Syros Pharmaceuticals, Inc.

Good morning and welcome to CRO's 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 and Media section of CRO's website at www.cros.com. Please be advised that today's call is being recorded. Following the former remarks, we will open the call up for your questions. At this time, I would like to turn the call over to Naomi Oki, Vice President of Corporate Communications and Investor Relations at Cirrus.

Thank you. This morning, we issued a press release with our first quarter 2021 financial results, along with anticipated future milestones and recent accomplishments. This release is available on the Investors and Media section of Cirrus' website at www.cirrus.com. We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer. and Joe Farah, our Chief Financial Officer. We'll then open the call for questions. 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, 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, our 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 operations 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 statements. I would now like to turn the call over to Nancy.

Thank you, Naomi, and good morning, everyone. Thank you for joining us today to review our first quarter 2021 progress and recent business highlights. At Cirrus, we believe that people with cancers and monogenic diseases deserve better. At the heart of everything we do is our dedication to deliver new medicines that provide a profound benefit for patients with these difficult-to-treat diseases. With that mission front and center, We are advancing a differentiated portfolio of product candidates, each with the potential to set a new standard of care. We remain laser focused on executing against the strategy we laid out last year with the aim of rapidly maturing Cirrhosis into a commercial stage company. That strategy is rooted in three priorities. Advancing a leading portfolio of targeted therapies for hematologic disorders, building on our leadership in selective CDK inhibition for difficult-to-treat cancers, and leveraging our foundational gene control discovery engine to fuel a robust and sustainable pipeline to support our long-term growth. Let me begin with our targeted hematology portfolio. We have two clinical stage programs, SY1425 and SY2101, for targeted patient populations and higher-risk myelodysplastic syndrome, acute myeloid leukemia, and acute promyelocytic leukemia. Together, these programs position us for two potential new drug application filings in higher-risk MDS and APL in 2024, with additional opportunities beyond that timeframe. We recently began dosing patients in our Phase III clinical trial of 1425 in combination with azacitidine in RARA-positive patients with newly diagnosed higher risk MDS. The trial will compare the complete response rate of 1425 and azacitidine to placebo and azacitidine. If successful, the trial could enable an NDA filing in 2024. The trial marks a tremendous milestone for serous as our first registration-enabling study and for patients with MDS who remain woefully underserved despite advances in hematologic malignancies more broadly. Hypomethylating agents, or HMAs, which are the existing standard of care for MDS, provide limited efficacy and many patients continuing to suffer mortality and morbidity from disease-related cytopenias. Aside from HMAs, no new therapies for MDS have been approved in over a decade. There is a clear need for new options that can deliver benefits to the thousands of people living with MDS and improving their quality of life. We believe that the combination of 1425 and azacitidine is ideally suited to address this need. In clinical studies, 1425 has shown single-agent activity in relapsed or refractory higher-risk MDS, and in combination with azacitidine, 1425 led to a 67% composite complete response rate in RARA-positive patients with low blast count AML which is a close to higher risk MDS on the disease continuum. Importantly, the combination of 1425 and azacitidine has been well tolerated with no evidence of increased toxicity relative to either as a single agent. Importantly, there was no increase in neutropenia or anemia, which is so important in treatments for patients with MDS. Taken together, These data suggest that the combination is highly differentiated. 1425 is an oral agent that in combination with azacitidine has the potential to deliver high rates of complete remissions without introducing additive cytopenias for a targeted subset of higher risk MDS patients. Turning to our efforts in AML, We remain on track to initiate a randomized phase two trial evaluating the triplet regimen of 1425 plus venetoclax and azacitidine in the second half of this year. This trial will compare the composite complete response rate of the triplet of 1425 ven-AZA to ven-AZA alone. Despite the emergence of ven-AZA as the standard of care in newly diagnosed AML, One-third of patients remain refractory to frontline therapy, and recent studies suggest that these patients are enriched for a monocytic form of the disease. Our data show that most RARA-positive patients, including those who have achieved complete responses with 1425, have this monocytic form of AML. AML is a heterogeneous disease, and we believe many patients will present up front with both monocytic and non-monocytic leukemia cells. By employing a triplet strategy that combines 1425 with Vaneza, we simultaneously target both monocytic and non-monocytic leukemia cells from the outset, potentially benefiting patients who are refractory to Vaneza while reducing the emergence of resistant disease. We look forward to initiating the trial later this year and reporting initial data in 2022. Turning to the second program in our hematology portfolio, 2101 is a novel oral form of arsenic trioxide in development for the treatment of APL, which is a genetically defined form of AML. We believe 2101 could significantly impact the lives of people with APL. IDATO, the current standard of care, offers a cure rate of over 80%, but it comes with an enormously heavy treatment burden. As an oral therapy, we believe that 2101 could dramatically reduce this treatment burden without sacrificing efficacy. We plan to initiate a dose confirmation study in the second half of this year, followed by a phase three study in 2022. If successful, this study could enable an NDA filing in 2024. Before moving to our broader portfolio, I want to take a moment to highlight the targeted hematology KOL event series that we announced this morning. Over the course of the next several months, we will be hosting three webcast conference calls focused on our hematology programs. In May, Dr. Amy DeZern of Johns Hopkins will join us to speak about higher risk MDS. In June, Dr. Daniel Paglia of the University of Colorado School of Medicine will present on unfit AML. And in July, Dr. Farhad Rabandi of the MD Anderson Cancer Center will speak about APL. We are very much looking forward to these webinars and hope you will join us to learn more about the unmet needs in MDS, AML, and APL, as well as the opportunities for 1425 and 2101 to set new standards of care for people with these diseases. Additional details at each call will be announced shortly. Turning to our focus on CDK7 inhibition, we continue to enroll patients in our phase one dose escalation study of SY5609, and we remain on track to announce updated dose escalation data, including clinical activity data in the third quarter. As a reminder, the dose escalation is enrolling patients with advanced breast, colorectal, lung, ovarian, or pancreatic cancer with solid tumors of any histology that harbor rb pathway alterations we are exploring various dosing regimens of 5609 is both a single and combination agent and we expect to move into the expansion phase of the phase one trial in the second half of 2021 in parallel we continue to invest in our gene control discovery engine with the goal of fully exploiting the power of our platform to advance additional programs in cancer and monogenic diseases, and we remain on track to name our next development candidate in 2022. As we've shared before, our most advanced preclinical program targets CDK12, another member of the transcriptional CDK family. Preclinical studies show a synthetic lethal relationship between PARP and CDK12, which are both involved in DNA damage repair, opening up several opportunities for combining a CDK12 inhibitor with PARP inhibitors, as well as other drugs that cause DNA damage or inhibit its repair. In addition to our work on sickle cell disease with global blood therapeutics, we are also making good progress with our second monogenic disease program in myotonic dystrophy type 1, or DM1. Our goal here is to develop a trinucleotide repeat modulator to decrease the expression of the toxic copy of the DNPK gene. As we continue to advance this program, we are gleaning key insights that could apply to other nucleotide repeat disorders. This has the potential to unlock massive opportunities. More than 40 genetic disorders are caused by nucleotide repeat expansion. kind of mutation in which simple DNA sequences repeat and increase in copy number and induce 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 where insights gleaned in one program can be applied to advance our next wave of efforts and where we can capitalize on our expertise as well as our clinical and commercial investments to advance multiple programs forward in parallel. We are entering a catalyst-rich period for Cirrus 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 2021 financial results.