, and importantly covers the development cost.

For both our lead programs to achieve our corporate objectives and milestones during the period.

Dr. Briggs Morrison: Great, thank you so much, Daphne. Let me close the call by again noting that we have begun the registrational trial for axetilab in chronic graft versus host disease and are on track to start the registration program for SNDX 5613 soon. 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.

Expense.

Full year 2021 guidance remains unchanged and we continue to expect R&D expenses to be $90 million to $100 million and total operating expenses to be $110 million to $120 million, including approximately 2 and a half million dollars of noncash stock comp.

Dr. Briggs Morrison: We're also very excited about the broad franchise opportunities for both programs beyond their initial registration indications. For example, we believe 5613 could have broad utility across a wide range of clinical settings in acute leukemia, and we are excited to be announcing our next steps in building out the S&DX 5613 franchise. Axiteelamount also holds the promise of a broad franchise opportunity, both in chronic graph versus host disease and across a broad range of fibronic diseases. We are comfortable, given our cash on hand, that we have the financial resources to aggressively advance our programs and achieve key upcoming models.

Patient expense per quarter with that I would like now to turn the call back over to Brad.

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

We believe 50.613 could have broad utility across a wide range of clinical settings in acute leukemia and were.

Dr. Briggs Morrison: 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'd like to thank the wonderful talented team here at Syndax, our collaborators, and, most importantly, the patients, trial sites, and investigators involved with our clinical program. In addition, I'd like to thank our committed long-term investors who are helping us build this great company. With that, I'd open the call to questions.

We're excited to be announcing our next steps in building out the F&B ex 50.613 franchise.

I could tell him out also holds the promise of a broad franchise opportunity both in chronic graft versus host disease and across a broad range of fibrotic disease.

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

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

As always I'd like to thank the wonderfully talented team here at syntax, our collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs.

Dr. Briggs Morrison: Thank you. Again, ladies and gentlemen, if you would like to ask a question, please press star and then one on your touch tone telephone. Again, to ask a question, please press star and then one. One moment for our first question. Our first question comes from Phil and Adieu of Cowan and Company, Yonan. Good afternoon.

In addition, I'd like to thank our committed long term investors, who are helping us build this great company.

Is that I would open the call for questions.

Thank you again, ladies and gentlemen, if you'd like to ask a question. Please press Star then 1 on your Touchtone telephone again to ask a question. Please press Star then 1 on them on my part first question.

Operator: Good afternoon, thanks for taking our questions. A few from us.

Our first question comes from Phil Nadeau of Cowen and company. Your line is open.

Thanks for taking my questions a few from US just first would you be willing to disclose what do you see your time above the ICU 94, the recommended phase 2 doses.

Phil: Just first, would you be willing to disclose the AUC or time above the IC90 for the recommended phase two doses? Second, will the updated data at ERAN include those phases of the initial experience from the recommended phase two doses? And then third, what clarity do you hope to get from the FDA meeting? Thank you.

The second well the updated data yearend on crude goes.

But the initial experience from the recommended phase 2 doses and then third we're quicker to do you hope to get from you after the meeting.

Dr. Briggs Morrison: So Phil, I think your first question, if I heard it correctly, you wanted to know the AUC and time above IC90 for the intermediate doses? Yeah, if you'd be wanting to disclose that.

So Phil I think your first question if I heard it correctly you wanted to know the AUC in time above IC 94, the intermediate doses, if you'd be willing to disclose that.

Dr. Briggs Morrison: Yeah, I think we were going to, I just don't know that off the top of my head, so let me dig into that, and we can get back to you on that. Your second question was, at year end, would we also have data from the intermediate doses? Yeah, that's right? Yep. And the answer to that is, yes.

Yeah.

I think we were going to I, just don't know that off the top line. So let me.

Let me dig into that and we can get back to you on that.

Your second question was at the year end. We also have data from the intermediate doses. Yeah. That's about right. Yeah I'd answer that is yes, okay. Perfect and then the F. D. A meeting there's sort of 4 things that we'd like to.

Dr. Briggs Morrison: Yep, and then at the FDA meeting, there are sort of four things that we'd like to get some agreement on. Number one, of course, is the recommended phase two dose. Number two are the endpoints. We are pretty clear that it's CRCRH, complemented by information on transfusion independence or infections or other palliative outcomes. Number three is the sample size, how many patients do we need to enroll, and number four is some endorsement that if the data is positive, these phase-to-expansion cohorts could be registrational. So those are some of the things that we want to get in our conversation. That's perfect. Thanks for taking our questions.

Get some agreement on number 1 of course is the recommended phase II dose.

Number 2 are the end points were pretty clear that its share CRH.

Complemented by information on transfusion independent or infections or other palliative endpoints.

Net number 3 is the sample size, how many patients do we need to enroll in.

And number 4 is some endorsement that if the data is positive that these are phase 2 expansion cohorts.

Could be registrational. So those are the some of the things that we want to get in our conversation with them.

That's perfect. Thanks for taking our questions.

Thank you.

Phil: That's perfect. Thanks for taking our question.

Our next comes from golf and Pamela.

Operator: Tomlin, a city group, your line is open.

Citigroup Your line is open.

Ashiq Alim Mubarack: Hi, this is Asha Mubarak, Andreagal. Congratulations on all the progress, and thanks for taking the time to answer my questions. I guess my first one will be on the Venetoplax combo. Is it correct to think that there may be an exposure or PK extension benefit for 61513, given that Benadlax is a Sip3 or 4 inhibitor? And maybe how does that affect the need for two different doses depending on SIFT3 or 4 usage? And I guess, how are you thinking about the dosing strategy with Venetoclax generally?

Oh, Hi, Kim this is awesome embark on a pretty girl congrats on all the progress and thanks for taking my questions.

I guess my first 1 would be on the the another clocks combo.

Is it correct to think that there may be an exposure or PK extension.

Benefit for 61613.

Given that the other classes of superior's or 4 inhibitor and maybe how does that affect the need for 2 different doses, depending on sort of 3 or 4 usage and I guess, how are you thinking about the dosing strategy with another clocks generally.

Dr. Briggs Morrison: Right, so just to clarify, Venetaclax is actually not a SIP-3-A-4 inhibitor, although it is metabolized by Sip-3-A-4. So if you look at the Venetaclax label, what you'll see is that if you give Venetaclax in combination with another drug that inhibits Sip-3-A-4, there's a dose adjustment for Venetaclac. Just as we anticipate there will be for 5613. So Venetaclax should not inhibit the metabolism of 5613 and 50613 and 506. 613 should not affect the metabolism of a person taking Venetaclax. So we're pretty optimistic that the combination of 5613 plus Venetacetacetam will be able, given the safety profile of 5613, to be able to get full doses of both our drug and Benaza in the triple.

Yeah.

Right. So just to clarify the net of class actually has not shipped through <unk> 4 inhibitor.

Net of classes metabolized by 3 or 4 so if you look at the vanilla class label, what you'll see is that if you'd give a net of cracks in combination with another drug that inhibits hippurate forward Theres a dose adjustment for genetic class just as do we anticipate there is 450.613, so the net of tax.

Should not inhibit the metabolism of 50, 613, and 50.613 should not affect the metabolism of genetic lax. So we're pretty optimistic that the combination of a 50.630, plus you know the class A's decided inc.

We should be able given the safety profile of 50.613 to be able to get full doses.

Both our drug and then either in the Triple net.

Ashiq Alim Mubarack: Okay, thank you for clarifying that. I guess my second question would be on acetylamab, and maybe how you are thinking about the evolving landscape, especially with the recent approval of Bill Dill and the recent Padufa extension for ruxlitnib. Sounds like the FDA is being cautious with jack, so I'm just kind of wondering how you and maybe physicians for GVHD are perceiving that. Thanks.

Oh, Okay. Thank you for clarifying that.

I guess my second question would be on I can tell him up and maybe how youre thinking about the evolving landscape, especially with the recent approval of the on most of the deal.

The reason Paducah extension for Russell isn't it.

It sounds like the FDA is being cautious with the Jack So I'm just kind of wondering how you and maybe physicians for gvhd or excuse me on that.

Dr. Briggs Morrison: Yeah, I mean, the initial data that we presented at Ash last year, we were quite encouraged to see efficacy from acetylamab in patients who had previously received rucks or had previously received valumosidil. So we think there is an evolving landscape now for drugs in chronic graft or soce disease, and we think that Axitilamab will provide a complementary mechanism that, again, either as monotherapy, in patients who have received other therapies or in combination with some of these emerging therapies, we think offers a very promising opportunity for those patients.

Yeah, I mean, the initial data that we presented at Ash last year, we were quite encouraged to see efficacy from ex until on the habit in patients who had previously received a rux or had previously received.

Adult so we think there isn't an evolving.

Now sort of approval landscape toward drugs in chronic graft versus host disease, and we think that ex until we're mad will provide a complementary mechanism a.

Operator: Okay, thank you very much. Thank you. Our next question comes from Joel Bader. Your line is open.

Okay. Thank you very much.

Thank you. Our next question comes from Joel Beatty of Baird. Your line is open.

Joel Lawrence Beatty: Hi, congrats on the progress. So it's great to see that there's no

Hi, congrats on the progress.

It's great to see Theres no dose limiting toxicities are great.

Joel Lawrence Beatty: These are great to create Q2Cs in

And the expansion in it.

Joel Lawrence Beatty: or intermediate doses. And I think the prepared remarks we mentioned may be attributed to efforts at clinical sites to minimize those,

On the print.

Paired remarks too much debt.

Maybe attributed to efforts that clinical sites on took the minimized those could you talk more about those efforts.

Joel Lawrence Beatty: To minimize those, could you tell us more about those efforts?

Yeah sure Joel so.

On the.

Dr. Briggs Morrison: Yeah, so, the observation has been made by some of our investigators and our clinical staff that a little more, I should say, aggressive correction of electrolytes, which again is this oral supplementation, it's not very complicated, it's a very straightforward thing, but rather than having patients who have their electrolytes in the normal range, the observations some have made is that if you can keep patients in the high normal range, you tend to see less So we've been working with the sites to help them with that and educate them on it, and it seems Again, it's pretty straightforward. It's just oral supplementation of their electrolytes, but once we get them into the right range, they do seem to be, again, a small number; we do seem to be seeing less QT prolongation.

Survey show that had been made by some of our investigators and our clinical staff that I'm, a little more Ah I should say aggressive correction and electrolyte.

Which again in fiscal supplementation is not very complicated, it's a very straightforward thing, but rather than having patients who have their electric lights in the normal range.

Net observation some have made as if you can keep patients on the high normal range you tend to see less.

Qt prolongation from any agent that is known to.

Joel Lawrence Beatty: Great, and then maybe one more question. It's on the Beat AML.

Great and then maybe 1 more question on the.

AML.

Joel Lawrence Beatty: trial that was

Trial that was announced today.

Joel Lawrence Beatty: Can you tell us a little bit more about the trial design, and it sounds like there may be multiple phases to it? I guess I'm curious; is there a point in time where there is maybe a go-no-go decision?

Could you talk a little bit more about the trial design.

Sounds like there may be multiple phases to it I guess I'm curious.

Yeah there are.

Point in time, where there'd be maybe on a go no go decision may be made.

Joel Lawrence Beatty: Decision that may be made to decide whether the drug should continue or not and, if so, on what basis could that decision be based? Yeah, so it's

Besides whether the drug continues or not and if so what could that decision be based on.

Yeah, so they're so it's on it.

Dr. Briggs Morrison: Yeah, so it's a program that essentially, we have collaborated with the BDML team. The first part, of course, is just a phase one to ask this earlier question of, you know, can you get, what is the right dose of the triplet for each of the agents in the triplet? So that's the phase one portion. Once we have confirmed that 5613, you know, we have the right dose to give in Venetia, that it goes into a randomized trial of Vannaza versus Vanneza plus 5613.

It's a program that essentially we have collaborated with the beat AML team. The first part of course is just it is a phase 1.2 assets earlier question of can you get what is the right dose of the triplet for each of the agents and the triplet. So that's the phase 1 portion.

Once we have confirmed that 50.613.

The right dose to give and Vanessa net it goes into randomized.

Ah trial.

Asia versus non Asia, plus 50, 613, and we'll say more in the future Joel about exactly what those that don't know goes are from phase 2 to phase III.

Dr. Briggs Morrison: And we'll say more in the future, Joel, about exactly what those that go-no-goes are from phase two to phase three. But it is sort of set up as... sort of a, the initial thought is there'll be a seamless phase two, and three, and there will be a go-no-go, which we'll say more about in the future.

But it is sort of set up beds.

The initial thought is there'll be a seamless phase II 3 and there will be a go no go which we'll say more about in the future.

Operator: Thank you. Our next question comes from Peter Lov on a bar comment.

Great. Thank you.

Thank you. Our next question comes from Peter Lawson of Barclays. Your line is open.

Operator: and a barclays, Yolina don't. Thanks.

Operator: Thanks for taking the question, thanks for the updates as well. Just on, as we think about patients rolling over to phase two pivotal for your men, and how many patients do you think you could have? as the phase two pivotal star.

Thanks for taking the question thanks for the updates as well.

On this as we think about patients rolling over.

Phase III pivotal.

Your line and if so how many patients do you think you could have.

The phase 2 pivotal studies.

Peter Richard Lawson: Yeah, so again, Peter, remember we said we could potentially, what the agency has said is, you know, as you continue to backfill cohorts where you've already seen efficacy, those could count. We haven't really said yet how many patients those are, but it just gives you a little bit of a head start as we head into phase two. But again, we don't know the final number of patients to be enrolled in phase two, so it's hard to say exactly what percent of the total phase two population that represents.

Yeah, So again, Peter and remember we had said we could potentially.

Agency has said as you know.

You continue to backfill.

Cohorts, where you've already seen efficacy.

Those could count on them.

We haven't really said yet how many patients those are but it just gives you a little bit of.

Head start as we head into the phase 2.

But again, we don't know the final number of patients to be enrolled in the phase 2 so hard to say exactly what.

Let them.

Percentage of the total phase II population that represents.

Peter Richard Lawson: Okay, thank you. And then on Augment 102, what chemotherapies are you looking to combine? Yeah, Michael Myers, are you on? Can you say more about that?

Got you Okay. Thank you and then on.

Augment 1 or 2 well chemotherapies that you're looking to combine with.

Yeah, Michael mirrors are you on can you just say more about that.

Michael Werner Schmidt: Yeah, Michael Myers, are you on? Can you say more about that? I don't know if Michael's still on. Sorry, I had trouble getting myself off the mute. So, yeah, Peter, what we were going to combine it with would be two different regimens that are typically used in relapse-refractory AML, one being a flag-based regimen for AML, and then the other would be a four drug regimen typically used in ALL.

Yeah.

Yes.

I don't know if Michael's go on.

Yeah.

Yes.

Okay, sorry, I had trouble getting myself book so.

Yeah, Peter what we were going to complying with would be 2 different regimens that are typically used in relapsed refractory <unk>.

M L 1 being a.

Oh swag based regimen for AML and then the other would be a poor drug regimen typically used in a O L.

Michael Werner Schmidt: Thank you. And then I guess the final question will just be about other frontline trials that you'd want to run so

Okay.

Thank you and then I guess the.

Peter Richard Lawson: want to run so nice to see

The final question would just be about other frontline trials that your growth once you run so.

Peter Richard Lawson: The one that is about to start, but are the other ones you want to run on the front line, and would that go?

Nice to see the.

But the 1 that's about to start.

Peter Richard Lawson: and Would that go through academic or non-for-profit organizations?

On the other ones you want to run frontline and would that go through academic farmer.

Dr. Briggs Morrison: Yeah, I think as we've talked about before, we've been doing quite a bit of work trying to understand what the various development opportunities are, obviously, a combination with Venza is timely and important given its increasing use as the standard of care in patients who are not candidates for induction chemotherapy. Combining with the so-called 7 plus 3 in patients who are candidates for induction chemotherapy also makes sense. And then there are other aspects of the program that we will be saying more about as the year progresses.

Non for profit.

Realizations.

Yeah. So we I think as we've talked about before we have been doing quite a bit of work trying to understand what are the debt.

The various <unk>.

Development opportunities, obviously, a combination with Vanessa we think is.

On a timely unimportant given its increasing use of standard of care in patients who are not candidates for induction chemotherapy.

Combining with so called 7 plus 3 in patients who are candidates for induction chemotherapy also makes sense and then there are there are other other aspects of the program that we'll be saying more about.

As the year progresses.

Peter Richard Lawson: Great. Thank you so much.

Okay. Thank you so much.

Operator: Thank you. Our next question comes from Justin Walsh with D. Raleigh Security. Hi, thanks for taking the questions. I have a couple on the Beat trial.

Yeah.

Thank you. Our next question comes from Justin <unk> with B Riley Securities. Your line is open.

Hi, Thanks for taking my questions I have a couple on the beat trial.

Justin Walsh: So I guess the first question is, is there a possibility that competitor metamin inhibitors could get added to that, or is it most likely one drug from a single class? And then the other question related to Beat is, are you guys actually running the trial yourselves, and how much control do you have over the data related to that? Yeah, so the first question, you know, I think we probably have to defer to the LLS team. I don't believe in the arrangement we have with them that they can't include another male inhibitor if they wish to. That's about all I can say.

So I guess the first is is there a possibility of that competitor menin inhibitors could get added to that or is it most likely 1 drug from a single class.

Then the other question related to beat is.

Are you guys actually running the trial yourselves and how much control you have over those data releases.

Yeah. So the first question you know I think we probably have to defer to the LLS team.

I don't believe in the in the arrangement, we have with them that they can't.

Include another met inhibitor, if they wish to.

And so on.

I don't see that that's about all I can say I don't know if they wish to.

And then the second question is part of the reason of working with the beat AML team is.

Because these trials are already up and running and the sites are all up and running and the beat AML team is a sort of ready to go.

We will let them run the trial.

They've proven that they can do this quite efficiently and effectively we think the trial actually will start faster.

Because you already have all their sites opened and this is just another part of adding into the trial.

Dr. Briggs Morrison: This is just another arm added to the trial. And we've worked closely with them on data disclosures. I think they're as excited to present data as we are. Got it. Thanks for the question that's been offered. Thank you. And our next question comes from David Levelwood of Morgan Stanley. Your line. Thank you very much for taking my question. When you look at the...

We've worked closely with them on that on data disclosures.

You know I think there is excited to present data as we are.

Got it thanks for the question that's all for it.

Thank you and our next question comes from David Lebowitz of Morgan Stanley. Your line is open.

Oh, Thank you very much for taking my question.

When you look at the a man on data to date, thus far.

Operator: metend data to date thus far.

David Levelwood: Could you, I guess, elaborate on the efficacy across the doses?

Could you I guess elaborate on the efficacy across the doses are.

David Levelwood: and how that plays into the ultimate dose selection.

Dr. Briggs Morrison: Yeah, so again, David, the dose selection, the recommended phase to dose selection is not based on efficacy. The dose selection is based upon safety, tolerability, and PK. What we have said previously is that when we were looking at the 113 arm B, 226 arm A, efficacy in that population is roughly the same as it is in the overall population, which is really the way that we presented the data. And obviously, we'll have a lot more to say about efficacy by dose, arm, and by mutational status at the end of the year at a medical conference. And as I said in my prepared remarks, we're excited to be able to show the initial durability of the CRH responses as well. Thank you for that.

And how that plays into the ultimate dose selection.

Yeah. So again, David day dose selection of recommended phase 2 dose selection is not based on efficacy dose selection, it's based upon safety Tolerability and PK.

What we have.

I said previously is that.

When we were looking at the 1014 RMB 226 RMA.

Africa C in that population is.

Roughly the same as it is in the overall population, which is really the way that we presented the data.

And obviously, we'll have a lot more to say about.

Efficacy.

By dose by arm 10 by mutational status.

At the end of the year at a medical conference and as I said on my prepared remarks will also we're excited to be able to show the initial durability of the Cri CRH responses as well.

Thank you for that and with respect to the Qt elongation.

David Levelwood: to the QT elongation. I guess you spoke about how practices were handling the newer patients on the different doses differently. Is there any way you could elaborate on how that changed and why those two doses seem to have no QT longation, whereas lower doses did at..., in the prior release.

I guess you spoke about.

How practices, we're handling I guess, the newer patients on the different doses differently.

Is there any way you could elaborate on on how.

How has that changed and why those 2 doses seem to have no Q2 on the elongation, whereas lower doses did it.

And the prior release.

Dr. Briggs Morrison: Yeah, so again, if you look at 113 arm B and 226 arm A, there was one DLT in each of those. And again, in Arm B, a relatively large number of patients. As I said, you know, helping sites to make sure that they're adequately or supplementing electrolytes seems to be helping on those intermediate doses. But we'll sort of see how that plays out as we make more patients. I think what we said at the last when we presented the data in April is that at the recommended phase two dose, we were seeing somewhere around 8 or 9% rate 3 QTC prolongation.

Yeah. So again, if you look at $1.6 debt $1.13, RMB 226 arm a there wasn't 1 DLT in each of those and again in RMB, a relatively large number of patients.

As I said with the.

Helping sites to make sure that there there are adequately or.

Supplement intellectually seems to be helping.

Helping on those intermediate doses.

But well.

Well, it's hard to see how that plays out as we make more of a patients I think what we had said at the last when we presented the data in April is that at the recommended phase 2 dose we were seeing somewhere around 8 or 9% re III Qt prolongation.

Dr. Briggs Morrison: It's possible with this, you know, closer interaction with the sites and people getting more comfortable with what needs to be done, that that rate could come down as we enroll more patients. Thank you for taking my questions.

It's possible with this closer interaction with the sites and people getting more comfortable with what needs to be done that that rate could come down.

As we enroll more patients.

Operator: I'm showing no further questions at this time. I would like to turn the call back over to Dr. Morrison for any closing remarks. Thanks so much, operator, and thanks everybody for joining us on the call. Again, we think it was a very productive quarter. We're excited about the data that we'll be updating at the end of the year at a medical conference, and we're excited to be able to start our first, first-line trial.

Thank you for taking my questions.

Thank you I'm.

I'm showing no further questions at this time I can try on the call back over to Dr. Morrison for any closing remarks.

Thanks, so much operator, and thanks, everybody for joining us on the call again, we think it was a very productive quarter.

We're excited about the data that we'll be updating at the end of the year at a medical conference and we're excited to be able to start.

Our first first line trial.

Operator: And, as Daphne pointed out, I think we're well financed to be able to get through a lot of this work. So thank you all for your attention and your questions. Anything else you can do, please get in touch with us.

Dr. Briggs Morrison: Thank you. Ladies and gentlemen, this does include today's conference. Thank you all for participating. You may all disconnect. Have a great day.

Thank you ladies and gentlemen, this does conclude today's conference. Thank you all for Pennsylvania, and you may all disconnect have a great day.

Q2 2021 Syndax Pharmaceuticals Inc Earnings Call

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