Tamibarotene

KYOTO, Japan, May 28, 2024 /PRNewswire/ -- Rege Nephro CO., Ltd. () has announced that patient enrollment began in April for the second stage of its Phase II clinical trial of tamibarotene as a developmental product for the treatment of autosomal dominant polycystic kidney disease (ADPKD) under the code RN-014. After reviewing all available safety data from the first stage, which started in December of last year, the decision was made to advance to the second stage. The company aims to complete patient enrollment by the end of 2024. Public Clinical Trial Information jRCT (Japan Registry of Clinical Trials): A system for the submission and publication of clinical research () ClinicalTrials.gov: A public website provided by the U.S. National Library of Medicine () Tolvaptan is the only approved drug for the treatment of ADPKD. Since the launch of tolvaptan, pharmaceutical companies worldwide have been developing numerous clinical trials of new drugs to treat ADPKD, but most of these drugs have already been discontinued due to inefficacy, highlighting the strong need for new treatment options. RN-014 is currently at the most advanced stage of development among the drugs in development for patients with ADPKD. About ADPKD Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease. It is characterized by the gradual development and enlargement of multiple cysts in both kidneys, leading to progressive renal dysfunction. Cysts can also occur in the liver and pancreas, and vascular abnormalities throughout the body are common, including high blood pressure, cerebral aneurysms, and heart valve abnormalities. Currently, tolvaptan, which inhibits cyst growth, is the only approved treatment for ADPKD, but there is no curative treatment available. About RN-014 Tamibarotene, under development for ADPKD, is a retinoic acid receptor (RAR) agonist expected to potently inhibit cyst formation and improve renal function. The clinical trial dose identified in multiple mouse model experiments is 4mg/day, and its safety has been confirmed in past studies. With advice from the Pharmaceuticals and Medical Devices Agency (PMDA), the Phase II clinical trial began in December 2023. This trial includes a pharmacokinetic (PK) phase and a randomization phase. Various safety measures have been established, including phased patient enrollment, periodic independent safety monitoring, strict criteria for dose reduction and discontinuation of the investigational drug, and criteria for discontinuation of the entire trial. About Rege Nephro CO., Ltd. Rege Nephro CO., Ltd. is a clinical-stage biotech company utilizing induced pluripotent stem cell (iPSC)-based technology from the Center for iPS Cell Research and Application (CiRA), Kyoto University. It is developing therapeutics and cell therapy for kidney, liver, and pancreas diseases. Media Inquiries: Katsuhisa Yamaguchi, CFO Rege Nephro CO., Ltd. TEL: 075-744-6858 E-mail: [email protected] SOURCE Rege Nephro CO., Ltd.

– Passed Interim Futility Analysis of the Primary Endpoint in Phase 3 SELECT-MDS-1 Trial of Tamibarotene; Pivotal CR Data Expected by Mid-4Q 2024; Company to Host HR-MDS-focused Webcast Event with Medical Experts on June 25, 2024 – – Received FDA Fast Track Designation for Tamibarotene for the Treatment of Unfit AML; Additional Data from SELECT-AML-1 Phase 2 Trial Expected in 3Q24 – -- Management to Host Conference Call at 8:30 AM ET Today – CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, today reported financial results for the quarter ended March 31, 2024 and provided a corporate update. “In 2024, we are acutely focused on execution across clinical and pre-commercial activities as we advance tamibarotene toward critical milestones, including additional data from the Phase 2 SELECT-AML-1 trial in the third quarter and pivotal CR data from the Phase 3 SELECT-MDS-1 trial in the fourth quarter,” said Conley Chee, Chief Executive Officer of Syros. “We are particularly pleased to share today that an independent data monitoring committee recently completed a pre-specified interim futility analysis on 50% of the patients enrolled in the SELECT-MDS-1 trial to support our primary endpoint analysis, and recommended that our study continue without modification. This recommendation, together with the FDA’s decision to grant Fast Track Designation to tamibarotene in AML, reinforces our confidence in the potential for our RARα agonist to offer improved clinical outcomes to HR-MDS and AML patients with RARA gene overexpression, supported by our belief that tamibarotene has a differentiated safety pro suited for use in these patients.” Mr. Chee continued, “In addition, following the completion of enrollment in the first quarter of 2024 of the 190 patients necessary for our primary endpoint analysis in the Phase 3 SELECT-MDS-1 trial, we have begun preparing for our first New Drug Application filing and subsequent launch in the United States. We look forward to engaging further with the medical community to drive awareness of tamibarotene and the companion diagnostic to identify RARA overexpression in patients with higher-risk MDS, as we work to deliver tamibarotene as the new frontline standard-of-care for patients with RARA overexpression.” Syros today announced plans to host a webcast event on June 25, 2024 to discuss disease biology and the current treatment landscape in HR-MDS, as well as the design of the ongoing pivotal Phase 3 SELECT-MDS-1 trial and opportunity for tamibarotene. The event will feature presentations from medical experts, in addition to Syros management. The event will be webcast live on the Investors & Media section of Syros’ website, . More details for the event are forthcoming. UPCOMING MILESTONES Report pivotal complete response (CR) data from the SELECT-MDS-1 Phase 3 trial in newly diagnosed HR-MDS patients with RARA gene overexpression by the middle of the fourth quarter of 2024. Report clinical activity and tolerability data from a prespecified analysis of over 40 patients from the SELECT-AML-1 Phase 2 trial in unfit AML patients with RARA overexpression in the third quarter of 2024. RECENT PIPELINE HIGHLIGHTS In March, the Phase 3 SELECT-MDS-1 clinical trial of tamibarotene passed a pre-specified interim futility analysis based on the CR rate, which was conducted by an Independent Data Monitoring Committee (IDMC). There were no concerning safety signals noted in the analysis and the IDMC recommended SELECT-MDS-1 continue without modification. Syros remains blinded to the data. In April, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to tamibarotene in combination with venetoclax and azacitidine for the treatment of newly diagnosed AML with RARA overexpression, as detected by an FDA approved test in adults who are over age 75 and who have comorbidities that preclude the use of intensive induction chemotherapy. The FDA previously granted this designation to tamibarotene in combination with azacitidine for the treatment of adults with HR-MDS and RARA overexpression in January 2023. First Quarter 2024 Financial Results The Company did not recognize any revenue in the first quarter of 2024, as compared to $3.0 million for the first quarter of 2023. The decrease reflects the termination of Syros’ collaboration agreement with Pfizer. Research and development (R&D) expenses were $24.7 million for the first quarter of 2024, as compared to $28.8 million for the first quarter of 2023. The decrease was primarily due to the reduction in external R&D consulting, contract manufacturing, and a reduction in headcount and related expenses. General and administrative (G&A) expenses were $6.3 million for the first quarter of 2024, as compared to $7.4 million for the first quarter of 2023. The decrease was primarily due to a reduction of headcount and related expenses, consulting fees, and facilities expenses. For the first quarter of 2024, Syros reported a net loss of $3.7 million, or $0.10 per share, compared to a net loss of $23.8 million, or $0.85 per share, for the same period in 2023. Cash and Financial Guidance On May 9, 2024, the Company agreed to amend its Loan Agreement with Oxford Finance LLC. The amendment will increase the amount of term loans available to Syros from $40 million to $100 million with tranches totaling $40.0 million in the aggregate becoming available upon the achievement of certain clinical development, regulatory and equity-raising milestones, and $20.0 million becoming available at Oxford's discretion. In addition, Oxford will extend the interest only period from September 1, 2024 to November 1, 2025 with further extensions to as late as November 1, 2026 upon achievement of certain milestones. Cash, cash equivalents and marketable securities as of March 31, 2024, were $108.3 million, as compared with $139.5 million as of December 31, 2023. Based on its current plans and the recently executed amendment with Oxford, Syros believes that its existing cash, cash equivalents and marketable securities will be sufficient to fund its anticipated operating expenses and capital expenditure requirements into the third quarter of 2025, beyond pivotal Phase 3 data from the SELECT-MDS-1 trial and additional data from the randomized portion of the SELECT-AML-1 trial. Conference Call and Webcast Syros will host a conference call today at 8:30 a.m. ET to discuss the first quarter 2024 financial results and provide a corporate update. To access the live conference call, please dial (800) 549-8228 (domestic) or (289) 819-1520 (international) and refer to conference ID 16518. A webcast of the call will also be available on the Investors & Media section of the Syros website at . An archived replay of the webcast will be available for approximately 30 days following the presentation. About Syros Pharmaceuticals Syros is committed to developing new standards of care for the frontline treatment of patients with hematologic malignancies. Driven by the motivation to help patients with blood disorders that have largely eluded other targeted approaches, Syros is developing tamibarotene, an oral selective RARα agonist in frontline patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia with RARA gene overexpression. For more information, visit and follow us on Twitter (@SyrosPharma) and LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including without limitation statements regarding Syros’ clinical development plans, the progression of its clinical trials, the timing to report clinical data, the ability to commercialize tamibarotene and deliver benefit to patients, and the sufficiency of Syros’ capital resources to fund its operating expenses and capital expenditure requirements into the second quarter of 2025. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including Syros’ ability to: advance the development of its programs under the timelines it projects in current and future clinical trials; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; sustain the response rates and durability of response seen to date with its drug candidates; successfully develop a companion diagnostic test to identify patients with the RARA biomarker; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the caption “Risk Factors” in Syros’ Annual Report on Form 10-K for the year ended December 31, 2023 and Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, each of which is on the Securities and Exchange Commission; and risks described in other filings that Syros makes with the Securities and Exchange Commission in the future. Financial Tables Syros Pharmaceuticals, Inc. Selected Condensed Consolidated Balance Sheet Data (in thousands) (unaudited) March 31, 2024 December 31, 2023 Cash, cash equivalents and marketable securities (current and noncurrent) $ 108,304 $ 139,526 Working capital1 74,899 108,299 Total assets 134,728 168,174 Total stockholders’ equity 15,057 16,662 (1) The Company defines working capital as current assets less current liabilities. See the Company’s condensed consolidated financial statements for further details regarding its current assets and current liabilities. Syros Pharmaceuticals, Inc. Condensed Consolidated Statement of Operations (in thousands, except share and per share data) (unaudited) Three Months Ended March 31, 2024 2023 Revenue $ — $ 2,954 Operating expenses: Research and development 24,655 28,761 General and administrative 6,266 7,405 Total operating expenses 30,921 36,166 Loss from operations (30,921 ) (33,212 ) Interest income 1,546 1,775 Interest expense (1,307 ) (1,217 ) Change in fair value of warrant liabilities 26,974 8,865 Net loss applicable to common stockholders $ (3,708 ) $ (23,789 ) Net loss per share applicable to common stockholders - basic and diluted $ (0.10 ) $ (0.85 ) Weighted-average number of common shares used in net loss per share applicable to common stockholders - basic and diluted 38,978,046 27,842,218