Good morning. And welcome to Syros Pharmaceuticals First Quarter 2021 Financial Results Conference Call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investors & Media section of Syros' website at www.syros.com. Please be advised that today's call is being recorded.

Following the formal remarks, we will open up the call up for your questions. At this time, I would like to turn the call over to Naomi Aoki, Vice President of Corporate Communications and Investor Relations at Syros..

Thank you. This morning we issued a press release with our first quarter 2021 financial results, along with anticipated future milestones and recent accomplishment. This release is available on the Investors & 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 will then open the call for question. Dr. David Roth, our Chief Medical Officer; and Dr. Eric Olson, our Chief Scientific Officer are also on the call and will be available for Q&A.

Before we begin and 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 statement 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, a quarterly report on Form 10-Q that we filed this morning and any other filings that we may make with the SEC in the future.

In particular, the extent to which the COVID-19 outbreak continues to impact our operation and those of third-parties on which we rely will depend on future developments which are highly uncertain and cannot be predicted with confidence.

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..

in Myotonic dystrophy type 1; a DM1. Our goal here, is to develop a trinucleotide repeat modulator to decrease the expression of the toxic copy of the DMP caging. If we continue to advance this program, we are gleaning key insights that could apply to other nucleotide disorders.

This has the potential to unlock massive opportunities more than 40 genetic disorders are caused by nucleotide repeat expansion, a kind of mutation in which simple DNA sequences repeat an increase in copy number and induced disease like DM1, Huntington Disease or Fragile X syndrome.

All in, I believe we are in an incredibly strong position as we thoughtfully and strategically advance an industry leading pipeline across key areas of unmet need in cancer and monogenic disease.

Since our founding, we have remained laser focused on building a synergistic portfolio or insights cleaned in one program can be applied to advance our next wave of efforts. And we can capitalize on our expertise as well as our clinical and commercial investments to advance multiple forward in parallel.

We are entering a catalyst rich period for Syros and look forward to updating you further as we continue to move through clinical development. With that, let me turn the call over to Joe to review our first quarter 2020 month's financial results..

Thank you, Nancy. We continue to operate from a position of financial strength. We ended the first quarter with $222 million in cash, cash equivalents, and marketable securities, compared to $174 million as of December 31st, 2020.

This increase reflects gross proceeds a $75.6 million from our public offering which closed in January 2021 partially offset by cash used to fund our operations in the first quarter.

Based on our current plans, we believe our cash position is sufficient to fund our business into 2023 enabling aggressive investment in each of our three strategic areas of focus. We recognized revenue of $4.8 million in the first quarter compared to $2.4 million in the first quarter of 2020.

This $4.8 million consists with the $4 million under our collaboration with Global Blood Therapeutics and $0.8 million under our collaboration with Insight. In the first quarter of 2020, we recognize $2.2 million from our collaboration with GBT, $1.2 million from our collaboration with Insight.

R&D expenses were $20 million in the first quarter of 2021 compared to $14.6 million for the same period in 2020. This increase was primarily due to the continued advancement of our clinical programs, including the addition of SY-2101 and an increase in employee related expenses.

G&A expenses were $5.7 million in the first quarter of 2021 compared to $5.1 million for the same period in 2020. This increase was primarily due to an increase in employee related expenses.

Finally, we reported net loss for the first quarter of $14.2 million or $0.23 per share compared to a net loss of $17.2 million or $0.39 per share for the same period in 2020. With that, I'll turn the call over to the operator for questions. Thank you all very much..

Our first question comes from the line of Phil Nadeau with Cowen & Company. Your line is now open..

Good morning. Congrats, on the progress. A few questions from us. First on the Phase 3 in HR MDS.

What's the most recent count for sites that are enrolling patients today? And have you experienced any COVID related issues and getting sites open and recruiting?.

Thanks, Phil.

David you want to take that?.

Sure. So, as you know we've recently initiated the trial and we're actively dosing the patients. We haven’t specifically guided to the specific number of sites or patients at this time.

And but we do want to remind you guys, yes as we look forward, all works out with the successful outcome we are, anticipating the tends to file an NDA in the 2024 timeframe. And as it relates to COVID, we are managing through COVID.

I think that there are no specific challenges that we confronted that we don’t feel can be mitigated and we remain on track moving forward right now..

Great. Then second on 5609, could you give us some sense of how many patients will be in the Q3 update.

Maybe what the duration of follow-up is likely to be and also some sense of the efficacy measures that you'll be able to disclose at that time?.

So, for 5609, we are planning for a data update in the third quarter of this year. And that update will include more information around the safety and tolerability, the PK and MPD that we've reported on previously. And we're also going to have to focus on the clinical activity.

We haven’t specifically guided to the numbers of patients or that would be included in our presentation. But I think you can anticipate we'll report the available data we have to us at the time in the presentation..

And then, last question. For that update, is there a specific form, is that likely to be in conjunction with the medical meeting or like could be a Syros to them itself..

Hi, Phil. A general practice has been to in our report, data some trials at medical meeting. So, that's been sort of our standard practice. Obviously last year with COVID with the questions on but that generally change but I think we that's the general approach we've been taking..

Got it. Thanks for taking the questions..

So, thanks Phil. I appreciate it..

Thank you. Our next question comes from the line of Jason Butler with JMP Securities. Your line is now open..

Hi, thanks for taking the questions. I'd start to we have the asset for several months now. Just wondering if you've had the opportunity for any dialogue with regulators or with KLO to confirm your development plans and the approval path..

Jason, you -- sorry, you cut out a little bit. For which program, I missed it. We just cut out..

For 2101..

Oh, the 2101, okay..

Yes..

Great. What -- I think we certainly have had and I think we've shared with you discussions with many KOLs. I think that I would just say there is a huge amount of interest and enthusiasm. I think which really speaks to the big need for an oral therapy an APL just given how burdensome the idea. So, we had a lot of input.

And as you know, we're going to have one of those KOLs speak at an upcoming event, I think believe it's in July, some N.D. Anderson. That reminded, he -- but there's a lot of interest and enthusiasm.

In terms of regulatory updates and discussions, I think we've shared with you that when we acquired that Oral Arsenic, had had discussions with the agency and sort of developed a plan that we're kind of it's on our current operating assumptions on that.

So, clearly if we move forward and do have any further updates, we'll allow most fully a product of those..

Thank you, great. And then, second question on 1425, are you in the triple combo, where was VenAZA. Are you screening for patients with monocytic cells or stratifying on that basis. And then just thinking forward to how that could change then to the - the set of care.

Are patients typically screened from monocytic cells today or would you not envision that to be necessary. You wouldn’t need to do that in clinical practice..

I know, good question. So, we are focused on RARA-positive maybe diagnosed unfit AMLs for that study. And so, we are not specifically looking for patients who have monocytic features where we're screening for RARA. What we showed at the ASH meeting was that the majority of the patients who were RARA-positive were indeed those monocytic type patients.

But we don’t foresee a need to further screen for those additional features since the vast majority of the RARA-positive patients R&D'd those patients. So, that simplifies things for us greatly which is really nice.

And we really do anticipate that this could significantly address a newly created on that need because that 130 patients do respond to the VenAZA combo. And the majority of which are considered these types of patients.

As far as the patient analysis when they come in their classified that way more traditionally just based on the appearances of the cells or certain small surface markers or genetic expression levels. Sometimes, these are done as part of the routine workup. They're not consistently done certainly in the research setting that's been done.

It has helped us make this connection..

Okay, great. I appreciate it. Thanks for taking the questions..

Thanks, Jason..

Thank you. [Operator Instructions] Our next question comes on the line of Mark Breidenbach with Oppenheimer. Your line is now open..

Hey good morning, guys and thanks for taking our question. I'm just wondering if you can offer any early observations from the patient screening through SEs rate in the Phase 3 MDS trial. I guess I'm just wondering if you see any total challenges in finding RARA-positive MDS patients who also qualified for high risk classification by IPSS criteria.

Thanks..

And sure yes, thanks for that question. We have analyzed our screening of well over 350 patients sometime back and the data continues to trend consistently over time. In patients with AML or a high risk MDS who've been previously eligible for our studies. And we see a 30% rate of RARA-positivity. So, 30% of patient have this.

And we foresee no specific challenges or obstacle to identify 30% of patients who are higher-risk MDS.

Those patients are out there and they're very excited about the opportunity to participate in a trial that offers and all medicine which is really convenient because keep in mind these high risk MDS patients are typically still managed in the outpatient study. And when you are enrolling in studies that require you get an i.p. drug.

It sort of it's next to burden. So, I think that's very appealing and having a targeted agent in that kind of lease space is also very exciting. And particular given the data that we've shown where we have such a high response rate in AML and as higher even higher in the lower blast count AML which is more closely aligned with the high risk diagnosis.

So, I think our data sets, the nature of our drug and the tolerability profile all support enthusiasm for the investigators direct patients into our study..

Alright, perfect. Thanks for taking the question..

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Thank you. Our next question comes from the line of Zegbeh Jallah with ROTH Capital Partners. Your line is now open..

Good evening, guys. And congrats on the progress. I just have a really quick question here. Just about any additional effort to kind of add with clinicians on.

There are biomarker especially since you're seeing but it particularly which you predictive for by patients that may not respond to been at a clock and then any additional progress and you're completely in day and night there..

Thanks Zegbeh, I'm going to have David answer that..

Sure. So, I would say that it's really important that there continues to be increasing awareness of our study. And I think the availability now and the data that we shared has a couple with the outreach that we don’t to initiate a glob al study has really helped us a great deal.

And in communicating our data our results and our hopefulness toward this drug and helping patients in the future. And so, I think we've already made some really good progress in explaining that. And I can say the data that we shared, that poster on the correlation of biomarker with a resistance phenotype venetoclax's really caught people's attention.

Because the physicians are really looking for like why doesn’t that work and how can we still address those patients. We don’t typically select for them but now there may be other option. So, the idea that one can select the RARA-positivity and channel those patients to our drug has really captured their imagination.

And I think we're seeing that in the interest to in participating in our study. So, we're working really hard to get that word out and we think that the data are helping us do our job..

Thanks for that..

And I would just add Zegbeh, stay. As you know we're so we have this 2K relevance. The first one is this month on higher-risk MDS with any difference and then in June and AML. So, I think that will be a great opportunity for you to hear directly from the KOLs not in terms of how they think about this..

Okay. And then, I just -- there was one other question we had about the companion diagnostic. And I know that we've shared with you that we had a lobby while our negative patients are early on in that study just to make that observation that there was indeed a selection advantage.

The biomarker itself is operating as we had anticipated and it's reaching quotations more likely to respond. And we're making great progress toward the I mean the commercial thing diagnostic such that it's available coordinately with the approval and launch of the drug..

And congrats on the path, I have been looking for it to look at your all event..

Thanks, Zegbeh..

Thank you. Our next question comes from the line of Ted Tenthoff with Piper Sandler. You line is now open..

Good morning, everyone. How are you doing? Thanks so much, for the update. I wanted to ask a little bit about sort of the discovery efforts. And appreciating that you guys are kind of moving down that chain a little bit here and development has become such a bigger part in the company.

But I still don’t understand I feel like there's so much still to do with this platform. So, maybe you can give us some updates on what's going on the discovery side and even future potential partnerships. Thank you..

Hi, Ted. Thanks for that. And we couldn't agree more. I think I'm going to have Eric address your question. But we have made just tremendous progress and insights with our gene control platform.

And it just seem to see so many other companies cropping up today in exactly the same space but we've been doing this for seven, eight years and I think just have gleaned somewhat the great insights in terms of how to develop important new drug. So, Eric let me turn this the need of the question over to you..

Sure. Thanks Ted, for the question. Obviously, I'll kind of take it away a couple of parts. First is our early pipeline itself. And as Nancy said in her remarks, CDK12 is looking like a really addressing target. We think that's a great opportunity to be combining a molecule like that with other DNA Damage or DDR agent such as PARP inhibitors.

In our collaboration with Global Blood Therapeutics has really allowed us to kind of accelerate our drug discovery capabilities in this platform space. Is how do you turn up or how do you turn down a gene. As you know that program is designed to that's a pretty multiple approaches fine small molecule that will turn up the expression of hemoglobin.

And then, kind of a third area is the whole feel of kind of transcription and gene regulation as impacts diseases across several different therapeutic areas is really exploding. What we said early at that the company that's 98% of the genome, it doesn’t quote for gene.

At this minute of explosion of information over the last few years, what that out of the genome is doing and more specifically how it's linked to just a specific users. And what are we're actively looking at all of that data and thinking about the brand new programs. So, it’s a very rich and exciting time to be in the kind of the gene control space.

So, lot of future but also executing on the programs that are right in front of us..

Sure, thanks. Well, thank you so much. You keep up the great work..

Thanks, Ted..

Thank you. There are no further questions. I would now turn the call back to Nancy Simonian for closing remarks..

Thank you, operator. And thank you everyone for joining us this morning. We are grateful for your continued support as we execute against our three strategic priority.

And look forward to updating you further as we pursue our ultimate goals of maturing Syros into a fully integrated biopharmaceutical company and delivering a portfolio a targeted small molecule medicine that profoundly impacts the life's of patients..

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