Naomi Aoki - Head of Corporate Communications Nancy Simonian - CEO David Roth - CMO Joseph Ferra - CFO.

Kenneth Atkins - Cowen and Company Ed Tenthoff - Piper Jaffray Konstantinos Aprilakis - JMP Securities David Nierengarten - Wedbush Securities.

Good morning and welcome to the Syros Pharmaceuticals' Second Quarter 2018 Financial Results Conference Call. At this time, all participants are in a listen-only mode. This call is being webcast live on the investor and 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 the call up for your questions. At this time I would like to turn the call over to Naomi Aoki, Head of Corporate Communications at Syros..

Thank you. This morning we issued a press release with our second quarter 2018 financial results along with upcoming milestones and recent platform and pipeline highlights. 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; Dr. David Roth, our Chief Medical Officer; and Joe Ferra, our Chief Financial Officer. Then we will open the call for questions. 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 as updated in our quarterly report on Form 10-Q and any other filings that we 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..

Thanks, Naomi. Good morning, everyone, and thank you for joining us today. Syros has had a very productive second quarter and we are pleased to share our recent progress with you.

We have spent the last five years building a strong pipeline of drug candidates to control the expression of genes with the aim of providing the profound benefit for patients with severe diseases that are not adequately addressed by 15 therapeutic approaches.

Through these efforts, we have advanced our two lead assets, SY-1425 and 1365 in the Phase 2 and Phase 1 clinical studies.

We have also generated a deep, early stage pipeline with three pre clinical programs including an oral CDK7 inhibitor, a CDK12/13 inhibitor and a macrophage related immuno-oncology program as well as two discovery programs in cancer and in sickle cell disease.

Over the course of the next several months, we plan to report initial, data from our Phase 2 trial of 1425 in combination with azacitidine and with daratumumab in AML and MDS patients.

We also expect to present what we believe will be the first ever data reported in patients on a selective inhibitor of CDK7, a drug target that is rapidly gaining recognition as an important new approach in a range of difficult to treat solid tumors and blood cancers.

Together, we believe these clinical results will yield important insights for these programs and we hope bring us closer to our vision of translating our leadership in gene control into medicines that provide a profound benefit for patients. Earlier this year we laid out several key objectives for 2018.

In addition to reporting clinical data for 1425 and 1365 in the fourth quarter of this year, these objectives included opening expansion cohorts in the Phase 1 trial to evaluate 1365 in ovarian and HR positive breast cancer in both a single agent and in combination with standard care therapies.

Naming a new drug development candidate from our preclinical pipeline, leveraging our platform to continue to advance and fuel our early stage pipeline and finally to continue to avail our developed and organization and capabilities to support our longer term evolution into a fully integrated company.

At mid-year, I am proud of the progress we made towards these goals, and I am confident that we are entering the second half of 2018 with positive momentum.

As our Chief Medical Officer David Roth will discuss shortly in greater depth, we expect to open the expansion cohorts in the Phase 1 trial of 1365 in the fall and remain on track to name our next development candidate by year-end.

We’re also pleased to report that the European Medicine’s agency recently granted 1425 orphan drug designation for the treatment of AML. On the people [ph] front, we welcome Michael Bonney to our Board of Directors in June.

Mike has tremendous, strategic, operational and commercial leadership experience and we are confident that he will provide invaluable guidance as we prepare to enter the next Phase of our growth and continue to mature as a company.

Our focus on controlling the expression of genes to treat disease represents our largely unexploited sale for drug discovery and development with broad potential and I’m excited about the opportunities ahead to make a difference for patients. I would now like to turn the call over to David for a more comprehensive overview of our clinical programs..

Thanks Nancy and good morning to everyone on the call. I would begin by discussing SY-1425. 1425 is our first-in-class selective RARα agonist that is currently in a Phase 2 combination trial in patients with AML and higher risk MDS who are positive for our RARA and IRF8 biomarkers.

The primary objective of the trial is to evaluate the safety and efficacy of 1425 in combination of azacitidine in newly diagnosed unfit AML patients and with daratumumab in relapsed or refractory AML and higher risk MDS patients.

In the pilot cohort with daratumumab, we are also accessing the time course and the level of CD38 induction that we see in patients with the aim of better understanding the potential relationship between CD38 induction and the clinical activity. Last month, we hosted a well attending KOL breakfast featuring two leading physicians, Dr.

Rachel Cook from the Knight Cancer Institute at Oregon Health and Science University in Portland and Dr. Eytan Stein, from Memorial Sloan Kettering Cancer Center in New York. Both have extensive experience treating AML and MDS.

In their presentations, both doctors spoke to the room [ph] prognosis for patients with these diseases and the significant unmet need that still remains despite recent drug approvals.

I highlighted the complexicity and heterogeneity of these diseases and the urgent need for new medicines that can be safely combined with other treatments to extend survival and to improve quality of life in this generally elderly population in which cure of intent is not the goal. Dr.

Cook noted that many older, unfit AML patients currently forgo treatment altogether because of concerns around side effects, accessibility and quality of life. Despite leasing [ph] drug approvals in AML, Dr.

Stein highlighted the dearth of approvals and the lack of treatment options to higher risk MDS patients despite the disease as an area of light the new drug developments. For anyone interested in hearing more an archived website, webcast of the event is available on our website.

Given 1425s unique mechanism of action, it’s tolerability profile, its single agent activity in biomarker positive AML and high risk MDS and the strong preclinical data supporting the combinations with azacitidine, and with daratumumab we believe these two combinations have the potential to address significant unmet needs for subsets of AML and MDS patients.

As Nancy mentioned earlier in the call, we remain on track to report initial clinical data on both these combinations in the fourth quarter. Turning now to our second candidate, SY-1365.

1365 is our first-in-class selected CDK 7 inhibitor which is currently in the dose escalation potion of our Phase 1 clinical trial in patients with advanced solid tumors.

As we discussed last quarter, there is growing recognition around the potential for CDK7 inhibition to be a transformative new approach for treating cancer with the potential to disrupt two important processes that cancer cells use to survive and fly. The increased expression of cancer promoting genes and the uncontrolled cell-cycled progression.

1365 is the most advanced selected CDK7 inhibitor in clinical development which adds to our excitement as we look forward to reporting data from the dose escalation portion of our trial in the fourth quarter As a reminder, the dose escalation portion of the trial is open to patients with advanced solid tumors of any histology and the primary purpose is to establish a maximum tolerated dose and an appropriate dose and dosing schedule for the expansion phase of the trial.

We expect data from the dose escalation to include details on safety, pharmacokinetics, pharmacodynamics and importantly we’re measuring direct engagement of the target CDK7 as well as downstream effects to determine proof-of-mechanism.

At the American Society of Clinical Oncology or ASCO meeting in June, we presented on the design of our Phase 1 trial. As Nancy mentioned, we expect to open expansion cohorts this fall to evaluate 1365 in multiple patient populations with ovarian and breast cancer as both the single, and combination agent.

For ovarian cancer we plan to evaluate 1365 as a single agent in patients who have relapsed after multiple lines of prior treatment and in patients with primary platinum refractory disease. We also plan to evaluate 1365 in combination with carboplatin in relapsed ovarian cancer patients who are still considered sensitive to platinum based therapies.

For breast cancer we're focused initially on patients HR positive metastatic disease who have progressed after treatment with a CDK4/6 inhibitor plus an aromatase inhibitor and we'll evaluate 1365 in combination with fulvestrant. The clinical strategy is routed in three key observations.

First, in pre-clinical studies, 1365 demonstrated robust antiproliferative and pro-apoptotic activity in a range of models of ovarian and breast cancers, as well as synergy in combination with existing therapies including carboplatin and fulvestrant. Second, there is a significant need for new therapies in both drug users.

The majority of ovarian cancer patients even those who initially respond to standard of care platinum based therapy relapsed within a year, and treatment options for these patients are limited.

In hormone receptive positive breast cancer CDK4/6 inhibitors have emerged as the standard of care, however, despite the success of these therapies patients eventually relapse and second line hormone based therapies have limited efficacy underscoring the need for new medicines for this growing patient population.

Third, in addition to the strong preclinical activity and unmet need there is a mechanistic rationale to start a new lease cancer.

As we presented at the American Association for Cancer Research or AACR meeting this past April, preclinical data suggest that alteration in the RB pathway, a known tumor suppressor, as well as in apoptotic control pathways are associated with sensitivity to SY1365 in ovarian cancer models.

Notably, genomic data tell us that approximately two thirds of high grades series ovarian cancer patients have alterations in the RB pathway and alterations in the RB pathway have recently emerged as a resistance mechanism to CDK46 inhibitors in breast cancer.

So while our initial focus is on ovarian and HR positive breast cancers we believe 1365 has potential in a number of difficult to treat solid tumors as well as in blood cancers where apoptotic signaling maybe important. We view the ongoing Phase 1 trial as setting the stage for a potential expansion into additional tumor types.

I’d like to conclude my remarks by saying how excited I am about the potential of these programs to make a difference in the lives of patients who are currently in dire need of better treatment options. I look forward to keeping you updated on our progress as we head into what promises to be a busy, and productive second half of 2018.

So with that, I’ll turn the call over to our Chief Financial Officer, Joe Ferra to review our financial results for the second quarter.

Joe?.

Thanks, David. Syros continues to maintain a strong financial position to support the advancement of our clinical programs while continuing to invest in our early stage pipeline and discovery engine.

Based on our current plans, we believe that our existing cash, cash equivalents and marketable securities will support our operating expenses and CapEx requirements into 2020. Now, for our second quarter 2018 financial results. We ended the second quarter with $124.4 million in cash, cash equivalents and marketable securities.

That compares with $72 million on December 31st, 2017. During the second quarter, we sold $16.6 million in common stock under our ATM sales facility. We recognized $0.4 million of revenue from collaboration with Incyte in the second quarter of 2018. We did not record any revenue for the same period in 2017.

R&D expenses for the second quarter were $11.1 million compared to $10 million for the same period in 2017. This increase was primarily attributable to an increase in cost associated with our Phase 1 clinical trial of 1365 and increased headcount.

G&A expenses were $3.8 million for the second quarter compared to $3.5 million for the same period in 2017. This increase was primarily attributable to an increase in employee related cost including salary, benefits and stock-based compensation.

Finally, we reported a net loss for the second quarter of $14 million, or $0.43 per share, compared to a net loss of $13.4 million, or $0.52 per share, for the same period in 2017. With that, I will turn the call over to the Operator for questions. Thank you..

Thank you. [Operator Instructions] And our first question comes from the line of Kenneth Atkins from Cowen and Company. Your line is now open..

Hi, thanks for taking my question.

For the 1365 program, I’m just wondering do you plan to insulate [ph] like the patients beds on biomarkers that you think would be [Indiscernible] protecting the response to CDK7 inhibitor and if so what biomarkers you anticipate would be for in that regard?.

David, I’ll have David answer that question, thanks Ken..

Sure.

So as we had presented at the ACR meeting we do have clinical data that shows our relationship between RB pathway and changes in the apoptotic pathways in particular Bcl-xL and we are certainly taking those things into consideration as we evaluate patients for the efficacy and the safety during our Phase 1 dose escalation and expansion cohorts..

Great, thanks.

And then just [Indiscernible] for the biopsy-accessible cohort in that same study, could you give us a bit more detail about what sort of analysis [ph] are planned for those patients?.

Sure, so we have a chemistry with preclinical that there is a correlation between target occupancy which specifically needs measurement of drug being bound to target CDK7 and we’re looking at evidence of target occupancy and target engagement during the course of the dose escalation we’re evaluating that in peripheral blood and we’re also going to be evaluating that during dose escalation in tumor tissues in patients who volunteer for tumor tissues.

We also have a selected cohort in the expansions with approximately ten patients who will be volunteering for tissue sampling during the course of their treatment and will be evaluating things in that context as well..

Okay, thanks..

Thank you. And our next question comes from the line of Ed Tenthoff from Piper Jaffray. Your line is now open..

Great. Thank you very much and thanks for the update, and looking forward to a busy back half. Just with respect to 1465.

What data should we be expecting in the back half year and in particular from some of the combination studies? And then I was intrigued to hear about the new candidate in sickle cell disease, I don't know if you can talk a little bit more about that?.

You're asking about 1425 combination data and what to expect?.

Yes. Correct..

Okay. So as we said, we plan to report our initial clinical data from the two combination arms with azacitidine and with daratumumab, and I think David laid out kind of the objectives in terms of those two cohorts.

So that, in our general approach is been to present a data when we think we have on kind of meaningful amount of data to present, so that was still planning to present data from those cohorts as we had data earlier this year.

In terms of sickle cell program, we're really excited about having branched, in addition to focusing on oncology now into monogenic diseases, where the approach is to use our platform to focus on diseases where we think or we know pretty definitively, if we could control the expression of a single gene we can have therapeutic benefit.

And first is disease that we are working and been working on for over year now is in sickle cell disease where as you probably know there is very strong genetic validation that if we can alter the level of expression of hemoglobin F, we can ameliorate the symptoms of the disease.

So our sickle cell program is focused on a particular target that we think can be important in controlling the level of expression of that gene, and currently that program is in the discoveries phase, but we're excited to continue to move that along..

Great. Looking for the data and more updates from this discovery affords. Thanks..

Thank you. And our next question comes from the line of Konstantinos Aprilakis from JMP Securities. Your line is now open..

Hey. Good morning guys and thanks for taking my question.

So regarding the upcoming readout for dose escalation portion of the Phase I trial of 1365, would y you be able to review the specifics of what we should be expecting? And if I recall correctly two dosing schedule are being tested weekly by weekly where we see data from both of those?.

Hey Konstantinos, I'll have David answer that question. .

Thanks Konstantinos. So, yes, the primary purpose of the dose escalation phase of the trial is to establish a maximum tolerated dose and as you quite to also to be able to choose an appropriate dose and dosing schedule to take forward into the expansion phase.

The data that you can expect to see in the fourth quarter certainly will relate to that dosing information and will also include information on safety, the PK, the pharmacodynamics and proof of mechanism, where we'll in addition to looking at things like the CDK7 binding and the target occupancy, we'll also be looking at other downstream changes that are induced by the drug.

As we know we've seen a strong in vivo correlation with target engagement and efficacy and we're using that in those – from those pre-clinical models to guide our dose and regimen optimization as we move forward. And so we'll be looking forward to reporting on those types of data..

David, what AEs are you expecting versus like a CKD4/6?.

Okay. So, with respect to the toxicities, we've obviously evaluated our drug in pre-clinical models and while we have specifically reported out the data that we've observed in our pre-clinical testing I think it’s fair to say that for pan-CDK inhibitors, as well as CDK4/6 inhibitors.

There have been some reports of myelosuppression as one of the toxicities that can be seen. Interestingly in our preclinical experiments we haven't seen a significant degree of effect on blood cells in particular white cells or the neutrophils.

So there will be reporting all the safety that we have available at the time, obviously that's about most importance particular during a dose escalation trial..

And let me just add, Konstantine, that – to part of your question, we are studying both weekly and twice weekly and the data that we plan to present will be all of that data from – of the dose escalation phase.

And I think it’s – I think David and his team has design a really great study, because that one of the key things is coming up with the optimal both dose and schedule and so the ability to kind of evaluate different types of schedules was always part of the plan in the dose escalation, so I think that will yield kind of the very robust package of data for us to choose dose in the expansion phase..

Okay, great. Thanks. Looking forward to it..

Thank you. [Operator Instructions] Our next question comes from the line of David Nierengarten from Wedbush Securities. Your line is now open..

Hey, thanks for taking the questions. I was wondering if the patients for 1365 or as you look to 1365 will have experience with or PARP experience with any PARP agents.

And also if so or if not either way what preclinical evidence or is there any that you've looked at for your 1365 either in combination with or for your or post-PARP treatment? Thank you..

Yes. Thank you. As we presented back at AACR we had a range of ovarian patient-derived xenograft, or PDX models which corresponded to very heavily previously treated with ovarian cancer. And we saw sensitivity for 1365 irrespective of BRCA status or prior PARP exposure.

Several of those models have patients who progressed despite prior treatment with olaparib as an example.

And so, when we designed our trial we specifically focused on earlier lines of therapy in combination with carboplatin, but also later lines as a single agent in patients who would not be expected to response to platinum and we think that in consideration of our preclinical data that supports the potential for therapeutic effects despite having progressed on PARP, and are using the drug in various lines of therapy will be well positioned to incorporate this drug into the treatment landscape..

And to add David, we are studying PARP inhibitors. Obviously, it's where we have a lot of focus in ovarian cancer. We're doing preclinical work right now, the study of the combination of 1365 with PARP inhibitors..

Just a quick follow-up, would you plan or you'll wait till you see the Phase 1 on any kind of bridging or safety study to take a look at either in combination or post-PARP given, obviously some of the PARP of different side effect profiles but myelosuppression being one of them? Or you just wait and see what is there in the Phase I and we'll go from there?.

I think as David was saying we're going to – the patients that would be in the trail some of them been on previously in PARP and others will have.

I think we're going to look at the data and we're constantly thinking about kind of what's the next step that we want to take strategically with this program based on the data that we get, that we want to be in the best position to think about how to maximize the benefit of this drug which is definitely going to be -- we're studying it both as a monotherapy and in combination.

We’ve started the first combination with carboplatin, but that's the start for us thinking more broadly about how we're going to use this drug including the PARP inhibitors..

Thank you. I show no further questions at this time. I would like to turn the call back over to Nancy Simonian for closing remarks..

Thank you all for your continued support and interest in Syros. I want to reiterate our excitement for the second half of 2018. I look forward to keeping you updated as we execute on vision of building a great and enduring company and work hard to translate our leadership in gene control into new medicines that provide a profound benefit for patients.

Thank you all and have a great rest of the summer..

Thank you, ladies and gentlemen for participating in today's conference. This does conclude the program and you may all disconnect. Everyone have a great day..