Category: 3. Business

  • PayrollOrg Webinar Highlights Need for Local Tax Automation

    In a recent PayrollOrg webinar titled “Local Payroll Taxes: The Practical Approach to Reducing Risk,” payroll professionals were given a detailed look at the growing complexity of local payroll tax compliance and the increasing need for automation. Held on July 23, 2025, the session featured Keegan Robinson, CPP, Head of Tax Research and Compliance at Symmetry, and Greg Lyon, Head of Product at Symmetry, who shared insights into how employers can better manage risk and streamline operations.

    Poll Results Reflect Cautious Optimism

    Despite the challenges, most webinar attendees expressed confidence in their current local tax processes. According to a live poll conducted at the start of the session, 85% of respondents said they felt either “somewhat confident” (59%) or “very confident” (26%) in the reliability and accuracy of their local tax assignment methods, though several acknowledged room for improvement. Only 9% indicated a lack of confidence, suggesting that while the majority are managing, there is still a clear opportunity for optimization—particularly through automation.

    A Growing Compliance Burden

    The presenters painted a picture of a rapidly evolving local tax landscape. Currently, 15 states impose local payroll taxes, with Pennsylvania alone accounting for more than 5,200 of the 6,296 local taxes nationwide. Ohio and Kentucky follow with over 1,000 and 280 local taxes, respectively. From July 2024 through June 2025, nearly 200 changes were made to local tax codes, including the introduction of 30 new taxes since the start of 2024.

    Robinson emphasized that the sheer volume and variability of local taxes—combined with the lack of a centralized data source—pose significant compliance challenges. Publicly available tools are often incomplete, and jurisdictions are increasingly modernizing their systems to enforce compliance more efficiently. This has raised the stakes for employers, who face penalties, amended returns, and reputational damage if they fail to get it right.

    Another live poll conducted during the webinar reinforced the scope of the compliance burden facing payroll teams. When asked to identify their biggest challenges in managing local payroll taxes, 59% of respondents selected all of the following: keeping up with frequent local tax law changes, ensuring address-level accuracy for remote and hybrid employees, managing the manual effort and time required, and correctly handling relocations and onboarding.

    The Case for Automation

    To address these challenges, Lyon advocated for automating local tax assignment. He explained that manual processes are not only time-consuming—taking up to 30 minutes per employee—but also prone to error. For companies onboarding thousands of employees annually, this can translate into thousands of hours lost. Automation, he argued, can eliminate these inefficiencies while improving accuracy and employee satisfaction.

    Four-Step Automation Process

    The webinar outlined a four-step automation process: triggering tax setup during onboarding or address changes, collecting residential and work addresses, determining applicable taxes using a technology partner, and updating the employee’s tax profile in the payroll system.

    Lyon stressed the importance of rooftop-level geolocation, noting that even buildings across the street from each other can fall under different taxing jurisdictions.

    What to Look for in a Compliance Tool

    Attendees were also advised on what to look for in a local tax compliance tool. Key features include plug-and-play API integration, transparent tax logic, auto-assignment capabilities, and downloadable audit trails. These tools not only ensure compliance but also provide peace of mind and audit readiness.

    The session concluded with a call to action for payroll teams to evaluate their current processes and consider modernizing their systems. As local tax regulations continue to evolve, the presenters stressed that automation is no longer a luxury—it’s a necessity.

     

    Take your tax and accounting research to the next level with Checkpoint Edge and CoCounsel. Get instant access to AI-assisted research, expert-approved answers, and cutting-edge tools like Advisory Maps and State Charts. Try it today and transform the way you work! Subscribe now and discover a smarter way to find answers.

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  • Tietoevry Create LT Joins Baltic Automotive Cluster (BACC)

    Tietoevry Create LT Joins Baltic Automotive Cluster (BACC)

    Tietoevry Create Lithuania, a leading digital engineering and software development organization within the global Tietoevry Group, is proud to announce that it has officially become a member of the Baltic Automotive Components Cluster (BACC) as of June 2025. This strategic step reflects the company’s commitment to long-term collaboration, innovation, and growth within the European automotive ecosystem.

    Founded in 2013, BACC is a business-driven cluster uniting experienced companies from Lithuania, Germany, and Sweden, operating across the entire automotive value chain. The cluster’s mission is to increase the global competitiveness of its members through joint initiatives, knowledge sharing, and innovation in manufacturing and engineering.

    Members of BACC offer capabilities in areas such as metal processing and forging, plastic injection moulding, cable harness production, tool design and manufacturing, electronics, as well as the development of drive systems, e-mobility charging solutions, advanced GPS tracking, anti-theft and recovery systems, and telematics technologies.

    Through this membership, Tietoevry Create Lithuania becomes part of a vibrant and interdisciplinary industrial ecosystem that exports over 90% of its production to leading automotive manufacturers (OEMs and Tier 1 suppliers) across Western, Northern, and Eastern Europe. The cluster not only fosters business connections and regional competitiveness but also promotes the visibility of the Lithuanian and Baltic automotive industries on the global stage.

    “We are excited to join BACC and contribute our digital and software competencies to a cluster of highly respected industrial and manufacturing companies. As the automotive sector undergoes fundamental transformation driven by connectivity, electrification, and software-defined vehicles, our role is to help accelerate this evolution by bringing scalable and secure software engineering into the core of product development”,  said  Jokūbas Savickas, Head of Business Development, Tietoevry Create Lithuania

     
    Tietoevry Create in Automotive
    As part of Tietoevry Create, the Lithuanian team brings deep experience in developing and scaling cutting-edge automotive solutions for the emerging reality of software-defined vehicles and smart mobility ecosystems:

    • Digital cockpit and modern infotainment platform development
    • Advanced automotive audio expertise for exceptional in-vehicle experience
    • High-quality embedded software
    • Component integration and quality assurance
    • Connected vehicles, fleet management & telematics solutions

    In Tietoevry Create we utilize our automotive software engineering services to deliver hands-on expertise, flexibility, and innovative solutions that accelerate our customers’ projects while ensuring high quality and compliance with industry standards. Our company supports OEMs, Tier 1 suppliers, and various participants in the automotive ecosystem across multiple domains throughout the entire Software Development Life Cycle (SDLC). By leveraging cross-domain expertise, we specialize in delivering tailored and comprehensive end-to-end, from chip to cloud solutions..

    About Tietoevry Create

    Tietoevry Create is the software and digital engineering arm of Tietoevry, delivering innovation and product development services to organizations worldwide. With expertise in AI, data, cloud, embedded software, and human-centered design, Tietoevry Create helps businesses bring future-ready digital products and services to life.
    In the automotive sector, Tietoevry Create partners with global OEMs, Tier1s, and technology companies to deliver secure, sustainable, and user-friendly software solutions that meet the demands of an increasingly digital and connected world.

    About Baltic Automotive Components Cluster (BACC)

    The Baltic Automotive Components Cluster (BACC) is a cross-border network of automotive-focused companies and organizations aimed at increasing the international competitiveness of its members. Founded in 2013, BACC unites a wide range of automotive-related competencies — from manufacturing and engineering to research, electronics, and mobility innovation — and works to position the Baltic region as a reliable, high-quality source of automotive solutions for the global market. As both a national association and an innovation cluster, BACC holds international memberships in the European Automotive Cluster Network (EACN) and the European Association of Automotive Suppliers (CLEPA), where it also holds a seat on the Board of Directors. This international presence enables BACC to contribute actively to shaping the future of the automotive supply chain in Europe.

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  • Trump deciding trade deals by Aug. 1, Commerce Secretary Lutnick says – Reuters

    1. Trump deciding trade deals by Aug. 1, Commerce Secretary Lutnick says  Reuters
    2. What’s in Trump’s trade agreement with Japan?  ABC News
    3. Uncertainty around US tariffs will not be over after August 1, even with signed trade deals  The Indian Express
    4. What is the status of US tariff negotiations?  France 24
    5. Where Do Trade Talks Stand? Who Hasn’t Got a Deal With the U.S. Yet?  The Wall Street Journal

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  • Investors are borrowing money to buy stocks at pace last seen in market bubbles

    Investors are borrowing money to buy stocks at pace last seen in market bubbles

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  • A Guide to Building Change Resilience in the Age of AI

    A Guide to Building Change Resilience in the Age of AI

    There’s near universal consensus that AI will fundamentally change how business is done, yet most organizations have not yet seen a substantive impact from their AI efforts. A BCG Global Survey of 1,000 CXOs in more than 20 sectors reports that just 26% of organizations have achieved value from AI, realizing an average cost savings of 45% and 60% higher revenue growth compared to peer firms.


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  • FiscalNote Files Preliminary Information Statement to…

    FiscalNote Files Preliminary Information Statement to…

    FiscalNote Holdings, Inc. (NYSE: NOTE) (“FiscalNote” or the “Company”), the leading provider of AI-driven policy and regulatory intelligence solutions, today announced that it has filed a preliminary information statement with the Securities and Exchange Commission (the “SEC”), providing notice that holders of over 67% of the voting power of its outstanding common stock have acted by written consent to authorize FiscalNote’s Board of Directors (the “Board”) to effect a reverse stock split at a ratio ranging from 1:2 to 1:15, in the Board’s discretion. The reverse stock split has been authorized in order to bring the company into compliance with the New York Stock Exchange (“NYSE”) continued listing standard requiring listed companies to maintain an average closing share price of at least $1.00 over a consecutive 30 trading-day period. The timing of the filing is driven by the October 10, 2025 deadline to regain compliance (the end of the 6-month cure period afforded by the NYSE) and takes into account the necessary steps to effect the split and regain compliance by that date. The Company plans to regain compliance and avoid delisting through either organic recovery of the stock price or, if necessary, a reverse split. In the event a reverse split becomes necessary, the final ratio will be determined by the Board when the Company files an amendment to its certificate of incorporation to implement the split. The split, if implemented, would not affect any shareholder’s percentage ownership interests or proportionate voting power.

    The Company and its advisors have reviewed select market precedents, and the Company believes that a reverse split may allow the Company’s common stock to be more attractive to a broader range of investors. Although numerous factors can influence post-split stock price performance (including macroeconomic and industry conditions, operating fundamentals, leverage ratio, and more), analysis of available market data suggests that effectuating a reverse split can have the following benefits:

    • Improving investor perception and driving demand by aligning the share price with public peers and institutional investment thresholds;

    • Ensuring continued compliance with NYSE listing standards, maintaining FiscalNote’s eligibility and visibility on major indices; and

    • Tightening bid-ask spreads and reducing order book congestion, which can facilitate trading in the stock and reduce volatility, thereby enhancing liquidity and potentially making the stock more attractive to long term investors.

    Shareholders may obtain a free copy of the preliminary proxy statement and other documents that the Company files with the SEC at the SEC’s website at www.sec.gov or on the Company’s Investor Relations website at https://investors.fiscalnote.com. The Company will file with the SEC and distribute to its shareholders a definitive information statement, following SEC review.

    Completion of the proposed reverse stock split is subject to market and other customary conditions. There are no assurances that the reverse stock split will be completed, that it will result in an increased per share price or that it will achieve its other intended effects. The Board reserves the right to elect not to proceed with the split if it determines that implementing it is no longer in the best interests of the Company and its shareholders.

    Safe Harbor Statement

    Certain statements in this press release may be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements generally relate to future events or FiscalNote’s future financial or operating performance. For example, statements regarding FiscalNote’s financial outlook for future periods, expectations regarding profitability, capital resources and anticipated growth in the industry in which FiscalNote operates are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “pro forma,” “may,” “should,” “could,” “might,” “plan,” “possible,” “project,” “strive,” “budget,” “forecast,” “expect,” “intend,” “will,” “estimate,” “anticipate,” “believe,” “predict,” “potential” or “continue,” or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other important factors that could cause actual results to differ materially from those expressed or implied by such forward-looking statements.

    Factors that may impact such forward-looking statements include:

    • concentration of revenues from U.S. government agencies, changes in the U.S. government spending priorities, dependence on winning or renewing U.S. government contracts, delay, disruption or unavailability of funding on U.S. government contracts, and the U.S. government’s right to modify, delay, curtail or terminate contracts;

    • FiscalNote’s ability to successfully execute on its strategy to achieve and sustain organic growth through a focus on its core Policy business, including risks to FiscalNote’s ability to develop, enhance, and integrate its existing platforms, products, and services, bring highly useful, reliable, secure and innovative products, product features and services to market, attract new customers, retain existing customers, expand its products and service offerings with existing customers, expand into geographic markets or identify other opportunities for growth;

    • FiscalNote’s future capital requirements, as well as its ability to service its repayment obligations and maintain compliance with covenants and restrictions under its existing debt agreements;

    • demand for FiscalNote’s services and the drivers of that demand;

    • the impact of cost reduction initiatives undertaken by FiscalNote;

    • risks associated with international operations, including compliance complexity and costs, increased exposure to fluctuations in currency exchange rates, political, social and economic instability, and supply chain disruptions;

    • FiscalNote’s ability to introduce new features, integrations, capabilities, and enhancements to its products and services, as well as obtain and maintain accurate, comprehensive, or reliable data to support its products and services;

    • FiscalNote’s reliance on third-party systems and data, its ability to integrate such systems and data with its solutions and its potential inability to continue to support integration;

    • FiscalNote’s ability to maintain and improve its methods and technologies, and anticipate new methods or technologies, for data collection, organization, and analysis to support its products and services;

    • potential technical disruptions, cyberattacks, security, privacy or data breaches or other technical or security incidents that affect FiscalNote’s networks or systems or those of its service providers;

    • competition and competitive pressures in the markets in which FiscalNote operates, including larger well-funded companies shifting their existing business models to become more competitive with FiscalNote;

    • FiscalNote’s ability to comply with laws and regulations in connection with selling products and services to U.S. and foreign governments and other highly regulated industries;

    • FiscalNote’s ability to retain or recruit key personnel;

    • FiscalNote’s ability to adapt its products and services for changes in laws and regulations or public perception, or changes in the enforcement of such laws, relating to artificial intelligence, machine learning, data privacy and government contracts;

    • adverse general economic and market conditions reducing spending on our products and services;

    • the outcome of any known and unknown litigation and regulatory proceedings;

    • FiscalNote’s ability to maintain public company-quality internal control over financial reporting; and

    • FiscalNote’s ability to protect and maintain its brands and other intellectual property rights.

    These and other important factors discussed in FiscalNote’s SEC filings, including its most recent reports on Forms 10-K and 10-Q, particularly the “Risk Factors” sections of those reports, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by FiscalNote and its management, are inherently uncertain. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place reliance on forward-looking statements, which speak only as of the date they are made. FiscalNote undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws.

    About FiscalNote

    FiscalNote (NYSE: NOTE) is the leading provider of AI-driven policy and regulatory intelligence solutions. By uniquely combining proprietary AI technology, comprehensive data, and decades of trusted analysis, FiscalNote helps customers efficiently manage political and business risk. Since 2013, FiscalNote has pioneered solutions that deliver critical insights, enabling effective decision-making and giving organizations the competitive edge they need. Home to PolicyNote, CQ, Roll Call, VoterVoice, and many other industry-leading products and brands, FiscalNote serves thousands of customers worldwide with global offices in North America, Europe, and Asia. To learn more about FiscalNote and its suite of solutions, visit FiscalNote.com and follow @FiscalNote.

     

    Contacts

    Media
    Yojin Yoon
    FiscalNote
    press@fiscalnote.com

    Investor Relations
    Bob Burrows
    FiscalNote
    IR@fiscalnote.com

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  • Great Lakes offshore wind could power the region and beyond

    Great Lakes offshore wind could power the region and beyond

    Offshore wind power could provide far more electricity than the U.S. uses for residential, commercial and industrial purposes. But the federal government has recently stopped approving offshore projects in the ocean.

    Another option is available, though: the Great Lakes, where we are based as water policy researchers, and where state agencies rather than federal officials are the trustees of the lakes. A January 2025 executive order from President Donald Trump attempts to stop all federal permits for offshore and onshore wind power pending a review of federal wind leasing and permitting practices.

    But the states, not the federal government, handle leases and permits for wind power on the Great Lakes, though federal agencies are involved in the overall process. It is unclear how this executive order might impede federal action, but at the very least states could lay the groundwork now to be prepared to act when the next shift in federal priorities arrives.

    A 2023 analysis from the National Renewable Energy Laboratory found that the Great Lakes states have enough offshore wind power potential to provide three times as much electricity as all eight Great Lakes states use currently, which would mean plenty left over to meet increasing demand or send power elsewhere in the country.

    States are looking for opportunities

    States have been forging their own paths separate from federal clean energy policy for decades. All eight Great Lakes states have state clean energy goals, and five of them – Illinois, Michigan, Minnesota, New York and Wisconsin – have a goal to achieve 100% clean or renewable energy by 2040 or 2050.

    The challenge is not just to transform the current energy supply. As transportation and other sectors electrify, that increases electricity demand. As artificial intelligence proliferates, tech companies need more and more electricity and water for their data centers. By 2028, data centers are projected to consume nearly 12% of the country’s total usage, which requires massive increases in production in the Great Lakes and other key locations.

    Companies and states are looking high and low to find enough electricity to meet the rising demand. They are extending the lives of coal-fired power plants and building new gas-fired power plants. Elon Musk’s xAI company has even been powering an artificial intelligence data center in Tennessee with massive generators that add air pollution without permits.

    Government and industry are also looking to other sources, such as investing in nuclear fusion advancement and building geothermal plants.

    A brief history

    In the 2000s and 2010s, the Great Lakes Commission Wind Collaborative, Wisconsin Public Service Commission and the Michigan Great Lakes Wind Council began to sketch out regulations for offshore wind in the Great Lakes and to identify locations that might be suitable for the turbines.

    In 2012, the Obama administration agreed to collaborate with five Great Lakes states – Illinois, Michigan, Minnesota, New York and Pennsylvania – to streamline a permitting process for offshore wind development. Multiple projects were proposed off the shores of Michigan, Ohio and Ontario, Canada, though Ontario banned offshore wind projects in 2011.

    Since then, momentum has stalled. One effort, the Icebreaker project off Cleveland, was approved and survived various legal challenges, but the project backers paused it indefinitely in 2023 due to the economic impacts of the legal delays.

    Community activists are split, with some embracing offshore wind in the Great Lakes as part of a clean energy future and others vocally opposing it, citing environmental, health and economic concerns.

    As of mid-2025, the Great Lakes were home to no offshore wind turbines.

    Wind speeds at the altitude of 460 feet (140 meters) above the surface of the Great Lakes are high enough to drive turbines that generate wind power.
    National Renewable Energy Laboratory, U.S. Department of Energy

    Big potential, big unknowns

    States continue to explore the possibility of offshore wind power in the Great Lakes. In early 2025, Illinois legislators again introduced a bill to create a pilot wind project off Chicago in Lake Michigan.

    Also in 2025, Pennsylvania legislators introduced a bill to facilitate offshore wind power in Lake Erie. If adopted, the law would map which areas are fit to be leased for development by avoiding nearshore areas, shipping lanes and migration pathways. The Ontario Clean Air Alliance is pushing the province to lift its moratorium and reconsider offshore wind in Canadian waters.

    A lot of details remain unknown. New York state supports offshore wind in the ocean but says “Great Lakes Wind does not provide the same electric and reliability benefits” by comparison. Ocean wind tends to be closer to areas where electricity demand is high, which can make those projects more cost-effective.

    New York also concluded in 2022 that despite the combined 144.5 terawatt-hours of annual technical potential in state waters in Lake Erie and Lake Ontario, “numerous practical considerations … would need to be addressed before such projects can be successfully commercialized.”

    To further explore the concerns New York’s report and others have raised, in 2024, with National Science Foundation funding, we collaborated with a team of researchers looking at a wide range of issues, including engineering, environmental effects and law. That effort resulted in articulating research questions whose answers would clarify how realistic different aspects of offshore wind could be in the Great Lakes, such as:

    People sit on a concrete pier sticking out over an area of water, with tall buildings in the background.
    The Great Lakes deliver beautiful views, recreation opportunities and commercial activity to a large area of the U.S. – and could supply renewable electricity too.
    Kamil Krzaczynski/AFP via Getty Images

    State jurisdiction is an opportunity

    In the oceans, U.S. states have jurisdiction from shore out three miles, with the federal government’s jurisdiction continuing out for hundreds of miles beyond that. So offshore project sites in the oceans are leased by the federal government.

    The Great Lakes are different. The state governments hold the lakes’ waters and submerged lands in trust for the public. And state jurisdiction extends from shore all the way out to the boundary of a neighboring state’s jurisdiction or the international boundary with Canada.

    Regulation of planning, site selection, leasing and other elements of offshore wind projects in the Great Lakes are the responsibility of one or another U.S. state. The federal government’s role is secondary, conducting environmental reviews and protecting navigation, but could still result in slowing state-led projects.

    In research we published in 2024 and 2025, we explain that states could evaluate and select offshore wind projects based on a range of social and environmental benefits, in addition to financial considerations. For instance, they could look for designs that provide fish habitat or seek corporate partners that agree to train local workers, manufacture turbines and ships near the lakes, and provide cheaper electricity to local consumers.

    Despite all the unknowns, we encourage greater support for research to harness the potential of offshore wind energy in the Great Lakes to be a renewable resource for states, the region and the nation as a whole.

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  • UnitedHealth signals prolonged pain as restored profit forecast underwhelms – Reuters

    1. UnitedHealth signals prolonged pain as restored profit forecast underwhelms  Reuters
    2. UnitedHealth says 2025 earnings will be worse than expected as high medical costs dog insurers  CNBC
    3. Over 60,000 Palestinians have died in the 21-month Israel-Hamas war, Gaza’s Health Ministry says  The Derrick
    4. UnitedHealth Group Stock Slips as Profit Disappoints, Outlook Cut Again  Investopedia
    5. UnitedHealth (NYSE:UNH) Reports Q2 In Line With Expectations  uk.finance.yahoo.com

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  • Halliburton sets standard in digital operations with LOGIX™ automated geosteering

    Halliburton sets standard in digital operations with LOGIX™ automated geosteering

    HOUSTON  July 29, 2025 — Halliburton (NYSE:HAL) launched LOGIX automated geosteering, a part of the LOGIX automation and remote operations family of solutions, that optimizes geological interpretation and well placement. The service combines automation, machine learning, and advanced geological insights to position the wellbore and maximize reservoir contact.

    LOGIX™ automated geosteering creates value for our customers with services that provide subsurface and drilling customization. We accomplish this with the optimization of well placement and recovery.

    Jim Collins, vice president, Halliburton Sperry Drilling

    The service updates and projects geological models to enable well trajectory optimization in real time. Advanced algorithms and machine learning technology help provide uniform, repeatable, and unbiased geological interpretations that empower customers with accurate data and faster diagnosis.  

    LOGIX™ automation and remote operations family of solutions includes well construction services that deliver reliability, consistency, and efficiency to maximize asset value for our customers.

    About Halliburton

    Halliburton is one of the world’s leading providers of products and services to the energy industry. Founded in 1919, we create innovative technologies, products, and services that help our customers maximize their value throughout the life cycle of an asset and advance a sustainable energy future. Connect with us on LinkedIn, YouTube, Instagram, and Facebook.

    Press Contact:
    Alexandra Franceschi
    PR@halliburton.com
    281-608-8839

    Investor Relations Contact:
    David Coleman
    investors@halliburton.com
    281-871-2688


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  • IMpact-MF Trial Aims to Show OS Benefit of Imetelstat in Relapsed Myelofibrosis

    IMpact-MF Trial Aims to Show OS Benefit of Imetelstat in Relapsed Myelofibrosis

    For patients with relapsed or refractory myelofibrosis, imetelstat (Rytelo) may offer a promising treatment option aimed at prolonging survival and modifying disease course following JAK inhibitor failure, according to John Mascarenhas, MD.

    In an interview with OncLive®, Mascarenhas discussed the rationale for investigating imetelstat in this setting, reviewed key findings from the preceding phase 2 data, and outlined the objectives of the ongoing phase 3 IMpact-MF trial (NCT04576156), which is evaluating imetelstat vs best available therapy.

    Mascarenhas is a professor of medicine at the Icahn School of Medicine at Mount Sinai and director of the Adult Leukemia Program at The Tisch Cancer Institute in New York, New York.

    OncLive: Can you provide an overview of the IMpact-MF trial and the rationale for evaluating imetelstat in patients with relapsed or refractory myelofibrosis?

    Mascarenhas: The IMpact-MF study is an ongoing, randomized phase 3 study evaluating imetelstat, which is a telomerase inhibitor. It’s a drug that has rationale [in this setting] and targets an enzyme that’s important for elongating DNA, which is critical for cell survival and proliferation. [hTERT] is a well-described and validated target in myelofibrosis that is upregulated in myelofibrosis hematopoietic stem cells and only transiently [expressed] in normal stem cells.

    What were the key findings from the prior phase 2 IMbark trial (NCT02426086) that evaluated imetelstat in JAK inhibitor–pretreated myelofibrosis and informed the design of the IMpact-MF study?

    We have phase 2 data demonstrating a [potential] improvement in overall survival [OS] in the relapsed/refractory setting in myelofibrosis. [For] patients who [progress on] ruxolitinib [Jakafi], their median survival is estimated to be approximately 12 to 14 months. And [in IMbark] we saw that [with imetelstat given] at 8.9 mg/kg every 3 weeks intravenously administered, median OS was 29.9 months [95% CI, 22.8-not evaluable (NE)]. It did suggest an [OS] benefit there. We had a lower-dose arm, I should point out, that had a median OS of 19.9 months [95% CI, 17.1-NE]. Therefore, [we saw] a dose-dependent improvement in survival, as well as improvement in symptomatology.

    Thirty-two percent [of patients treated at the 8.9-mg/kg dose achieved] a total symptom score reduction of 50% or greater, and a 10% [achieved] a 35% spleen volume reduction or better. It hit multiple disease feature hallmarks, and we were able to show a relationship between the biomarkers for telomerase inhibition with these clinical outcome measures.

    What is the primary goal of this ongoing phase 3 trial, and what differentiates imetelstat from currently available treatment options in this setting?

    The randomized phase 3 study of patients who [progressed on] ruxolitinib or other JAK inhibitor therapy is looking for improvement in disease burden [and] prolongation of OS as an outcome. [Enrolled patients] are randomly assigned to imetelstat vs best available therapy [BAT]. Imetelstat, again, is intravenously administered every 3 weeks, and BAT could be investigator’s choice, with the exception of a JAK inhibitor; the study does exclude JAK inhibitors in that control arm.

    The primary end point is OS. That is unique in the myelofibrosis field because spleen and symptom assessment that are typically the regulatory endpoints. This study is ongoing, and I’m hoping we’ll finish accrual in 2025. Then, of course, we need to follow these patients [closely].

    This is [seeking to fulfill] an unmet need: improving OS. We do look at end points beyond survival, including spleen response, symptom response, [and] anemia response. We did see anemia responses with this drug in the phase 2 study.

    I should point out that imetelstat is an approved drug in myelodysplastic syndromes [MDS] for lower-risk, transfusion-dependent MDS, [based on data from the phase 3 IMerge trial (NCT02598661)]. There’s a lot of rationale for why this drug would work in myeloid malignancies.

    What important factors and potential challenges should clinicians consider when evaluating patients for trial enrollment?

    [One] barrier may be [that] patients are often really sick and may not qualify for a trial once they [progress on a] JAK inhibitor. My recommendation always is, don’t just wait for the patient to become quite ill. If they’re not doing well on ruxolitinib or another JAK inhibitor that they’re on, get them into centers that have [the Impact-MF study] ongoing so they can be evaluated for this trial, particularly those patients where the emphasis might be on prolongation of survival, which is not always the case for every patient.

    You might have a very elderly patient where the focus is on comfort, and [the goal is] not necessarily trying to improve survival. The goal of therapy obviously dictates what treatment makes sense for each individual patient. It has to be personalized.

    [Imetelstat] is an infusional agent, so a patient needs to be at the infusion center every 3 weeks for a drug like this. There is the potential for myelosuppression, so patients who already have significant cytopenias are probably not great candidates for a drug like this. The cytopenias are reversible, but that’s also a factor that might influence decision-making for treatment like this.

    For some patients, it may [also] be a nice bridge to the ultimate treatment, which is the only treatment we have that has curative potential, which is a bone marrow transplant. [However], not every patient is a transplant candidate; in fact, many patients are not. For many patients, this drug could be used outside of the usual world of JAK inhibition, for those patients that are looking to achieve disease course modification, progression-free survival, [and] OS.

    Reference

    Mascarenhas J, Harrison C, Bose P, et al. IMpactMF, randomized, open-label, phase 3 trial of imetelstat versus best available therapy in patients with intermediate-2 or high-risk myelofibrosis relapsed or refractory to Janus kinase inhibitors. Presented at: 2025 EHA Congress; June 13, 2025; PF841.

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