Q3 2020 Syndax Pharmaceuticals Inc Earnings Call
Listen Chief Executive Officer of FedEx.
Oh, thank you very much Melissa. Thank you to everyone who's joining us on today's call and webcast. The third quarter has been quite busy for us here at cindex. So let's just Jump Right In fact slide three provides a high-level summary of our current corporate priorities as we strive to realize a future in which people with cancer and live longer and better than ever before. We are intensely focused on our too exciting and promising programs while we also continue to look for additional oncology pipeline opportunities.
It's now turn to slide for & S index 5613 are genetically targeted agent for the treatment of leukemia as you've noted previously. There's extensive validation of both mll-r and 10 p.m. When mutations and molecular targets and Leukemia and well-established diagnostic tests, routinely identify patients with these genetic mutation a premier Publications provide the scientific rationale and preclinical validation of our ongoing clinical trial and historic precedent supported rapid regulatory path 458 agents in acute leukemias flight five briefly summarizes the ongoing augment 101 trial the first-in-human phase 1/2 trial in the account already the understanding of men in or augment program.
Good.
Justin with what we communicated on our last call we anticipate presenting the completed phase one portion of the trial it early 2021.
We've been busy over the last quarter preparing for the phase two portion of the trial which will enroll three distinct expansion cords Each of which consists of a specific genetically defined wage for refractory acute leukemia. And which is on track to initiate early next year. The three cohorts will include patience with mll-r acute lymphoid leukemia or a l l patience with mll-r acute myeloid leukemia or AML and patience with npm one mutant AML the phase two portion will further characterize the safety package that's in DX 5613 and we'll provide an initial estimate of the complete response rate as the primary measure of therapeutic benefit.
The proportion will enroll both pediatric and adult patients. Thereby providing us a potential path to regular with a broad label including both adults and Pediatrics. I should note that the results are positive this phase two portion of augment 101 could potentially support a regulatory filing giving wage listing right Detroit press
Over the last. We've also been conducting extensive research into the broad landscape of clinical opportunities for S. Index 5613 beyond the initial approval in relapse refractory leukemias as Illustrated on slide 6 while we are not in a position today to lay out the specific next steps and building out the sndx 5613 franchise. I can say that we're using this ongoing analysis to inform specific combination regimens that we anticipate started to study in the near future.
Several investigators have already reached out to us with novel exciting ideas for the future development of s index 5613.
Let me now turn to slide seven and accept them AB formally known as fx-6350 to our potentially best-in-class monoclonal antibody therapy charging to CSF receptor. As you know, we've been conducting a phase 1/2 trial with accent element and chronic graft-versus-host disease and are pleased to announce that the organizing Committee of voltaire's Ash has selected are abstract for oral presentation, which will be on December 6th. The abstract itself includes twelve patients and we'll publish this Thursday November 5th the data in the abstract was current as of the abstract submission date back in August was a data cut-off date in July and we anticipate that dead on a presentation will have a larger data set about 15 patients who enrolled in the phase one portion of the trial.
We are not in.
Able at this time to comment comment on the actual data in the abstract given that it is currently embargoed and yet we would encourage investors to pay attention to the patient demographic especially the number and type of Prior therapies. The patients had before they went on to our trial the response rate the tolerability profile and clinical efficacy in hard-to-treat organs.
Our team has completed the end of phase one regulatory discussions with the FDA and we're pleased to announce that we have agreed on a pivotal trial for acts and chronic graft-versus-host disease.
This trial is the exit for a chronic graft-versus-host disease trial called Agave 201 and it's outlined on slide eight. Trial will enroll patients with chronic graft-versus-host disease whose disease has progressed after two prior therapies patients must be at least six years of age and have met overall entry criteria off. This is a pivotal that was strange in trial in which patients will be randomized to one of three treatment groups each investigating a distinct dose of asatoma wage either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft-versus-host in a secondary endpoints will include duration of response and validated quality-of-life assessments using the symptoms scale. We anticipate beginning enrollment this year off.
With top-line data likely available in 2023. We believe that chronic graft-versus-host disease represents a high unmet medical need and an important commercial opportunity with approximately 14000 patients suffering from chronic graft-versus-host disease in the u.s. Today.
With the recent positive pivotal results from both inside. Jakafi and cadman's kd025. We may soon see commercial launches that will begin to describe the commercial opportunity in chronic graft-versus-host disease despite recent advances in this area to our knowledge exit l a magnetic only agent in clinical development. That's specifically targets the monocyte macrophage lineage. We believe the data generates date with access to suggest. It has the potential to play an important role in the treatment of chronic graft-versus-host disease both as monotherapy and give it its safety profile in combination with complementary medicines.
It's also been working extensively with experts in the field the fiber-optic diseases and have found a strong consensus that the scientific rationale for the efficacy of accent. I had in chronic graft-versus-host disease firmly supports its potential in a wide variety of fibrotic diseases such as idiopathic pulmonary fibrosis and Scleroderma are actively evaluating options by which to build out the actual amount franchise Beyond chronic graft-versus-host disease and take advantage of what we believe are significant set of opportunities that could materially enhance shareholder value.
finally slide
Nine summarizes the transactions that led to the acquisition of the men and mlr and exit to amount of programs you believe that we will be able to continue to expand our pipeline through the acquisition off in licensing of quality differentiated assets. We believe that we have the necessary skill to evaluate and identify high-quality assets and the clinical development experience. Bring those compounds through valuable inflection points. We expect to remain among the preferred partners of such transactions.
I'll turn the call over to Daphne to review our financial results.
Thank you for eggs, the results of our operations for the third quarter of 2020 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 will be available in our third-quarter report on form 10-q, which will be filed later this week. I would like to point out that our operating loss for the quarter was twenty point four million dollars or five fifty six cents per share compared to twelve point eight million dollars or $0.41 per share for the same period last year turning to slide ten. We ended the third quarter with a hundred seventy point two million dollars in cash and cash equivalents and 44.4 million shares and pre-funded warrants outstanding looking ahead. I'd like to provide Financial guidance for the the manger of the Year our second half operating expense guidance remains unchanged at 40 to 45 million dollars including approximately 2 million dollars of non-cash. Birth.
Operator: BF-WATCH TV 2021 Good day, everyone, and welcome to the Syndax third quarter 2020 earnings call. Today's call is being recorded. At this time, I would like to turn the call over to Melissa Force of Argot Park. Please begin.
Sensation expense per quarter and four million dollars in Milestone payments to UC be based on achievement of positive Milestones associated with accidental amount for the fourth quarter of 2020. R&D expenses are expected to increase as our development activities for both snd X5 $600 and exit omad continue to ramp up heading into registration trials for both programs. Fourth-quarter. G&A expenses are expected to remain a third quarter level for the fourth quarter. We expect R&D expenses to be between 15 to $20,000 and total operating expenses to be between 20 to 25 million, given our cash operating expense guidance for the fourth quarter of 2020. We continue to expect to end the game with approximately $145 million dollars of cash, which gives us cash Broadway in 22222 to meet our key development milestones. I would like to now turn the call back over to Briggs.
Melissa Force: Thank you, operator. Welcome and thank you to those of you joining us on the line and the webcast this afternoon for a view of Syndax's third quarter 2020 financial 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 Kouridis, Chief Financial Officer. Also joining us on the call today for the question and answer session will be Michael Metzger, President and Chief Operating Officer, Dr. Michael Myers, Chief Medical Officer, and Dr. Peter Ordentlich, Chief Scientific Officer. This call is being accompanied by a slide deck that has been posted on the company's website, so I would ask you to please turn to forward-looking statements on slide two.
Melissa Force: 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 of the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC.
Great. Thanks so much Daphne as I hope you have appreciated from my prepared remarks. We are increasingly excited about both of our clinical programs. We look forward to oral presentation of the phase one a Satilla map data at in December of this year followed soon thereafter by the phase one data on S and x 56 13-in early 2021. We currently anticipate having both programs in Phase too early. Next year. Agave 201 is a pivotal trial for acetone ab and it's possible that the phase two portion of off 101 could also be registration for sadx 5613. So by early next year, we could have two registration of programs ongoing we are also getting increasingly excited about the broad franchisee opportunities for both programs beyond their initial registration all indications We Believe fndx 5613 could have broad utility across a wage.
Melissa Force: Any forward-looking statements represent the company's views as of today, November 2, 2020, only. A replay of this call will be available on the company's website, www.syndax.com, following the call. So with that, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer of Syndax. Thank you very much, Melissa, and thank you to everyone who's joining us on today's call and the webcast. The third quarter has been quite busy for us here at Syndax, so let's just jump right in.
Dr. Briggs Morrison: 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 are intensely focused on our two exciting and promising programs, while we also continue to look for additional oncology pipeline opportunities. Let's now turn to slide 4, and SNDX5613, our genetically targeted agent for the treatment of leukemia. As we've noted previously, there is extensive validation of both MLLR and NPM1 mutations as molecular targets in leukemia, and well-established diagnostic tests routinely identify patients with stage genetic mutations.
Dr. Briggs Morrison: Premier Publications provided scientific rationale and preclinical validation of our ongoing clinical trial, and historic precedents support a rapid regulatory path for such targeted agents in acute leukemia. Flight 5 briefly summarizes the ongoing Augment 101 trial, the first in-human Phase 1-2 trial in the Accelerated Understanding of Menin, or Augment, program. Consistent with what we communicated on our last call, we anticipate presenting the completed phase one portion of the trial in early 2021. We have been busy over the last quarter preparing for the Phase II portion of the trial, which will enroll three distinct expansion cohorts, each of which consists of a specific, genetically defined relapse or refractory acute leukemia, and which is on track to initiate early next year. And three cohorts will include patients with MLLR acute lymphoid leukemia, or ALL, patients with MLLR acute myeloid leukemia, or AML, and patients with NPM1 mutant AML.
Dr. Briggs Morrison: The Phase 2 portion will further characterize the safety of SNDX5613 and will provide an initial estimate of the complete response rate as the primary measure of therapeutic benefits. The Phase 2 portion will enroll both pediatric and adult patients, thereby providing us with a potential path to regulatory approval with a broad label including both adults and pediatrics. I should note that if the results are positive, this Phase 2 portion of Augment 101 could potentially support a regulatory filing given existing regulatory precedent. Over the last period, we have also been conducting extensive research into the broad landscape of clinical opportunities for SNDX5613 beyond the initial approval in relapsed refractory acute leukemias, as illustrated on slide 6. While we are not in a position today to lay out the specific next steps in building out the SNDX5613 franchise, I can say that we are using this ongoing analysis to inform specific combination regimens that we anticipate starting to study in the near future.
I'd range of clinical settings.
An acute leukemia and that's a telematic could represent a broad franchise opportunity in fibrotic diseases. We are comfortable that given our cash on hand that we have the financial resources to aggressively Advance our programs and Achieve Ki upcoming milestones.
We also remain optimistic that we could continue to identify and bring in novel molecules to deepen our portfolio. We have a proven track record of delivering on this color of our strategy and I believe this is a core strength of our company as always I would 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. In addition. I would like to thank are committed long-term investors who are helping us to build this great company with that. I'd like to open the call for questions.
Thank you at this time in order to ask a question, please. Press star in the number one on your telephone, press the pound key. Please stand by while we compiled the Q&A roster.
Your first question comes from the line of Phil.
Good afternoon. Thanks for taking my questions in congrats on the progress. Just a few on the men and program I guess first for the phase two in order to support a filing. Do you have a sense if they conversations with? The CR rate would need to be how durable the responses would have to be in and how many patients would be required in the initial analysis.
Hi, thanks for your question. So what I would say is there's regulatory precedent. If you look at for example, the ID age inhibit or is that were approved as monotherapy based upon single-arm trials and I think in those cases see our rate was in the somewhere in the mid-20s with a durability of response me, the ability of response somewhere around eight months. So I think something in that ballpark the regulatory president would suggest could be an acceptable package to submit the FDA the exact number of patients, um is still to be determined.
Perfect. That's that's helpful second. I'm sure getting this question all the time. We are two cures going to obviously have data Dash with something coming on the on strikes this week investors are curious. What implications that data could have Force index. I'm curious from your opinion. What will you be evaluating in that data in any any pointers for us as we as we look through as I'm try to interpret the impact on cindex.
Dr. Briggs Morrison: Several investigators have already reached out to us with novel, exciting ideas for the future development of SNDX5630. Let me now turn to slide 7, and Axitilumab, formerly known as SNDX6352, is a potentially best-in-class monoclonal antibody therapy targeted at CSF1 receptors. As you know, we've been conducting a Phase I-II trial with axotelimab in chronic graft-versus-host disease, and we are pleased to announce that the organizing committee of this year's ASH has selected our abstract for an oral presentation, which will be on December 6th.
Yeah, look, I think.
But you know when we presented data at ACR validating that this mechanism can work for mll-r leukemias both companies benefitted from that page. Um, should they present data on npm1 leukemias that validates at the this mechanism can work there? I think both companies would benefit from that. But to be honest, I think our our Focus right now is I said in my prepared remarks, we we're trying to get our sights open for phase two and getting ready to start that phase two trial. So we're interested in what our competitor has but our key focus is really trying to deliver our molecule through its potentially registration program. Perfect. Last question for me is on next month. You mentioned that as we look at the abstracts, we should look at the patient demographics. Can you give us some sense of what the historical response rates would be to God?
Dr. Briggs Morrison: The abstract itself includes 12 patients and will be published this Thursday, November 5th. The data in the abstract was current as of the abstract submission date back in August with a data cutoff date in July. And we anticipate that the oral presentation will have a larger data set of about 15 patients who enrolled in the phase one portion of the trial. However, we are not able at this time to comment on the actual data in the abstract, given that it is currently embargoed.
Given or in light of the patient demographics in in your study. What would be kind of the relevant compare? Yeah. It's actually hard to have a relative comparator because the patients that we've been a very heavily pre-treated. You may remember that the vast majority of them have received ibrutinib many of them have received trucks of talented and many have received wage. Um, the cat would compound. So this is a very refractory population of patients. So there's not really a precedent. I would say if you go up, you know in earlier lines of therapy the data some of those patients had received a rock some had not you know, I think given that that picture having anything above a 50% response wage in this heavily refractory population. We would be quite excited with and I think the other thing to look at is not just the overall response rate, but the specific organs because there are you know, some organs that have been harder. Yep.
Dr. Briggs Morrison: And yet, we would encourage investors to pay attention to the patient demographics, especially the number and type of prior therapies the patients had before they went on to our trial. The response rate, the tolerability profile, and clinical efficacy in hard-to-treat or, Our team has completed the end of Phase 1 regulatory discussions with the FDA, and we're pleased to announce that we have agreed on a pivotal trial for afetalimab in chronic graft-versus-host disease. This trial is the axotilumab for a chronic graft-versus-host disease trial The trial will enroll patients with chronic graft-versus-host disease whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met the overall entry criteria.
Faith in others and TV HD perfect. Thanks for taking my questions and we look forward to the abstracts on Friday.
Your next question comes from the line Bert Haslett btig.
Dr. Briggs Morrison: This is a pivotal, dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axotelomide given either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft-versus-host disease. Secondary endpoints will include duration of response and validated quality of life assessments using the Lee Symptom Scale
Yeah, thank you. Congratulations on the progress as well and I'll just follow on there with regard to tell him AB is the development of the molecule then set toward the refractory setting and if it is initially do you plan to potentially move it forward to more Frontline settings just a little bit more color. Just giving the data. We're about to see and change your thoughts on the overall development scheme for the program. Thanks for the question Bert. So we do believe as I as I pointed out in the the pivotal trial will be patients who have failed at least two prior therapies. So it is a refractory population again, as I pointed out in my prepared remarks. I think that the the emerging safety profile for accessing that makes it quite amenable to combine with other agents so we can certainly foresee a future development where the drug gets month.
Dr. Briggs Morrison: We anticipate beginning enrollment this year, with top-line data likely available in 2023. We believe that chronic graft-versus-host disease represents a high unmet medical need and an important commercial opportunity. Approximately 14,000 patients suffering from chronic graft-versus-host disease in the U.S. today. With the recent positive pivotal results from both Insight's Jackify and Cadman's KD025, we may soon see commercial launches that will begin to delineate the commercial opportunity for chronic graft-versus-hostility. Despite recent advances in this area, to our knowledge, Taxotelomab is the only agent in clinical development that specifically targets the monocyte macrophage lineage.
up into earlier lines potentially and
Combination with other mechanisms remember acetone math is really the only agent in development for gvhd that is specifically focused on the monocyte macrophage lineage off. The other agents that are round work on T cells or B cells and it may well be that a a combination of a drug that it's a it's t cells and a drug visit macrophages or monocytes is the right combination and I think because of the tolerability profile I think those types of combinations are you know things that were starting to think about
Dr. Briggs Morrison: We believe the data generated to date with axitilumab 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 medicine. We have also been working extensively with experts in the field of fibrotic diseases and have found a strong consensus that the scientific rationale for the efficacy of axitilamide in chronic graft They're actively evaluating options by which to build out the Axitilumab franchise beyond chronic graft-versus-host disease. And take advantage of what we believe are a significant set of opportunities that could materially enhance shareholder value. Finally, slide 9 summarizes the transactions that led to the acquisition of the Mennon MLR and Acetelimab programs.
So the initial potentially pivotal portion will be in this in there for every population and then you look to move it kind of more front-line overtime and combination exactly. That's a fair summary and then just with regard to 5613. Thank you for the comments there as well. Is there an ability to hack of a rapid development course in the Pediatric Group specifically, you know, there's obviously some urgency to move it into pediatric patients that effective dosing levels that came from the the Pediatric add come earlier this year. Is there a separate course to be pursued there or is that just something that will be wrapped in the the overall development program?
Daphne Kouridis: We believe that we will be able to continue to expand our pipeline through the acquisition or in-licensing of quality differentiated assets. We believe that we have the necessary skills to evaluate and identify high quality assets and the clinical development experience to bring those compounds to valuable inflections. We expect to remain among the preferred partners of such transactions. I now turn the call over to Daphne to review our financial results. Thank you, Briggs.
So so the ongoing trial augment 101 is open at this point to patience basically a month of age or older and off the phase two portion if that phase two portion were registration all that will be open to Pediatrics as well as adults. So the the initial if you will monotherapy relapse your factory population, we will study abroad age group. I do believe that as I send my prepared remarks there. There are accommodations both in kids and adults that we're looking at, you know, bring a fuller picture to the power of the molecule, but the the single-agent trial is open to both Pediatrics and adults
Daphne Kouridis: The results of our operations for the third quarter of 2020 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 will be available in our third quarter report on Form 10-Q, which will be filed later this week. I would like to point out that our operating loss for the quarter was $20.4 million, or $0.46 per share, compared to $12.8 million, or $0.41 per share, for the same period last year.
Thank you. And then just one more for me just on that point and the potential combination regimens with 5613. Is this something we're thinking about the strategy of five or six thirteen more broadly and the strategy of syndics. Is this something where you're just looking to engage in potential combinations with 5613 or is this a licensing m a g n a m l or or blood-based tumors more Broadway. Just how do we think about that from a strategic standpoint Force index?
Daphne Kouridis: Turning to slide 10, we ended the third quarter with $170.2 million in cash and cash equivalents and 44.4 million shares and pre-funded warrants outstanding. Looking ahead, I'd like to provide financial guidance for the remainder of the year. Our second half operating expense guidance remains unchanged at $40 to $45 million, including approximately $2 million of non-cash stock compensation expense per quarter and $4 million in milestone payments to UCB based on achievement of positive milestones associated with Axitilumab. For the fourth quarter of 2020, R&D expenses are expected to increase as our development activities for both SNDX5613 and Ectetilamab continue to ramp up, heading into registration In the fourth quarter, GNA expenses are expected to remain at third quarter levels.
Yeah, I'll I'll ask that Michael Mesker. Take that question.
Sherbert thanks for the question. So, you know, I think we we think about this as a indication by indication strategy build out. And so I think we're we're evaluating all the opportunities from a commercial perspective you need perspective and those maybe those maybe trials that we do on our own maybe trials that we do in collaboration through clinical collaboration or more broadly than maybe something more strategic than that at some time in the future. So we're we're looking at all those opportunities and what's the best way to advance a molecule?
Dr. Briggs Morrison: For the fourth quarter, we expect R&D expenses to be between $15 to $20 million and total operating expenses to be between $20 to $25 million. Given our cash operating expense guidance for the fourth quarter of 2020, we continue to expect to end the year with approximately $145 million of cash, which gives us cash runway into 2022 to meet our key development milestone. I would like to now turn the call back over to Brig. Thanks so much, Daphne.
Okay. Thank you. Congratulations on the progress expert.
Your next question comes from the line of Joel with City.
Hi guys, this is Sean Egan calling in for Joel. Thank you for taking my questions the first one on a quick. Hello AB when you guys had your end of phase one meeting with the FDA. Was there any kind of agreement on the threshold for a success and Academy on had a lower bound of thirty 30% response rate? Um, what does look like for you guys?
Dr. Briggs Morrison: As I hope you have appreciated from my prepared remarks, we are increasingly excited about both of our clinical programs. We look forward to the oral presentation of the Phase I astratilumab data at ASH in December of this year, followed soon thereafter by the Phase I data on SNDX5613 in early 2021. We currently anticipate having both programs in Phase 2 early next year. Agave 201 is a pivotal trial for Axotilumab, and it's possible that the Phase II portion of Augment 101 could also be registrational for SNDX5613. So by early next year, we could have two registrational programs on the go. We are also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indication. We believe SNDX5613 could have broad utility across a wide range of clinical settings in acute leukemia, and anaxetilumab could represent a broad franchise opportunity in fibrotic disease. We are comfortable that, given our cash on hand, we have the financial resources to aggressively advance our programs and achieve key upcoming milestones.
There we haven't disclosed what the stats are on the program. But yes there there is an implied lower bound and the in the number of patients that are being in a
Great and then 456 13 V to monotherapy, you know potentially registration will trial and the broad age group. Would that be in the factory setting or could you go a little bit more color on the inclusion criteria, though?
Right. So I think we'll say more about that. Once we have full amount that it is registration all but the way the trial is set up now and you can see on clinicaltrials.gov. These are wage gaps refractory patients. Um, that's the population that's being studied in Phase One and that's the population that we anticipate studying in phase two.
Great, and I noticed you guys gave a little bit more color on kind of moving at the table Mebane to some additional indications. Maybe did you talk about how quickly we can expect that to happen with any kind of priority on whether I P F or s clips Kodomo. We'll kind of move ahead first.
I don't know Michael mask or do you want to take that question?
Dr. Briggs Morrison: We also 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 strategy, and I believe this is a core strength of our company. As always, I would like to thank the wonderful talented team here at Syndax, our collaborators, and, most importantly, the patients, trial sites, and investigators involved in our clinical program. In addition, I would like to thank our committed long-term investors who are helping us to build this great company.
Sure to look I think we see we see the the exit on that franchise as being you know, very significant and also say we're fully committed to unlocking value for the program and building shareholder value around around it. I think there are many opportunities by which to do that. And so really we're just looking at all the all the differential is currently exploring all the options to to build value that that's that's essentially Where We Are
Operator: With that, I'd like to open the call for questions. Good afternoon, thanks for taking my questions and congrats on the progress. Just a few on the MED-IN-IN program.
Great. Thank you so much for answering my questions.
Your next question comes from the line of
hey, thanks for taking our questions, you know first one relates to access to any reason to 5613. How do you think about the potential of this drug being used as a bridge to transplant or they can oppose transplant maintenance studied in various leukemia?
I would do things for your question. So first off I would say in our ongoing trial and as we go into phase two, if a patient has relapsed refractory leukemia and goes into a complete response and is eligible for transplant. It's not it is perfectly acceptable and probably should be anticipated wage many of the investigators want to take their patients a transplant. They tend not to take a patient a transplant unless they can get him into remission. So a 56-13 can get them into remission. There will be some patients who go on to track from their if their transplant eligible the question of do you continue 5613 after the transplant in a maintenance type of way is a is an important question that you know, we're thinking about and thinking about designs that could address that.
Dr. Briggs Morrison: I guess first for the Phase 2, in order to support a filing, do you have a sense from your FDA conversations about what the CR rate would need to be, how durable the responses would have to be, and how many patients would be required in the initial analysis? Hi Phil, thanks for your question. So what I would say is there's regulatory precedent if you look at, for example, the IDH inhibitors that were approved as monotherapies based on single-arm trials, and I think in those cases, the CR rate was somewhere in the mid 20s with a durability of response, median durability of response, somewhere around eight months. So I think something in that ballpark, regulatory precedent would suggest, could be an acceptable package to submit to FDA. The exact number of patients is still to be determined. Perfect, that's helpful. Second, I'm sure you're getting this question all the time.
Okay, and then what are the question we've got? No.
Lot, since April was April the observations of QT prolongation inside the early stages of the dose-escalation. So obviously you can't get into it and it's happened further on the line for a what is the response from Physicians about thinking about the you've seen so far and see how they would management and management of the real impact of India.
Dr. Briggs Morrison: We are, too, curious. We're going to obviously have data at Ash with something coming out of the abstracts this week. Investors are curious what implications that data could have for Syndex. I'm curious, in your opinion, what you will be evaluating in that data, and any pointers for us as we look through it and we try to interpret the impact on Syndex? Yeah, look, I think that when we presented data at AACR validating that this mechanism can work for MLLR leukemias, both companies benefited from that. Should they present data on NPM1 leukemias that validate that this mechanism can work there? I think both companies would benefit from that.
Yeah, again, I think the positions that we've spoken to are quite used to seeing drugs that cause minor abnormalities and QT prolongation. Um, it's it they're very comfortable, um monitoring for this if there's a dose adjustment that needs to be made should there be you know, a a prolonged QT prolongation there's a table with that. So it's I think the the box that we have spoken to particularly in the relapse refractory population. If you've got a drug that is getting patients into remission, they really don't see this as a as a significant barrier to using the drug.
One last question bigger picture question was strategy and kind of capital deployment. How do you balance tabula claiming to find new assets versus the fully unlocked in development of things off until like how do you strike that stuff?
Dr. Briggs Morrison: But to be honest, I think our focus right now, as I said in my prepared remarks, is trying to get our sites open for Phase 2 and getting ready to start that Phase 2 trial. So we're interested in what our competitors have, but our key focus is really trying to deliver our molecule through its potential registration program. Perfect, and last question for me is on ex-telemem. You mentioned that as we look at the abstracts, we should look at the patient demographics. Can you give us some sense of what the historical response rates would be, in GVHD given or in light of the patient demographics in your study? What would be the kind of relevant comparison?
Daphne maybe you want to take that question. Yep. Thank you for the question. You know, we we look at all of the opportunities and I think about as Michael mentioned earlier maximizing shareholder value. And as we move forward our priorities are certainly to meet important Milestones on the current programs and continually evaluating and look at the opportunities with respect to irr and npv values of internal versus external opportunities and always looking to be very efficient and thoughtful about how we deploy Capital but it's the constant evaluation process.
Dr. Briggs Morrison: Yeah, it's actually hard to have a relative comparator because the patients that we've enrolled are very heavily pretreated. You may remember that the vast majority of them have received ibrutinib, many of them have received ruxotilamib, and many have received the cadmium compound. So this is a very refractory population of patients. So there's not really a precedent.
Well, that's one. Thank you so much.
Our next question comes from the line of Peter Lawson with Barclays. Hey, thanks. Thanks for taking the question and congratulations on the oral presentation of actual law. I guess firstly the abstract that we see is is that going to be D too rich in terms of trying to understand response rates and tolerability and prior therapy.
Dr. Briggs Morrison: I would say if you go up, you know, in earlier lines of therapy, the cat data, some of those patients had received ibrutinib or ruxamib, not. You know, given that picture, I think anything above a 50% response rate in this heavily refractory population, we would be quite excited with. And I think the other thing to look at is not just the overall response rate but the specific organs, because there are, you know, some organs that have been harder to treat than others.
Yeah. So the abstract comes out on Thursday. And as I said in my prepared comments that again it's the data was as of July so there's twelve patients but there's there's information there on prior therapies on response rates and on Oregon specific response rate off and then where do you see it fitting into the the emerging treatment Paradigm just with you know, a couple of new drugs in that space over the next couple of years. Yeah, as I said, I think that you know, it's the only drug in development that specifically targets the monocyte macrophage lineage. Um, and so I think it and again you'll get a sense. I think a sense you probably already have it sent from data. We've released from somewhere other trials that have access to a map. That's a well-tolerated agent. So, you know, I think that the initial dead
Dr. Briggs Morrison: Thanks for taking my questions, and we look forward to the abstract. Yeah, thank you. Congratulations on the progress as well. And I'll just follow on there with regard to axotilumab. Is the development of the molecule then set towards the refractory setting?
Dr. Briggs Morrison: And if it is initially successful, do you plan to potentially move it forward to more frontline settings, just a little bit more color, just given the data we're about to see and your thoughts on the overall development scheme for the program? Yeah, thanks for the question, Bert. So we do believe, as I pointed out in the pivotal trial, these will be patients who have failed at least two prior therapies, so it is a refractory population. Again, as I pointed out in my prepared remarks, I think that the emerging safety profile of exotilamide makes it quite amenable to combine with other agents. So we can certainly foresee a future development where the drug gets moved up into earlier lines, potentially in combination with other mechanisms. Remember, exotilamide is really the only agent in development for GVHD that is specifically focused on the monocyte macrophage lineage. Some of the other agents that are around work on T-cells or B-cells, and it may well be that a combination of a drug that hits T-cells and a drug that hits macrophages or monocytes is the right combination.
It's really to get the drug.
Proved in these patients who have probably failed all other therapies and then as an earlier question alluded to think about ways of moving it into earlier lines of therapy going to potentially in combination with with other agents that work through complementary mechanisms.
Thank you. And then just on the men and program so early 2021 for data. Is that going to be at a medical conference or is that going to be press released? And then just how enrollment be going within the various arms that subscribe 8 4 Alpha with and without kind of thing. And also are you seeing em p.m. 1 patients? So they were on that continues to go very often. I think we mentioned on our last call that one of the changes we made to the trial was to be able to expand backfill cohorts where we had cleared safety and seen wage and that was in large part driven by the investigators who were asking for more slots to put patients onto the trial given what they're seeing. So, um enrollment continues to go vet. Well, we haven't given any more information about where we are on the two arms or the types of patients all that will be presented when we we present the completed phase one trial.
Dr. Briggs Morrison: And I think because of the tolerability profile, I think those types of combinations are things that we're starting to think about. So the initial potentially pivotal portion would be in the refractory population, and then you'd look to move it kind of more to the front line over time in combination with others.
Dr. Briggs Morrison: Thank you. And then, just with regard to 5613, thank you for the comments there as well. Is there an ability to have a rapid development course in the pediatric group specifically? You know, there's obviously some urgency to move it into pediatric patients at effective dosing levels that we heard from the pediatric outcome earlier this year. Is there a separate course to be pursued there, or is that just something that will be incorporated in the overall development program?
Okay. Thank you so much to get back into the queue.
And there are no further questions at this time. So I would like to turn the call over to dr. Morrison.
Well first let me thank everybody for joining us on the Web cast and on the call and for your continued interest in cindex. As I said in my prepared remarks an incredibly exciting time for us here at the office. You know, it's it's quite possible that by early next year. We will have two programs in pivotal registration trials, and that's really super exciting. So I don't want to keep people from getting their rest before they have to go vote tomorrow, but thanks so much for for your attention and your time.
Dr. Briggs Morrison: So the ongoing trial, Augment 101, is open, at this point, to patients basically a month of age or older. And the Phase II portion, if that Phase II portion is registrational, that will be open to pediatric patients as well as adults. So the initial, if you will, monotherapy relapsed refractory population, we will study a broad age group. I do believe that, as I said in my prepared remarks, there are combinations both in kids and adults that we're looking at to bring a fuller picture to the power of the molecule. But the single-agent trial is open to both pediatric patients and adults. Thank you. And just one more for me.
Ladies and gentlemen, thank you for your participation. This concludes today's conference call.
Michael A. Metzger: Just on that point and the potential combination regimens with 5613, is this something where, you know, thinking about the strategy of 5613 more broadly and the strategy of Syndax, is this something where you're just looking to engage in potential combinations with 5613, or is this a licensing strategy for AML or blood-based tumors more broadly? Just how do we think about that from a strategic standpoint for Syndax? Yeah, I'll ask Michael Metzger to take that question. Sure, Bert.
Thursday
Michael A. Metzger: Thanks for the question. So I think we think about this as an indication-by-indication strategy build-out, and so I think we're evaluating all the opportunities from a commercial perspective, the unmet need perspective, and those may be trials that we do on our own.
Michael A. Metzger: They may be trials that we do in collaboration through clinical collaboration. Or, more broadly, there may be something more strategic than that at some time in the future. So we're looking at all those opportunities and what's the best way to advance the molecule. Okay, thank you. Congratulations on the progress. Thanks, Bert.
Operator: Hi guys, this is Sean Egan calling in for Joel. Thank you for taking my questions. The first one on Ectetalumab, when you guys had your end of Phase 1 meeting with the FDA, was there any kind of agreement on the threshold for success? I know Katamon had a lower bound of 30% response rate. What did it look like for you guys?
Dr. Briggs Morrison: We haven't disclosed what the stats are on the program, but yes, there is an implied lower bound in the number of patients that are being enrolled. Great. And then for 5613, the Phase II monotherapy, you know, potentially registrational trial in the broad age group, will that be in the relapsed refractory setting? Or could you give a little bit more color on the inclusion criteria there?
Dr. Briggs Morrison: Right, so I think we'll say more about that once we have full FDA agreement that it is registrational. But the way the trial is set up now, and you can see on ClinicalDraw.gov, these are relapsed refractory patients. That's the population that's being studied in phase one, and that's the population that we anticipate studying in phase two. Great. And I noticed you guys gave a little bit more color on kind of moving exatilumab into some additional indications. Maybe could you talk about how quickly we could expect that to happen? And any kind of priority on whether IPF or scleroderma will kind of move adversely? Uh, I don't know, Michael Metzger, do you want to take that question?
Michael A. Metzger: Sure. So look, I think we see the Exit TeleMAT franchise as being very significant, and I'll also say we're fully committed to unlocking value for the program and building shareholder value around it. I think there are many opportunities by which to do that, and so really, we're just looking at all the different options, currently exploring all the options to build value that have, Great, thank you so much for answering my question. Your next question. Hey, uh, thanks for taking our question. So, you know, um, the first one relates to access to the reasons of 5613.
Dr. Briggs Morrison: How do you think about the potential of this drug being used as a bridge to transplant or in the kind of post-transplant maintenance studies in various locations? Hi Madhu, thanks for your question. So first off, I would say in our ongoing trial and as we go into phase two, if a patient has relapsed or fractured leukemia and goes into a complete response and is eligible for transplant, it's not, it is perfectly acceptable and probably should be anticipated that many of the investigators will want to take their patients to transplant. However, they tend not to take a patient to transplant unless they can get them into remission. So if 5613 can get them into remission, there will be some patients who go on to transplant from there if they're transplant eligible.
Dr. Briggs Morrison: The question of whether you continue 5613 after the transplant in a maintenance type of way is an important question that we're thinking about and thinking about designs that could address that. Okay, and then one other question we've gotten a lot since April was the observations of QT prolongation inside the early phases of the dose escalation. So obviously, you can't get into anything that's happened further along the line, but what has been the response from physicians to thinking about the QT events you've seen so far and how they would manage them in the relapsing impact of leukemia? Yeah, again, I think the physicians that we've spoken to are quite used to seeing drugs that cause minor abnormalities and QT prolongation. It's, they are very comfortable monitoring for this.
Dr. Briggs Morrison: If there's a dose adjustment that needs to be made, should there be, you know, prolonged QT prolongation, they're comfortable with that. So, I think, the AML docs that we have spoken to, particularly in the relapsed refractory population, if you've got a drug that is getting patients into remission, they really don't see this as a significant barrier to using the drug. One last question on strategy and capital deployment: how do you balance the idea of capital deployment to find new assets versus the fully unblocked development of things like Accenture? I don't know if, Daphne, maybe you want to take that question?
Daphne Kouridis: Yep, thank you for the question. You know, we look at all of the opportunities and think about, as Michael mentioned earlier, maximizing shareholder value. And as we move forward, our priorities are certainly to meet important milestones on the current programs and continually evaluate and look at the opportunities with respect to IRR and NTV values of internal versus external opportunities, and always looking to be very efficient and thoughtful about how we deploy that capital.
Daphne Kouridis: But it's a constant evaluation process. Alright, excellent. Thank you so much. Peter Lawson, Rick Barth, Thanks for taking the questions and congratulations on the oral presentation. I guess, firstly, the ASH abstract that we see, is that going to be data-rich in terms of trying to understand response rates and tolerability and paratherapy? Yeah, Peter, so the abstract comes out on Thursday, and as I said in my prepared comments, again, the data were as of July, so there are 12 patients, but there's information there on prior therapies, on response rates, and on organ-specific response rates. Great, thank you. And then, where do you see it fitting into the emerging treatment paradigm, just with, you know, a couple of new drugs in that space? Yeah, as I said, I think that, you know, it's the only drug in development that specifically targets the monocyte macrophage lineage.
Dr. Briggs Morrison: And so I think it, and again, you'll get a sense, I think you'll get a sense, you probably already have a sense from data we've released from some of our other trials of axotelomab that it's a well-tolerated agent. So you know, I think that the initial path is really to get the drug approved in these patients who have probably failed all other therapies. And then, as an earlier question alluded to, think about ways of moving it into earlier lines of therapy, again, potentially in combination with other agents that work through complementary mechanisms.
Dr. Briggs Morrison: Great, thank you. And then just on the MED-IN program, so early 2021 for data, is that going to be at a medical conference or not? [inaudible] Enrollment continues to go very well. I think we mentioned on our last call that one of the changes we made to the trial was to be able to backfill cohorts where we had cleared safety and seen efficacy. And that was in large part driven by the investigators who were asking for more slots to put patients on the trial given what they're seeing. So enrollment continues to go very well.
Dr. Briggs Morrison: We haven't given any more information about where we are on the two arms or the types of patients. All that will be presented when we present the completed phase one trial. Okay, thank you so much. I'll get back into the queue.
Operator: And there are no further questions at this time, so I would like to turn the call over to Mike. Well, first, let me thank everybody for joining us on the webcast and on the call and for your continued interest in Syndax. As I said in my prepared remarks, it's an incredibly exciting time for us here at the company. You know, it's quite possible that by early next year, we will have two programs in pivotal registration trials. And that's really super exciting, so I don't want to hold people from getting their rest before they have to go vote tomorrow. But thanks so much for your attention and your time. This concludes today's conference. My outro for my 20th birthday.