Category: 3. Business

  • RS Group plc (EENEF) Q2 2026 Earnings Call Transcript – Seeking Alpha

    1. RS Group plc (EENEF) Q2 2026 Earnings Call Transcript  Seeking Alpha
    2. RS remains on track despite soft markets  Investors’ Chronicle
    3. RS Group stock rating upgraded to Buy by Deutsche Bank on improved trends  Investing.com
    4. Deutsche Bank backs RS Group for recovery as sales and cash flow steady  Proactive Investors
    5. RS Group posts profit rise amid improved second-quarter sales trend  MarketScreener

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  • Chan Breaks Down the Need for Dose Escalation With Somatostatin Analogs in GEP-NETs

    Chan Breaks Down the Need for Dose Escalation With Somatostatin Analogs in GEP-NETs

    Pending the results of the ongoing phase 3 SORENTO trial (NCT05050942), increasing the dose or shortening the treatment interval of somatostatin analogs may be a viable route to take for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in need of symptom and/or disease control, according to Jennifer Chan, MD, MPH.

    “We’re awaiting the results of the SORENTO trial, which is looking at a novel highly bioavailable formulation of octreotide, a self-administered formulation of octreotide, that will be addressing this issue of whether dose and bioavailability matter,” Chan said in an interview with OncLive® during the 2025 NANETS Multidisciplinary NET Medical Symposium.1,2

    “In that trial, patients were randomly assigned to receive CAM2029, this novel version of octreotide, or standard dose octreotide or lanreotide. [Results] from that trial [will inform] whether that formulation, which is more bioavailable [than octreotide or lanreotide], may have superior efficacy to standard dosing,” Chan added.

    In the interview, Chan, the clinical director of the Gastrointestinal Cancer Center, director of the Program in Carcinoid and Neuroendocrine Tumors, and an institute physician at Dana-Farber Cancer Institute, and an associate professor of medicine at Harvard Medical School in Boston, Massachusetts, discussed the relationship between dose escalation and symptom control, the evidence that supports potential disease control benefits, and how results from the SORENTO trial could redefine current standards.

    Chan’s Topline Takeaways on Optimizing Somatostatin Analog Use in GEP-NETs

    • Increasing octreotide LAR to 40 mg or 60 mg or shortening lanreotide intervals can improve control of carcinoid syndrome symptoms like flushing and diarrhea.
    • Observational data from trials such as NETTER-1, NETTER-2, and CLARINET FORTE suggest higher doses or shorter dosing intervals may prolong disease stability.
    • The ongoing phase 3 SORENTO trial is testing a novel, self-administered, highly bioavailable octreotide that could reshape somatostatin analog dosing paradigms.

    OncLive: What new data support individualized dose escalation or interval shortening of somatostatin analogs in patients with uncontrolled symptoms or disease progression?

    Chan: We often will adjust the dose of somatostatin analogs either by increasing the dose of octreotide long-acting repeatable [LAR] from the standard dose of 30 mg, [to] 40 mg or 60 mg, if there are uncontrolled symptoms of carcinoid syndrome. Sometimes that dose escalation can help minimize the symptoms of flushing and diarrhea, for instance. We also have information from the control arms from, for instance, the NETTER-1 [NCT01578239] and the NETTER-2 [NCT03972488] trials, that suggest that even in patients who might have higher grade disease, for instance in the NETTER-2 trial, or patients who may have progressed after standard dose somatostatin analog, as was the case in the NETTER-1 trial, that there may be some period of disease control by increasing the dose from 30 mg to 60 mg of octreotide LAR.

    There was also the phase 2 CLARINET FORTE trial [NCT02651987] that showed for lanreotide, another somatostatin analog, that if you shorten the interval from the usual 120 mg every 4 weeks to 120 mg every 2 weeks, patients who had progressed on standard dose [therapy] might achieve some progression-free survival benefit with the dose escalation.

    What factors should guide the decision to intensify or switch somatostatin analog therapy, and how do these strategies align with evolving guideline recommendations?

    In clinical practice, we probably most commonly will escalate the dose. For octreotide, [we’ll either] increase from the standard [dose of] 30 mg to 40 mg or 60 mg to help with symptom control. Uncontrolled carcinoid syndrome is probably the most common reason we adjust the dose.

    The same thing could be said for lanreotide. The 120 mg every 4 weeks, we may give more frequently, either every 3 weeks or every 2 weeks, mainly for symptom control. That is consistent with what’s in the National Comprehensive Cancer Network guidelines, for instance, for dose adjustment for symptom control. There’s less controlled data about dose escalation for disease control, but there are some observational results from the control arms of other studies that suggest [we] may achieve some disease control, but we’re awaiting the results of trials to help us understand that better.

    References

    1. Dose optimisation of SSAs: the evolving story in GEP-NET management; supported by Camurus. Presented at: 2025 NANETS Multidisciplinary NET Medical Symposium; October 23-25, 2025; Austin, Texas.
    2. A trial to assess efficacy and safety of octreotide subcutaneous depot in patients with GEP-NET (SORENTO). Clinicaltrials.gov. Updated November 6, 2025. Accessed November 7, 2025. https://clinicaltrials.gov/study/NCT05050942

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  • Evaluating Valuation After Recent Share Price Pullback

    Evaluating Valuation After Recent Share Price Pullback

    ACI Worldwide (ACIW) shares moved lower after the company’s latest trading session, closing down 3% to $48.96. While the decline caught some attention, it follows an otherwise resilient performance over the past month.

    See our latest analysis for ACI Worldwide.

    Zooming out, ACI Worldwide’s 1-year total shareholder return is down 15.6%, even as the stock still holds a notable 135.6% total return over three years. While momentum has been uneven, longer-term holders have seen substantial gains compared to short-term setbacks. This indicates that sentiment can change quickly based on recent events or evolving risks.

    If you’re watching for the next market mover or sector trend, this is a great moment to broaden your view and discover fast growing stocks with high insider ownership

    With mixed signals from recent returns and a sizable discount to some analyst price targets, the question is whether ACI Worldwide is an overlooked bargain or if the market has already priced in its growth potential.

    ACI Worldwide’s most followed narrative places its fair value sharply above the current stock price. This makes the recent dip appear even more striking. The gap suggests upbeat future expectations and invites a closer look at what is fueling such optimism.

    The official launch and positive customer reception of Connetic, ACI’s next-generation cloud-native payments hub with AI-powered decisioning and real-time capabilities, positions the company to capitalize on increasing demand for scalable, secure digital payment processing and real-time payments globally. This supports accelerating recurring revenue growth and higher margins. ACI’s established ability to facilitate alternative payment types, including stablecoins and digital currencies, enables it to capture new market opportunities as the complexity and adoption of digital payment methods rise. This development may translate into increased transaction volumes and elevated per-transaction economics, potentially driving revenue uplift.

    Read the complete narrative.

    Want to discover the secret behind this premium price tag? The narrative depends on a future where record bookings, cutting-edge innovation, and shifting profit margins shape a bold valuation. Could these projections become game-changers or merely raise more questions? Explore the full story to see the metrics that matter most.

    Result: Fair Value of $64.6 (UNDERVALUED)

    Have a read of the narrative in full and understand what’s behind the forecasts.

    However, intensifying competition from fintechs and ongoing heavy investment demands could limit ACI Worldwide’s ability to deliver on its ambitious earnings projections.

    Find out about the key risks to this ACI Worldwide narrative.

    If the current story doesn’t fit your outlook or you prefer digging into the numbers on your own, crafting your personal analysis takes just minutes, so why not Do it your way

    A great starting point for your ACI Worldwide research is our analysis highlighting 5 key rewards and 1 important warning sign that could impact your investment decision.

    Why stop at one idea? There’s a world of potential winners waiting for you, and the right tool makes all the difference. Use Simply Wall Street’s screener to spot tomorrow’s top performers before everyone else. Maximize your search and gain an edge. Don’t let standout investments pass you by.

    This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

    Companies discussed in this article include ACIW.

    Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

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  • Assessing Valuation After Record Q3 Output, Hess Acquisition, and Shareholder Return Strength

    Assessing Valuation After Record Q3 Output, Hess Acquisition, and Shareholder Return Strength

    Chevron (CVX) caught investors’ attention this week after the company topped third-quarter earnings forecasts and set a new production record. This was supported by the freshly integrated Hess assets and output growth in key fields.

    Even as oil prices wavered and analysts weighed short-term concerns, Chevron maintained steady shareholder returns through both dividends and share buybacks. These latest results have become a talking point on Wall Street.

    See our latest analysis for Chevron.

    Shares of Chevron have climbed 5.7% year-to-date, and while the 1-year total shareholder return stands at a modest 3.3%, the company is coming off a highly active quarter. The quarter capped record output and the completion of its transformative Hess acquisition. Recent board changes and robust buybacks further highlight Chevron’s evolving strategy, keeping sentiment constructive even as near-term earnings forecasts soften. Overall, momentum is steady, and big-picture performance remains healthy for long-term holders.

    If you’re keen to uncover more opportunities in energy, now could be a smart time to check out fast growing stocks with high insider ownership.

    With Chevron trading at a double-digit discount to analyst price targets, but facing declining earnings estimates, investors are left to consider whether there is value still on the table or if the market fully reflects its future growth prospects.

    Chevron’s most widely followed narrative places its fair value at $172.04, which is noticeably above the last close of $155.02. With this gap in focus, Chevron’s current price may not reflect the narrative’s full expectations for long-term growth, earnings, and operational leverage.

    Strength in low-cost production and strategic acquisitions positions Chevron for revenue growth, operational leverage, and resilience to commodity price cycles. Investment in efficiency, renewables, and cost reductions supports industry-leading margins, shareholder returns, and diversified growth amid regulatory shifts.

    Read the complete narrative.

    Want to know the growth blueprint behind this high valuation? The key element of this narrative is record-breaking earnings and a future profit multiple usually associated with tech leaders. Interested in which bold financial projections support that price target? Dive deeper to see the surprising numbers that drive this fair value calculation.

    Result: Fair Value of $172.04 (UNDERVALUED)

    Have a read of the narrative in full and understand what’s behind the forecasts.

    However, persistent reliance on hydrocarbons and slow progress in renewables could impact Chevron’s revenue growth and long-term earnings stability.

    Find out about the key risks to this Chevron narrative.

    When we compare Chevron’s share price using standard industry ratios, the numbers present a very different story. The company trades at a price-to-earnings ratio of 24.4x, which is much higher than both the US Oil and Gas industry average (13.5x) and the peer average (20.7x). This suggests that, even accounting for Chevron’s scale and strengths, investors are paying a substantial premium. This premium exceeds what our fair ratio of 23.5x would indicate. Is this premium justified, or could it be leaving investors with less upside?

    See what the numbers say about this price — find out in our valuation breakdown.

    NYSE:CVX PE Ratio as at Nov 2025

    If you see Chevron’s value differently or want to examine the numbers from another angle, you can build your own narrative in minutes, Do it your way.

    A great starting point for your Chevron research is our analysis highlighting 2 key rewards and 2 important warning signs that could impact your investment decision.

    Smart investors look beyond the headlines. Don’t let great opportunities pass you by; take action now and broaden your research with these proven stock screeners:

    • Unlock potential income by targeting companies offering strong payouts through these 16 dividend stocks with yields > 3%, which reveal stocks yielding above 3% and rewarding shareholders.

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    • Build value by starting with these 870 undervalued stocks based on cash flows, highlighting stocks currently trading below their calculated cash flow and positioning yourself for long-term returns.

    This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

    Companies discussed in this article include CVX.

    Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

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  • JFrog (FROG) Is Up 26.4% After Surpassing Q3 Estimates and Lifting Full-Year Cloud Outlook

    JFrog (FROG) Is Up 26.4% After Surpassing Q3 Estimates and Lifting Full-Year Cloud Outlook

    • JFrog has reported third-quarter results that exceeded analyst expectations, highlighted by a record US$136.91 million in revenue and a 50% year-over-year increase in cloud revenue, with the company also raising its outlook for the fourth quarter and full year 2025.

    • Cloud revenue now accounts for 46% of total sales, indicating a marked shift toward cloud-based services and reinforcing JFrog’s role in software supply chain management as enterprises increase adoption of AI-driven solutions.

    • We’ll explore how JFrog’s accelerating cloud revenue growth impacts its investment narrative and future expectations for sustainable earnings expansion.

    Uncover the next big thing with financially sound penny stocks that balance risk and reward.

    Owning JFrog means believing that trusted software supply chain management, especially with a focus on cloud and AI model delivery, will see ongoing enterprise adoption at scale. The recent Q3 results and raised 2025 guidance are clear positives for near-term sentiment, particularly given the 50% surge in cloud revenue; however, the most important catalyst, continued acceleration of cloud and security product adoption, remains vulnerable to competition and evolving enterprise IT buying patterns, while ongoing operating losses highlight the biggest risk right now. The strong quarter strengthens the company’s growth narrative, but does not remove the risk of lumpy enterprise deal flow and longer sales cycles tied to cloud migration trends. One announcement standing out this quarter is JFrog’s launch of new AI agent-based features and JFrog Fly, which enhance automation and developer workflow within its core platform. These innovations tie directly to the catalyst of deeper enterprise integration for trusted AI and hybrid deployments, supporting the potential for sustained growth but not fully offsetting risks associated with margin pressure as larger rivals embrace similar strategies. Yet even amid this progress, investors should pay close attention to how heightened competition could pressure JFrog’s pricing power and margins…

    Read the full narrative on JFrog (it’s free!)

    JFrog’s narrative projects $736.3 million revenue and $96.4 million earnings by 2028. This requires 15.8% yearly revenue growth and a $182.7 million increase in earnings from -$86.3 million.

    Uncover how JFrog’s forecasts yield a $56.44 fair value, a 6% downside to its current price.

    FROG Community Fair Values as at Nov 2025

    Four recent fair value estimates from the Simply Wall St Community put JFrog’s share price between US$35 and US$141. Some see opportunities as AI-driven DevOps gains traction, but others caution that risks like pricing pressure could limit upside. Consider exploring a range of these views.

    Explore 4 other fair value estimates on JFrog – why the stock might be worth over 2x more than the current price!

    Disagree with existing narratives? Create your own in under 3 minutes – extraordinary investment returns rarely come from following the herd.

    • A great starting point for your JFrog research is our analysis highlighting 1 key reward and 2 important warning signs that could impact your investment decision.

    • Our free JFrog research report provides a comprehensive fundamental analysis summarized in a single visual – the Snowflake – making it easy to evaluate JFrog’s overall financial health at a glance.

    Opportunities like this don’t last. These are today’s most promising picks. Check them out now:

    This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

    Companies discussed in this article include FROG.

    Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

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  • Rheinmetall AG (RHM:CA) Q3 2025 Earnings Call Transcript – Seeking Alpha

    1. Rheinmetall AG (RHM:CA) Q3 2025 Earnings Call Transcript  Seeking Alpha
    2. Financial report for Q3 2025 – Rheinmetall shows steady growth  Rheinmetall
    3. Rheinmetall (RNMBF) Stays on Track Amid Order Delays  GuruFocus
    4. Rheinmetall on track for FY25 targets as backlog rises 22.9%  Army Technology
    5. Rheinmetall looks to international partners as its sales grow  Shephard Media

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  • A crisis at chipmaker Nexperia sent automakers scrambling. Here’s what to know

    A crisis at chipmaker Nexperia sent automakers scrambling. Here’s what to know

    A battle for control of a little-known chipmaker has threatened global auto production by choking off the semiconductor supply chain, though there are signs the crisis is inching toward a resolution.

    The power struggle over Nexperia, a Chinese-owned Dutch semiconductor maker, highlights how technology supply chain vulnerabilities are squeezing auto makers, most notably forcing Honda to halt production at a Mexican factory making its popular HR-V crossover for North American markets. It also exposes how Europe is caught in the middle of the wider geopolitical showdown between Washington and Beijing.

    Here’s a look at the dispute:

    The turmoil erupted into public view in mid-October, when the Dutch government announced it had invoked a rarely used World War II-era law to take effective control of Nexperia weeks earlier.

    The Dutch ministry of economic affairs said it took action because of national security concerns. Officials said they intervened because of “serious governance shortcomings” at Nexperia, asserting control to prevent the loss of crucial tech know-how that could threaten Europe’s economic security.

    Nexperia’s Chinese owner Wingtech Technology, a partially state-owned company, is at the heart of the dispute. Amid the boardroom battle, a Dutch court granted the ministry’s request to oust Nexperia’s Chinese CEO Zhang Xuezheng. American officials told the Dutch government he would have to be replaced to avoid trade restrictions, according to a court filing.

    Nexperia makes simple semiconductors such as switches and logic chips. The auto industry — one of Nexperia’s biggest markets — uses its chips for numerous functions, such as adaptive LED headlight controllers, electric vehicle battery management systems and anti-lock brakes.

    Headquartered in the Dutch city of Nijmegen, Nexperia was spun off from Philips Semiconductors two decades ago. It was eventually purchased by China’s Wingtech Technology in 2018 for $3.6 billion.

    Nexperia has wafer fabrication plants in Britain and Germany. It operates an assembly and testing center in China’s southern manufacturing heartland of Guangdong — which accounts for around 70% of its end-product capacity — and similar centers in the Philippines and Malaysia.

    The dispute is part of the broader struggle between the U.S. and China over tech supremacy, which has left Europe caught in the middle.

    It stems from Washington’s decision late last year to place Wingtech on its “entity list,” which subjects companies to export controls because of national security risks. In late September, the U.S. expanded that list to Wingtech’s subsidiaries, including Nexperia, pressuring allies to follow suit.

    After the Dutch government asserted control of Nexperia, Beijing responded soon after, blocking the export of Nexperia chips from its assembly plant in the Chinese city of Dongguan. It blamed the Netherlands for “turmoil and chaos” in the chip supply chain.

    There were signs of hope following last month’s high-profile meeting between U.S. President Donald Trump and Chinese leader Xi Jinping, when the White House said Beijing would ease the export ban as part of a U.S.-China trade truce.

    Despite Beijing also confirming exports would be allowed to resume, Nexperia’s Chinese unit said headquarters suspended shipments of wafers used to make chips to its Chinese factory, potentially crimping its ability to deliver finished products.

    Nexperia’s head office hit back in a statement Wednesday, saying the Chinese unit refused to pay for the wafers and accused it of “ignoring the lawful instructions” from its global management team. The company said it can’t guarantee the quality of any chips delivered from its China plant since Oct. 13.

    Modern automobiles rely on so-called discrete chips made by companies like Nexperia, which, unlike more advanced microprocessors, perform a single function. Leaders at big carmakers spelled out their worries in the latest round of earnings calls, saying that finding a replacement for Nexperia at scale in the short term will be difficult.

    “While Nexperia makes up only about 5% of the automotive silicon discrete market in term of revenue, its share is much higher in terms of discrete chip volume,” S&P Global Mobility analysts wrote in a recent note.

    Nexperia’s parts are widely used across vehicle systems — often dozens to hundreds per vehicle — and carmakers in North America, Japan and South Korea are at risk, they added.

    “It’s an industrywide issue. A quick breakthrough is really necessary to avoid fourth quarter production losses for the entire industry,” Ford CEO Jim Farley said.

    General Motors CEO Mary Barra warned that production could be hit. The company has “teams working around the clock with our supply chain partners to minimize possible disruptions,” she said.

    Nissan CEO Ivan Espinosa told CNBC that the company is setting aside a 25 billion yen ($163 million) provision for supply risks, in part to “absorb” the impact from the Nexperia crisis on production.

    Mercedes-Benz is “scurrying around the world to look for alternatives,” CEO Ola Kallenius said. The European Automobile Manufacturers’ Association said members including BMW, Renault, Volkswagen and Volvo have been forced to use their reserve stockpiles of chips and warned of assembly line stoppages if they run out.

    The European Union’s trade commissioner, Maros Sefcovic, on Saturday noted “encouraging progress,” writing on X that China’s Commerce Ministry had confirmed “further simplification” of export procedures for Nexperia chips to the EU and global customers.

    In Beijing, the Commerce Ministry also said Saturday that it agreed to a Dutch request to send representatives to China for “consultations.”

    But it noted that the Netherlands had not taken any concrete actions yet to restore the global semiconductor supply chain since the Dutch government said days earlier it would take “appropriate steps on our part where necessary.”

    Economics Affairs Minister Vincent Karremans had said in that statement that “the Netherlands trusts that the supply of chips from China to Europe and the rest of the world will reach Nexperia’s customers over the coming days.”

    Honda has received word that Nexperia’s shipments from China have resumed, Executive Vice President Noriya Kaihara told reporters Friday. He said the Japanese automaker expects to resume production during the week of Nov. 21 at its plant in Celaya, Mexico, which can make up to 200,000 vehicles a year.

    ___

    AP Business Writer Yuri Kageyama in Tokyo contributed to this report.

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  • Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Phase 3 CORALreef Lipids Trial

    Enlicitide, designed to deliver antibody-like efficacy, has the potential to be the first approved oral PCSK9 inhibitor to lower LDL-C with a safety profile comparable to placebo

    Enlicitide may help address unmet needs in ASCVD, a key driver of the ongoing cardiovascular (CV) epidemic


    Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the first presentation of results from the pivotal Phase 3 CORALreef Lipids trial demonstrating that treatment with enlicitide decanoate, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, resulted in a statistically significant and clinically meaningful reduction in low-density lipoprotein cholesterol (LDL-C) of 55.8% (primary analysis; 95% CI: -60.9, -50.7; p<0.001) and of 59.7% in a post-hoc reanalysis (95% CI: -62.3, -57.1; p<0.001) compared to placebo at week 24. These late-breaking data will be presented for the first time today at the American Heart Association (AHA) Scientific Sessions 2025 (Abstract #4391578) and were selected for the Late-Breaking Science News Briefing.

    In CORALreef Lipids, adults with or at-risk for atherosclerotic cardiovascular disease (ASCVD) on background lipid-lowering therapies or a documented statin intolerance who received once-daily oral enlicitide had statistically significant and clinically meaningful reductions in LDL-C at week 24 (primary endpoint) and statistically significant and sustained reductions in LDL-C through one year (week 52). Enlicitide demonstrated statistically significant reductions in secondary endpoints including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) at week 24. The overall safety profile was comparable to placebo. High adherence with study intervention (97%) and dosing instructions (≥97%) were observed across treatment groups.

    “Enlicitide demonstrated impressive LDL-C reductions with placebo-like safety in the CORALreef Lipids study, underscoring the practice-changing potential of an oral PCSK9 inhibitor,” said Dr. Ann Marie Navar, a lead author of the study and Associate Professor of Medicine in the Division of Cardiology at UT Southwestern Medical Center. “Despite the availability of lipid-lowering therapies such as statins and injectable PCSK9 inhibitors, the majority of patients with atherosclerotic cardiovascular disease do not reach their LDL-C goal. Enlicitide has the potential to help close gaps in achievement of lipid goals in patients with and at risk for cardiovascular events and ultimately help address the ongoing CV epidemic.”

    “Enlicitide was designed to deliver PCSK9 antibody-like efficacy and specificity in an easy-to-use pill,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “Enlicitide, if approved, adds to physicians’ armamentarium to lower LDL-C. This moment is the result of Merck’s legacy and commitment to researching ways to help improve ASCVD outcomes for millions worldwide and our strength in medicinal chemistry using our novel macrocyclic peptide platform. Cardiovascular disease is the leading cause of death globally, and we look forward to bringing a potential new option to help address the CV epidemic.”

    At one year, enlicitide showed a sustained statistically significant reduction in LDL-C of 47.6% (primary analysis; 95% CI: -52.7, -42.5; p<0.001) and of 52.4% (post-hoc reanalysis; 95% CI: -55.1, -49.7; p<0.001) compared to placebo. At week 24, enlicitide demonstrated reductions in non-HDL-C of 53.4% (95% CI: -55.5, -51.2; p<0.001), ApoB of 50.3% (95% CI: -52.1, -48.5; p<0.001) and Lp(a) of 28.2% (95% CI: -30.3, -26.0; p<0.001) compared to placebo. The study also showed that 67.5% of patients treated with enlicitide achieved the rigorous prespecified goal of at least 50% reduction in LDL-C along with an LDL-C <55 mg/dL (1.42 mmol/L) compared to 1.2% in the placebo arm at week 24.

    Enlicitide had a safety profile similar to placebo. There were no apparent differences between the enlicitide and placebo groups in the incidence of any adverse events (AEs), serious AEs or deaths. Discontinuations due to AEs were low and similar between enlicitide (3.1%) and placebo (4.1%).

    Merck plans to share data from this trial, along with data from CORALreef HeFH and CORALreef AddOn with regulatory authorities worldwide.

    About CORALreef Lipids

    CORALreef Lipids (NCT05952856) is a Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of enlicitide decanoate in adults with hypercholesterolemia and a history of a major atherosclerotic cardiovascular disease (ASCVD) event or increased risk for a first event. Participants were required to be treated with stable lipid-lowering therapies including at least a moderate or high intensity statin (or have documented statin intolerance). The study enrolled 2,912 participants who were randomized 2:1 to receive either 20mg of once-daily oral enlicitide (n=1,942) or placebo (n=970). The primary endpoints were mean percent change in LDL-C from baseline at week 24 versus placebo, number of participants with one or more AEs, and number of participants who discontinued study drug due to an AE. Multiplicity-controlled secondary efficacy endpoints included: mean percent change from baseline in LDL-C at week 52, mean percent change from baseline in other key atherogenic lipids at week 24 (non-HDL-C, ApoB and Lp(a)).

    A post-hoc reanalysis was conducted to revise missing data handling rules that resulted in 5 biologically impossible baseline values being included in the primary analysis. The intent of the reanalysis was to provide a more clinically accurate estimate of the treatment effect.

    CORALreef Lipids is the largest completed Phase 3 study evaluating enlicitide in a broad range of participants with elevated LDL-C.

    About enlicitide and PCSK9

    Enlicitide has the potential to be the first FDA approved oral PCSK9 inhibitor. It is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel small molecule macrocyclic peptide candidate that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

    PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

    About CORALreef Clinical Trial Program

    The efficacy and safety profile of enlicitide is being evaluated through the comprehensive CORALreef Clinical Trial program evaluating over 19,000 participants who have hypercholesterolemia. As previously announced, enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in three pivotal Phase 3 studies: CORALreef Lipids (NCT05952856), CORALreef HeFH (NCT05952869) and CORALreef AddOn (NCT06450366). Enlicitide is continuing to be evaluated in the large cardiovascular outcomes trial, CORALreef Outcomes (NCT06008756), which has completed enrollment with over 14,500 participants. Additional CORALreef clinical trials include CORALreef Extension (NCT06492291), CORALreef Pediatric (NCT07058077) and CORALreef Combination (NCT07216482).

    About hypercholesterolemia

    Hypercholesterolemia, a type of hyperlipidemia, is a disorder in which there are elevated LDL-C levels in the blood. It affects approximately 86 million adults in the U.S. and is a major risk factor for ASCVD. Nearly 70% of people with ASCVD who are treated with lipid-lowering therapies do not reach target LDL cholesterol levels. High LDL-C, if left untreated, can lead to ASCVD events such as heart attacks and strokes.

    About the CV epidemic and atherosclerotic cardiovascular disease

    The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths. It is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.

    Merck’s focus on cardiovascular disease

    Merck has a long history of developing treatments for cardiovascular disease. Nearly 70 years ago, we introduced our first cardiovascular therapy—and our scientific efforts to understand and treat cardiovascular-related disorders have continued. Cardiovascular disease continues to be one of the most serious health challenges of the 21st century and is the leading cause of death worldwide. Approximately 18 million people across the globe die from cardiovascular disease every year; in the United States, one person dies every 36 seconds from cardiovascular disease.

    Advancements in the treatment of cardiovascular disease can make a critical difference for patients and health systems around the world. At Merck, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally.

    Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.merckclinicaltrials.com/cardiovascular.

    About Merck

    At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

    Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

    This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

    Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

    The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).


    Source: Merck & Co., Inc., Rahway, NJ, USA


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  • Fish Oil Shows Cardiovascular Benefits in Dialysis Patients – Medscape

    1. Fish Oil Shows Cardiovascular Benefits in Dialysis Patients  Medscape
    2. Fish oil supplementation may reduce CVD risks for people on dialysis  Healio
    3. Fish Oil Cuts Risk of Serious Heart Events in Dialysis Patients  MedPage Today
    4. PISCES: Fish Oil Slashes Cardiovascular Event Risk of Maintenance Dialysis  HCPLive

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  • ABC chair warns ‘extremely autocratic’ views of some AI investors could lead to ‘dangerous and sinister’ outcomes | Australian Broadcasting Corporation

    ABC chair warns ‘extremely autocratic’ views of some AI investors could lead to ‘dangerous and sinister’ outcomes | Australian Broadcasting Corporation

    The chair of the ABC has warned that AI could become “dangerous and sinister” considering some who finance it hold views that are “extremely autocratic”.

    Kim Williams, who has been chair of the national broadcaster since March 2024, is a prolific user of various AI applications, including ChatGPT, Gemini and Perplexity, saying it is important for people to understand the technology.

    “I make myself use it and try to understand it … I don’t pretend to be an expert, but I’m certainly actively, passionately interested because it’s the next major technology that is going to change our world,” he told Guardian Australia.

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    “As with all technology, this is an immensely useful tool. But it’s a tool and we should not treat it as so many others … have: in a rather undisciplined, romantic way.”

    Williams warned that technology can encompass the values of those who create or control it, and said he was concerned what this might mean for AI.

    “There are many value constructs that are reflected in AI that can be seen in some ways as being potentially dangerous and sinister,” he said.

    “Many of the participants in the financing – and even in the origination and leadership of some of the AI [companies] – have unusually severe views of human organisation and politics, and in some instances … have views that are extremely autocratic, and believe in an anointed few being in charge of the many.”

    Williams said that as a believer in democracy and the contest of ideas, it’s “clearly immensely socially dangerous” for people to limit and censor the views of those they disagree with.

    “We should not underestimate the potency and power of these technologies – and we are seeing living examples of the technologies in the hands of some governments, where we have real life demonstrations of just how dangerous this can be.”

    Asked whether, he thought media organisations – including News Corp and the Guardian – should be signing deals with AI companies, Williams said everyone needed to carry the responsibility of using these technologies with a sense of the public and national interest.

    “I speak about it openly with colleagues because I think these things are immensely important.”

    Kim Williams says: ‘I think the impact on journalism will probably be a lot more benign. Well, actually, a lot more positive than people think …’ Photograph: Mike Bowers/The Guardian

    AI companies failed to insert a text and mining data exemption into Australian copyright law, which would have allowed them to train AI on creative works without paying for it. Last month, the Albanese government ruled out introducing such an exemption.

    Williams, who chaired the Copyright Agency for six years said people have a right to derive income from their creative work.

    “Anything that is going to compromise that is not cool, and it’s not acceptable, and that is, as far as I know, illegal,” he said.

    “And it should get the full … defence and prosecution by government. You’ve got to pay people who have invested their lifetimes in creating works.”

    Williams said he saw AI as potentially devastating for entry-level jobs in industries such as accounting or law, but he believed the effect on journalism jobs would not be as damaging.

    “I think the impact on journalism will probably be a lot more benign. Well, actually, a lot more positive than people think because journalists are smart, perspicacious people, and they’ll figure out ways that AI will actually make them better and stronger and will improve journalism,” he said.

    “But boy, in so many other areas, I just think it can be an employment destroyer.”

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