Syros Pharmaceuticals, Inc.

Good morning, and welcome to the Ciros Pharmaceuticals First Quarter 2022 Financial Results Conference Call. At this time, all participants are in listen-only mode. This call is being webcast live on the Investors and Media section of Ciros' website at www.ciros.com. Please be advised that today's call is being recorded. At this time, I would like to turn the call over to Courtney Solberg, Manager of Corporate Communications and Investor Relations at Ciros.

Thank you. This morning, we issued a press release announcing our first quarter 2022 financial results and a broader business update. The release is available on the investors and media section of Cirrus's website at www.cirrus.com. We will begin the call with prepared remarks by Dr. Nancy Simonian, our chief executive officer, and Jason Haas, our chief financial officer. We will then open the call for questions. Dr. David Roth, our Chief Medical Officer, Kristen Stevens, our Chief Development Officer, Dr. Eric Olson, our Chief Scientific Officer, and Conley Chee, our Chief Commercial 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 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 and our quarterly report on Form 10-Q for the first quarter that we filed this morning and any other filings that we may make with the SEC in the future. Any forward-looking statements made on this call representing 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, Courtney. Good morning, everyone, and thank you for joining us. The first quarter of 2022 was very productive for Cirrus. as our team continued to execute against our goal of discovering and developing small molecule medicines for patients with cancer and monogenic diseases. We are very excited about the upcoming months, as we expect to have important clinical data readouts. To start off, our select MDS-1 Phase III clinical trial of temiberitine and higher-risk MDS continues to be on track, and we look forward to reporting our pivotal data in late 2023 or early 2024, giving us the potential to file a new drug application with the FDA in 2024. Tamiberitone has the potential to set a new treatment paradigm for the approximately 30% of RARA-positive higher-risk MDS patients by offering them a convenient oral therapy that can deliver high complete response rates without sacrificing safety or tolerability. Despite successful advancements in blood cancers more broadly, MDS has largely lagged behind in drug development. Hypomethylene agents, or HMAs, remain the existing standard of care while providing limited efficacy. And aside from HMAs, no new therapies have been approved in over a decade. We believe tamiberitine has the potential to be the first therapy for a targeted population in high-risk MDS and has the opportunity to change the standard of care. We are also looking forward to providing safety and clinical activity data from the safety lead-in portion of the select AML1 trial of tamiberitine in the second half of this year. The Phase II trial will be evaluating tamiberitine combined with venetoclax and azacitabine compared to venetoclax and azacitin alone, which is the standard of care. We believe tamiviratine has the potential to deliver a significant benefit to the approximately 30% of newly diagnosed unfit AML patients who are RARA positive. Our translational and clinical data support the potential for the RARA biomarker to enrich for patients more likely to respond to tamiviratine and for whom the standard of care may be suboptimal. So we are excited about tamiberitine's potential, and expected data from our select AML1 trial will provide key insights into the safety, efficacy, and compatibility of tamiberitine and azacytidine and venetoclax. Additionally, we expect to provide pharmacokinetic and safety data mid-year from our dose confirmation study of 2101 in APL. As announced today, given the current market conditions, We do not intend to advance 2101 into a Phase III trial until we have secured additional capital. However, we remain confident in the 2101 program. We believe it has the potential to replace the standard of care for APL patients by offering a significantly reduced treatment burden and increased access to therapy without sacrificing clinical benefit. We also plan to announce safety, and clinical activity data from the safety-leading portion of the 5609 trial in relapsed pancreatic cancer in the second half of 2022. The 5609 pancreatic expansions are designed to establish proof-of-concept in combination with chemotherapy using a doublet regimen of 5609 and gemcitabine and a triplet regimen of 5609, gemcitabine, and abraxane. By exploring both the doublet and triplet regimens, we believe this will deepen our understanding of the combination tolerability profile as well as clinical activity while maximizing the opportunity in an area of high unmet need. Currently, the only approved agent for second-line pancreatic cancer is Onavid plus 5-FU-leucovorin, which offers progression-free survival of just three months. We believe 5609 in pancreatic cancer represents a large market opportunity and has the potential to make a big difference in these patients' lives. As a reminder, in the Phase I dose escalation, 5609 showed promising clinical activity with good tolerability as a single agent in heavily pretreated patients, most notably in patients with pancreatic cancer and with K-resputations, including prolonged stable disease, along with tumor shrinkage and tumor marker reductions. We believe this single-agent activity is clinically important, and coupled with our preclinical data, which showed regressions in KRAS mutant models and potentiation of gemcitabine antitumor activity, sets the stage for our current approach of evaluating 5609 in combination with chemotherapy. We look forward to sharing safety data and the initial clinical activity data from the trials at the time of the data readout. At the upcoming ASCO and EHA conferences, we are looking forward to sharing trial-in-progress abstracts detailing the designs of our 5609 trial in pancreatic cancer, our select MDS-1 trial, and our select AML-1 trial. As announced this morning, given the current market environment, we are deep prioritizing the development of 5609 in hematologic malignancies at this time. We continue to believe that 5609 has the potential to make a transformative impact on patients with many difficult-to-treat tumors. Beyond the work we are doing in pancreatic cancer, we are also pursuing the development of 5609 in BRAF mutant colorectal cancer, or CRC. Based on the agreement we entered into with Roche in August of last year, 5609 in combination with atezolizumab is being explored in patients with BRAF mutant CRC. Under the terms of the agreement, we are supplying 5609 for a combination dosing cohort in the Roche-sponsored ongoing phase 1, 1B intrinsic trial. This arm of the study is expected to be open for enrollment in the first half of 2022. The milestones expected this year and beyond will help inform next steps for each of our programs and will provide insights on the potential of our investigational medicines to change the standard of care for patients. Finally, turning to our gene control discovery engine. In April at AACR, we presented a poster on our selective CDK12 inhibitor program, detailing the potency, selectivity, and antitumor activity of one of our lead compounds. This CDK12 inhibitor impaired DNA repair, caused cell cycle dysregulation and genomic instability, leading to tumor growth inhibition and apoptosis as a single agent in preclinical models. Additionally, this CDK12 inhibitor induced tumor regressions in small cell lung and breast cancer in vivo models and demonstrated activity in combination with lorbinuctin in a small cell lung model as well as Olaparib, showing anti-tumor activity and a PARP inhibitor-resistant patient-derived xenograft model of ovarian cancer. Taken together, these data support our belief that CDK12 inhibition could play a key role in the treatment of breast, lung, and ovarian cancer. We look forward to naming a development candidate from our CDK12 program in the second half of the year. We are confident that our clinical pipeline, which is focused on advancing our ongoing phase two and three trials of Tamivaratine for AML and MDS respectively, our dose confirmation trial of 2101 in APL, as well as our 5609 trial in pancreatic cancer, will allow us to provide benefit to patients and maximize value for our company and our shareholders. We look forward to executing on our near-term value drivers and continuing to work towards achieving our mission of making a profound difference in patients' lives. I will now turn the call over to Jason to review our financial results.