Good morning, and welcome to Syros Pharmaceuticals' third quarter 2023 financial results conference call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Syros' website at www.syros.com. Please be advised that today's call is being recorded. At this time, I would like to turn the call over to Karen Hunady, Director of Investor Relations and Corporate Communications at Syros. Please go ahead.
Thank you. This morning, we issued a press release announcing our third quarter 2023 financial results. The full release is available on the Investor and Media section of the Syros website at www.syros.com. We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer, Conley Chee, our Chief Commercial Officer, Chief Business Officer, and incoming Chief Executive Officer, Dr. David Roth, our Chief Medical Officer, and Jason Haas, our Chief Financial Officer. We will then open the call for questions. Kristen Stevens, our Chief Development Officer, is also on the call and will be available for Q&A. Before we begin, I would like to remind everyone that the statements we make on this conference call will include forward-looking statements.
Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the Risk Factors section of our quarterly report on Form 10-Q that we filed this morning, our annual report on Form 10-K that we filed earlier in the year, and any other filings that we may make with the SEC in the future. Any forward-looking statements 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. With that, I'd now like to turn the call over to Nancy. Nancy?
Thank you, Karen. Good morning, everyone, and thank you for joining us. Today's call marks my last as the CEO of Syros. In October, we announced my planned retirement as CEO and the appointment of Conley Chee as Syros' next CEO. I am incredibly proud of the company we've built over the last eleven years. We have made tremendous progress toward our mission of translating breakthrough science into new medicines that can make a profound difference for patients on the foundation of a strong, experienced leadership team and a collaborative, patient-focused culture. I look forward to supporting Syros and partnering with Conley and the team as I continue my service on Syros' board of directors. Following our strategic prioritization earlier this fall, Syros is a company with a singular focus.
We are devoting our resources to the advancement of tamibarotene, our oral, selective, and potent RARα agonist for the frontline treatment of hematologic malignancies. As Conley and David will detail this morning, we believe tamibarotene has the opportunity to become the standard of care for higher-risk MDS in unfit AML patients with RARA overexpression. Tamibarotene has a differentiated profile. It is a biologically targeted agent that has demonstrated high complete response rates, a rapid time to response, and a favorable tolerability profile across multiple clinical trials. I am incredibly proud to have taken Syros from a scientific discovery in 2014 to late-stage development on the path to commercialization.
As a company, we are approaching this important transformation with data from our first pivotal study in higher-risk MDS to be reported next year and initial data from the randomized portion of our phase 2 study in AML that we plan to present in early December. As we prepare for our maturation into a commercial company, it is a natural time to transition leadership to Conley, our Chief Commercial and Business Officer, who is an expert at building effective commercial organizations and launching targeted oncology therapies. Conley has been a valuable member of our leadership team for over two years, informing all aspects of our business. Having worked with Conley during this time and during our transition over the last month, I am confident he will be an impactful and effective leader in this next stage for Syros.
With that, I would like to turn the call over to Conley to provide some brief remarks. Conley?
Thank you, Nancy. I'm incredibly honored to lead Syros into its next exciting phase and to build on the foundation that Nancy and the team have established. Speaking on behalf of all our colleagues, I would like to thank you, Nancy, for all your years of leadership. I'm eager to work closely alongside my colleagues and partners in my new role as CEO to execute on our development plan for tamibarotene, prepare for our first NDA filing and launch, and ultimately deliver tamibarotene to the thousands of MDS and AML patients in need of better options.... Since I joined Syros two years ago, we've made great strides in building a roadmap to commercialization. With the recent restructuring, we've also now streamlined our operations to focus on our tamibarotene program.
We continue to execute on our clinical development to prepare for an NDA filing and are developing the plan for commercial infrastructure. As we approach the initial data readout from the randomized portion of SELECT-AML-1 in early December and the pivotal data from SELECT-MDS-1 next year, we are increasingly focused on building a robust commercial business that can cement tamibarotene as a standard of care for patients with RARA overexpression. We believe the market for tamibarotene is significant. Both higher-risk MDS and unfit AML are diseases that are notoriously difficult to treat. The number of frontline therapies in late-stage development have shrunk in recent months, and existing frontline options are insufficient. Given that these patients are often elderly and frail, it is important to have new treatment regimens that are tolerable and manageable.
With tamibarotene, we are advancing a first-of-its-kind targeted therapy, which could become standard of care for approximately 50% of higher-risk MDS and 30% of unfit AML patients who are positive for RARA overexpression. As we've noted before, approximately 21,000 people are diagnosed with higher-risk MDS, and nearly 25,000 people are diagnosed with unfit AML annually in the U.S. and Europe. Altogether, this creates a substantial market opportunity for tamibarotene. As we move closer to potentially delivering tamibarotene to this market, we're beginning to engage in critical pre-commercial activities. If approved, we plan to deliver tamibarotene to patients through our own commercial efforts in the United States and are well-positioned to execute on this opportunity. I look forward to leading the team through these important efforts as we work to realize the potential for tamibarotene to provide profound benefit to patients.
With that, I'll now turn it over to David to review our programs and upcoming milestones in more detail. David?
Thank you, Conley. We are very pleased by the continued progress in advancing tamibarotene through clinical development in both AML and higher-risk MDS. We are on track to share initial randomized data from approximately 20 patients in SELECT-AML 1 in early December. As a reminder, the randomized portion of the SELECT-AML 1 study is designed to evaluate the safety and efficacy of tamibarotene in a combination with venetoclax and azacitidine, compared to venaza alone in approximately 80 newly diagnosed unfit AML patients with RARA overexpression. Patients are randomized 1-to-1 into the two treatment arms, with the composite CR rate or the CR/CRI rate as the primary endpoint. We expect this initial data will inform our understanding of the potential clinical benefit of adding tamibarotene to venaza, the standard of care. In this initial set of patients, we expect most will have completed at least 2 cycles of therapy.
Given that the randomized portion of the trial started enrollment in the first quarter of this year, the focus of this initial data will be on the composite complete response rates and, of course, tolerability. We believe this first direct and randomized assessment of patients with RARA overexpression treated with the triplet regimen of tamibarotene plus venaza, compared to the doublet of venaza alone, will meaningfully inform our understanding of the potential benefits of our novel approach. We previously shared compelling data to support our tamibarotene triplet strategy in AML late last year. Data from the safety lead-in portion of our SELECT-AML-1 study showed a composite complete response rate of 83%, with patients experiencing a rapid time to response and favorable tolerability, with no additive myelosuppression compared to historical data with venaza alone.
In early December, we'll provide data on an additional set of patients, all with RARA overexpression, treated with the triplet, as well as a direct randomized comparison to patients with RARA overexpression treated with the venaza doublet. Today, the standard of care for unfit AML patients is venetoclax with azacitidine, which has shown a 66% composite CR rate and a median overall survival of less than 15 months. Unfortunately, approximately one-third of AML patients do not respond to the current standard of care with venaza, and nearly all who initially respond will relapse. Post-relapse, patients have a very poor prognosis, with a median survival of only a few months. Based on data that informed the SELECT-AML-1 study, we believe tamibarotene is uniquely positioned to improve upon the standard of care in unfit AML, and we look forward to sharing initial randomized data next month.
In parallel, we continue to evaluate tamibarotene for the treatment of higher-risk MDS, which, like AML, represents an area of high unmet need. The existing standard of care provides limited efficacy, with a 17% complete response rate and a median overall survival of just 18.6 months.... No new therapies beyond hypomethylating agents or HMAs have been approved in well over a decade. This, too, provides a unique opportunity for our biologically targeted approach to improve the care and treatment of patients with RARA overexpression, who can be readily identified using a simple blood test assay. Tamibarotene also benefits from a generally well-tolerated safety profile, which is particularly well-suited to this generally elderly and frail population. We continue to enroll patients in the ongoing SELECT-MDS1 phase 3 trial evaluating tamibarotene plus azacitidine.
As a reminder, the primary endpoint of the trial is complete response rate in the initial 190 patients, with overall survival now included as a key secondary endpoint based on continued enrollment to approximately 550 patients. We're very excited as we approach the completion of enrollment for the primary endpoint. We can now project the enrollment trends more precisely and expect to complete enrollment of the initial 190 patients necessary to support approval using a CR endpoint in the first quarter of 2024, and plan to report pivotal CR data by mid-Q4 of 2024.
Given the biologic and clinical similarities that establish the well-understood relationship between higher-risk MDS and AML, and the supportive data we've seen across these patient populations to date, we believe that tamibarotene can provide significant benefit to readily identifiable, genomically defined subsets of the MDS and AML patient populations, and potentially establishes a new standard of care for people with RARA overexpression. I would now like to turn the call over to Jason, our Chief Financial Officer, to review our third quarter financial results. Jason?
Thank you, David. Now turning to our third quarter financial results. We recognized $3.8 million in revenue in the third quarter of 2023, consisting entirely of revenue recognized under our sickle cell disease collaboration with Pfizer that ended in October. Syros recognized $3.9 million in revenue in the third quarter of 2022, consisting of $3.7 million in revenue recognized under our collaboration with Pfizer and $200,000 recognized under our former collaboration with Insight. R&D expenses were $28.3 million in the third quarter of 2023, as compared to $25.8 million for the third quarter of 2022. Our R&D expenditures are now principally focused on the advancement of tamibarotene.
G&A expenses were $7.8 million in the third quarter of 2023, as compared to $8.1 million for the third quarter of 2022. Restructuring costs were $2.4 million for the third quarter of 2023, and these restructuring costs were comprised of $2 million of severance, post-employment benefits, stock-based compensation, and outplacement services, as well as $400,000 of asset impairment charges related to the laboratory equipment that is classified as assets held for sale. We reported a net loss for the third quarter of $40.1 million, or $1.43 per share, compared to a net loss of $30.3 million, or $3.21 per share for the same period in 2022.
Cash, cash equivalents, and marketable securities as of September 30, 2023, were $112 million, as compared with $144 million on June 30, 2023. We continue to believe our current cash position will be sufficient to fund our anticipated operating expenses and capital expenditure requirements into 2025, which is beyond phase 3 data from the SELECT-MDS1 trial and additional data from the randomized portion of the SELECT-AML1 trial. With that, I will turn the call over to the operator for questions.
Thank you. And ladies and gentlemen, should you have a question, simply press star followed by the number one on your telephone keypad. You will hear a three-tone prompt acknowledging your request, and your questions will be pulled in the order they are received. Should you wish to decline from the polling process, simply press star followed by the number two. And if you're using a speakerphone, please lift the handset before pressing any keys. One moment, please, for your first question. Your first question comes from the line of Ted Danto from Piper Sandler. Your line is open.
Great. Thank you very much, and good morning. So I just wanna start by asking about sort of how the landscape is changing, both in the AML and MDS, and whether or not you think there's any major changes that have occurred since you designed the SELECT studies. And I also just wanna thank Nancy for all of her hard work. And really, I can't say how much I've enjoyed working with you. And Conley, I know you're gonna do a great job with the company, but Nancy, thanks so much, and I wish you all the best.
Thank you, Ted. It's been a real honor and pleasure and also working with you and your team. I'm gonna turn the question over to David to talk a little bit about how the MDS and AML landscape has changed since we designed the SELECT studies.
Yeah. Thanks for that question, Ted. I think let me just start by saying some things have not changed. What hasn't changed is the fact that there remains a very significant unmet need for patients with higher-risk MDS.
... It's really a challenging disease to treat. The majority of patients are elderly or frail, and the need for a well-tolerated, preferably, I think, an orally available therapy that's easy to administer and helps maintain quality of life continues to this day, and that's really what motivates us to continue our development of tamibarotene. What has changed, however, is that there have been many drugs put into development over several years over even the time that we've had tamibarotene in development, which have not been successful. And, you know, we've watched this evolution of various trials that advanced to phase three that haven't made it. And of course, you know, we reflect on that.
You know, we have a sort of a concern that, you know, patients need more, and we sort of do wish the others have success. But, you know, we look at our mechanism, it's distinct, and we think that these issues separate us from the rest of the pack. So we have reason to remain hopeful that our program will deliver ultimately, and that's why we're so excited today.
Can I talk about AML?
Yeah. So just in AML, sorry, I didn't, you know, answer specifically, but for AML, I think the same sort of holds true. We, you know, have, I think, seen an evolution of a standard of care that now includes venetoclax and azacitidine in AML. It has been developed primarily for patients who are unfit. And, you know, we all do appreciate the properties of venetoclax, which, while highly effective, can be associated with myelosuppression that makes it a bit more challenging for use in the patient population for which it was targeted. And so even in that context, we still feel there's opportunity to improve on that standard.
We know, obviously, we have a program where we're adding tamibarotene into the backdrop of venetoclax and aza, with a hope to improve upon the performance there. You know, and I think there still remains significant unmet need, with a third of patients not responding to venaza or patients who initially respond will ultimately relapse. So we think there's still much that can be addressed there. There's a range of new drugs in development that are being entered into the clinic. There's a large focus on immuno-oncology drugs, but you know, it's still early days, and I think it's really a great place to be focused on our efforts for helping patients.
And let me just add one thing, Ted. It's, it's pretty remarkable to think about the frontline treatment of these hematologic malignancies, where the median overall survival in AML, based on the standard of care of venaza, is just a little over a year, and in MDS, it's a year and a half. I mean, there is just such a continued high unmet medical need in these spaces. And despite a lot of attempts to change that, I really do think that we are beginning to see sort of a, a potential inflection point, but, that part has not changed over the years. And as David said, that's why we're continuing to be so excited about the opportunity with tamibarotene.
Excellent. Great perspective. Thank you, all.
Thank you. And ladies and gentlemen, once again, if you would like to ask a question, simply press star followed by the number 1 on your telephone keypad. Your next question comes from the line of Phil Nadeau from TD Cowen. Your line is open.
Good morning. Thanks for taking our questions. First, Nancy, let us add our congratulations on your tenure and coming retirement. Very well-deserved. A couple questions from us. First, on select AML, I think, in the prepared remarks, you said that this initial data will give us some idea of the efficacy, of adding TAMI to the, to the combination. Can you talk a bit more about that? What delta between the arms would give you confidence that you are seeing additive efficacy amid the relatively small patient numbers? And in terms of the control arm, and specifically, I think you said a 66% CR/CRi rate would be expected in the general population, what's the most recent data on what a RARA positive population would generate for CR/CRi for venaza?
Okay, thanks, Phil. I'll take that one. So just to, again, remind for everyone who's listening, we're undergoing a randomized trial. All the patients are positive for RARA overexpression. They all have unfit AML, and this represents the very first prospective clinical evaluation of tamibarotene being used in RARA-positive patients in combination with venaza compared to venaza. So your question about what we know about the performance of venaza in RARA-positive patients is unknown, and this will be our first data update that gives us initial insights into that.
We are very excited that we can look forward to reporting on approximately 20 patients, reminding you it's randomized 1:1, so you can expect a relatively equal split across that population, and we're specifically focused on those patients who have enrolled into the randomized portion. So, reminding you, this is a group who started enrollment in the first quarter, and here we are in the fourth quarter giving you this update. So we're largely focused on the response rates. We focus on our primary endpoint, which is the composite CR rate, the CR/CRi rate. And of course, you know, we'll report on the tolerability. As you mentioned, the venaza response is about 66%, but tami-aza response in this population is about 61% from our prior phase 2 trial.
So we're looking for a response to the triplet that is north of that. We haven't specifically stated exactly how far north we need to be of that. That said, from our prior data last year, the safety lead-in in a smaller number of patients had an 83% CR/CRi rate, which we were very excited about. And in that case, the tolerability supported advancements with randomized portion. So that just sort of gives you a sense as to you know what it is we're we're hopeful for as we move into the early December data disclosure.
That's very helpful. And then just one question on Select MDS. It sounds like enrollment completions now Q1 2024. I think in the past, guidance had been year-end 2023. Is there any reason for that? Were there any unforeseen challenges, or is it simply now that enrollment is near completion, you can give a more definitive and accurate guidance as to when it's gonna complete?
Yeah, I think that the latter is the case. You know, we do our very best over time when a trial initiates, you know, with all kinds of ways to project enrollment rates based on the numbers of sites that are activated and the delivery of the active sites to the trial. And as you get closer and closer to the finish line, the data are, you know, more robust in terms of the accuracy of how they lead us to come to our predictions. So now that there's light at the end of the tunnel, I think we're feeling very, very confident that we can project completing the enrollment for the primary endpoint, that 198 patients should be delivered in the first quarter of the year.
Since it's just a little different than what we previously said, we just thought it was appropriate to update that at this time.
Fair enough. Thanks again for taking our questions. Nancy, congrats again on a great tenure.
Thank you, Phil.
Thank you. There are no further questions at this time. I would like to turn it back to Dr. Nancy Simonian for closing remarks.
Thank you, operator, and thank you everyone for joining us today. I am deeply grateful for the opportunity to start up and lead Syros over the past 11 years. I am proud of the achievements we've made together, and I'm excited about the potential for tamibarotene to transform the lives of patients. I look forward to Syros's next chapter on the path to commercialization and continuing my service as a member of the board. Finally, and importantly, I want to express my thanks to you, our investors and analysts, and the entire Syros team for your support over the years. It truly makes a difference for patients. Thank you.
Thank you, presenters. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.