Q4 2020 Syndax Pharmaceuticals Inc Earnings Call
Good day, everyone and welcome to this index fourth quarter and full year 'twenty 'twenty earnings Conference call. Today's call is being recorded at this time I would like to turn the Covid, maybe my yourself Argot partners and speaking.
Okay.
Welcome and thank each of those of you joining us on the line and the webcast. This afternoon for you of Syntex's fourth quarter, 'twenty, and 'twenty financial and operating results.
I'm, making Myers with Argot partners and with me. This afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison Chief Executive Officer.
Definitely create us Chief financial Officer.
Also joining us on the call today for the question and answer session is Michael Metzger, President and C. O L. Dr. Michael Meyers, Chief Medical Officer, and Dr. Peter or debt like Chief Scientific Officer.
This call is being accompanied by a slide deck that has been posted to the company's website.
So I would ask you to please turn to our forward looking statements on slide two.
Before we begin I would like to remind you that any statements made during this call that are not historical are considered to be forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these statements and was as a result and various important factors.
Putting those discussed and the risk factors section on the company's most recent quarterly report on form 10-Q, and the other reports filed with the S E C.
Any forward looking statements represent our views as of today March eight 2021 only.
A replay of this call will be available on the company's website www dot <unk> dot com following this call.
With that I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive officer of syntax.
Hi, Thanks, very much Megan and thank you to everyone for joining us on today's call and webcast.
Slide three provides a high level summary of our current corporate priorities as we strive to realize the futures and which people with cancer live longer and better than ever before.
2020 was a transformational year for subjects over the course of the year, we've made great progress and our two clinical stage programs, both of which are on track to be and Registrational programs. This year.
Thanks to the support of our many committed investors we ended the year well financed to vigorously pursue both of our existing programs and took.
And as it aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline.
Let's now turn to slide four and Jeff and Dx 50, 613, our genetically targeted agent for the treatment of leukemia.
And you've noted previously there's extensive validation nipples MLR and N P M, one mutations and molecular targets and leukemia and.
And well established diagnostic tests routinely identify patients with the genetic mutations per.
The other publications provide the scientific rationale and preclinical validation of our ongoing clinical trial and historic precedent support and rapid regulatory path for such targeted agents and acute leukemias.
Slide five briefly summarizes the ongoing augment 101 trial the first in human phase one two trial and the accelerated understanding of men and for augment program.
Consistent with what we communicated on our last call. We are on track to present, the completed phase one portion of the trial and the near future and to start to see phase II expansion cohorts and soon thereafter.
We have received several questions about the upcoming data disclosure and so I just want to provide some guidance.
Our intent is to present the completed phase one trial.
The primary objectives of the phase one art determine are to determine the safety tolerability. The maximum tolerated dose and the recommended phase two dose of S and D X 56, <unk> and patients with relapsed or refractory acute leukemia.
We anticipate addressing these primary objectives and our data presentation.
And also have characterized the PK parameters are 50 630.
We anticipate having data for at least 30 patients with relapsed refractory leukemia.
There'll be patients, whose leukemia has and MLR rearrangement.
And there'll be patients, whose leukemia has and N P N one seed mutation.
Patients, whose leukemia has neither of these genetic lesions.
Although clinical efficacy and not an objective of the phase one trial, we anticipate summarizing the efficacy that has been observed.
We anticipate that the data will be presented by the principal investigator of the augment 101 trial and Dr. Etan Stein and front of Memorial Sloan Kettering Cancer Institute.
And extremely well respected international experts and the field of adult leukemias, who has extensive experience and experience developing novel targeted agents doctors.
Dr. <unk> presentation will be similar and content to a typical presentation at a scientific Congress such as dash and.
Opportunities for Q&A.
We are working with Doctor Stein to find a suitable date, but anticipate securing a day prior to the end of April.
We have of course been busy preparing for the phase two portion of the trial, which will enroll three distinct expansion cohorts each of which consists of a specific genetically defined relapsed or refractory acute leukemia.
And we're still on track to initiate over the next couple of months.
The three cohorts will include patients with MLR acute lymphoid leukemia, a L L patients with MLR acute myeloid leukemia AML.
Patients with N P M, one and U K M L.
The phase II portion will further characterize the safety of 50, 613 and will provide a robust estimate of the complete response rate as the primary measure of therapeutic benefit.
The phase two portion and 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 debt if the results are positive. This phase two portion of augment 101 could potentially support a regulatory filing giving existing regulatory precedence.
Over the last period has also been conducting an extensive research and to the broad landscape of clinical opportunities for 50 613 beyond the initial approval and relapsed refractory acute leukemias and sale.
Illustrated on slide six.
While we are not in a position today to lay out the specific next steps and building out. The 50 613 franchise I can say that we are using this ongoing analysis to inform a specific combination regimens that we anticipate starting this study later this year.
Several investigators and leading companies have already reached out to us with novel exciting ideas for future development.
And do you have 50, 613, and we are evaluating those opportunities.
Let me now turn to slide seven and after telematics, formerly known as S Index 63 52.
Potentially best in class monoclonal antibody therapy targeting the CSF one receptor.
As you know, we recently presented our phase one chronic graft versus host disease data at Ash and have initiated our pivotal trial for acts and tell them that and chronic graft versus host disease.
This trial is the X until I'm Mad for graft versus host disease trial called a Gaba a two on one and as outlined on this slide a.
Travel 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.
This is a pivotal dose ranging trial in which patients will be randomized to one of three treatment groups. Each investigating a distinct dose that's the telematics given either every two weeks or every four weeks.
The primary endpoint is overall response rate you've seen in the 2014 NIH consensus criteria for chronic graft versus host disease setting.
Secondary endpoints will include duration of response and validated quality of life assessments using the Lee symptom scale.
Enrollment to the study is underway and we are on track to develop.
And to deliver topline data in 2020 three.
We believe that chronic graft versus host disease represents a high unmet medical need and and an important commercial opportunity with approximately 14000 patients suffering from chronic graft versus host disease and the U S. Today.
With the recent positive pivotal results from both inside and Jakafi and cabinets.
025, we made seems soon see regulatory approvals and commercial launches that will begin to delineate the commercial opportunity she chronic graft versus host disease.
Recent advances in this area to our knowledge asks the telematics and only agent and clinical development that specifically targets. The monocyte macrophage lineage. We believe the data generated to date with X until and that suggests it has the potential to play an important role and the treatment of chronic graft versus host disease, both as monotherapy and.
And given its safety profile potentially in combination with complementary medicines.
We've also been working extensively with experts and the field of fibrotic diseases and they found a strong consensus that the scientific rationale for the efficacy of Bax until a mad and crew.
And at graft versus host disease firmly supports its potential and a wide variety of fibrotic diseases, such as idiopathic pulmonary fibrosis and scleroderma.
Actively about evaluating options by which to build the ax Telemark and all of that 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 eight summarizes the transactions that led to the acquisition of the Menin and all are can't ask tell him that programs.
We believe that we will be able to continue to expand our pipeline through the acquisition or in licensing of quality differentiated assets.
Leave that we have the necessary skills to evaluate and identify high quality assets and the clinical development experience to bring these compounds through valuable inflection points.
We expect to remain among preferred partners.
Such transactions.
And now I'll turn the call over to Daphne to review our financial results.
Definitely thank you Fred.
And you break the results of our operations for the fourth quarter of 2020 and a comparison to the prior year quarter are included in our press release, so I won't repeat them and need for Mark <unk>.
Dish and all financial details will be available and our fourth quarter and full year report on form 10-K, which will be filed later this week I would like to point out that our net loss for the quarter was $24 million or 44 cents per share compared to $14 million or 44 cents per share for the same period last year.
Turning to slide nine we ended the fourth quarter with $293 $1 million and cash and cash equivalents, including net proceeds of approximately $135 million from our public offering completed in December of 'twenty, and 'twenty and 51 4 million shares and pre funded warrants outstanding.
This cash balance provides us cash runway well into 2020 three and importantly covers the full development costs of both acts and tell them NAV and the 50 613 registration ready program as well as provides us flexibility for continued business development looking ahead I'd like to provide financial guidance for the first quarter.
And full year of 2021.
The first quarter of 'twenty 'twenty, one we expect R&D expense to be $25 million to $30 million and total operating expense to be $30 million to $35 million, including approximately $2 million of noncash stock compensation for the full year of 'twenty 'twenty, one we expect R&D X.
And to be $90 million to $100 million and total operating expense to be $110 million to $120 million, including approximately $2 million of noncash stock compensation expense per quarter. We expect first half expenses to be more heavily weighted and the second half.
Due primarily to the ramp up and CMC activities for both programs during the first two quarters that the here.
With that I would now like to turn the call back over to Brad.
Oh, Thanks, very much Stephanie let me close the call bike and noting that 2020 was a transformational year for our company and we anticipate that 'twenty 'twenty, one will be no less exciting.
And we've begun to Registrational trial, Fracs, and telematics and chronic graft versus host disease and are eager to present, our phase one data from the augment one and one trial in the coming weeks and to start the Registrational program for F. N D X 50, 613th shortly thereafter.
We are also getting increasingly excited about the broad franchise opportunities for both programs beyond their initial registrational indications.
We believe that 50 613 could have broad utility across a wide range of clinical settings, and acute leukemia, and acetyl them Abbott could represent a broad franchise opportunity and fibrotic diseases.
And are comfortable with given our cash on hand that we have the financial resources to aggressively advance our programs and achieve key upcoming milestones.
Also we remain optimistic that we can continue to identify and bring and 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 wonderfully talented team here its index, our collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs.
In addition, I would like to thank our committed long term investors, who are helping us to build this great company.
With that I'd like to open the call for questions.
Ladies and gentlemen, if you have a question at this time. Please press Star then the number one key on your Touchtone telephone.
And then sorry, and then the number one key on your Touchtone telephone.
Your first question comes from the line of Fiona <unk> from Cowen and company your line and shipping.
Good afternoon, and congratulations on the progress and thanks for taking my questions.
First a few for you just on some of the parameters we laid out for the data we should expect a late this month or next month.
In terms of arm a versus RMB. He actually didn't give any color there or should we have any expectations for relative weighting of those arms.
Hi, Phil Yeah. Thanks for your question.
And I don't think I'll give you any guidance on the relative weighting I think what we have what we anticipate is that we will have.
Our recommended phase two dose for each of the individual arms.
Got it Okay, and then second.
I'm not sure you want to come and I'm gonna see there, but in the past you've suggested the MLR should be more heavily represented and M. P M. One and.
And what are the history of the trial and particularly with some of the heavier enrolling centers.
Because that's still your expectation or could MLR and and pay more and be more evenly balanced.
So that's our expectation that they'll be more MLR and again just to clarify for people otherwise noticed Kmt <unk> rearranged and spent more of the MLR Kmt two ways and N P M. One grid.
Great and then just last question on the data.
How will you present, the safety data I guess, specifically, where you gave us the safety results for all the patients who were enrolled or specifically for the phase two dose.
And I, both actually so we'll present the full safety profile.
You know that.
The entire population that was enrolled and we'll break out the safety profile for the for the recommended phase two dose.
Perfect and then one.
A question for definitely definitely you mentioned each one expenses are going to be heavily more heavily weighted and age too.
Do you expect Q2 to kind of look similar to Q1 or is Q1 really going to be the heaviest and <unk>.
<unk> quarter of the year.
Thanks, Phil So yeah, just to clarify I'm a day comment was we expect the first half expenses to be more heavily weighted and the second half and we would.
The first two quarter to be similar and cadence.
Perfect. Thanks for taking my questions and congrats again on the progress.
And so thanks Phil.
Your next question comes from the line of Bert Hazlett from B P. I G. Your line is open.
Thanks, Thank you for the update and taking the question.
Could you just describe a little bit more Briggs please about.
A little bit more about the phase two expansion.
Augment 101.
Any sense for the size and scale of each of them and individual arms at this point.
And do you have any sense for the potential piece of enrollment or or or the length of enrollment that debt.
The phase two might take.
Yeah. Thanks for the question Bert.
And that the precise size of each of the independent and phase two expansion cohorts again will be sort of sized on.
And what the.
Sort of and all hypothesis is on on response rate and what's the alternative debt. That's still I think a final discussion we have to have with FDA.
There is there sort of a.
And related question of.
Whats the total number of patients that we need from a safety point of view across the three cohorts.
And clearly the phase one data.
I will emphasize that each of the three are independent essentially parallel independent phase two cohorts, we could potentially registered one or two or all three.
But.
And then your second part of your question.
I guess, it's dependent upon the first but.
And the potential of all the timing per time enrollment might take.
Yeah, we haven't we haven't given guidance on the timing because exactly to your point until we know the precise numbers, it's a little hard to give precise definitely other timing, but what I would say is thus far at least the phase one trial has progressed very very nicely.
And so.
It's it's really just a question of knowing how many patients we need and then we'll give you guidance on how long we think it'll take to enroll.
Okay. Thank you and then just a more strategic question with regard to the.
Hi, this is multiple commercial opportunities and acute leukemia and multiple pathways.
Or are you thinking strategically about.
Potential expansion here.
And in licensing effort, which you've been successful up previously.
Our corporate collaborations at some point just general framework for.
And how youre thinking about prosecuting these additional efforts.
Yeah. So I think the first part is just to lay out what we where we believe that the drug can be used and and in some cases that might entail.
Our combination with <unk>.
Established therapies that are generic and available such as chemotherapy might require.
My to be enabled by a corporate partnership with somebody who has.
And drug that we think makes sense combining but this the strategy is first let's lay out where we think the best.
We're the largest unmet medical need is where there's a trial that we can get done reasonably quickly and then decide if there is a corporate partner, who are who would want it and work with us on that or is it single agent or is there a combination regimen debt that we can sort of do ourselves.
Okay. Thank you for that that's all I had thanks.
Your next question comes from the line of Konstantinos <unk>.
From Stifel. Your line is open.
Hey, good afternoon, guys. Thanks for taking my question so for the sake of clarity and the size of the 50 613 update we're looking forward to later this quarter. Early next does the 30 patients include the six patients presented last year and me.
Should we expect 30 additional patients or 30 total patients and where did the compassionate use patients fit and.
Yeah, Hi, Todd and thanks for your question so it's a.
And I said debt.
And at least 30 patients 30 patients total so that includes the six that were presented last year that is the that's the number of patients from the augment 101 trial. So that does not include the compassionate use patients and we're discussing with a ton of what's the right. If you what's the AR.
Whether we focus completely on the phase one trial and will be also presents some other data from the compassionate use patients.
Okay perfect. Thanks for that clarification, and then and one more quick one just you mentioned it in your prepared remarks 50 613 combinations at this juncture. If you had to say what do you think is sort of most promising it sounds like we're going to get something on that and the near term, but any thoughts at this juncture would be helpful.
Yeah again relative to <unk> question, I think that you know the first order of business from our point of view is just to lay out where is the right place to further develop the drug and then and see if that requires a combination.
Clearly I think if you were gonna do first line.
With with this agent.
And there is the so called.
Population of patients, who can tolerate intensive chemotherapy and so there might be a regimen, where you combine with.
Standard upfront chemotherapy, and then theres the population of patients and so called and fit where they don't get chemotherapy. They get other agents and so combining with agents and that space makes sense as well so where we're looking at both the patients who are candidates for intensive therapy and patients who are not.
Alright, perfect. Thank you congrats on the progress.
Your next question comes from and the line of David Lebowitz from Morgan Stanley. Your line is open.
Thank you very much for taking my question when looking at the 30 patients will be seeing them towards the end of this quarter.
I know theres going to be a certain number of patients that don't have either the M. O R or M. P. M. One and initial trials that have all comers with leukemia and I guess my question is as well.
Will there be patients beyond the initial cohorts and we saw.
That's.
Where it does not have mutation and if so do you know how many at this point and can they can the number of I guess none.
N P M ones and.
Can you disclose at this point or I guess.
To what extent, how how large is the number of other.
And number should we expect.
Yes, Hi, David Thanks for your question. So as you correctly pointed out when the trial first started it was an all comers trial and the data we presented at ACR last year three of the patients.
And had neither N P M, one nor MLR and.
The trial pad.
And the continued did allow continued enrollment of that population I think.
Last summer on our on our August call. We had mentioned that we had refocused the the trial to focus only on enrolling and P. M. One and MLR. So there will be patients who have neither.
We haven't said specifically how many of those patients they will be but there will be some because of that early early design other trial.
Yeah.
And thank you for that and on the initial description the call you were referring to the population as a cute.
Leukemias.
So we've seen a.
A L L patience and we're going to see M. P. M. One patients. So are we going to also see AML patients and the trial.
Right.
And we will see both the <unk> and AML and as you may remember from our ACR presentation. One of the patients had what is known as mixed phenotypic acute leukemia, where their leukemia actually has markers consistent with both AML and so there'll be a L. L. A M L and.
Excellent and I guess my last question would be I know that there's a competing men and inhibitor out there and.
Would you be able to I guess compare and contrast, what you know and understand about your molecule.
Molecule.
Yeah.
Yeah, and I don't think I'm, not quite sure which competitor you're referring to.
But.
I don't think we're and the position to do a lot of comparing and contrasting our the other molecule. That's in the clinic, there's actually very little known about the molecule itself.
So.
I think we can say too much about that at this point.
Thanks for taking my questions.
Your next question comes from the line of Trust and Walsh from B Riley and Securities. Your line is open.
Hi, Thanks for taking my question and congrats on the progress.
The C. Gvhd opportunity is quite intriguing to me can you provide any color on how you view that space evolving over the coming years, specifically I'm wondering if you think the opportunity is growing with a trend towards increased number of stem cell transplants or could it be getting crowded with with rux and other drugs going through approval.
Yes, I'd like.
And a new product planning and we can't go live and to take that question.
Thanks, Craig Thank Justin for other question, Yeah, you know what I think there's a lot of change and that faces you mentioned, there's a couple of new drugs that are under review from the FDA for potential approval and but you know I think there's two parts to that answer with the advent and the new leukemia drugs.
There are very promising and helping patients get to transplant, there could be and increase in overall number of patients, who unfortunately that and develop them.
And chronic gvhd as a consequence of that transplant and there. There's also I think a lot of underserved patients that exist today with chronic gvhd, who have been treated with therapies that weren't developed to treat that disease and and haven't done as good a job.
And as we think actually tell them that could do and maybe perhaps some of the other agents in controlling their disease. So we think that is really going to be a displacement of some of the.
No. None are labeled agents the agents used off label to treat chronic gvhd and there'll be ways to actually.
And maybe better help these patients better serve these patients and.
And help them.
Live longer and and better with their disease.
Got it and I have one follow up I know that we aren't expecting the topline agave tool one guy to until 2023, but could we see any data readouts before that or anything this year or maybe next year for the earlier trial.
Right. So you may remember.
We had started a.
Phase two expansion cohort and as part of our phase one trial at one make per keg.
And it is.
The team is still allowing that trial to enroll while we get agave and up and running so if a site doesn't yet have agave up and running but still has patients. They want to put on trial. We can put a few more on and it's not clear yet when we're going to present that data, but there may be data on that updated phase two court at.
The one Meg per kg and later this year.
Yes.
Perfect. Thank you and that's all for me.
Once again to ask a question you will need to press star one on your Touchtone telephone and then that starts and number one on your Touchtone telephone.
Your next question comes from the line of Peter Lawson from Barclays. Your line is open.
Hey, Thanks for taking my questions. Thanks for the update.
Briggs I'm just on the side effect profile, you've seen so far for 5613.
Does that preclude or point to any particular combination agents.
And presumably frontline.
Okay.
Yes, so obviously, we will present the safety data because somebody asked earlier.
And from what we've seen it doesn't preclude combining with any other agents that we would be interested and combined anyway.
And then the other place, we're both kind of a and b.
It applies to the so called <unk>.
Chemo eligible patients and the the unfit.
Got you, Okay, and then as you move from phase one into phase II do you expect any changes and endpoints or how should we think about the I guess the.
The inclusion exclusion and how that potentially changed from phase one to phase two and points.
Yeah, No we don't.
And again, obviously the phase one trial, the primary objectives as I alluded to or.
PK and safety.
And defining a recommended phase two dose the phase two portion the primary endpoint is a CR rate for.
Efficacy, but the <unk>.
All inclusion and exclusion don't change.
The phase one trial has.
Changed over time, we've amended the protocol and many times to.
And you know allow pediatric patients and to focus on N P M one and MLR.
But overall the general population of patients that were enrolling and in terms of relapsed refractory leukemia doesn't significantly change from phase one to phase two.
Thank you and then and that kind of.
And third group of patients.
Mentioned about present and so that no.
Oh and the.
The non NPA and one patients would you expect to see any kind of response and those patients.
Well I think that's why the FDA asked.
And the companies to enroll a broader population so.
I think the their perspective was.
We're convinced that your drug potentially could work and N. P M. One and MLR theres been extensive preclinical validation.
We're convinced that your drug probably would not work and D. C are able we've always used debt as a negative control and our preclinical models, but there are other forms of leukemia that it might be of interest for you to studies. So I think that was why the FDA asked us to to enrolling all comers population.
Okay, and so we could get kind of.
Patient vignettes and that group that could be of interest.
Yeah.
Well as I said I think the FDA asked us to enroll a broad population of patients to begin to look at that it's obviously not a definitive assessment of that population.
We focus much more on the MLR and N P and one for the simple reason debt, we can diagnose those patients today and.
He has a clear unmet need in a population of patients debt from a regulatory point of view you can identify and you can get an indication for.
Got you okay. Thanks, so much thanks, thanks for the answers.
Okay.
Once again to ask a question you will need to press stories and the number one and you touched on telephone and again that's tons and the number and one on your Touchtone telephone.
Yeah.
Once again to ask a question that sorry that the number one on your Touchtone telephone.
There are no further questions at this time I would now like to turn the call and I'll go back to Mr. Briggs Morrison Chief Executive Officer, That's index.
Thank you very much operator and again, thank you everybody for joining us on our call as I said I think.
2020 was a transformational year and we anticipate that 2021 will be no less exciting and.
First piece of news of course will be the presentation of our phase one data from the augment 101 trial and.
I think we're really quite excited to present that data and then to take additional questions from everybody and once you have a chance to see that so thanks, so much for joining the call.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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