Core Insights - Rege Nephro Co., Ltd. has successfully acquired Tamibarotene-related clinical and non-clinical assets from Syros Pharmaceuticals, enhancing its operational capabilities for clinical trials in the United States [1][3] - Tamibarotene (RN-014) is currently in a Phase 2 clinical trial in Japan for autosomal dominant polycystic kidney disease (ADPKD), with plans to initiate trials in the U.S. following efficacy and safety confirmation [2][5] - The acquisition includes critical data and contracts that will streamline Rege Nephro's clinical trial operations [3] Company Overview - Rege Nephro, founded in 2019, is a clinical-stage biotech company focused on developing therapeutics and cell therapies for kidney, liver, and pancreas-related diseases [4] - The company leverages technology based on research from Prof. Kenji Osafune at Kyoto University [4] Product Information - RN-014 is a retinoic acid receptor (RAR) agonist aimed at suppressing cyst formation and improving renal function in ADPKD patients [5] - The Phase 2 clinical trial for RN-014 began in December 2023, with the second stage enrollment completed and no significant safety concerns reported [5]

Core Viewpoint - Syros Pharmaceuticals' shares dropped 86.9% following the failure of its late-stage study of tamibarotene for treating higher-risk myelodysplastic syndrome (HR-MDS), which did not meet the primary endpoint of complete response (CR) rate [1][2]. Group 1: Study Results - The phase III SELECT-MDS-1 study evaluated tamibarotene in combination with azacitidine in newly diagnosed HR-MDS patients, showing a CR rate of 23.8% in the treatment arm compared to 18.8% in the placebo arm, failing to demonstrate statistical significance [2]. - Despite the disappointing CR rates, the combination treatment was reported to be well-tolerated among the enrolled HR-MDS patients, with treatment-related adverse events similar to previous studies [3]. Group 2: Company Impact - Following the study's failure, Syros has decided to halt the HR-MDS study and will conduct a thorough review of the clinical data to determine next steps, marking a significant setback for the company as it now lacks a pipeline candidate [3]. - This incident follows another setback in August 2024, when Syros discontinued enrollment in a mid-stage acute myeloid leukemia (AML) study of tamibarotene due to poor interim results [4]. Group 3: Financial Performance - Year to date, Syros shares have plummeted 95.4%, contrasting sharply with the industry’s decline of 3.8% [3]. - The failure of the SELECT-MDS-1 study to meet its primary endpoint has been classified as an event of default under Syros' secured loan facility with Oxford Finance [3].

Core Insights - Syros Pharmaceuticals Inc's SELECT-MDS-1 Phase 3 trial of tamibarotene did not meet its primary endpoint of complete response rate in patients with higher-risk myelodysplastic syndrome [1][3] - The trial involved tamibarotene in combination with azacitidine, showing a complete response rate of 23.8% in the treatment arm versus 18.8% in the control arm, which was not statistically significant [2] - The failure of the trial constitutes an event of default under the company's secured loan facility with Oxford Finance [3] Company Response - The CEO of Syros expressed disappointment over the trial outcome and indicated plans to stop the study and review clinical data for future steps [4] - The company previously discontinued enrollment in the SELECT-AML-1 Phase 2 trial due to low probability of success in demonstrating superiority [4][5] Market Impact - Following the trial results, Syros stock experienced a significant decline of 86.43%, trading at 37 cents [5]

Revenue and Financial Performance - The company has not generated any revenue from product sales and does not expect to do so for the foreseeable future, with collaboration revenue of $3.8 million and $9.6 million recognized for the three and nine months ended September 30, 2023, respectively [126]. - Revenue for the three months ended September 30, 2024 was $0, a decrease of 100% compared to $3.8 million for the same period in 2023 [141]. - For the nine months ended September 30, 2024, revenue was $0, a decrease of 100% compared to $9.6 million for the same period in 2023 [150]. - Interest income for the nine months ended September 30, 2024 was $3.4 million, a decrease of 38% compared to $5.5 million in 2023 [149]. - The change in fair value of warrant liabilities resulted in a gain of $51.7 million for the nine months ended September 30, 2024, compared to a loss of $77,000 in the same period in 2023 [149]. - The company reported a net cash used in operating activities of $81.5 million for the nine months ended September 30, 2024, a decrease from $91.1 million in the same period of 2023, primarily due to a reduction in losses from operations [167]. Research and Development - Research and development expenses for the three months ended September 30, 2024, totaled $20.5 million, a decrease from $28.3 million for the same period in 2023 [131]. - The company expects significant research and development expenses as it advances the clinical development of tamibarotene [131]. - Research and development expenses for the nine months ended September 30, 2024 decreased by approximately $19.5 million, or 23%, from $86.7 million in 2023 to $67.1 million [151]. - The SELECT-MDS-1 Phase 3 clinical trial for tamibarotene in HR-MDS patients with RARA overexpression is expected to report pivotal complete response data in mid-November 2024 [122]. - The company completed enrollment of 190 patients necessary for the primary endpoint analysis in the SELECT-MDS-1 trial in Q1 2024 [122]. - The SELECT-AML-1 Phase 2 clinical trial was discontinued based on interim analysis results [123]. - The FDA granted Fast Track Designation to tamibarotene in combination with azacitidine for newly diagnosed HR-MDS patients with RARA overexpression in January 2023 [122]. Market Opportunity - Approximately 9,000 HR-MDS patients are diagnosed in the United States each year, with a total market opportunity for HR-MDS therapeutics projected to be $1.6 billion by 2029 [121]. - The total United States market opportunity for tamibarotene in HR-MDS patients with RARA overexpression is projected to exceed $800 million by 2029 [121]. Expenses and Losses - General and administrative expenses decreased by approximately $2.1 million, or 27%, from $7.8 million in Q3 2023 to $5.7 million in Q3 2024 [144]. - Total operating expenses decreased by approximately $12.2 million, or 32%, from $38.4 million in Q3 2023 to $26.2 million in Q3 2024 [141]. - Net loss for the three months ended September 30, 2024 was $6.4 million, a significant improvement of 84% compared to a net loss of $40.1 million in Q3 2023 [141]. - General and administrative expenses for the nine months ended September 30, 2024 decreased by approximately $5.0 million, or 22%, from $22.4 million in 2023 to $17.4 million [153]. Cash and Funding - As of September 30, 2024, the company had cash and cash equivalents of approximately $58.3 million and an accumulated deficit of $756.2 million [175]. - The company expects to incur significant expenses related to the clinical development of tamibarotene and may require additional funding to support ongoing operations [170]. - The company has a total of $203.6 million of securities available for future issuance under the 2023 Registration Statement as of September 30, 2024 [164]. - The company issued and sold 350,000 shares of common stock for gross proceeds of $1.4 million during the year ended December 31, 2023, under the 2023 sales agreement [161]. - The company anticipates that its cash and cash equivalents will fund its expenses into the third quarter of 2025 [170]. - The company incurred a net cash used in financing activities of $0.2 million during the nine months ended September 30, 2024, compared to a net cash provided of $0.1 million in the same period of 2023 [169]. Risks and Concerns - The company has significant losses and negative cash flows from operations, raising substantial doubt about its ability to continue as a going concern for at least 12 months [178]. - Plans to mitigate liquidity risk include raising additional capital through equity or debt financings and potentially selling SY-2101-related assets [178]. - The company is exposed to market risk related to interest rate sensitivity, but a 10% change in market interest rates is not expected to materially impact its financial condition [179]. - The company contracts with vendors in Asia and Europe, exposing it to foreign currency exchange rate fluctuations, but does not currently hedge this risk [180]. - As of September 30, 2024, the company did not have significant liabilities denominated in foreign currencies [180]. - Inflation has increased costs related to labor and clinical trials, but it did not have a material effect on the company's financial condition during the nine months ended September 30, 2024 and 2023 [181].

Core Viewpoint - Syros Pharmaceuticals, Inc. is under investigation for potential claims related to its decision to discontinue enrollment in a key clinical trial for acute myeloid leukemia treatment, which may impact investor confidence and stock performance [1][2]. Investigation Details - On August 12, 2024, Syros announced the discontinuation of enrollment in the SELECT-AML-1 Phase 2 clinical trial evaluating a triplet regimen of tamibarotene, venetoclax, and azacitidine for newly diagnosed, unfit patients with acute myeloid leukemia (AML) and RARA gene overexpression [2]. - The decision was based on a prespecified interim analysis indicating a low probability of demonstrating superiority at the final analysis [2]. Next Steps - Investors who purchased Syros securities and have relevant information are encouraged to assist the investigation by visiting the law firm's website or contacting their representatives [3]. Legal Representation - Bronstein, Gewirtz & Grossman, LLC operates on a contingency fee basis, meaning they will only seek reimbursement for expenses and attorneys' fees if successful in recovering funds for investors [4]. Firm Background - Bronstein, Gewirtz & Grossman, LLC is a nationally recognized firm specializing in securities fraud class actions and has recovered hundreds of millions of dollars for investors across the nation [5].

Core Viewpoint - Syros Pharmaceuticals' shares dropped 61.7% after the company halted enrollment in the mid-stage acute myeloid leukemia (AML) study of tamibarotene due to poor interim analysis results [1][4]. Group 1: Study Details - The phase II SELECT-AML-1 study evaluated tamibarotene in combination with AbbVie's Venclexta and azacitidine against a doublet regimen of Venclexta and azacitidine in newly diagnosed, unfit AML patients with RARα gene overexpression [2]. - Data from 51 patients were analyzed, including a planned futility analysis of the first 40 randomized patients who had received approximately three months of treatment or had discontinued it [3]. - The study found similar complete response (CR) rates of 65% for the triplet therapy and 70% for the doublet therapy, leading to the conclusion that the likelihood of demonstrating superiority at the final analysis is low [4]. Group 2: Financial Impact - Year to date, Syros shares have declined 75.4%, while the industry has seen a 2.4% decline [4]. - Tamibarotene was reported to be well-tolerated, with no new safety signals identified, and patients already enrolled can opt to remain in the study [5]. Group 3: Future Focus - Following the discontinuation of the AML study, Syros will concentrate on the pivotal phase III SELECT-MDS-1 study, which is evaluating tamibarotene in combination with azacitidine compared to azacitidine monotherapy for higher-risk myelodysplastic syndrome patients [6]. - The SELECT-MDS-1 study has passed a prespecified futility analysis, and pivotal CR data is expected to be shared by mid-fourth quarter of 2024 [7]. Group 4: AbbVie and Venclexta - AbbVie's Venclexta generated revenues of $1.25 billion in the first half of 2024, reflecting a 16% growth driven by strong demand in AML and chronic lymphocytic leukemia (CLL) indications [9]. - AbbVie anticipates Venclexta's peak revenues to approach $5 billion, with ongoing studies to expand its label into other hematologic malignancies [8].

Core Viewpoint - Syros Pharmaceuticals, Inc. (SYRS) has experienced a significant decline of 70.6% in its stock price over the past four weeks, but it is now in oversold territory, suggesting a potential turnaround as analysts expect better earnings than previously predicted [1]. Group 1: Stock Performance and Technical Indicators - The stock's Relative Strength Index (RSI) reading is at 20.05, indicating that the heavy selling pressure may be exhausting, which could lead to a price rebound [5]. - A stock is generally considered oversold when its RSI falls below 30, making the current RSI reading a potential signal for investors to look for entry opportunities [2][3]. Group 2: Earnings Estimates and Analyst Consensus - Over the last 30 days, the consensus earnings per share (EPS) estimate for SYRS has increased by 3.2%, indicating a positive trend in earnings revisions that typically correlates with price appreciation [5]. - SYRS holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate revisions and EPS surprises, further supporting the potential for a turnaround [6].

Core Viewpoint - Syros Pharmaceuticals is discontinuing enrollment in its SELECT-AML-1 Phase 2 clinical trial due to interim analysis results indicating that the trial is unlikely to meet its primary endpoint [1][2]. Group 1: Clinical Trial Update - The SELECT-AML-1 Phase 2 clinical trial was assessing the effectiveness of tamibarotene in combination with venetoclax and azacitidine for treating acute myeloid leukemia (AML) patients with RARA gene overexpression [2]. - Data from 51 patients showed similar complete response rates when compared to the treatment using only venetoclax and azacitidine, suggesting limited efficacy of the combination therapy [2]. Group 2: Stock Market Reaction - Following the clinical trial update, Syros Pharmaceuticals' stock is down 62.3% as of Tuesday morning, and it has decreased 36.1% year-to-date as of the previous market close [3]. - The trading volume for SYRS stock has significantly increased, with nearly 1 million units traded, compared to the daily average of about 118,000 shares [3].

Financial Data and Key Metrics Changes - The company did not recognize revenue in Q2 2024, compared to $2.8 million in Q2 2023, reflecting the termination of a collaboration agreement with Pfizer [36] - R&D expenses decreased to $22 million in Q2 2024 from $29.6 million in Q2 2023, primarily due to reduced external R&D consulting and headcount [37] - G&A expenses were $5.5 million in Q2 2024, down from $7.2 million in Q2 2023, attributed to headcount reductions and lower consulting expenses [38] - The net loss for Q2 2024 was $23.3 million or $0.59 per share, compared to a net loss of $36.3 million or $1.30 per share in the same period of 2023 [38] - Cash, cash equivalents, and marketable securities as of June 30, 2024, were $79 million, down from $108.3 million as of March 31, 2024, expected to fund operations into Q3 2025 [39] Business Line Data and Key Metrics Changes - The company is focusing on the advancement of tamibarotene for higher-risk MDS and AML patients, with ongoing trials showing promising results [44][45] - SELECT-MDS-1 trial is evaluating tamibarotene in combination with azacitidine, with a primary efficacy endpoint of complete response in the first 190 enrolled patients [28] Market Data and Key Metrics Changes - Approximately 50% of MDS and 30% of AML patients are positive for RARA overexpression, representing significant market opportunities for tamibarotene [19] - The company plans to commercialize tamibarotene in the U.S. through its own efforts, while considering partnerships for European markets due to fragmentation [61] Company Strategy and Development Direction - The company aims to establish tamibarotene as a new standard of care for higher-risk MDS and AML patients, addressing significant unmet needs in these diseases [43] - The focus is on preparing for NDA filing and launch, with a strong emphasis on commercialization plans and launch readiness activities [18][26] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming data readouts for tamibarotene in AML and higher-risk MDS patients, with pivotal data expected in Q4 [27][80] - The company is being judicious with expenses, indicating a new run rate relative to previous years [53] Other Important Information - The SELECT-AML-1 trial is evaluating tamibarotene in newly diagnosed unfit AML patients, with initial data showing a 100% CR/CRi rate in a small cohort [34] - The company hosted a webinar with medical experts discussing the potential of tamibarotene to transform the standard of care for higher-risk MDS patients [31] Q&A Session Summary Question: What is the timeline for advancing tamibarotene into pivotal studies in AML? - Management indicated that the data from 40 patients in September will be crucial for decision-making, but full data from all 80 patients will provide a clearer picture [40][60] Question: What are the commercialization plans for Europe? - The company plans to license or find a partner in Europe due to the fragmented market, while focusing on U.S. commercialization [61] Question: Were the reduced expenses in Q2 due to timing or cost-cutting initiatives? - Management confirmed that the reduced expenses reflect a new run rate, with minor cost-cutting initiatives contributing to the decrease [62]

Revenue Generation - The company has not generated any revenue from product sales and does not expect to do so for the foreseeable future, with no revenue recognized during the three and six months ended June 30, 2024 [124]. - For the three and six months ended June 30, 2023, the company recognized revenue of $2.8 million and $5.8 million, respectively, from a collaboration with Global Blood Therapeutics, which was terminated in October 2023 [124]. - Total revenue for the three months ended June 30, 2024 was $0, a decrease of $2.8 million or 100% compared to $2.8 million in the same period of 2023 [138]. - The company did not recognize any revenue during the six months ended June 30, 2024, compared to $5.8 million in revenue for the same period in 2023 [147]. Clinical Trials and Research - The SELECT-MDS-1 trial is evaluating tamibarotene in combination with azacitidine in newly diagnosed HR-MDS patients with RARA overexpression, with a total of approximately 550 patients enrolled to assess overall survival as a key secondary endpoint [118]. - In the SELECT-AML-1 trial, the CR/CRi rate was 100% among response evaluable patients treated with tamibarotene, venetoclax, and azacitidine, compared to 70% in the control arm [120]. - The median time to CR/CRi response was 21 days for the triplet arm, compared to 25 days for the control arm [120]. - The FDA granted Fast Track Designation to tamibarotene in combination with azacitidine for the treatment of adults with newly diagnosed HR-MDS who are positive for RARA overexpression [118]. - The company completed enrollment of 190 patients necessary to support the primary endpoint analysis for the SELECT-MDS-1 trial in the first quarter of 2024 [118]. - The company anticipates reporting pivotal CR data from the SELECT-MDS-1 trial by the middle of the fourth quarter of 2024 [118]. Financial Performance - Research and development expenses decreased by approximately $7.7 million, or 26%, from $29.6 million in Q2 2023 to $21.9 million in Q2 2024 [139]. - General and administrative expenses decreased by approximately $1.7 million, or 24%, from $7.2 million in Q2 2023 to $5.5 million in Q2 2024 [142]. - Net loss for the three months ended June 30, 2024 was $23.3 million, a decrease of $12.9 million or 36% compared to a net loss of $36.3 million in Q2 2023 [137]. - Total operating expenses for the six months ended June 30, 2024 were $58.3 million, a decrease of $14.7 million or 20% compared to $73.0 million in the same period of 2023 [146]. - Interest income for the three months ended June 30, 2024 was $1.1 million, a decrease of $1.0 million or 49% compared to $2.1 million in Q2 2023 [137]. - Change in fair value of warrant liabilities resulted in a gain of $4.4 million for the three months ended June 30, 2024, compared to a loss of $3.1 million in Q2 2023, representing a change of $7.5 million or 241% [137]. - Research and development expenses for the six months ended June 30, 2024 totaled $46.6 million, down $11.8 million or 20% from $58.4 million in the same period of 2023 [146]. - General and administrative expenses decreased by approximately $2.9 million, or 20%, from $14.6 million for the six months ended June 30, 2023, to $11.7 million for the six months ended June 30, 2024 [149]. - Interest income decreased by approximately $2.0 million, or 6%, due to a lower average cash balance during the six months ended June 30, 2024, compared to the same period in 2023 [150]. Cash Flow and Liquidity - Net cash used in operating activities was $60.8 million during the six months ended June 30, 2024, compared to $59.3 million for the same period in 2023, reflecting an increase in net operating assets and liabilities [162]. - As of June 30, 2024, cash and cash equivalents were approximately $79.0 million [159]. - The company expects to incur significant expenses related to ongoing clinical trials and commercialization efforts for tamibarotene, necessitating substantial additional funding [166]. - As of June 30, 2024, $203.6 million of securities remained available for future issuance under the 2023 Registration Statement [158]. - The company issued shares resulting in gross proceeds of $45.0 million in December 2023, before deducting transaction costs [157]. - Interest expense increased due to a higher interest rate during the six months ended June 30, 2024, compared to the same period in 2023 [151]. - The company anticipates that its cash and cash equivalents will fund planned operating expenses into the third quarter of 2025 [167]. - As of June 30, 2024, the company had cash and cash equivalents of $79.0 million and an accumulated deficit of $749.8 million [171]. - The company has incurred significant net operating losses every year since inception and expects to continue incurring significant losses for at least the next several years [171]. - The company anticipates that its current cash and cash equivalents will meet liquidity requirements into the third quarter of 2025, but there is substantial doubt about its ability to continue as a going concern for at least 12 months from the issuance date of the financial statements [173]. - The company has plans to mitigate liquidity risks, including raising additional capital through equity or debt financings and reducing cash expenditures [173]. Market Risks - The company is exposed to market risk related to changes in interest rates, but an immediate 10% change in market interest rates is not expected to materially impact its financial condition [174]. - The company is also exposed to foreign currency exchange rate fluctuations due to contracts with vendors in Asia and Europe, but it does not currently hedge this risk [175]. - Inflation has increased the company's cost of labor and clinical trial costs, but it did not have a material effect on its business during the six months ended June 30, 2024 [176].