Syros Pharmaceuticals, Inc.
Q4 2020 Earnings Call Transcript

Published: 4 Mar 2021

[Operator:]

Good morning and welcome to Syros Pharmaceuticals Fourth Quarter and Full Year 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode. This call is being webcast live on 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 the call up for your questions. At this time, I'd like to turn the call over to Naomi Aoki, Vice President of Corporate Communications and Investor Relations at Syros.

[Naomi Aoki:]

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 recent accomplishments. This release is available on the Investors & Media section of Syros's 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. We will then open the call for question. 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 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 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 operations, and those of third-parties on which we rely, will depend on future development, 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.

[Nancy Simonian:]

Thanks, Naomi. And good morning, everyone. Thank 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 a profound difference for people living with cancer and monogenic diseases. In recent months, we made significant strides toward achieving that goal. We focused in on three key strategic priorities to fuel our growth. We expanded our clinical stage portfolio with the acquisition of SY-2101. And we fortified our cash position through two financings, which together resulted in gross proceeds of over $165 million. As we enter 2021, we are focused on executing against the ambitious strategy we laid out last year, with a goal of rapidly maturing Syros into a commercial-stage biopharmaceutical company.

[David Roth:]

Thank you, Nancy. And good morning, everyone. We believe there's a significant opportunity for 1425 across both MDS and AML. Approximately 30% of both patient populations are RARA-positives, and many patients continue to be underserved either due to the lack of effective options, tolerability challenges or a disease phenotype that is resistant to standard of care therapy.

[Joe Ferra:]

Thank you, David. We are entering 2021 in a strong financial position. In January, we completed a $75.6 million public offering and in December, we completed a $90.5 million private placement. Together, the proceeds from these financings extend our anticipated cash runway into 2023 and allow us to invest along our three strategic priorities, building franchises in hematology and CDK inhibition, while continuing to unlock the full potential of our gene control discovery engine. We are grateful to our new and existing investors for their continued support.

[Operator:]

Thank you, sir. I show our first question comes from the line of Phil Nadeau from Cowen. Please go ahead.

[Phil Nadeau:]

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 2, plus, I missed I actually didn't hear where your primary endpoint is going to be? Can you discuss your choice of endpoint in light of the fact that it sounds like you're looking at the depth and durability of responses? So perhaps CR rate - wouldn't even be the correct endpoint. Maybe you need some like MRD or progression free survival.

[Nancy Simonian:]

Thanks. So I'm going to have David to answer that question. Great to talk to you. Go ahead, David.

[David Roth:]

You know, thanks, Phil. And so just to provide you know the context, this is a randomized Phase 2 in RARA-positive, newly diagnosed unfit AML, comparing the triplet of 1425 plus venetoclax and aza to venetoclax and aza. And for that the primary endpoint is going to be the composite complete response rate. And we believe that, you know, this rate will very well reflect the clinical activity we expect to deliver with our triplet compared to the control arm, which is just that of VenAZA. And just to remind you again, from the data that we presented at the ASH Meeting, we demonstrated that the majority of RARA-positive patients have this monocytic AML phenotype, which has been demonstrated by multiple independent groups to correlate with resistance to treatment with venetoclax and aza. So, you know, 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 a performance of that doublet in the population, and that would give us a technical advantage for this randomized approach.

[Phil Nadeau:]

Is there any way that you could look at MRD as an endpoint of the markers exist to differentiate the leukemia clones from normal in this patient population?

[David Roth:]

Absolutely. One could certainly look at MRD. And, you know, obviously, there's a lot of interest in seeing the depth of the response, and how that translates into the duration of the response and long-term survival. You know, I will say that in our current program, in you know, in RARA-positive newly diagnosed AML, we demonstrated a very high overall response rate of about 67%, 61%were, you know, CR to CRis, which is consistent with the planned composite primary endpoint for the go-forward program against VenAZA. And almost all of those approximately 89% were deep responses molecular or cytogenetic CRs. So we are feeling really good about our current data and you know predicting you know the appropriate next steps and the path forward for this program in newly diagnosed AML.

[Phil Nadeau:]

That's very happy - very helpful. Second question is on the Phase 3 study in high-risk MDS. Have you disclosed or would you be willing to disclose the powering of the trial? What CR rate are you assuming for the control arm versus treatment? And what's the power to detect that difference?

[David Roth:]

Yeah. So we haven't provided that level of detail, what I can say is, it's 1425 plus aza versus aza. It's a 190 patients with complete responses, the primary endpoint, randomized 2

[Phil Nadeau:]

Great. And then last question from us. In terms of 5609's proof-of-concept data coming in Q3, can you give us some sense of what you need to see in an indication in order to continuing to advance 5609 for that tumor type?

[David Roth:]

So, again, so 5609, this is our selective CDK7 inhibitor, we presented that data at ENA that was our early data coming out of the Phase 1. As you know, we're continuing in our, you know, dose escalation, we reported evaluating various regimens, seven on and seven off, five days on and two days off in escalating doses. And we have various tumor types indications. We're setting the stage for advancing the program in either simulation or in combinations in specific patient populations that certainly will be informed by the data. Obviously, the ability to continue to demonstrate a tolerable safety profile, which we're very pleased, which we have demonstrated in the context of achieving proof-of-mechanism at doses that were tolerable. You know, 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 in the study, to help inform the best next steps. And I think generally, 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.

[Phil Nadeau:]

That's very helpful. Thanks for taking my questions.

[Nancy Simonian:]

Thanks, Phil.

[Operator:]

Thank you. Our next question comes from the line of Ted Tenthoff from Piper Sandler. Please go ahead.

[Ted Tenthoff:]

Great, thank you very much. And congrats on all the progress you set up for this year. I wanted to ask about 5609 and sort of the expectations there. There's been a lot going on in breast cancer in general, and just wanted to get a sense of you see sort of the changing landscape, changing your thinking about the and the potential path development path? Thanks so much.

[Nancy Simonian:]

Yeah, Ted. You know, we are - remain very excited about the opportunity for 5609, you know with this single target, the data suggests that could work across a whole range of difficult-to-treat tumors. And obviously, our dose escalation study, we're examining multiple different tumor types, including breast cancer, both HR-positive with fulvestrant, as well as in the single-agent on 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 unmet medical need and that patient population, what else is emerging in that space? And where are some optimal places to take it forward in expansion, to get to proof-of-concept and a plan forward towards commercialization. So we're fully aware of what's happening in the HR-positive breast cancer landscape. And, you know, more novel endocrine therapies coming forward, which we think is really exciting and also offers up opportunities for us to think about how we develop 5609 in that space, but we will be looking at the totality of both the data from the trial as well as what's happening in the external landscape. But we think that there's a tremendous opportunity across many different tumors, including breast cancer with 5609.

[Ted Tenthoff:]

That's great, awesome. Thank you very much.

[Nancy Simonian:]

Thanks, Ted.

[Operator:]

Thank you. Our next question comes from the line of Jason Butler from JMP Securities. Please go ahead.

[Jason Butler:]

Hi, thanks for taking the question. Just had one on 1425 and MDS, can you maybe just talk to us a little bit about, I know you're not disclosing the powering, but based on your interactions with physicians, what you would need to see to change standard of care and whether or not CR rate would be enough data - a benefit there would be enough to change standard of care? Thanks.

[Nancy Simonian:]

Let me start out and then I'm going to turn it over to David. You know, we, as you know, in the higher-risk MDS space, there hasn't been a new drug approved other than HMAs in decades and azacitidine alone, you know, provides limited opportunity for these patients. And I think what we find quite compelling about the 1425 profiles in - in MDS, and you know obviously, this is in discussion with physicians is one of the major problems these patients have is, they have sort of cytopenias related to their disease, neutropenia, as an example. And they get into infection-related complications or require a lot of transfusions. And that results in a lot of morbidity and mortality from the disease. So the opportunity to have a drug that doesn't and can - give efficacy, but doesn't exacerbate the cytopenias as I think are really compelling profile that physicians have expressed to us and these patients is a little bit more of a chronic disease. It's not like they're acutely blasting off from their AML. So something that it works well, well-tolerated, convenient. These patients are typically outpatient as, is a really wonderful profile. But David, let me turn it over to you and see if you can add a little bit more about the CRs and endpoint in how physicians feel about that.

[David Roth:]

Yeah, no, it's an important question. And I think that, you know, we are obviously looking at the totality of our data. And the CR endpoint is an accepted surrogate for long-term benefit. And technically, you know, it may serve our purposes for obtaining an accelerated approval or even a full approval, you know, based on the totality of our data package. And, you know, as you - you're assuming, I'm sure that you know, that the other data that we'll be collecting is going to help, you know, the swift evolution of the standard of care to include Fortune 25 for RARA-positive patients, and that's what we're expecting. You know, 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 problematic for these patients, as Nancy mentioned. You know, the length of the duration of the response, you know, and survival and things of that nature will all roll up into what we believe will be a compelling reason for an adoption of this drug in the treatment of these patients.

[Jason Butler:]

Okay, great. Thank you very much.

[Nancy Simonian:]

Thanks, Jason.

[Operator:]

Thank you. Our next question comes from the line of Mark Breidenbach from Oppenheimer. Please go ahead.

[Mark Breidenbach:]

Hey, good morning, and thanks for taking my questions. This one's probably in toward, David. But just with respect to the Phase 3 trial and MDS, are there any plans to include an interim analysis before enrolling the full 190 patients?

[David Roth:]

Yeah, a good question. So we, you know, we've currently not been very specific with the details. Our current plans are that, you know, as we said today, we've initiated the trial, we're very proud of that. It's open for enrollment. And, you know, our estimates and projections at this point would have us filing an NDA in the 2024 timeframe, we haven't provided additional guidance to when data would be available and made public.

[Mark Breidenbach:]

Okay, understood. And with respect to 5609, are the expansion cohorts likely going to be inclusive of all the same tumor types that made it into Phase 1 dose escalation? Or do you think you're going to be going after a narrower and more narrow or more specific subset of tumor types in expansion?

[David Roth:]

So, the - another good question. So right now, our current plan for that trial is to share data in the third quarter. We would expect this data to include additional information from the patients that have been enrolled at the time of ENA, and then those subsequently enrolled to help better understand, you know, what the objectives of the trial we're seeking to understand, the safety and also, we're going to have a focus on clinical activity. So we're excited about that. And then in the second half, we'll be opening these expansions. We haven't provided 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 in that respect. So right now we are focused on patients with you know pancreatic, colorectal, lung, breast ovarian cancer as a single-agent we also have a combination with fulvestrant. But we also have lots of other work going on to explore other things that you know, will potentially find their way into the study design, depending on how our data is, you know, sorts itself out. So we'll give you more context on that around the time of the expansions that are moving forward.

[Mark Breidenbach:]

Okay. Okay, fair enough -

[Nancy Simonian:]

And maybe I'll just - and maybe, Mark I'll just add that, you know, generally, if you look at what we did with 1365, and it's pretty typical to when you one move into an expansion phase that the various expansion cohorts are a more homogeneous set of patients. So that - that's what we've done with 1365. And I think it's something that one can expect. So as you hone in for that next phase, you focus in on, you know, one or more populations based on multiple cohorts.

[Mark Breidenbach:]

Got it, got it. And finally, just one last quick one. Do you have any plans to present preclinical data this year from you know the fetal hemoglobin inducers? So just that we haven't heard much from that program in a while. Just curious. Thanks.

[Nancy Simonian:]

Yeah, we're, the discovery partnership at Global Blood Therapeutics is going very well, I'm really excited about that. They're really wonderful partners. And we continue to be very bullish about the opportunity to provide a potential functional cure with a small molecule, you know, get in that relationship, we have not disclosed, you know, when we're going to be presenting data or if, but I would just say it's been to data, a highly productive collaboration with Global Blood.

[Mark Breidenbach:]

Okay, thanks so much for taking the questions and congrats on the progress.

[Nancy Simonian:]

Sure. Thank you, Mark.

[Operator:]

Thank you. Our next question comes from the line of Zegbeh Jallah from ROTH Capital. Please go ahead.

[Zegbeh Jallah:]

Good morning, guys. Just had two quick questions, excited to see all the progress 1425 specifically, so just wanted to ask if you had any updates regarding the development of companion diagnostic for that program, and then any factors influencing the timeline for the APL program? I think you said it in the 2024. So just kind of wanted to understand the mechanics around that.

[Nancy Simonian:]

Yeah, hey, Zegbeh. So yeah, you know the companion diagnostic is a very important part of the development strategy for 1425, because at the end of the day, we will be launching that drug in the RARA-positive patient population. We've had a clinical trial assay in 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 suffice it to say that, that development is very important. And it's progressing quite nicely in parallel with the clinical development. I'm sorry, your second question, Zegbeh?

[Zegbeh Jallah:]

It's just about the timeline for the APL program.

[Nancy Simonian:]

Yeah. So you know, we just acquired the asset in December. And the team has done - the Syros team a remarkable job, you know, pulling together things very quickly that enables us to initiate the dose confirmation study in the second half of this year, and to be gearing up to start a Phase 3 trial next year. So we're excited about both the asset and the pace upon which, you know, the team has been able to very quickly, you know, pull everything together to be on the cusp of a - potential Phase 3 start next year, which obviously involve both the clinical work, but a lot of the manufacturing work as well. So, we feel great about that. And I think the other thing is, we've just got in a tremendous amount of enthusiasm from the KOLs in the field, that just I think underscores just how much of a need there is for this therapy. And that just gives us a lot of great confidence in the execution on the plan as well. So -

[Zegbeh Jallah:]

Thanks -

[Nancy Simonian:]

That help you answer your question, Zegbeh? Okay, awesome. Great to talk to you.

[Operator:]

Thank you. Our next question comes from the line of Matthew Cross from Alliance Global. Please go ahead.

[Matthew Cross:]

Hi, all. Good morning and thanks for taking a couple of questions from me. Both relating to the Phase 2 triplet study with VenAZA. In particular, I guess I was wondering if anything had been decided about the dosing considerations for adding in ven in order to manage cytopenias and the like or maybe to balance out some of the 1425 specific tox we've seen such as the hypertriglyceridemia? And then the second one was, you know, Gilead just posted a new Phase 3 study yesterday, I believe, of magrolimab plus aza compared to VenAZA or 7 plus 3, NTP53, mutant AML. And I guess I'm curious how you think about the positioning of 1425 as an add-on therapy to VenAZA, as these efforts to maybe replace VenAZA in certain settings advanced? Do you feel there's any meaningful risk that by the time you're looking at a Phase 3 study in newly diagnosed AML, the landscape may have shifted away from VenAZA as a backbone to combine with? Thanks.

[David Roth:]

Okay, so maybe I'll start with the initial part of the question and that related to the dosing. So, you know, I mentioned a little earlier that you know, where we're going to be dosing 1425 plus venetoclax and aza versus venetoclax and aza. The trial is designed and planned to start in the second half of this year, making great progress on that we've great enthusiasm and input from, you know, the cadre of experts that are going to help deliver that strategy together with us. That we'll proceed with a very brief safety lead in just to focus on the question you're sort of getting at with how it's all going to be dosed. And we haven't provided more detail on the specifics of that strategy. But I think we have a fairly straightforward plan. And, you know, I think it's also important to remind you that one of the attributes of SY-1425, which increases our conviction of why it's going to be so important for use in these populations is that, it's not known to be a myelosuppressive drug. And it's generally well-tolerated safety profile affords at the ability to be used in various combination contexts. We don't anticipate additive toxicities, we haven't seen concerning issues that would suggest we're going to run into, you know, challenges there. So, you know, so that's why, we are going to start just to you know make sure and authorizing cross our Ts you know do that, to start with, but we expect this to move forward efficiently through that initial phase. You maybe - asked a question of the adverse events within triglycerides, and those have largely been you know laboratory abnormalities veterans have been, you know, clinically quiet, so to speak. And we don't expect that to you know cause problems in this particular population that we're focused on.

[Nancy Simonian:]

And then on the aspect of just you know, where the field is going in other combinations. You know, this is obviously, the AML space is a very dynamic space. We are - we feel quite confident that VenAZA is currently kind of the standard of care and will continue to be an important standard of care going forward. But the really great thing about 1425 is that, it combines, we believe it has the opportunity to combine well with multiple different drugs. It's a novel mechanism of action, it doesn't have the associated toxicities of other drugs. And so as additional doublets or triplets are emerging in the field, we think that will just provide an opportunity for us to think about how to have a 1425 also part of that backbone, and I think back to the days of development of Velcade in myeloma, and it was exactly that, we were combining with a couple of things. And then as things were 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 us where the market is going to be in the future.

[Matthew Cross:]

Great, okay. No, thanks for addressing the questions. Appreciate the insight and the reminders on the designs. Thanks, guys.

[Nancy Simonian:]

Thank you, Matt.

[Operator:]

Thank you. I show no further questions in the queue. At this time, I'd like to turn the call back to Dr. Nancy Simonian, CEO for closing remarks.

[Nancy Simonian:]

Thank you, operator. I want to thank you all for joining us today and for your continued support of Syros. We are focused on executing against three strategic priorities, and advancing toward our vision of building Syros 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.

[Operator:]

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