Syros Pharmaceuticals, Inc.

Good morning and welcome to CROS Pharmaceuticals second 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 CROS website at www.cros.com. Please be advised that today's call is being recorded. Following the formal remarks, we will open up the call 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 CIROS.

Thank you. This morning, we issued a press release with our second quarter 2021 financial results, along with anticipated future milestones and recent accomplishments. This release is available on the Investors and Media section of Cirrus's website at www.cirrus.com. We'll begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer, Dr. David Roth, our Chief Medical Officer, Gerald Quirk, our Chief Operations Officer. We'll then open the call for questions. Dr. Eric Olson, our Chief Scientific Officer, and Kristen Stevens, our Chief Development 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 the 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. The first half of 2021 was very productive for CERO. and I am pleased to provide an update on our recent progress. As we outlined at the end of last year, we are focused on three strategic priorities. First, we are advancing a growing portfolio of targeted therapies for hematologic disorders, each with the potential to set a new standard of care. Second, we are building on our leadership in selective CDK inhibition for difficult-to-treat cancers. And third, we are continuing to leverage our gene control discovery engine to fuel a robust and sustainable pipeline. Together, we believe these efforts will enable us to build Cirrus into a fully integrated company with medicines that provide profound benefits for people with cancer and monogenic diseases. In the second quarter, we made great strides across all our clinical stage programs. Starting with SY5609, as we announced this morning, we have entered into an agreement with Roche to evaluate 5609 in combination with atezolizumab, a PD-L1 inhibitor, in patients with colorectal cancer. We are very excited to work with Roche to explore this novel combination. There is strong preclinical and mechanistic rationale for combining 5609 with a PD-L1 inhibitor which David will discuss later in the call. Notably, this marks the first clinical investigation of a selective CDK7 inhibitor with immunotherapy, potentially paving the way for additional combination strategies for 5609 with immunotherapy. We also announced this morning the data from the dose escalation portion of our phase one study of 5609 will be highlighted in an oral presentation at the ESMO Congress in September. We remain on track to move into the expansion portion of the Phase I trial in the second half of the year, and at the time of the data readout, we plan to further detail our next steps for advancing the development of 5609 to further explore its potential as a transformative, targeted approach for difficult-to-treat cancers. Turning now to our targeted hematology portfolio, We continue to make progress and select MDS1, our phase three clinical trial of tamiberitine, formerly known as SY1425, in combination with azacitidine in RARA-positive, higher risk MDS patients. We are also on track to initiate both select AML1, our randomized phase two trial of tamiberitine plus venetoclax and azacitidine, as well as our dose confirmation study of SY-2101 in APL this year. Together, these programs put us on track for two potential NDAs in 2024, for tamiberitine in MDS and for 2101 in APL. Our recent three-part KOL webinar series highlighted the opportunities for tamiberitine in 2101 to set new standards of care in MDS AML, and APL, further defining the value proposition for these programs. These three webinars featured key opinion leaders who are intimately involved in the treatment of people living with MDS, AML, and APL. These were incredibly impactful events for us at Xero. Each physician articulated a tremendous gap in the treatment landscape, highlighting the urgent demand for new therapies that can provide patients with better clinical outcomes, or in the case of APL, a dramatically reduced treatment burden. The KOLs described the potential of Tamiveritin and 2101 to address these needs, and also shared their views on how Tamiveritin and 2101 are distinguished within the current treatment and development landscape. Beginning with our MDS-focused event in May, Dr. Amy DeZern of Johns Hopkins provided an overview of the higher risk MDS landscape, underscoring the need for tolerable therapies that can improve outcomes while offering quality of life. HMAs, including azacitidine, are the current standard of care and offer limited efficacy. Prognosis after HMA failure is very poor. Moreover, most higher risk MDS patients are elderly and either can't or don't want to undergo the intensive chemotherapy necessary to bridge to a potentially curative bone marrow transplant. Dr. DeZern highlighted one of the major challenges in MDS drug development. MDS often presents as a polyclonal disease, making it difficult to treat with therapies that target individual genetic mutations. In her view, a combination of factors distinguishes Tamiberitone in the current landscape. the fact that it targets a biologic process fundamental to the differentiation of blood cells as opposed to targeting a single genetic mutation, the ability to select for patients most likely to respond, the high complete response rates in AML, which have a reasonably likelihood of translating to higher risk MDS, and a favorable tolerability profile that does not exacerbate neutropenia and other complications when combined with azacitidine. Turning now to our AML-focused event. In June, we were joined by Dr. Daniel Pallier of the University of Colorado. Dr. Pallier's presentation focused on the unmet need in AML and the paucity of options available to put people in long-term remission. While Vaneza has emerged as a tremendous option for many patients, a third of newly diagnosed unfit AML patients don't respond, and many more relapse, leaving them with poor options. Dr. Paglia explained that these non-responders tend to be patients with monocytic disease. As we presented at ASH, our translational data suggests that the RARA biomarker enriches for the monocytic disease phenotype associated with venetoclax resistance. Simply put, By selecting Ferrara, we believe we may be enriching for the very patients who are in the greatest need for new treatment options. Dr. Paglia also highlighted the characteristics of an optimal AML therapy. An oral medicine that allows for deep, durable remissions with minimal or manageable toxicities and that has rapid impact on disease progression, where you can tell quickly if the therapy is working. Based on our data to date, we believe tamiberitine may offer this product profile. In our phase two trial, tamiberitine plus AZA delivered high CR rates with a rapid onset of action, meaningful durability, and a good tolerability profile in RARA positive newly diagnosed unfit AML. This gives us confidence in our triplet strategy with tamiberitine plus then AZA. Like MDS, AML can be a polyclonal disease. By employing the triplet combination upfront, we hope to achieve high initial response rates while reducing the emergence of resistance disease by simultaneously targeting both monocytic and non-monocytic leukemia cells that may be present at diagnosis and lead to a short duration of response and relapse. We look forward to beginning to enroll patients in the select AML1 trial later this year. Our final KOL webinar, on APL was just a few weeks ago. APL is a clinically distinct form of AML defined by a RARA gene fusion. We were joined by Dr. Farhad Ravandi Kashani of MD Anderson Cancer Center, who highlighted how an oral therapy would represent a major advance for patients. While IV ATO plus ATRA, the current standard of care, is curative in greater than 80% of patients, it comes with an enormously heavy treatment burden. The regimen involves up to 140 lengthy infusions over nearly a year. 2101, a novel oral form of ATO, has the potential to deliver comparable efficacy while dramatically reducing the treatment burden. We plan to initiate our dose confirmation study this year with the phase three trial to follow in 2022. If you are interested in hearing more, a full audio replay of each of these events, as well as the accompanying slide presentation, is available on our website. With that, I'd like to turn the call over to David.