Ladies and gentlemen, thank you for standing by, and welcome to the Fourth Quarter 2019 Syros Pharmaceuticals, Inc., Earnings Conference Call. [Operator Instructions] It is now my pleasure to introduce Vice President of Corporate Communications and Investor Relations, Naomi Aoki. .

Thank you. This morning, we issued a press release with our fourth quarter and full year 2019 financial results along with anticipated future milestones and recent accomplishments. This release is available on the Investors and Media section of Syros' website at www.syros.com. .

We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer; and Joe Ferra, our Chief Financial Officer. We'll then open the call for question. Dr. David Roth, our Chief Medical Officer; Dr. Eric Olson, our Chief Scientific Officer; and Dr.

Jeremy Springhorn, our Chief Business Officer, are also on the call and will be available for Q&A. .

Before we begin, I would like to remind everyone that 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 statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our annual report on Form 10-K that we filed this morning, and any other filings that we may make with the SEC in the future.

In addition, 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 statements. .

I would now like to turn the call over to Nancy. .

Thank you, Naomi. Good morning, everyone, and thank you for joining us today. At Syros, we are redefining the power of small molecules to control the expression of genes, with the aim of delivery medicines that provide a profound benefit to currently underserved patients with cancer and monogenic diseases. .

In 2019, we made important progress toward this goal. We continue to advance our lead program, SY-1425, a first-in-class selective RAR-alpha agonist, currently in a Phase II trial, presenting promising clinical data in newly diagnosed unfit RARA-positive AML patients and initiating a trial cohort in relapsed or refractory RARA-positive AML patients. .

We continue to build on our leadership in selective CDK7 inhibition, prioritizing the development of SY-5609, our highly selective and potent oral CDK7 inhibitor, which is now in a Phase I trial in patients with select solid tumors.

And we entered into a collaboration with Global Blood Therapeutics to expand our effort in sickle cell disease and beta thalassemia with the aim of accelerating the development of novel oral medicines that could provide a functional cure for patients with these diseases. .

Together, these accomplishments provide a tremendous foundation as we enter 2020. We expect this year to be important for Syros, marked by continued clinical execution and culminating in meaningful data readouts in both 1425 and 5609 in the fourth quarter. .

In parallel, we continue to enhance our gene control platform, which has proven a productive discovery engine, shedding light on regulatory mechanisms that play a key role in disease, revealing new targets for therapeutic intervention and generating selective small molecules against transcriptional targets. .

Let me begin today with an update on 5609. We believe that 5609 represents a potentially transformative targeted approach for difficult-to-treat cancers. It is a highly selective and potent oral CDK7 inhibitor that has demonstrated robust antitumor activity, including complete regressions as a single agent in a range of preclinical cancer models. .

In January, we dosed the first patient in our Phase I trial of 5609. This multicenter, open-label dose escalation trial is expected to enroll approximately 60 patients with advanced breast, colorectal, lung or ovarian cancer or with solid tumors of any histology that harbor RB pathway alterations.

We have designed the trial to move through dose escalation as rapidly as possible, while giving us opportunities to expand cohorts at certain doses to gather more data along the way. Importantly, we have focused the trial on patient populations that we believe are most likely to respond to treatment with 5609. .

5609 has shown substantial antitumor activity in the tumor types we are studying at doses below the maximum tolerated dose. And in preclinical models of breast, lung and ovarian cancers, deeper and more sustained responses were associated with RB pathway alterations.

By enriching for these patient populations in our Phase I trial, we believe we will increase our chances of seeing early signals of clinical activity. .

We expect to report initial safety, tolerability, PK and PD data in the fourth quarter of this year and additional dose escalation data, including clinical activity data in mid-2021.

Following dose escalation, we plan to initiate multiple expansion cohorts to further evaluate the safety and antitumor activity of 5609 as both a single agent and in combination with other therapies. .

Moving to 1425. We believe 1425 has broad combination potential in RARA-positive patients with AML and high-risk MDS. We remain on track to report potential proof-of-concept data in the fourth quarter of this year on 1425 in combination with azacitidine and RARA-positive patients with relapsed or refractory AML.

If positive, we believe these data could support an accelerated development path to market. .

We also expect to report mature data on 1425 in combination with azacitidine in the fourth quarter in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy, which we think is important in determining the optimal path forward in newly diagnosed patients. .

Together, we hope these data will bring us closer to addressing the significant need for well-tolerated oral therapies for people with AML. While the AML landscape is rapidly evolving with new medicines coming to market, the disease is not being cured. Patients with relapsed or refractory disease still face a grim prognosis.

Recently approved therapies target only limited patient subsets with composite complete response rates in the 20% to 35% range and limited duration of response. Survival remains low at less than 6 months. .

For newly diagnosed unfit AML patients, tolerability of therapy and the ability to combine with other agents are particularly important. More than half of the newly diagnosed patients are elderly or otherwise unfit for intensive chemotherapy, and combination approaches are emerging as the standard of care.

The goal in this patient population is to develop combination regimens that improve outcomes while also providing quality of life. .

Based on the data we presented at ASH in October in the newly diagnosed unfit AML patients, we believe that 1425, in combination with azacitidine, may offer an important new treatment option for a readily identifiable subset of these very sick patients.

Our data showed a high aggregate CR, CRi rate, many of which were deep molecular and cytogenetic CRs in RARA-positive patients. We saw rapid onset of action and early evidence of durability as well as high rates of transfusion independence. All of these with a favorable tolerability profile.

Importantly, these data also give us confidence as we look toward our data readout for RARA-positive relapsed or refractory AML patients. .

While our key strategic priority is to advance our clinical stage programs, we firmly believe that ongoing investment in our gene control platform is critical to building a robust and sustainable pipeline to support our vision of becoming a fully integrated biopharmaceutical company.

In the fourth quarter and in recent months, our leadership in gene control was highlighted in several presentations. .

In December, we presented new data in an oral presentation at the ASH Annual Meeting on our identification and validation of NFIX as a fetal hemoglobin repressor.

This finding stem from our broader effort in sickle cell disease and beta thalassemia to develop an oral medicine to turn on the fetal globin gene, which is typically turned off at birth, to make healthy red blood cells.

Based on the promise of this approach and our progress in the 2 years of starting this program, we entered into a collaboration with GBT in December to discover, develop and commercialize new medicines for sickle cell disease in beta thalassemia patients.

Importantly, this collaboration allows us to explore multiple targets and approaches in parallel for inducing fetal hemoglobin, accelerating our efforts and increasing our chances of success. .

In January, we announced our second monogenic disease program, which is focused on myotonic dystrophy type 1. DM1 is an autosomal dominant monogenic disease caused by nucleotide repeat in the DMPK gene.

It affects organs as well as the central nervous system and can shorten lifespan, with the most common causes of death being respiratory and cardiac symptoms.

As with our approach in sickle cell disease, our goal is to use our platform to elucidate the regulatory mechanisms controlling a single gene with the aim of developing a small molecule medicine to alter the expression of that gene. In this case, turning off the expression of the faulty copy of the DMPK gene..

We were also pleased to present new preclinical data at the 2020 Keystone Symposia Cancer Epigenetics Meeting in January, demonstrating that CDK12 inhibition has different transcriptional effects from CDK7 inhibition.

The results suggest that a selective CDK12 inhibitor presents distinct therapeutic opportunities from a selective CDK7 inhibitor, such as increasing susceptibility of cancer to targeted therapies involved in DNA damage repair, such as PARP inhibitors.

Also at Keystone, our team presented new data highlighting our platform's ability to identify essential genes and transcriptional dependencies that could serve as potential drug targets for cancer. .

These presentations underscore our leadership in the field of gene control and the potentially vast reach of our platform to address diseases that have eluded effective treatment. They also reinforced our confidence that this is just the beginning for Syros.

The progress we have made with 1425, 5609 and across our pipeline provides a tremendous foundation for growth. And it is a testament to our people, our program and our platform. .

We look forward to continuing to execute with excellence as we build Syros into an enduring company with a deep portfolio of transformative medicines for currently underserved patients. .

With that, I will turn the call over to Joe to review our financial results in the fourth quarter and full year 2019. .

Thank you, Nancy. We are entering 2020 in a position of financial strength. Last month, we announced the closing of a $60 million loan facility with Oxford Finance, including the funding of initial tranche of $20 million.

Proceeds from this tranche extend our anticipated cash runway into 2022, allowing us to advance both 1425 and 5609 through key clinical readouts this year and next, while continuing to invest in our preclinical portfolio and leading gene control platform. .

Turning now to our fourth quarter and full year 2019 financial results. We ended 2019 with $91.4 million in cash, cash equivalents and marketable securities compared with $99.7 million at the end of 2018.

This amount does not take into account the $20 million upfront we received from GBT in January and the $20 million from the initial tranche of the Oxford loan facility in February. We recognized $0.5 million in revenue in the fourth quarter of 2019 compared to $0.9 million in the fourth quarter of 2018.

For the full year 2019, we recognized $2 million in revenue compared to $2.1 million in 2018. Revenues in both periods were earned entirely under our collaboration with Incyte. .

R&D expenses were $14.3 million in the fourth quarter of 2019 compared to $15.1 million for the same period in 2018. R&D expenses for the full year 2019 were $58.2 million compared to $50.2 million for the full year 2018.

This increase in full year R&D expense was primarily due to the continued advancement of our clinical trials as well as the completion of 5609 IND-enabling studies. .

G&A expenses were $6.4 million in the fourth quarter of 2019 compared to $4.4 million for the same period in 2018. G&A expenses for the full year 2019 were $21.5 million compared to $16.2 million for the full year 2018. This increase was primarily due to an increase in employee-related expenses. .

Finally, we reported a net loss for the fourth quarter of $19.7 million or $0.46 per share, compared to a net loss of $18 million or $0.54 per share for the same period in 2018. Our net loss for the full year 2019 was $75.4 million or $1.88 per share compared to a net loss of $62.3 million or $1.91 per share for the full year 2018. .

With that, I will turn the call over to the operator for questions. Thank you. .

[Operator Instructions] And our first question comes from the line of Kenneth Atkins with Cowen and Company. .

What profile do you think the 1425 plus the aza combination needs to show in the relapsed/refractory AML setting to be successful in terms of response rate and durability of response?.

Ken, I'm going to ask David Roth, our Chief Medical Officer, to answer that question. .

Okay. Thanks for that question. Yes, as you know, we are focused right now on cohort of patients with relapsed/refractory AML, and we're testing the combination in those patients. There is a significant unmet need in those patients.

And in total, we'll be obviously looking at the clinical activity and the overall tolerability and safety in order to understand how it's working in those patients.

Specifically, there is data in the relapsed population with hypomethylating agents that shows response rates on the order of about 16%, with duration of responses and median overall survival of about 0.5 year. .

And as you also know, there have been some recent approvals in the relapsed AML setting with some of the targeted agents that have come to market of late. And they've shown response rates in the 20% to 30% range with response durations in the 4- to 8-month range.

So those types of outcomes are going to provide us with the context to interpret our data. And we're looking forward to reporting on potential proof-of-concept in the fourth quarter. .

Got it. Okay. That makes sense. And then in the data you shared at ASH, it seemed as though unlike the RARA biomarker, the IRF8 biomarker was not as good of a predictor of response.

What do you think accounts for that difference, and how do you apply any of those learnings to your platform?.

Yes. So another good question. In the beginning of this program, we applied our discovery platform approach, looking at the presence of a super enhancer driving high levels of RAR-alpha gene expression.

It was an unanticipated observation, a novel discovery that we made, and we've translated that into our clinical trial with a specific focus on RAR-alpha. .

In the course of our preclinical development leading into the trial, we did make the observation that, on occasion, there were certain model systems, which had IRF8 positivity, which also responded to the drug.

And in an effort to make this drug as broadly available to as many patients as possible, we chose to evaluate that prospectively in our trial. The best time to check this out is early on, so as you don't leave patients who could benefit behind.

But our analysis didn't support that exploration and so we have just basically refocused where we started, which was back on the RAR-alpha. And I think the learning is that it's always good to work with your data and take the opportunity to do the best you can to make potentially promising drugs available for patients.

And I think we're going to continue to apply those types of approaches moving forward. .

And our next question comes from the line of Jason Butler with JMP Securities. .

Just one on 5609.

Just as you start to move through enrollment here, any updates you can provide on the presence of RB pathway alterations in the target tumor types?.

Jason, I'm going to ask David to answer that question. .

Yes. So as you, I assume, are aware, the -- we're very excited about the fact that we initiated dosing in our clinical trial this past January.

And we are still anticipating the reporting of our data in the fourth quarter, which will focus on safety and tolerability, but also we'll have some information related to pharmacokinetic/pharmacodynamics on that. .

And we are focused on patients who have various tumor types that we think are enriched to see an early signal of activity. I know Nancy mentioned that in her opening comments. We're including patients with breast cancer, ovarian cancer, lung cancer as well as colorectal cancer.

And importantly, we're focused on patients who have a tumor that may have any other histology, provided it has an alteration in the RB pathway. There are common mutations that are mutually identified in screening of patients when they present for treatment and care.

And they should have these available to us when they show up to be considered for enrollment in the trial. .

With respect to the outcomes, just to preview or review for you, about 1/3 of patients with basal breast cancer are known to have these types of abnormalities. And that is largely overlapping population with triple negative breast.

We know that patients who have hormone receptor positive breast cancer who have been previously treated with CDK4/6 inhibitor in hormonal therapy and then progress, about 1/3 of them will have abnormalities in RB pathway. And that's been now an emerging and well-characterized mechanism for developing resistance to the CDK4/6 inhibitor.

So we think that's a really important and emerging population with significant unmet need that we potentially can address with a CDK7 inhibitor. .

Lung cancer includes a population of small cell lung cancer. It's -- in some respects it's been considered somewhat ubiquitous for having RB pathway abnormalities, RB null or mutations in about 75% to 90% of small cell lung cancer. So there, a majority should have this. .

And from our prior discussions around our focus on ovarian cancer, we know through analysis of the TCGA database that's been published about 67% of high-grade serious ovarian cancer also has these types of abnormalities. .

So all told, we think they're fairly prevalent and of course, we'll continue to focus on these populations as we move through dose escalation and frame our plans going forward for the expansions. .

Okay, great. And then just a platform question.

Can you maybe just speak to how the experience with sickle cell informs how you approach new diseases like MDT1? Obviously, different diseases but are there efficiencies that you gain as you move through each program that maybe leads on time lines or helps you think about probability of success?.

Jason, I'm going to have Eric Olson, our CSO, answer that question. .

Yes. Thanks, Jason. Yes, the efficiencies and the synergy we get from our -- all of our platform programs, whether on oncology or in the monogenic diseases, really arise from our ability to understand mechanisms and the regulatory networks that are driving sets of genes or specific genes. So that's really the focus of our platform.

And when we started the company, it was clear that platform could be applied to lots and lots of different diseases and settings. .

In the case of the monogenic diseases, sickle cell, for example, is a disease where we are using our platform to understand the mechanisms of fetal globin repression and then come up with small molecules that will induce the expression of fetal globin. .

In DM1 and other diseases where we know turning down the expression of the gene could be really beneficial, based on human genetic data and what we understand about the pathophysiology of the disease, and in this case, we're using exactly our, say, methodologies and approach and way of thinking and sets of technologies to identify the targets to down-regulate the expression of DMPK in DM1.

.

And our next question comes from the line of Mark Breidenbach with Oppenheimer. .

Probably both of these are kind of directed at David.

Maybe first, if you could start by giving us a little more color on dose escalation in the Phase I trial of 5609, can you maybe tell us how many single patient cohorts you have to fill before you'd move to a 3+3 design? And maybe just give us a sense for how many cohorts you expect to have to move through before you would advance into a therapeutically relevant range.

.

Sure. Happy to answer that question. So we designed the protocol to be as efficient as possible with an objective to move this program forward and get the drug to patients as rapidly as we can. And again, I think it goes without saying that patients are always driving our approaches in everything we do here. .

So we started out with single patient accelerated titration cohorts. And so that's how we're going to initiate the trial, and then we plan to transition to the more standard 3+3 design. We haven't specified the point at which that transition might occur.

But you can anticipate that, for instance, if we were to observe changes in these PD markers that we're incorporating to efficiently drive toward the appropriate dose to move forward, we might choose to expand to 3+3, just to better characterize those types of effects and use that knowledge to influence our decision making. .

And just because I'm mentioning that, I do want to remind you all that we, as leaders in the research field of CDK7 and their development of the inhibitors to that drug, that compound, have uncovered some novel biomarkers that biologically help us understand how the drug may be working.

And we have worked to incorporate them into our clinical trial design. We've had lots of learnings from our prior experience with our 1365 program, and have really looked very deeply at the patient materials that we've collected on that trial and have done a lot of work to establish PK/PD efficacy models with both drugs.

And we've been able to sort of triangulate across both programs to really inform our thinking about how to move 5609 forward efficiently. And hopefully, we'll be able to report out some very interesting information in the fourth quarter of this year as that progresses. .

And we haven't -- yes, I just wanted to say we haven't specifically set the numbers of cohorts that would be required before reaching expansions. But in general, when we have sufficient information to inform our selection of the dose that we want to take into the expansions, that would be the trigger.

It wouldn't necessarily be at a particular point in time or after a prespecified number of cohort levels. .

Okay. Got it. And in those expansion cohorts, I see you're already thinking about both single and combination agent -- combination therapy.

What are you kind of seeing as an ideal combination agent? Would it be with chemotherapy, with a CDK4/6, with a CDK12 or something else?.

Another good question. So the nice thing about this particular target is the breadth of activity it has across so many different tumor types. And so as someone who's helping the organization think through strategically how to approach clinical development, we have many options. We have worked very hard.

We have a wonderful translational medicine team here and discovery organization that are working to help define our future paths forward. .

And we are looking at various combinations that make sense, both from a mechanistic point of view and from an efficiency and clinical development point of view. So we have options to use various targeted agents. There may be hormonal therapies that nicely combined with our drug.

And as well, there may be chemotherapeutics, which mechanistically makes sense. We haven't specified the details of which particular combination partners we want to proceed with, but much of that is in process, and we're hoping to get there as soon as possible. .

Okay. One more quick one for me with regard to the Phase II in relapsed/refractory AML. I'm just wanting to make sure that this trial is open to patients who have had prior azacitidine exposure. And I'm also curious if the trial would potentially enroll a few patients with MDS as well or the focus is exclusively on AML. .

Okay. So the relapsed/refractory AML trial -- the key inclusion criteria requires you have relapsed/refractory AML and you would be RARA positive. So you must be a biomarker positive. So you need to either had a prior treatment response, which then you lost, so you relapsed or you've actually never been able to attain a prior treatment response. .

This can include fit patients who are progressing off of intensive chemotherapy without hypomethylating agent exposure or it can include unfit patients who may have had a hypomethylating agent in their prior treatment history. So we don't -- we're agnostic to that. I think we're going to learn important information about that.

We believe that it's important to make this as widely available in the early stages, so we can understand the best way to move this forward after evaluating the totality of our data. .

And there was a second question -- yes, about whether or not MDS patients -- so this is really specifically focused on relapsed/refractory AML. There obviously is great excitement about MDS. I think that we have previously explored our drug as a single agent, including patients with relapsed high risk MDS.

And I'll remind you, we did see evidence of single-agent activity there with hematologic improvement, and we even had a patient with a complete response that lasted for quite a while, associated with heme improvement in at least 2 of their cell lineages. .

So our drug has the potential for utility in that population as well. And that's further underscored by the presence of the RARA biomarker in patients with MDS. So we're looking at that very carefully. But at the moment, our focus is like a laser beam right on the AML population, and that's where we're looking to make our immediate impact. .

Okay, very helpful and congrats on the progress. .

And our next question comes from the line of Ted Tenthoff with Piper Sandler. .

Great. Kind of a similar question but with respect to 1425 and obviously, azacitidine is the ideal agent.

But I'm wondering, as you see new mechanisms and, thankfully, some advancement with respect to agents, novel mechanisms in AML, are you seeing anything that makes sense to evaluate?.

Certainly, we're waiting for the relapsed/refractory data, but have you done any preclinical work to look at other mechanisms that might be synergistic?.

Ted, we have shown in preclinical in vitro analysis that 1425 is quite synergistic or at least additive with multiple agents that are used in the AML setting, both experimental as well as sort of standard of care. And that's always what's been really exciting for us.

It looks like 1425 could be a great combination partner broadly, not only because it's a novel mechanism of action. It appears to be synergistic and/or additive with many agents. And also, the tolerability profile doesn't typically overlap with these other agents. And so I think that makes it, in some ways, an optimal combination partner. .

And so as we think about our ultimate vision for the program, it is to explore it in other combinations and also in other patient settings where our RARA is elevated. So we think that there's a lot of opportunity more broadly beyond aza.

But we think, right now, kind of focusing on the aza combination and getting the proof-of-concept and approach forward is the current focus. But it's just the beginning for, I think, a much broader potential for the drug. .

[Operator Instructions] Our next question comes from the line of Zegbeh Jallah with Roth Capital Partners. .

Just had a couple of questions here.

For 1425, just wanted to know what are you hoping to see in the newly diagnosed patient population? And are you looking for a partner to further develop 1425 in this patient population?.

I'll have David answer the first question about what we're looking for in the newly diagnosed data and then I can address the partnering question. .

Sure. So in the newly diagnosed, at the moment, we're very excited about the data. As you know, we shared that information back at a presentation in October, where we showed a very high complete response rate.

And these responses were deep responses, the majority being molecular or cytogenetic, which is encouraging because those are the most typically associated with a long-lasting effect. And we have early evidence of durability and we see a high degree of transfusion independence. .

So that all coupled with what is really a generally well-tolerated combination safety profile is very encouraging to us. So the things that we're looking forward to in the more mature data set are just to see these data in a larger number of patients.

And then to get a more robust sense of the duration of the responses when we have more time to observe the responses. And so that's the type of information we're looking for. .

And Zegbeh, on the question around our partnership with 1425, I would just step back and say our vision and goal is to build a fully integrated biopharmaceutical company. We have a discovery engine, a very rich clinical and preclinical and discovery pipeline.

And of course, we're always thinking about strategically, is there something that we think that we can create more value by doing in partnership versus alone, the timing about in which we might think that there could be more value for patients or for investors. .

And so I'd say broadly, we think corporate development is going to be important and we've done now 2 collaborations on our discovery engine. So it's important, and we continue to evaluate it really across our portfolio and pipeline. .

Just asking since the initial focus will first be the relapsed/refractory patient population and then I was just kind of wondering, the strategy about moving forward, if the data in the larger cohort does look better. .

But moving on to 5609, just kind of want to get a general sense of how are you reaching for the patient population of breast, lung and ovarian cancer.

And then also, I know you mentioned that you couldn't specify what combinations you're looking to explore, but just kind of want to get a sense of how you may be thinking about your CDK12/13 inhibitor differently from a CDK7 inhibitor, and then with respect to also how you're going to think about combination approaches for those 2 different inhibitors.

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Okay. So let me -- I think there's a couple of questions in there. First, there was a question around how might CDK7 -- or 5609, CDK7 program differ from 12. I'll have Eric answer that question. Then you had a question around the patient population for 5609. I'm not sure I -- you might need to repeat that question. .

breast, lung or ovarian?.

Okay. All right. So then I'll have David answer that question.

But Eric, you want to first touch on the 7, 12?.

Sure. As you know, we've been working on CDK -- transcriptional CDK inhibitors for many years now. And we actually have a good understanding of how to make selective molecules for both 7 and 12.

And in the course of that work, the preclinical work, looking at the mechanism and the tumor types and the types of context where inhibition plays a role in cancer, we have a pretty good understanding of how to differentiate between 7 and 12 inhibitors from our preclinical work. .

As Nancy said at the beginning, clearly -- and work that we presented at the Keystone conference, 12 inhibition really affects the expression of very long genes, many of which are involved in DNA repair and DNA damage.

So that's kind of our initial hypothesis about -- hypothesis about where we might enrich for patients in a clinical program with a 12 inhibitor. .

Great. And then I'm going to have David answer the question on 5609. .

Sure. So we're open to patients who have breast cancer, lung cancer, ovarian cancer, colorectal cancer and patients with RB mutations just regardless of the tumor histology. And the -- there are no prespecified targets for the numbers of patients of each of those tumor types during the dose escalation. .

We do anticipate a significant proportions of the patients that are enrolled to have, for instance, RB pathway abnormalities because intrinsically, they're just enriched. And also because our investigators are fully aware of our preclinical data that show very compelling preclinical activity in that context. .

And I'll remind you, we presented data at the ENA meeting this past fall, which showed that 100% of the models we surveyed over a range of different tumor types have significant tumor growth inhibition. But those with RB pathway abnormalities had complete regressions that lasted for quite some time after stopping the drug.

So that tends to influence selection of patients into the early phase of the trial. .

And the last comment I would have is just that we have the opportunity to incorporate additional groups of patients along the dose escalation. We're calling these cohort extensions.

There are sort of many expansions during dose escalation, and we can target the populations into those extensions as we see fit, based on emerging preclinical or even clinical outcomes from the trial itself to further enrich and to build a sufficiently robust dataset to appropriately inform our formal expansion strategy later.

So I think that's my approach to how we're going to move this ahead. .

Perfect. Congrats on a productive 2019. Looking forward to the readout the rest of the year. .

And I'm showing no further questions at this time. I will now turn the call back over to CEO Nancy Simonian, for closing remarks. .

Thank you, operator. In closing, 2020 will be an important year for Syros, with meaningful clinical data expected for both 1425 and 5609. We are focused on executing with excellence to advance those programs as well as our preclinical and discovery pipeline.

And we look forward to keeping you updated as we work toward our ultimate goal of bringing small molecule medicines to market that provide a profound benefit for people with cancer and monogenic diseases that have eluded effective treatment with other genomics-based approaches. .

Thank you all for joining us today and for your continued support of Syros. Have a good day. .

Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect..