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Breaking News: Italy is Celebrating Ruffo Caselli's Robotics in Art 12-10-2024 09:34 PM CET | Leisure, Entertainment, Miscellaneous Press release from: Getnews / PR Agency: Headlineplus Before the advent of AI, there was Cybernetic Existentialism. Image: https://www.getnews.info/uploads/67ec679e5aaa4c7c7c86efddc25617ea.jpeg The Center for the Multidisciplinary Study of Cybernetic Existentialism of New York City announces an upcoming art installation featuring the works of Italian artist Ruffo Caselli. This highly anticipated event will celebrate half a century of Caselli's influential contributions to the art world. Revered as the father of Cybernetic Existentialism, he envisioned a world of robotics and brought it to life on canvas with the incorporation of microchips. Ruffo Caselli, (born 1932 and died in 2020), was a pioneering artist known for merging traditional artistic techniques with cutting-edge technology. He was renowned for his wit and innovation in incorporating microchips into his creations. Based in Milano, Ruffo Caselli actively exhibited his work in prominent galleries, with his most recent exhibition being held at the Azimut headquarters in Via Foro Bonaparte in Milan, running for five months. While the exact details for the upcoming exhibition are yet to be finalized, it is expected to be open to the public in the near future in Genoa. A telepathic observer, supported by a renowned gallery in Manhattan since the early 1980s, displayed his masterpieces from New York across the globe, including South America, South Korea, and Russia. His work from the 1970s and 1980s garnered significant acclaim from art collector and curator Elena Garas, who extensively researched the artist's work for several years and shared her findings through lectures and elegant presentations. Image: https://www.getnews.info/uploads/ac30b6c9bbdae86c16415dff257d7b2c.jpeg Elena Garas introduced Ruffo Caselli work to prestigious galleries and museums, including the Chelyabinsk Historical Museum and the Uray City Museum, with lectures and conferences conducted by Zaitsev Dmitry Stanislavovich, curator of the Ruffo Caselli exhibition in Uray, Khanty-Mansi Autonomous Okrug-Yugra, PhD in Cultural Studies, and Strelets Oksana Yurievna, Director of the Museum. For more information, please visit http://www.cyberneticexistentialism.com Please visit the YouTube channel to learn more https://m.youtube.com/@ruffocasellipaintings6978 About Ruffo Caselli Italian artist Ruffo Caselli paints canvasses representing elegant robots dotted with little squares, sensors and microchips. He is one of the world's leading interpreters of the changes that have taken place in our lifetime. About The Center for the Multidisciplinary Study of Cybernetic Existentialism The Center for the Multidisciplinary Study of Cybernetic Existentialism is a presentation platform for TECHNOLOGY IN ART. Carmen Gallo founded the Center in Manhattan in early eighties as a platform to present Art, Philosophy, Technologies and Trends of the Day in Technology. Media Contact Company Name: The Center for the Multidisciplinary Study of Cybernetic Existentialism Contact Person: Media Relations Email: Send Email [ http://www.universalpressrelease.com/?pr=breaking-news-italy-is-celebrating-ruffo-casellis-robotics-in-art ] Phone: 212-7807526 Country: United States Website: http://www.cyberneticexistentialism.com This release was published on openPR.

Brock Purdy participated in the start of Thursday's practice with the 49ers but the San Francisco starting quarterback was not on the field for the majority of the workout, casting doubt over his availability to play Sunday at Green Bay. Purdy is dealing with a right shoulder injury and the 49ers are also potentially without left tackle Trent Williams and Nick Bosa due to injuries. Bosa was listed as out of Thursday's practice with an oblique injury. Williams also didn't suit up Thursday. He played through an ankle injury last week after being listed as questionable. Purdy's typical Thursday post-practice media session was scrapped until Friday as the 49ers did not make any quarterback available. Kyle Allen would step in for Purdy as the starter if he can't play against the Packers. Run game coordinator Chris Foerster said the 49ers aren't where they want to be at 5-5 because they haven't won close games, not because of injuries. "Seven games left is like an eternity," Foerster said. "So much can happen. Do the math. What was our record last year? It was 12-5. I was on a 13-win team that was nowhere near as good as the team last year." With or without Purdy, Foerster said the challenge for the 49ers is not to give up the ball to a defense that has 19 takeaways. The 49ers have 13 giveaways this season. --Field Level Media

Trump wants pardoned real estate developer Charles Kushner to be ambassador to FranceTexas, Arizona State to meet in CFP clash of old vs. new Big 12 champs

De'Vondre Campbell's mid-game quitting overshadowed the 49ers' offensive woesAMGEN ANNOUNCES 2025 FIRST QUARTER DIVIDENDAs Trump prepares to take office, ports and dockworkers are facing down a new strike

Black Friday, November 29, has passed, but that doesn't mean it's too late to score the best deals of 2024. I've worked through numerous Black Fridays over the years, and my experience has always been the same: about half of the deals end on Black Friday at midnight, and the other half will stay live through the weekend and end on Cyber Monday (which lands on December 2). I have seen some amazing deals this year and at this point many are still available. I can promise you there will not be a shortage of incredible deals from now until December 2. In terms of deal quality, Black Friday 2024 has shaped up to be a golden year across several categories and expect this gravy train to continue into Cyber Monday. There are better-than-expected discounts on gaming consoles like the PlayStation 5 , Nintendo Switch , Meta Quest 3S , and Steam Deck, several Apple iPads , AirPods , and Apple Watches, including new 2024 models, rarely discounted video games (including top-shelf Switch games priced well under $40), powerful gaming PCs and laptops, and much, much more. Whether you're hunting down a specific deal, or casually perusing the top 100 Black Friday deals so far, I've got you covered. TL;DR - Best Black Friday Deals Meta Quest 3S (Free $75 Amazon Credit) - $299 Meta Quest 3 (Free $75 Amazon Credit) - $499 Nintendo Switch OLED Holiday Bundle - $274.99 Nintendo Switch Holiday Bundle - $224.99 PS5 Cobalt Star Disc Bundle - $424.99 PS5 NBA 2K25 Digital Bundle - $374.99 Hulu for $0.99/mo for 12 Months Apple AirPods Pro - $153.99 JLabs JBuds Lux Noise Cancelling Headphones - $29 The Legend of Zelda: Tears of the Kingdom - $30 Star Wars Outlaws - $39.99 The Best Black Friday VR Headset Deal At $299.99, the Meta Quest 3S was inarguably the best value out there in the world of VR gaming, but the deal's even better. Both Amazon and Target are including freebies: Amazon shoppers get a bonus $75 in Amazon digital credit , and Target shoppers get a bonus $75 Target gift card . The Quest 3S also includes the Batman: Arkham Shadow VR game. What really sets this deal above all other VR deals (like the PlayStation VR2 ) is that the Meta Quest 3S can be played completely untethered. That means you can play games like Beat Saber or Pistol Whip without having to own a powerful gaming PC or a PlayStation 5 console. Try to find another standalone VR headset at this price and you'll come up empty. The Other Best Black Friday VR Headset Deal Deep into Black Friday, Amazon has finally offered a pretty sweet deal on a Meta Quest 3 512GB VR headset. You can get it for the current retail price of $499.99, however Amazon is throwing in a bonus $75 in Amazon digital credit. Reminder that it was less than two months go that Meta dropped the official retail price from $649.99 to $499.99. The Meta Quest 3 is the best standalone consumer-oriented VR headset you can get right now. The Quest 3S has very similar internals, and the same Touch controllers, but with downgraded optics. That's more significant than it reads on paper. How much enjoyment you get from VR headset is largely determined by the visual quality of the display.. If the image that you see is blurry, or distorted, it takes you out of the immersion. Sony released its entire set of Black Friday PlayStation deals last week and most major retailers have followed suit. The best deal is definitely on the consoles themselves and not the accessories: The PS5 Slim Disc Edition has dropped to $424.99 (originally $500) and the PS5 Slim Digital Edition has dropped to $374.99 (originally $450). I would choose the Disc Edition because it's only $50 more and then I have the option to buy (and later sell or trade) physical disc media. But if you want to save some money and go the Digital Edition route, I would suggest getting the NBA 2K25 bundle (see below), which also includes a game. Although the Fortnite Cobalt Star bundle has a fancy-looking box, no actual game is included. More PlayStation Black Friday Deals Star Wars: Outlaws was released only three months ago and it's already 33% off for Black Friday. Maybe Ubisoft is trying to boost sales after a lackluster launch , but that means you get to enjoy a AAA title at a great discount. IGN's Tristan Ogilvie gave it a 7/10 review, which is still good, but I've beaten the game and immensely enjoyed it, so I would have given it an 8. It definitely has an "Assassin's Creed game in a Star Wars skin" vibe, and there's nothing wrong with that. More Black Friday Video Game Deals for PS5/Xbox Compared to the PS5 and Xbox Series X, the Nintendo Switch console has the best discount for Black Friday. The early holiday bundles, which were released back in October, included your choice of the Switch or Switch OLED , a digital download voucher for Mario Kart 8 Deluxe , and a 12-month Switch Online membership. I thought that this was going to be the official Black Friday deal. Alas, Target ( but not Amazon, due to its supposedly shaky relationship with Nintendo ) has just knocked another $75 off the price tag. That means you can pick up a Switch bundle for as low as $225. I have both models and, if I were to buy a third, it would be the Switch OLED. The screen is that much better. More Nintendo Switch Black Friday Deals For the moment, Walmart is the only retailer offering Tears of the Kingdom for $30. IGN gave it a 10/10 "Masterpiece" rating and I would have to agree. Tom Marks wrote that "The Legend of Zelda: Tears of the Kingdom is an unfathomable follow-up, expanding a world that already felt full beyond expectation and raising the bar ever higher into the clouds." I wouldn't wait too long to get this deal; Walmart is already sold out of physical copies. More Black Friday Video Game Deals for Nintendo Switch The least expensive adjustable dumbells Bowflex isn't the only option when it comes to adjustable dumbbell sets, especially on Black Friday. FitRX is another popular brand at a much, much lower price point. As part of the Walmart Black Friday Sale , you can pick up a pair of FitRx Adjustable Dumbbells for only $139.97. A comparable set of Bowflex 551 adjustable dumbbells costs three times more . Walmart even offers free shipping, which is great since the package will weigh in at well over 100 pounds. The Best Black Friday Streaming Deal This Black Friday, Hulu is available for just $0.99/month for an entire year – down from $9.99/month, and at 90% off that's hard to beat. Similarly, the Disney+ bundle is being offered at $2.99/month for a year , down from $10.99/month, making these some of the best Black Friday streaming deals available. Don't miss out. Hulu stands out as one of the top streaming platforms today, yet it’s often underrated. With critically acclaimed movies like Anatomy of a Fall and Talk to Me , and standout, Emmy-winning TV series such as Shogun , Abbott Elementary , The Bear , and Only Murders in the Building , there’s always something exceptional to watch. The best Black Friday AirPods deal has arrived and it's better than I predicted . Amazon, Target, and Walmart have all dropped the price of the second-generation Apple AirPods Pro wireless noise-cancelling earbuds to $153.99. This discount brings the price down to the same level as the Apple AirPods 4 with noise cancellation . Between the two, the AirPods Pro is still Apple's best earbuds because it offers better sound quality and better noise cancellation performance. There are a lot of amazing iPad deals today, like the new iPad Mini for $399.99 or the iPad Pro M4 for $850 , but this is the best deal for most people. The standard iPad is the model I'd recommend; it offers snappy performance and the intuitive iOS interface at a low price. Tenth gen improvements over its predecessor include a larger 10.9" screen and a faster A14 Bionic chip, Magic Folio keyboard support so you can convert it into a mini laptop (making it one of the best iPads for students ), a USB Type-C port, better camera, and updated Wi-Fi 6 protocol. For anyone on a budget, this is the Apple Watch to get . The second generation Apple Watch SE starts at just $149 only at Amazon and Walmart . This is the best price we've ever seen for a brand-new Apple Watch with a warranty. Despite the affordable price tag, you actually don't lose out on much functionality if you opt for an Apple Watch SE. It's powered by the same S8 processor found in the Apple Watch Series 8 and the first-generation Apple Watch Ultra. It also features a bright and sharp OLED Retina display, IPX7 water resistance, fall detection, sleep tracking, Apple Pay, and nearly all the fitness tracking functionality including heart rate monitoring. More Apple Black Friday Deals Lots of interactive elements for a display-worthy set This popular LEGO Creator set rarely goes on sale. Today, LEGO Shop is offering the LEGO NASA Space Shuttle Discovery 10283 set for $159.99, or a savings of 20%. You'll need to be a LEGO Insiders member, but signing up is free. This impressive set consists of 2,354 bricks, which averages out to about 6.7 cents per brick. As its namesake suggests, this is a replica of the Space Shuttle Discovery, with a center compartment that opens up and houses a separate Hubble telescope, which can be deployed with a robot arm. It looks amazing as a display, but it's also very interactive. Up to 50% Off These Smart Glasses There's a very intriguing – if a bit controversial – deal going on that you might want to check out for yourself. Both Amazon and Target are offering a 20% discount off the Ray-Ban Meta Wayfarer Smart Glasses , with prices starting at $239.20. That's the same deal you'll find at other retailers, however Amazon and Target are throwing in additional freebies: either $90 in Amazon digital credit or a $90 Target gift card. The Meta Wayfarer glasses are an influencer's dream, and that's exactly what they're designed for: social media. They're surprisingly slim and lightweight for glasses equipped with an integrated 12MP video camera and speaker. You can use them to take quick snapshots or up to 60 second videos that you can then upload to your social media of choice. You can even livestream 30 second videos in 720p. Includes One-Time $20 Audible Credit See deal in the UK - £0.99/month for three months (was £7.99) From now until December 31, non-current Audible subscribers are eligible for three months of Audible Premium Plus for $0.99 per month and a bonus one-time $20 Audible credit. Premium Plus is Audible's best plan and three months would normally cost you about $44.95. You also get a free audiobook of your choice each month that you get to keep indefinitely. Audible is a subscription service that gives you access to hundreds of thousands of the best audiobooks without ever having to purchase them. Premium Plus is Audible's highest tier plan and it gives you access to a whopping 500,000 audiobooks. These include all-time classics like Frank Herbert's Dune , Harry Potter, Game of Thrones (A Song of Ice and Fire), The Witcher , The Sandman Series, and The Lord of the Rings . Where Are the Xbox Deals? Xbox gamers might be wondering why I haven't listed Xbox consoles. Unfortunately, Microsoft seems to have taken a step back and decided not to host any outstanding console deals for Black Friday. All of the consoles are marked down by $50, but these deals aren't exceptional. If you're already an Xbox owner, however, and are looking for discounts on peripherals, there are two great deals to consider. The WD Black C50 Storage Expansion Card is down to $99.99 from $150. Also, Xbox wireless controllers are down to as low as $39.99. Even better, the limited edition Ghost Cipher and Sky Cipher controllers are both on sale for just $45 each. One of the best gaming PC deals to come out of the Alienware Black Friday Sale is this Alienware Aurora R16 configuration for $1,499.99. It's the least expensive desktop computer equipped with an RTX 4070 Ti Super GPU. The rest of the specs are up to snuff as well, like an Intel Core i7-14700 CPU, 16GB of DDR5 RAM, and a 1TB NVMe SSD. The RTX 4070 Ti Super GPU is good enough to run even the newest games at up to 4K resolution (in fact, it's the least expensive GPU that I'd recommend for high-framerate 4K gaming), although I'd say that 1440p is its sweet spot. More Black Friday Gaming PC Deals The Walmart Black Friday Sale brings with it this excellent gaming laptop deal. Walmart is offering a Lenovo LOQ RTX 4070 gaming laptop for only $879.99. Yes, you read that right. The LOQ is Lenovo's lineup of budget-oriented gaming laptops. This system features a 15" 1080p display, a low-voltage AMD Ryzen 7 7435HS CPU, GeForce RTX 4070 GPU, 16GB of RAM, and a 512GB SSD. The RTX 4070 GPU is a fully powered (115W TGP) model, not a throttled one like on some other budget laptops. Despite its low cost, this laptop will perform almost as well as the best RTX 4070 gaming laptops. You should be able to play any game comfortably on the 1080p display. More Black Friday Gaming Laptop Deals Perhaps the best Black Friday deal on a high-end gaming monitor has arrived. Amazon is offering the massive 57" Samsung Odyssey Neo G9 Dual 4K UHD gaming monitor at the exclusive price of $1,499.99. That's $100 less than everyone else's gaming monitor Black Friday deal and nearly 50% off the retail price. Keep in mind that there is no other monitor to compare it with. If you're looking for the biggest and sharpest super ultra-wide gaming monitor on the planet, this would be it right here. Just make sure that your GPU is up to snuff. Alienware just sweetened the deal on its best gaming monitor for Black Friday Sale. Right now, the 32" Alienware AW3225QF 32" 4K QD OLED gaming monitor is down to $899.99. That's the lowest price I've seen all year long. However for Black Friday only, Alienware just tossed in a bonus $100 Dell promotional e-gift card with your purchase. The Alienware AW3225QF was released earlier this year and is actually Dell's one and only monitor that combines a 4K resolution with an OLED panel. More Black Friday Gaming Monitor Deals Best Buy is the only retailer to drop the price on the new Asus ROG Ally X so far for Black Friday. Right now you can get it for $699.99 after a $100 instant discount. In our Asus ROG Ally X review , gaming guru Jacqueline Thomas wrote that "the Asus ROG Ally X is simply the best handheld gaming PC on the market right now. With more and faster memory and double the battery as the original Ally, the Ally X will run any modern game without dying in an hour and a half." More Black Friday PC Gaming Deals Black Friday TV Deals These JLabs JBuds Lux are an incredible value. First of all, they feature both wireless connectivity and noise cancellation for under $30. Better yet, unlike virtually all other headphones at this price point, they're actually very good! SoundGuys recently reviewed the JLabs JBuds Lux and gave it an absolutely glowing review, mentioning that they were one of the best headphones under $100. SoundGuys considered them an extremely good value at their retail price of $79 . Imagine their opinion at the current $29 price point. More Black Friday Headphone Deals You can pick up a copy of Azul for only $20 for Black Friday. Many board games are about mystery or war, but Azul is totally different. Players in Azul compete to design the most beautiful tiled mosaics they can. In our Azul review , Matt Thrower writes, "Between its beautiful presentation, simplicity and depth there’s little doubt that Azul has earned its place as a modern classic. While the tinkering with its formula undertaken by its sequels has created more challenging games, none has captured the fine blend of accessibility and interactivity that makes it special." More Black Friday Board Games The Coolest Toy for Gamers One deal you might have missed is this really awesome MEGA Microsoft Xbox 360 Collector Building Set . It's normally $150 but there's a 50% discount for Black Friday that drops it to only $74.99. The MEGA Microsoft Xbox 360 Collector Building Set is a buildable 3:4 scale replica of the Xbox 360 console with a brick count total of 1,342 pieces (5.5 cents per brick). The details in this build are, frankly, incredible, and include interactive elements, lighting effects, and the coolest accessories. This is such an interesting product that I wrote up a dedicated Black Friday article just for this deal . iFixit might be a familiar brand name for you from all of the helpful teardown videos of various electronics that've hosted on YouTube. Well, they also sell an extremely practical and high quality toolkit that helps you do the same. Amazon is offering the iFixit Pro Tech Toolkit for electronics, smartphones, gaming consoles, PCs and laptops, and tablets for only $59.96. It normally retails for $75 and we've only seen a price drop only once this year back in May. This is one of the very best tool kits you can buy for disassembling and repairing your electronics -- including your Nintendo Switch and Steam Deck -- without spending hundreds of dollars on a commercial kit. More Random Black Friday Deals Amazon, Target, Walmart, and Best Buy are all one-stop shopping sites, so it makes sense that their Black Friday sales extend beyond gaming and tech. Here are the best deals I've seen so far on small kitchen appliances, personal care products like hair dryers and toothbrushes , vacuum cleaners , and other convenient necessities that everyone – gamers included – might find useful. On a personal note, although air fryers are all the rage these days, I bought my Instant Pot pressure cooker over 10 years ago and I still use it weekly. My air fryer sits in the cabinet. If you prefer to shop by retailer, we've written up Black Friday Deals roundups for each of the major retailers: Amazon, Target, Walmart, Best Buy, and Gamestop. Check them out below: Amazon Black Friday Sale Target Black Friday Sale Walmart Black Friday Sale Best Buy Black Friday Sale Gamestop Black Friday Sale Dell Black Friday Sale Alienware Black Friday Sale Lenovo Cyber Monday Sale HP Black Friday Sale Secretlab Black Friday Sale Sonos Black Friday Sale Will the Deals Change for Cyber Monday? In my experience, many of the same deals we saw on Black Friday will return for Cyber Monday 2024 , including deals that were sold out or expired. Retailers usually release their hottest selling items in batches so that every sale event has at least some inventory reserved. That said, I also expect plenty of new, never before seen deals. Traditionally, Black Friday was known as the "retail holiday," where the best deals were found in-store, and Cyber Monday was known as the "online holiday," where the best deals were online only. Although today the lines have blurred, it is still true that many online only retailers still consider Cyber Monday the sale event of the year instead of Black Friday . Expect some amazing sales to come out of online-only sites like Amazon, Newegg, Dell, HP, Lenovo and several online-only deals from traditional retailers like Best Buy, Target, and Walmart. In fact, Amazon has taken the preemptive and already switched over to Cyber Monday. Eric Song is the IGN commerce manager in charge of finding the best gaming and tech deals every day. When Eric isn't hunting for deals for other people at work, he's hunting for deals for himself during his free time.

(WEST PALM BEACH, Fla.) — First it was , then the . Now, again wants . The President-elect is renewing unsuccessful for the U.S. to buy Greenland from Denmark, adding to the list of allied countries with which he's picking fights even before taking office on Jan. 20. In a Sunday announcement naming his ambassador to Denmark, Trump wrote that, “For purposes of National Security and Freedom throughout the World, the United States of America feels that the ownership and control of Greenland is an absolute necessity." Trump again having designs on Greenland comes after the President-elect suggested over the weekend that the U.S. could retake control of the Panama Canal if something isn't done to ease rising shipping costs required for using the waterway linking the Atlantic and Pacific oceans. He's also been suggesting that Canada become the 51st U.S. state and referred to Canadian Prime Minister as “governor” of the “Great State of Canada.” Stephen Farnsworth, a political science professor at the University of Mary Washington in Fredericksburg, Virginia, said Trump tweaking friendly countries harkens back to an aggressive style he used during his days in business. “You ask something unreasonable and it’s more likely you can get something less unreasonable,” said Farnsworth, who is also author of the book “Presidential Communication and Character.” Greenland, the world’s largest island, sits between the Atlantic and Arctic oceans. It is 80% covered by an ice sheet and is home to a large U.S. military base. It gained home rule from Denmark in 1979 and its head of government, Múte Bourup Egede, suggested that Trump’s latest calls for U.S. control would be as meaningless as those made in his first term. “Greenland is ours. We are not for sale and will never be for sale,” he said in a statement. “We must not lose our years-long fight for freedom.” Trump after his was rejected by Copenhagen, and ultimately . He also suggested Sunday that the U.S. is getting “ripped off” at the Panama Canal. “If the principles, both moral and legal, of this magnanimous gesture of giving are not followed, then we will demand that the Panama Canal be returned to the United States of America, in full, quickly and without question,” he said. Panama President responded in a video that “every square meter of the canal belongs to Panama and will continue to,” but Trump fired back on his social media site, “We’ll see about that!” The President-elect also posted a picture of a U.S. flag planted in the canal zone under the phrase, “Welcome to the United States Canal!” The United States built the canal in the early 1900s but relinquished control to on Dec. 31, 1999, under a treaty signed in 1977 by President . The canal depends on reservoirs that were hit by 2023 droughts that forced it to substantially reduce the number of daily slots for crossing ships. With fewer ships, administrators also increased the fees that shippers are charged to reserve slots to use the canal. The Greenland and Panama flareups followed Trump recently posting that “Canadians want Canada to become the 51st State" and offering an image of himself superimposed on a mountaintop surveying surrounding territory next to a Canadian flag. Trudeau about annexing his country, but the pair met recently at Trump's Mar-a-Lago club in Florida to discuss Trump's threats to impose on all Canadian goods. “Canada is not going to become part of the United States, but Trump’s comments are more about leveraging what he says to get concessions from Canada by putting Canada off balance, particularly given the precarious current political environment in Canada,” Farnsworth said. “Maybe claim a win on trade concessions, a tighter border or other things.” He said the situation is similar with Greenland. “What Trump wants is a win," Farnsworth said. "And even if the American flag doesn’t raise over Greenland, Europeans may be more willing to say yes to something else because of the pressure.” __ Associated Press Writer Gary Fields in Washington contributed to this report.CRENESSITY, the first new treatment available in 70 years to the classic congenital adrenal hyperplasia (CAH) community, offers a paradigm-shifting treatment approach FDA approval supported by data from the largest-ever clinical trial program in pediatric and adult patients with classic CAH CRENESSITY is expected to be commercially available in approximately one week Rare Pediatric Disease Priority Review Voucher granted in connection with approval SAN DIEGO , Dec. 13, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. NBIX today announced the U.S. Food and Drug Administration has approved CRENESSITYTM (crinecerfont) capsules and oral solution as an adjunctive treatment to glucocorticoid replacement to control androgens in adult and pediatric patients four years of age and older with classic congenital adrenal hyperplasia (CAH), a rare, serious and lifelong genetic condition involving the adrenal glands. CRENESSITY, a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF 1 ) antagonist, is the first and only classic CAH treatment that directly reduces excess adrenocorticotropic hormone (ACTH) and downstream adrenal androgen production, allowing for glucocorticoid dose reduction. It is a breakthrough in the treatment landscape for classic CAH. "For the last three decades, Neurocrine Biosciences, together with our late founder, Wylie W. Vale , has conducted groundbreaking research uncovering the critical role of corticotropin-releasing factor and its receptor, CRF 1 , in the pathophysiology of congenital adrenal hyperplasia," said Kyle W. Gano , Ph.D., Chief Executive Officer, Neurocrine Biosciences. "The approval of CRENESSITY is a significant milestone for the CAH community, and we are grateful to the individuals who participated in our clinical trials, including their families and caregivers, and to the clinical investigators who helped advance a new therapy and class of medicines." "Patients and families struggle to achieve balance between managing the symptoms of CAH and the side effects or complications of treatment with high-dose steroids, which may impact quality of life," said Dina Matos , Executive Director, CARES Foundation. "We are grateful to Neurocrine Biosciences for engaging with our community throughout the drug development process to understand our needs and ultimately providing this new medication that can help reduce excess adrenal androgens and the need for high-dose steroid treatment for individuals living with CAH." CRENESSITY is expected to be commercially available in approximately one week. The medication will be provided through PANTHERx Rare, a specialty pharmacy, to centralize and simplify CRENESSITY prescription fulfillment. Neurocrine Biosciences is committed to supporting patients in obtaining treatment with CRENESSITY by offering Neurocrine Access Support, a free, comprehensive assistance program created for patients, caregivers and healthcare providers. It offers a range of options to make sure patients have everything they need to begin and continue taking CRENESSITY. A dedicated Care Coordinator, backed by a team, is available to help patients and caregivers navigate the insurance process and identify appropriate financial assistance options. Most patients will pay $10 or less per month for CRENESSITY*. For more information, visit www.NBIacces.com/crenessity or call 1-855-CRNSITY (276-7489) Monday-Friday 8 am-8 pm ET . *Additional terms and conditions apply. CAHtalyst TM Clinical Program Overview: The FDA approval is supported by the largest-ever clinical trial program of classic CAH, the CAHtalyst Pediatric and Adult Phase 3 global registrational studies. CAHtalyst Phase 3 data results in pediatric and adult patients with classic CAH were published in The New England Journal of Medicine . "The clinical results across both CAHtalyst studies support the efficacy and safety profile of CRENESSITY and its ability to reduce the overproduction of adrenal androgens, allowing for a meaningful reduction in glucocorticoid dosage, while maintaining or enhancing control of these androgens," said Richard Auchus , M.D., Ph.D., Professor, University of Michigan Health, Principal Investigator. "Chronic treatment with supraphysiologic glucocorticoids can cause a number of short- and long-term health consequences, such as obesity, hypertension and osteoporosis, so the ability for patients with CAH to lower their glucocorticoid dose to a more physiologic level can have profound benefits." In both CAHtalyst studies, CRENESSITY enabled lower steroid doses and decreased androgen levels. Phase 3 CAHtalyst Pediatric Study: The CAHtalyst Pediatric study met its primary endpoint, with CRENESSITY significantly decreasing androstenedione levels from baseline to Week 4 versus patients taking placebo who experienced a substantial increase in androstenedione levels. Children taking CRENESSITY were also able to significantly reduce their GC doses at Week 28 while maintaining or improving androgen levels, a key secondary endpoint. Children taking CRENESSITY saw approximately four times greater reduction in androstenedione compared with those taking placebo. Approximately four times greater steroid dose reduction in children taking CRENESSITY was seen compared with those taking placebo. Children taking CRENESSITY saw approximately 12 times greater reduction in 17-hydroxyprogesterone (17-OHP) compared with those taking placebo. Headache, abdominal pain, fatigue, nasal congestion and nosebleed were the most common adverse drug reactions (ADRs) among the pediatric population treated with CRENESSITY. Most side effects were temporary and mild to moderate in severity. Phase 3 CAHtalyst Adult Study: The CAHtalyst Adult study met its primary endpoint with CRENESSITY enabling significant GC dose reductions at Week 24 (while maintaining or improving baseline androstenedione levels) and key secondary endpoint of decreasing androstenedione levels at Week 4. A significantly higher number of patients taking CRENESSITY (63%) achieved a GC dose in the physiologic range while androstenedione was maintained or improved compared with patients taking placebo (18%). Approximately two times greater steroid dose reduction was seen in people taking CRENESSITY compared with those taking placebo. People taking CRENESSITY saw an eight times greater reduction in androstenedione compared with those taking placebo. People taking CRENESSITY saw a 37 times greater reduction in 17-OHP compared with those taking placebo. Fatigue, headache, dizziness, joint pain, back pain, decreased appetite and muscle pain were the most common ADRs in the CRENESSITY treatment group. Most side effects were temporary and mild to moderate in severity. CRENESSITY was well tolerated with few treatment-related adverse events in both CAHtalyst studies. Pediatric and adult patients taking CRENESSITY had no treatment-related serious adverse events. Adrenal insufficiency and crisis are risks of living with CAH that CRENESSITY does not address and can occur when a patient's GC dose is too low. In the CAHtalyst Pediatric study, there were no cases of adrenal crisis among patients taking CRENESSITY or placebo. In the CAHtalyst Adult study, two patients (1.6%) taking CRENESSITY experienced adrenal crisis. No patients on placebo experienced adrenal crisis. However, one patient (1.7%) on placebo experienced adrenal insufficiency. Patients should work with their healthcare provider to manage GC dosing while taking CRENESSITY. For more information about CRENESSITY, visit Crenessity.com . About Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia (CAH) is a rare genetic condition that results in an enzyme deficiency that alters the production of adrenal steroid hormones, such as cortisol, aldosterone and adrenal androgens, which are essential for life. Approximately 95% of CAH cases are caused by variants of the CYP21A2 gene that leads to deficiency of the enzyme 21-hydroxylase (21-OH). Severe deficiency of this enzyme leads to an inability of the adrenal glands to produce enough cortisol and, in approximately 75% of cases, aldosterone. Because individuals with CAH are still able to produce androgens, the unused precursors that would normally be used to make cortisol instead result in the production of excess amounts of androgens. If left untreated, CAH can result in salt wasting, dehydration and even death. Historically, exogenous glucocorticoids (GCs) have been used not only to correct the endogenous cortisol deficiency, but doses used are higher than cortisol replacement needed (supraphysiologic) to lower the levels of adrenocorticotropic hormone (ACTH) and adrenal androgens. However, GC treatment at high doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease and osteoporosis. Additionally, long-term treatment with high-dose GCs may have psychological and cognitive impact, such as changes in mood and memory. Adrenal androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as excess facial hair growth and menstrual irregularities, testicular rest tumors in males and fertility issues in both sexes. About The CAHtalystTM Studies The Phase 3 CAHtalystTM global registrational studies were designed to evaluate the safety, efficacy and tolerability of CRENESSITY in children and adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The CAHtalyst studies were the largest-ever clinical trial program in classic CAH, including 285 pediatric and adult patients. The CAHtalyst Pediatric study included 103 pediatric patients aged four to 17 years. The study tested two questions. The first question evaluated whether four weeks of CRENESSITY treatment could improve androgen control. The second question evaluated whether an additional 24 weeks of CRENESSITY treatment enabled customized glucocorticoid (GC) down-titration while androstenedione levels were maintained or improved. The CAHtalyst Adult study included 182 adult patients aged 18 to 58 years. Similarly, the first question of the study evaluated whether four weeks of CRENESSITY treatment could improve androgen control, and the second question evaluated whether an additional 20 weeks of CRENESSITY treatment enabled GC reduction to physiologic range while androstenedione levels were maintained or improved. Data from the CAHtalyst Phase 3 studies supported approval of CRENESSITY by the U.S. Food and Drug Administration in December 2024. The open-label extension treatment portions of both studies are ongoing. About CRENESSITYTM (crinecerfont) CRENESSITYTM is a potent and selective, oral corticotropin-releasing factor type 1 receptor (CRF 1 ) antagonist developed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism for the treatment of classic congenital adrenal hyperplasia (CAH). Antagonism of CRF 1 receptors in the pituitary has been shown to decrease ACTH levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with CAH. The robust clinical study data demonstrate that lowering adrenal androgen levels with CRENESSITY enables lower, more physiologic dosing of GCs to replace missing cortisol. CRENESSITY comes in capsules and an oral solution. The capsule formulation is available in 50 mg and 100 mg doses. The oral solution is available as a 50 mg/mL strength formulation. For adults 18 years and older, the recommended dosage is 100 mg twice daily taken orally with a meal. For pediatric patients four to 17 years of age weighing less than 55 kg (121 lbs), the recommended dosage is based on body weight and is administered twice daily, taken orally with a meal. For pediatric patients weighing more than 55 kg (121 lbs), the recommended dosage is 100 mg twice daily taken orally with a meal. Healthcare providers can work with patients to determine the appropriate formulation for use depending on patient needs. Patients receiving CRENESSITY should continue GC therapy for cortisol replacement. Important Information Approved Uses CRENESSITY (crinecerfont) is a prescription medicine used together with glucocorticoids (steroids) to control androgen (testosterone-like hormone) levels in adults and children 4 years of age and older with classic congenital adrenal hyperplasia (CAH). IMPORTANT SAFETY INFORMATION Do not take CRENESSITY if you: Are allergic to crinecerfont, or any of the ingredients in CRENESSITY. CRENESSITY may cause serious side effects, including : Allergic Reactions. Symptoms of an allergic reaction include tightness of the throat, trouble breathing or swallowing, swelling of the lips, tongue, or face, and rash. If you have an allergic reaction to CRENESSITY, get emergency medical help right away and stop taking CRENESSITY. Risk of Sudden Adrenal Insufficiency or Adrenal Crisis With Too Little Glucocorticoid (Steroid) Medicine. Sudden adrenal insufficiency or adrenal crisis can happen in people with congenital adrenal hyperplasia who are not taking enough glucocorticoid (steroid) medicine. You should continue taking your glucocorticoid (steroid) medicine during treatment with CRENESSITY. Certain conditions such as infection, severe injury, or shock may increase your risk for sudden adrenal insufficiency or adrenal crisis. Tell your healthcare provider if you get a severe injury, infection, illness, or have planned surgery during treatment. Your healthcare provider may need to change your dose of glucocorticoid (steroid) medicine. Before taking CRENESSITY, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take , including prescription and over-the counter medicines, vitamins, and herbal supplements. The most common side effects of CRENESSITY in adults include tiredness, headache, dizziness, joint pain, back pain, decreased appetite, and muscle pain. The most common side effects of CRENESSITY in children include headache, stomach pain, tiredness, nasal congestion, and nose bleeds. These are not all the possible side effects of CRENESSITY. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088. Dosage Forms and Strengths: CRENESSITY is available in 50 mg and 100 mg capsules and as an oral solution of 50 mg/mL. Please see full Prescribing Information About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com , and follow the company on LinkedIn , X (formerly Twitter) and Facebook . (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. CRENESSITY and CAHtalyst are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from CRENESSITY for the treatment of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency; the value and benefits CRENESSITY brings to patients with CAH; the ability of Neurocrine Biosciences to ensure patients have access to CRENESSITY; and whether the results from our clinical trials of CRENESSITY are indicative of real-world results. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of CRENESSITY; whether CRENESSITY receives adequate reimbursement from third-party payors; the degree and pace of market uptake of CRENESSITY; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; risks associated with the Company's dependence on third parties for development and manufacturing activities related to CRENESSITY, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for CRENESSITY or other product candidates may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding CRENESSITY; risks that post-approval CRENESSITY commitments or requirements may be delayed; risks that CRENESSITY may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended September 30, 2024 . Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. © 2024 Neurocrine Biosciences, Inc. All Rights Reserved. CP-CFT-US-0070 12/2024 View original content to download multimedia: https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-fda-approval-of-crenessity-crinecerfont-a-first-in-class-treatment-for-children-and-adults-with-classic-congenital-adrenal-hyperplasia-302331772.html SOURCE Neurocrine Biosciences, Inc. © 2024 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.