Q4 2020 Syros Pharmaceuticals Inc Earnings Call
[music].
Good morning, and welcome to the Cirrus Pharmaceuticals fourth quarter, and full year 2000, and 'twenty financial results conference call at.
At this time, all participants on the listen only mode.
This call is being webcast slides on the investors and media section of serious website at Www Dot zeros dotcom.
Please be advised that today's call is being recorded.
Following the formal remarks, we will open the call up for your questions.
And at this time I would like to turn the call over to Naomi Aoki, Vice President of corporate Communications and Investor Relations at Sears.
Thank you. This morning, we issued a press release with our fourth quarter and full year, 2020 financial results, along with anticipated future milestones and reach and accomplish that.
The available on the investors and media section of <unk> website at Www Dot Dot com.
We will begin the call with the prepared remarks by Doctor and Nancy Simonian, Our Chief Executive Officer, Dr. David Roth, Our Chief Medical Officer, and Joe Ferra, Our Chief Financial Officer.
And the call for question and Doctor Eric of Jackson, Our Chief Scientific Officer, and Doctor Jeremy Spring Horn, Our Chief business Officer are also on the call and will be available for Q&A.
The board, we began I would like to remind everyone. The statements. We make on this conference call will include forward looking statements.
Actual events or results could differ materially from those expressed or implied by any forward looking statement and if there is.
All of various risks uncertainties and other factors, including those set forth and the risk factors section of our annual report on form 10-K that we filed this morning and any other filings and we may make with the FTC and the future.
And in particular, the extent of which the COVID-19 outbreak continues to impact our operations and those of third parties all of which we rely will depend on future developments, which are highly uncertain and cannot be predicted with confidence and any forward looking statements made on this call represent our views only as of today and should.
Not be relied upon as representing our views as of any subsequent date, we specifically disclaim any obligation to update or revise any forward looking statement I would now like to turn the call over to Nancy.
Thanks, Naomi and good morning, everyone.
You for joining us today as we review our recent progress.
2020 marked a year of remarkable progress for syros.
Our vision has always been to build a great and enduring company that makes the profound difference for people living with cancer and monogenic diseases.
In recent months, we made significant strides toward achieving that goal.
We focused on three key strategic priorities to fuel our growth.
Expanded our clinical stage portfolio with the acquisition of FY 'twenty one out of one.
And we fortified our cash position true two financing, which together resulted in gross proceeds of over $165 million.
And we enter 2021, we are focused on executing against the ambitious strategy. We laid out last year with the goal of of rapidly maturing zeros and to a commercial stage biopharmaceutical company.
Our strategy is rooted in three priorities.
Advancing and leading franchise of targeted therapies for hematologic disorders.
Building on our leadership and selected CDK inhibition for difficult to treat cancers.
And leveraging our foundational gene control of discovery engine to fuel a robust and sustainable pipeline to support our long term growth.
And the fourth quarter, we made tremendous progress on the first of these three priorities.
<unk>, our hematology franchise through the acquisition of 21 O one and the announcement of new clinical data that support and next steps for 14, and 25, including a registration, enabling phase III trial, and RARA positive patients with Myelodysplastic syndrome or Mds.
Let me begin with 21 of one which we acquired from Orthopedics and December.
21 of one is a novel form of arsenic trioxide or a T O for patients with acute promyelocyte of leukemia or a P. L. We are incredibly excited about this program.
Based on everything we know about this market and the overwhelming enthusiasm of physician. We believe 21 O. One has the potential to quickly become the frontline standard of care and provide a huge benefit for the approximately 2000 people in the U S and the EU, who are diagnosed with APL each year.
And many of you know I D. A T is a transformative therapy for a P L.
Which in combination with Acura, it's curative for more than 80% of patients.
But it comes with an enormously heavy treatment burden the.
The current course of treatment is up to 140 daily two to four hour infusion over the first year.
As an oral agent and we believe 21 O one could dramatically reduce the intense burden of treatment and patient.
And more broadly on the health care system.
We plan to initiate a dose confirmation study and the second half of the year followed by the phase III trial of 21 O, one plus acura and frontline and E. P. L next year.
We believe a successful phase III study could enable us to file an NDA as early as 2024.
Turning to 14, and 25, we presented but share of clinical data at ash, which demonstrated compelling activity and RARA positive newly diagnosed unfit patients with acute myeloid leukemia or AML.
The profile of 14 and 25.
And oral targeted therapy with compelling activity and a well tolerated safety profile gives us confidence that 14, and 25 could serve as the foundation of care for RARA positive patients with AML or Mds.
And provide a clear path for further development across multiple underserved patient population.
We are working hard to execute on our next wave of clinical studies with 14 and 25 for RARA positive patients.
We are pleased to report that our phase III trial of 14, and 25 and Asa side of Dean and RARA positive newly diagnosed higher risk Mds is now open for enrollment.
If successful this trial could enable a second NDA filing in 2024.
We also remain on track to initiate a randomized phase II study evaluating the triplet regimen of 14, and 25, plus the net o'clock and as the siding and RARA positive newly diagnosed unfit AML and the second half of this year.
Taken together, we view 21 O one and 14 and twenty-five it's highly complementary assets, which provide us the opportunity to leverage our existing expertise and capabilities and hematologic disorders and capitalize on synergies as we build out our commercial infrastructure to of.
Dress three genomically defined patient population with high unmet medical need.
In parallel we continue to make progress against our second and third strategic priority by advancing our selected CDK inhibitor franchise and earlier stage pipeline.
Following promising initial phase one data for 56 or nine that we presented at the E. O R. T C and C. I, a ACR symposium and October 2020, we continue to actively enroll patients and our ongoing trial. We are on track to report additional dose escalation data from this study.
Including clinical activity data and the third quarter and and to enter into the expansion phase of the trial and the second half of 2021.
Additionally, we are working hard to exploit the full power of our gene control of discovery engine to date, our platform continues to fuel a rich early stage pipeline and cancer and monogenic diseases and.
And our most advanced preclinical program, which targets C. D. K 12, and a member of the transcriptional CDK family that offers distinct therapeutic opportunities from CDK <unk> inhibition.
And our two discovery stage partnerships with global blood therapeutics, and insight, which enable us to potentially accelerate our efforts and expand our reach to many more patients.
We look forward to and nominating our next development candidate and 2022.
Before turning the call over to David Let me take a moment to thank my colleagues at zero.
And we all know 2020 was a difficult year and the initial months of 'twenty 'twenty, one and have remained challenging.
I could not be prouder or more appreciative of my colleagues for their continued hard work resilience and dedication which has enabled us to make excellent progress internally and in collaboration with our partners across each of our clinical and preclinical programs.
And I firmly believe that people are what distinguished great companies from good one and we have a tremendous team across the board here at zero.
With that let me turn the call over to David to review, our recent data for 14 and 25 as well as next steps for the program and both Mds and AML.
David.
Thank you Nancy and good morning, everyone.
We believe there is a significant opportunity for 14 and 25.
Ross, both Mds and AML.
Approximately 30% of both patient populations are RARA positive and many patients continue to be underserved either due to the lack of effective options.
And the ability challenges for a disease phenotype that is resistant to standard of care therapy.
We believe for $2 25 unique constellation of attributes, including its oral delivery targeted patient population.
Robust efficacy and distinguished Tolerability profile make it a highly differentiated therapy.
With a meaningful opportunity to benefit thousands of patients in need of better options.
The data from our phase II trial that we presented at Ash and further strengthen our conviction and the fortune 25.
Phase two trial was designed to assess the safety and efficacy of 14, and 25 and combination with Asia side of Jeep.
The trial included both RARA positive and RARA negative newly diagnosed unfit AML patients as.
And as well as RARA positive patients with relapsed or refractory AML.
As Nancy alluded to earlier the data showed high complete response rates and RARA positive patients as well as the rapid time to response and.
Clinically meaningful durability and.
Importantly, the combination of $40 25, and <unk> was generally well tolerated with no evidence of increased toxicities beyond what has been seen with either 14, and 25 or <unk> alone.
Rates of Milo suppression, including neutropenia, and anemia and were comparable to a single agent and Asus hydrogen and these patient populations and adverse events were consistent with prior clinical experience.
And the Tolerability profile is so important and these generally elderly patients who need therapies to control their disease and not impact the quality of life.
We also presented new translational data at ash, suggesting that the RARA biomarker not only select for patients most likely to respond to fortune 25, but also enriches for patients likely to be resistant to the combination of kinetic lax and ease of siding or and Asia.
Despite the emergence of and Asia.
Standard of care and newly diagnosed unfit AML over 30% of patients remain refractory to frontline therapy.
Recent studies show these patients are enriched for a monogenic form of AML.
And our data show that most RARA positive patients, including those who achieved a CR or cri with fortune 25 half of this form of AML, suggesting about the combination of 14, and 25 and Asia could benefit AML patients who are likely to be resistant to venues.
Based on these data we believe we have a clear and compelling path forward for for $2 25, and both AML and <unk>.
And MTS and we are advancing into later stages of development and both indications.
Let me begin with MTS.
We believe newly diagnosed higher risk Mds represents the ideal opportunity for for $2 25 in combination with <unk>.
This is for three reasons for.
First higher risk Mds is closely related to AML.
The two diseases exists on a continuum and our distinguished largely by the percent glass and the bone marrow and fact about half of all higher risk Mds patients eventually progress to AML.
There is significant mortality and morbidity from disease related Cytopenia is making 14 and 25 overall tolerability profile, including its combinability with Acer without increasing hematologic toxicities, particularly attractive and there's more chronic disease.
Second we've seen 14, and 25 single agent activity and higher risk Mds and high rates of complete responses and combination with Asia and low blast count AML, which is close to Mds on the disease continuum.
Third we have the opportunity to set a new standard of care Heiko.
And <unk> agents are the current standard and they offer low CR rates with the median overall survival and the range of 15 to 25 months.
We recently initiated our phase III trial of 14, and 25 and combination with a society of gene and RARA positive newly diagnosed high risk Mds patients and are actively screening patients.
This trial will enroll approximately 190 patients randomized two to one to receive either 14, and 25% and Asia siding or Asia side of gene alone.
The primary endpoint of the trial will be complete response rate, which we believe informed by feedback from the FDA could support accelerated or full approval and this patient population.
Moving to AML based on the data linking the RARA biomarker with resistance to them and you saw we also plan to initiate a randomized phase II trial and the second half of the year evaluating the triplet regimen of 14, and 25, plus and then Asia compared to <unk>.
The alone and approximately 80 RARA positive newly diagnosed unfit AML patients.
The rationale for this study is simple we think the best approach and this patient population is a multi pronged upfront approach that allows us to address the heterogeneity of AML.
Triplet strategy has the potential to reduce the emergence of resistant disease like simultaneously targeting both mono and civic and non us non myasthenic leukemia cells that may also be present at the outset.
Thus, increasing the likelihood of deeper and more durable responses.
In closing we believe for $2 25 has the potential to set new standards of care for targeted populations of patients with Mds and AML, who currently have few options and I'm excited about the opportunities that lie ahead to help these patients.
And look forward to updating you on our progress as we continue to move through clinical development.
With that.
Let me turn the call over to Joe to review, our fourth quarter and full year 2020 financial results.
Thank you David.
We're entering 2021 and a strong financial position in January we completed of $75 $6 million public offering and in December we completed of $90 $5 million of private placement debt.
The proceeds from these financing and extend our anticipated cash runway into 2023 and allowed us to invest on our three strategic priorities building franchises and hematology and CDK inhibition, while continuing to unlock the full potential of our gene control of discovery engine, we have.
We're grateful to our new and existing investors for their continued support.
Turning now to our fourth quarter and full year of 2020 of financial results.
We ended 2020 with $174 million and cash cash equivalents and marketable securities compared with $91 $4 million at the end of 2019.
Our cash position as of December 31, 2020 does not include proceeds from our January 2021 follow on offering.
We recognized $5 7 million and revenue in the fourth quarter of 2020, consisting of $3 6 million from our collaboration with GBT and $2 1 million from our collaboration with insight for.
For the full year 2020, we recognized $15 1 million and revenue consisting of $11 7 million under our collaboration with GBT and $3 4 million under our collaboration with insight.
For the fourth quarter and full year of 2019, we recognized <unk> 5 million and $2 million respectively.
All revenues in 2019 of our earned entirely under our collaboration with insight.
R&D expenses were $29 million in the fourth quarter of 2020, and $76 1 million for the full year 2020, as compared to $14 3 million for the fourth quarter of 2019, and $58 2 million for the full year 2019.
This increase was primarily due to the 12 million paid for the acquisition of 21 O one from <unk> and as well as the continued advancement of around $14 25, and $56 nine clinical trials and our preclinical programs.
G&A expenses were $5 9 million and the fourth quarter of 2020, and $21 3 million for the full year 2020.
For 2019, our G&A expenses were $6 4 million for the fourth quarter and $21 5 million for the full year.
Finally, we reported a net loss for the fourth quarter of $31 million for 62 per share.
Compared to a net loss of $19 $7 million of 46 per share for the same period and 2019.
The net loss for the full year, 2020 was $84 million or $1 82 per share compared to a net loss of $75 $4 million or of $1 88 per share for the full year 2019.
With that and I will turn the call over to the operator for questions. Thank you very much.
Thank you Sir.
As a reminder to ask a question you would need to press star one on your telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.
I show our first question comes from the line of Phil Nadeau from Cowen. Please go ahead.
Good morning, Thanks for taking my questions and congrats on the progress.
A few on the trials that you just described first for the randomized phase two.
Perhaps I missed it I actually didn't hear where your primary endpoint is kind of be can you discuss.
The choice of endpoint and in light of the fact that it sounds like Youre looking at the depth and durability of responses, so, perhaps cri and it wouldn't even be the correct and point, maybe you need some of like Mardi or progression free survival.
Thanks for all of them and I have David the answer that question for.
Great to talk to you go ahead David.
Thanks, Bill and so just to.
And provides the context. This is a randomized phase II in RARA positive newly diagnosed unfit AML and comparing the triplet of Fortune 25, plus <unk> and Asia.
<unk> and <unk> and I guess and.
For that the primary endpoint is going to be the composite complete response rate.
And we believe that this rate will very well reflect the clinical activity, we expect to do.
The liver with our triplet.
Compared to the control arm, which is just out of that Asia and just to remind you again from the data that we presented at the Ash meeting.
<unk> demonstrated that.
The majority of RARA positive patients have this monostich AML phenotype, which has been demonstrated by multiple independent groups to correlate with resistance to treatment, but has been out of class and Asia.
And so.
If this translates into the clinic as we anticipate it might we would expect the control arm might do less well than what we generally think of for performance of the doublet and the population and that would give us the technical advantage for this randomized approach.
Is there any way that you could look at and Marty as an end point of the markers of success too.
Differentiate the leukemic crohn's from from normal.
And this patient population.
Oh, absolutely one one.
One could certainly look at M D and.
And obviously, there's a lot of interest and seeing the depth of the response and.
And how that translates into the duration of the response of the long term survival.
I will say that in our current program.
And RARA positive newly diagnosed AML, we demonstrated a very high overall response rate of about 67% 61% were.
The Crs the Cri, which is consistent with the the planned.
The primary endpoint for for the the go forward program against the Pan Asia.
And almost all of those.
89% were deep.
Deep responses molecular cytogenetics CR. So we're feeling really good about our current data and predicting.
And the appropriate next steps and the path forward for this program and newly diagnosed and.
That's very happy.
Very helpful.
The second question is on the Phase III study and high risk Mds.
Have you disclosed or would you be willing to disclose the powering of the trial.
And with CR rate per you're assuming for the control arm versus versus treatment and and what's the part of the tech that difference.
Yes, so we haven't provided that level of detail of what I can say is it's it's 14 and 25 plus as of versus Asia.
And so 190 patients with complete response is the primary endpoint.
Randomized two to one using the CR and focus on RARA positive. This is all.
Information.
That.
We plan to take forward informed by feedback from the FDA. So we're feeling really good about the strategy and I'm confident and and the way in which we've designed.
Great and then last question from US in terms of 50 690, <unk> proof of concept data come in and Q3.
Can you give us some sense of what you need to see and Ah.
Indication in order to continuing to advance 56 of nine for that tumor type.
So.
Again, I'll sort of from 56, one and this is our selective CDK <unk> inhibitor, we presented that data at <unk> that was our early data coming out of the phase one.
As you know, we're continuing and our.
The new dose escalation, we reported evaluating various regimens of $7 75.
And five days on two days off and escalating doses and we have various tumor types and indications we're setting the stage for.
Advancing the program.
And the either single agent or and combinations.
And in specific patient populations that certainly will be informed by the data obviously the ability to continue to demonstrate a tolerable safety profile of which we're very pleased to have demonstrated in the context of achieving proof of mechanism at doses that were tolerable.
That will inform how we want to take this forward, we're looking at our biological activity through the PD markers that we've employed and the study to help inform the best next steps and I think generally of the totality of the data is going to really help frame, how we pick the specific tumor types and the potential combinations to take it forward.
That's very helpful. Thanks for taking my questions.
Thanks, Bill Thank you.
Thank you. Our next question comes from the line of Ted <unk> from Piper Sandler. Please go ahead.
Sure.
Oh, great. Thank you very much.
And congrats on all of the progress of total for the tier I wanted to ask about part of 600 related ex.
The expectations are there has been a lot going on and.
Breast cancer, and general and just wanted to get a sense of FCC sort of the changing landscape.
Changing your thinking about the comp and the potential development paths. Thanks, so much.
Net had.
Uh huh.
We are remain very excited about the opportunity for $56 nine with the.
Yes.
Single target the data suggests that could work across the whole range of difficult to treat tumors and then obviously our dose escalation study, we're examining multiple different tumor types, including breast cancer, both the HR positive with the best threat.
And as well as in the and the.
The single agent patients, including Triple negative breast. So if we think about the go forward as David said earlier, we're going to be looking at the combination of the data that we're generating during the dose escalation the.
And unmet medical need and that patient population and what else is emerging in that space and.
Where are some optimal places to take it forward and expansion to get to proof of concept and our plan for ice for its commercialization. So we're fully aware of what's happening and the HR positive breast cancer landscape and the more novel endocrine therapies coming for but we think is really exciting and also offers opportunities for us to think.
About how we develop 50.
And 50, 609 and that space, but we are we will the looking at the totality of both the data from the trial as well as what's happening and the external landscape, but we think that there is of tremendous opportunity across.
Many different tumors, including breast cancer better piece ex airlines low.
Awesome. Thank you very much.
Thanks Ted.
Thank you. Our next question comes from the line of Jason Butler from JMP Securities. Please go ahead.
Hi, Thanks for taking the question just had one on for <unk> 'twenty and M. D. S. Can you maybe just talk to the little bit about I know, you're not disclosing the powering the based.
Based on your interactions with physicians.
What you would need to see to change standard of care and whether or not see our rate would be sort of would be enough data of benefit there would be enough to change standard of care.
<unk>.
Let me start out and then I'm going to turn it over to David.
We as you know and the higher risk Mds space.
There hasn't been a new drug approved other than HMA and decades and as of Friday being alone.
And you know provides limited.
And for these patients and I think what we find quite compelling about the 14 twenty-five profile in the.
And Mds and you. Obviously this is in discussion with physicians is the one of the major problem of these patients have is they have sort of cytopenia is related to their disease neutropenia as an example, and they get into infection related complication or require a lot of transfusions and that's read out results and a lot of morbidity and mortality.
<unk> from the disease, so the opportunity to have of drug.
That doesn't and Ken.
And good efficacy, but doesn't exacerbate the cytopenia.
And as I think a really compelling profile of that physicians have expressed to us and these patients it's a little bit more of a chronic disease, it's not like they're acutely blasting off from their AML. So something that is works well well tolerated convenient and.
And these patients are typically outpatients.
As is as Ive really wonderful profile.
David Let me turn it over to you and see if you can add a little bit more about the Crs and endpoint and how physicians feel about that.
Yeah, No. It's an important question and I think that.
We are obviously looking at the totality of our data and see our endpoint is and accepted surrogate for long term benefit and technically.
It may serve our purposes for obtaining and accelerated approval or even a full approval based on the totality of our data package and as you you're assuming I am sure that the other data that we'll be collecting is going to help.
The the Swift evolution of the standard of care to include 14, and 25 for RARA positive patients and that's what we're expecting.
And we'll be looking at other parameters that will help provide that convincing evidence. So for instance, things like transfusion independence.
Hematologic improvement, which.
Involves the normalization of the peripheral blood counts that can be so.
The problematic for these patients so as Nancy mentioned.
And the length of the duration of the response.
And survival and things of that nature of will all roll up into what we believe will be a compelling reason for.
Sure.
The adoption of this drug and the treatment of these patients.
Okay, great. Thank you very much.
Thanks, Jason.
Thank you. Our next question comes from the line of Mark Breidenbach from Oppenheimer. Please go ahead.
Hey, good morning, and thanks for taking my questions.
This one's probably and toward David but just with respect to the the phase III trial in Mds are there any plans to include the from analysis before enrolling the pool of 190 patients.
Yes, a good question. So we we've currently not been very specific with the the details of our current plans our debt as we said today, we initiated the trial, we're very proud of that it's.
It's open for enrollment and are our estimates and projections at this point would have us filing and NDA and the 2024 timeframe. We haven't provided additional guidance to when data would be available and made public.
Okay understood and when.
With respect to 56 of nine or the expansion cohorts likely going to be inclusive of all of the same tumor types that made it into phase one dose escalation or do you think theyre going to be going after and narrower more narrow or more specific subset of tumor types and expansion.
So the and.
Other good question. So right now our current plan for that trial is to share.
The data in the third quarter, we would expect this data to include.
Additional information from from the patients that had been enrolled at the time of DNA and the subsequently enrolled to help better understand what.
And what the objectives of the trial, we are seeking to understand the safety and and also we're going to have a focus on clinical activity. So we're excited about that and then and the second half will be opening these expansions we haven't provided more.
More information on the nature of what those expansions would be like I think we certainly look to our experience to help inform our decision, making we generally we are data driven and that respect. So right. Now we are focused on patients with <unk>.
Pancreatic colorectal lung breast ovarian cancer as the single agent. We also have the combination with the full first Trent.
But we also have lots of other work going on and to explore other.
The things that will potentially find their way and to the study design and depending on how our day dose sorts itself out. So we will give you more context on that.
Around the time of the expansions for the curve.
Moving forward.
Okay. Okay.
And maybe Mark I'll, just add debt generally if you look at what we did with 13 65, and it's pretty typical.
And one moved into an expansion phase at the various the expansion cohorts are of more homogeneous set of patients.
So that that's what we've done with 30 and 65 and I think it's.
And that one can expect so if you hone in for that next phase of focusing on one or more.
Populations based on multiple cohorts.
Got it and kind of.
And finally, just just one one last quick one.
Do you of any plans to present preclinical data and this year from either of the the fetal hemoglobin inducers. So we haven't heard much from that program and are in a while just curious thanks.
Yeah, where are the.
The discovery partnership with global Blood Therapeutics is going very well I'm really excited about that and really wonderful partners and.
And we continue to be very bullish about the opportunity to provide.
The potential functional cure with the small molecule.
And you'll get in that relationship we have not disclosed.
When we're going to be presenting data of our F. But I would just say it's been to data and highly productive collaboration with blah blah blah and.
Yeah.
Okay. Thanks, so much for taking the questions and congrats on the product.
Thank you Mark.
Thank you and next question comes from the line of Bad July from Roth Capital. Please go ahead.
Good morning, guys.
Two quick questions I'm excited to tell the plaza for.
The two and 25, specifically and I just wanted to ask if you had any updates regarding the development of a companion diagnostic.
Moving and then any factors influencing.
And the timeline on the APL two of them I think you said and indeed in 2020 for it they just kind of wanted to understand the mechanics around that.
Yeah, Hey, Paul So yeah. The companion diagnostic is a very important part of the development strategy for 14 and 25 because at the end of the day, we will be launching that drug and the RARA positive patient population, we've had a clinical trial assay and place that's been quite robust and we are.
In parallel working on the development of a companion diagnostic we haven't given more detail but.
And suffice it to say that that development is very important and it's progressing quite nicely and parallel with the clinical development.
I'm sorry, your second questions like that.
Are you thinking about that trial and for the ACO program.
Yeah. So you know we we.
And we just acquired the asset in December.
And of the team has done and the Cirrus and a remarkable job pulling together things very quickly that enabled us to initiate the dose confirmation study and the second half of this year and could be gearing up to start of phase III trial next year. So so we're excited about both the.
The asset and the pace of upon which.
The team has been able to very quickly.
And our pull everything together to be on the cusp of a startup of.
The potential phase III start next year, which obviously involves both the clinical work, but a lot of day of manufacturing bucket as well.
And so we.
And we feel great about that and I think the other thing is we've just got and a tremendous amount of enthusiasm from the kols and the field.
Just I think underscore just the how much of a need there is for this therapy and that gets it gets us a lot of.
Great confidence and the execution on the plan as well.
Thanks for that help the answer your question Greg that okay awesome.
Great to talk to you.
Thank you.
And as a reminder to ask a question you would need to press star one on your telephone to which all of your question. Please press the pound key.
I show. Our next question comes from the line of Matthew Cross from Alliance Global. Please go ahead.
Hi, all good morning, and thanks for taking a couple of questions from me both relating to the the phase II triplet study with within Asia.
In particular, I guess I was wondering if anything had been decided about the dosing considerations for adding and then in order to manage kind of opinions and the like or maybe the balance out some of the fortune 25 of specific talks we've seen such as the hyper triglyceride email.
And then the second one was.
Can we just posted a new phase III study yesterday I believe of.
The girl of Mab, plus as of the compared to <unk> <unk> or seven plus three.
And $2 53, mutant AML and I guess I'm curious, how you're thinking for the positioning of 14 and 25 as an add on therapy. The Vanessa as these efforts to maybe replacement of these are in certain settings advance do you feel there's any meaningful risk that but by the time of we're looking at the at the phase III study in newly diagnosed AML the <unk>.
Landscape me of shifted away from from vendors as the backbone to combine with.
Okay, So maybe I'll start with the the and.
Initial part of the question and that related to the dosing so.
I mentioned, a little earlier that where we're going to be dosing 14, and 25, plus and that of clocks and Asia versus the medical acts and Asia.
The trial is designed and planned to start in the second half of this year, making great progress on that got great enthusiasm and input.
From the.
The country of experts that are kind of help deliver that strategy together with us.
And we'll proceed with a very brief safety lead and just to focus on the question you are sort of getting out with how it's all going to be dosed and we.
We haven't provided more detail on the specifics of of that strategy, but I think we have a fairly straightforward plan and.
I think it's also important to remind you.
And that one of the attributes of FY, 14, and 25, which.
The increase of our conviction of why it can be so important for use of these populations is that it is not.
None to be of Milo suppressive truck and.
And it's generally well tolerated.
The safety profile and affords us the ability to be used and various combination contexts, we don't anticipate.
Additive toxicities.
We haven't seen kind.
Turning issues that that would suggest we're going to run into it.
<unk> was there. So that's why we are going to start just to make sure and dot our I's and cross our Ts to do that to start with but we expect this.
To move forward efficiently through that from the initial phase.
You may have.
Ask the question of the adverse events of the triglycerides and those have largely been of laboratory abnormalities of patterns have been.
Clinically.
Quiet so to speak and we don't expect that to cause problems and this particular population.
We're focused on.
And then on the on the.
The aspect of just where the field is going and other combinations.
This is obviously the AML spaces.
Very dynamic space.
We are we feel quite confident that that is off.
And is currently kind of dust standard of care of and will continue to be and important standard of care going forward, but they really great thing about 14, and 25 is the it combined we believe it has the opportunity to combine well with multiple different drugs and that's all.
Novel mechanism of action it doesn't have the associated toxicities of other drugs and so as additional doublets or triplets are emerging and the field. We think that will just provide an opportunity for us to think about how to have a 14 and 25 also part of that backbone and I think back to the days of development of Velcade.
And myeloma and as it was exactly that we were combining with a couple of things and then there's things. We're emerging we didn't have overlapping toxicities and we were able to look at a variety of different sort of doublets and triplets.
So we are watching the competitive and commercial landscape very carefully to ensure that we have a strategy that will best position of where the market is gonna be and the future.
Great. Okay. Thanks, Thanks for addressing the questions and I appreciate the insight and and the reminders on the designs. Thanks guys.
Thank you Matt.
Thank you I show no further questions in the queue at this time I'd like to turn the call back to Dr and Nancy Simonian CEO for closing remarks.
Thank you operator, I want to thank you all for joining us today and for your continued support of zero and.
We are focused on executing against three strategic priorities and advancing toward our vision of building <unk> into a fully integrated biopharmaceutical company with a portfolio of targeted medicines that make a profound difference for people with cancer and monogenic diseases.
Thank you so much.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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