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A dazzling speculative novel ponders life's possibilities

A dazzling speculative novel ponders life's possibilities

Washington Post20-07-2025
The Oscar-nominated film 'Past Lives' was the wistful story of a love triangle. But the tension for its female protagonist was not simply between two partners but between two selves — a past in Seoul lived in Korean and a present as a New Yorker thriving in English. Suspended in that tension between here and there, its screenplay by director Celine Song was a classic work of immigrant fiction. Counterfactuals and imagined homelands have always haunted and inspired displaced artists. In his debut novel, 'Archive of Unknown Universes,' the brilliant young writer Ruben Reyes Jr. turns that art of speculation into a riveting saga of answers.
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Horror's middle class is vanishing – and that's bad news for all film fans
Horror's middle class is vanishing – and that's bad news for all film fans

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Horror's middle class is vanishing – and that's bad news for all film fans

Does no one want to watch people get butchered any more? Horror, long recognised as one of Hollywood's most reliable cash cows, is in a panic: few scary movies are breaking through financially in 2025, many more are cratering completely, and questions are being asked about the future of a genre that once seemed as durable as Jason Voorhees. Forget the death of the archetypal movie star: if sassy psycho-cyborg M3GAN can't open a movie, who can? Back in 2022, the first M3GAN – about an artificially intelligent doll with a bloodthirst – grossed $182m (£135m), including $78m of pure profit for its backers at Universal Pictures and the micro-budget horror studio Blumhouse, off a production budget of just $12m. Thanks to smart marketing, which turned its leading lady's incongruous dancefloor skills into a spooky meme, M3GAN ended up exemplifying the dream outcome of the modern studio horror film: low-cost, big-brain thrills with such inescapable dazzle that audiences couldn't not seek it out. Why, then, did last month's M3GAN 2.0 go so badly? In four weeks, the more action-oriented sequel has grossed a measly $38m worldwide, a result so mortifying that the head of Blumhouse put his hands up within days of its release and admitted to having totally missed the mark. M3GAN 2.0 isn't alone, either. This year has seen a staggering number of horror films die at the box office, among them Blumhouse's reboot of Wolf Man ($34m gross on a production budget of $20m), the Ayo Edebiri horror comedy Opus ($2m gross/$10m budget), Jenna Ortega vehicle Death of a Unicorn ($16m gross/$15m budget), the well-received adoption chiller Bring Her Back ($23m gross/$15m budget), and last week's revival of the Nineties hit I Know What You Did Last Summer, which opened to a flat $13m in the US. Yes, these films' production budgets are lean (though the extent of marketing budgets is largely kept under lock and key), and many of the above titles will ultimately break even once video-on-demand grosses are factored in – but none of their respective backers will be happy with what amounts to loose change. On the other end of the spectrum, meanwhile, are this year's handful of out-and-out horror smashes, most significantly the Michael B Jordan vampire film Sinners, which cost a reported $100m to make but has grossed $365m. There's also been Final Destination: Bloodlines ($285m and counting on a budget of $50m) and Danny Boyle's 28 Years Later, which has so far grossed $145m on a budget of $60m – not wildly profitable, by any means, but decent enough. So people are still going to see horror on the big screen, but – echoing the Western world as a whole – horror's middle class is evaporating. The genre seems to either go big or collapse entirely. Any kind of financial in-between is rapidly becoming a thing of the past. All this leaves a film such as next week's Weapons carrying undue levels of pressure. A missing-persons thriller starring Julia Garner and Josh Brolin, it revolves around the disappearance of a class of children in small-town USA, and serves as filmmaker Zach Cregger's follow-up to his 2022 sleeper hit Barbarian. Promotion for the film has been strong – lots of abstract and eerie imagery in trailers, and attempts at virality via the publishing of two hours of 'surveillance footage' from the night of the children's 'disappearance'. But the stakes feel particularly high. Weapons sparked a bidding war between rival studios when Cregger first unveiled his script, with Warner Bros so eager to get the up-and-comer on side that they coughed up a $38m budget for the film, and allowed him final cut. If Weapons underperforms, this kind of investment in a young, ambitious filmmaker's original ideas may become even rarer than it is already. Why this is bad for everyone is that, in the last decade or so, horror has been one of the few genres to wholeheartedly embrace fresh ideas and fresh voices. The likes of Jordan Peele's Get Out (2017), Coralie Fargeat's The Substance (2024), Ari Aster's Hereditary (2018) and Robert Eggers's The Witch (2015) proved that audiences will turn out in droves for intriguing new concepts, no matter how wild they might seem on paper – and in the process, an entire generation of buzzy new filmmakers developed fanbases, industry clout, and (relative) name recognition. Speaking to The Town podcast shortly after M3GAN 2.0 bombed, Blumhouse head Jason Blum suggested that there is simply too much horror being released for many films to break through, and that the cheap-to-produce movies that were Blumhouse's bread and butter (their biggest hits have included Get Out, Us, The Invisible Man and the Purge franchise) no longer cut it. 'We need to up the budgets,' he insisted. 'People need theatrical events.' Which is, I suppose, accurate. This year's most successful horror films had heavy promotional spends behind them, while even the most financially lucrative horrors of 2024 – meaning the low-cost, high-return likes of The Substance and Oz Perkins's Silence of the Lambs pastiche Longlegs – were transformed into must-see 'events' via relentless and effective marketing. But just as important is the actual quality of material on offer, with far too many modern horror movies settling for tedious mining of intellectual property and repetitive premises (Knives Out and Midsommar have created an unfortunate cottage industry of star-studded, eat-the-rich, religious-cult disappointments). Blumhouse have been particularly guilty of this over the last 18 months, tossing out a raft of movies that felt as if they were formed backwards from an already unimpressive elevator pitch: Night Swim (haunted pool!); AfrAId (haunted Alexa device!); House of Spoils (Ariana DeBose!). Things may, however, be looking up. As much as it pains me to slander a film that made smart use of Nineties stalwarts Freddie Prinze Jr and Jennifer Love Hewitt, it is something of a relief that I Know What You Did Last Summer couldn't get people in cinema seats last week. A largely serviceable but poorly directed slasher pastiche, the film may have lifted the story beats and faces from the 1997 original, but it failed at the things that truly matter: character development, suspense, memorable chase sequences. It seemed to prove that, when it comes to horror, box-office success in 2025 requires far more than just dusting off some old IP and hoping for the best. Hollywood does have a knack for taking all the wrong lessons from its success stories. (Just look at how Barbie's gargantuan box office has led to the development of loads of other movies about toys.) But wouldn't it be lovely if the triumph of Sinners sparked an influx of expensive, original horror movies moving forward – and not, well, Sinners 2. 'Weapons' is released 8 August

How Happy Gilmore 2 subtly honors Adam Sandler's late co-star Cameron Boyce
How Happy Gilmore 2 subtly honors Adam Sandler's late co-star Cameron Boyce

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How Happy Gilmore 2 subtly honors Adam Sandler's late co-star Cameron Boyce

Adam Sandler managed to sneak in a subtle, yet heartwarming, tribute to his late Grown Ups co-star Cameron Boyce in the new Happy Gilmore sequel. Happy Gilmore 2, out now on Netflix, follows Sandler's titular retired golfer, Happy Gilmore, as he returns to the sport in order to pay for his daughter to attend a Parisian ballet school. It comes nearly 30 years after the original 1996 classic sports comedy. In one scene, Happy is seen walking up to a golf course check-in booth with a bag of clubs on his shoulder. As he nears the desk, the attendants inside are watching what appears to be an episode of Disney Channel's sitcom Jessie. The screen quickly flashes to show Boyce's character Luke Ross, whom he played throughout the show's entire 2011 to 2015 run. The brief nod to Boyce — who starred as Sandler's on-screen son in the 2010 family comedy Grown Ups and its 2013 sequel before his sudden death in 2019 — has left fans overcome with emotion. 'Adam Sandler honoring Cameron Boyce in Happy Gilmore 2 melts my heart,' one said on X, while a second added: 'Excuse me while I sob.' A third commented: 'Adam Sandler subtly including Cameron Boyce in this scene from #HappyGilmore2 hits different.' 'Happy Gilmore 2 was great,' another praised. 'The honoring of Cameron Boyce was such a cute and awesome Easter egg. Bottom right of the screen they're watching them on TV. Adam Sandler you killed it. Family is very happy.' Someone else on TikTok wrote that the tribute 'is hurting and healing my heart at the same time.' Boyce was only 20 when he died after experiencing a seizure in his sleep. At the time, his family released a statement, explaining the seizure 'was a result of an ongoing medical condition for which he was being treated.' 'The world is now undoubtedly without one of its brightest lights, but his spirit will live on through the kindness and compassion of all who knew and loved him. We are utterly heartbroken,' they added. Sandler was among many celebrities to honor Boyce after his death, posting on X: 'Loved that kid. Cared so much about his family. Cared so much about the world. Thank you, Cameron, for all you gave to us. So much more was on the way. All our hearts are broken.' Boyce isn't the only celebrity to make a surprise cameo in the new movie. Dozens of other cameo appearances from professional golfers, athletes and celebrities — some of which were announced when the film was in production — are also featured. Happy Gilmore 2 is streaming now on Netflix.

Genentech and Roche Present New Insights in Alzheimer's Disease Research Across Its Diagnostics and Pharmaceutical Portfolios at AAIC
Genentech and Roche Present New Insights in Alzheimer's Disease Research Across Its Diagnostics and Pharmaceutical Portfolios at AAIC

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Genentech and Roche Present New Insights in Alzheimer's Disease Research Across Its Diagnostics and Pharmaceutical Portfolios at AAIC

– Trontinemab's Phase Ib/IIa Brainshuttle™ AD study continues to show rapid and robust clearance of amyloid plaques, with 91% becoming amyloid PET negative and ARIA-E remaining <5% – – Design of the Phase III TRONTIER 1 and 2 studies of trontinemab in early symptomatic Alzheimer's disease featured, with initiation planned in 2025 – – Plans for new Phase III trial investigating trontinemab in preclinical Alzheimer's disease, in people at high risk of cognitive decline – – New real-world data support Elecsys pTau217 as a standalone blood test, comparable to a PET scan, for rule-in and rule-out identification of amyloid pathology – SOUTH SAN FRANCISCO, Calif., July 28, 2025--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) announced today that new data from its Alzheimer's development portfolio is being presented at the Alzheimer's Association International Conference (AAIC) in Toronto, Canada (July 27-30). These data exemplify the comprehensive approach Roche is taking in addressing Alzheimer's across the entire patient journey. Featured oral presentations include the latest results from the ongoing Phase Ib/IIa Brainshuttle™ AD study, which continue to support rapid and robust reduction of amyloid plaques, and design of the Phase III TRONTIER 1 and 2 studies of investigational trontinemab for early symptomatic Alzheimer's disease, with initiation planned later this year. As part of its growing Alzheimer's development program, Roche announced today its plans for an additional Phase III trial to investigate trontinemab in preclinical Alzheimer's disease. The trial will focus on individuals at risk of cognitive decline, with the goal of potentially delaying or preventing the progression of the disease to symptomatic stages. "Alzheimer's disease represents one of the greatest challenges in healthcare today and tackling it requires early detection and effective therapeutics," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "Trontinemab is designed to target a key driver of Alzheimer's disease biology more effectively in the brain. Combining new treatment avenues with advanced diagnostics may enable earlier and potentially more effective intervention. With plans for Phase III trials in both early symptomatic and preclinical Alzheimer's disease, we are advancing science with the goal of delaying—and ultimately preventing—progression of this devastating condition." Late-breaking oral and poster presentations highlight the potential of Roche's Elecsys® pTau217 as a reliable and accessible blood-based biomarker test, providing comparable results to PET scan and cerebrospinal fluid (CSF) diagnostics for rule-in and rule-out diagnosis of amyloid pathology, a hallmark of Alzheimer's disease, across care settings. The test, which received Breakthrough Device Designation from the U.S. Food and Drug Administration last year, will also be utilized in Roche's TRONTIER studies. "Blood based testing for Alzheimer's disease has the potential to greatly improve patient access and decrease the time to definitive disease diagnosis," said Matt Sause, CEO of Roche Diagnostics. "Our data show that the Elecsys pTau217 test performs comparably to PET scans but can be performed with a simple blood draw and analyzed in a routine clinical laboratory. This has the potential to transform the diagnosis of Alzheimer's and provide clear answers to caregivers, patients, and their families." Up to 75% of people living with symptoms of Alzheimer's disease globally have not been diagnosed, and those who have, waited an average of 2.8 years, and even less have received any form of treatment. Diagnostics play a crucial role in addressing the global challenge of Alzheimer's, not only to detect and identify people with the disease early, even before the first symptoms, but also to rule out those who may or may not benefit from specific treatments. Pharmaceuticals In a 90-minute Featured Research session, designs were shared for the Phase III studies, TRONTIER 1 and 2, which will initiate later this year, investigating the efficacy and safety of investigational trontinemab in people with early Alzheimer's disease. The primary endpoint will measure the change in cognition and function based on the Clinical Dementia Rating – Sum of Boxes scale after 18 months of treatment. Secondary endpoints will include assessments of cognition, function, behavioral symptoms, and quality of life. A pre-screening study, TRAVELLER, based on a brief clinical assessment and a plasma biomarker, which will be identified using the Elecsys pTau217 test, has also been initiated, to enable broader community outreach and extend access to these trials to more diverse populations representative of Alzheimer's disease. New data on the latest results for trontinemab from the completed dose-expansion part of the 1.8 mg/kg and 3.6 mg/kg cohorts from the ongoing Phase Ib/IIa Brainshuttle AD study continued to show rapid and robust reduction of amyloid plaques in the brain as measured by amyloid positron emission tomography (PET). In the 3.6 mg/kg cohort, trontinemab reduced amyloid levels below the 24 centiloid positivity threshold in 91% of participants (n=49/54) after 28 weeks of treatment; 72% (n=39/54) achieved deep clearance below 11 centiloids. These data were reinforced by early and significant reductions in fluid biomarkers of Alzheimer's disease, including total tau, phosphorylated Tau (pTau)181, pTau217, and neurogranin measured in CSF and continues to show a favourable safety and tolerability profile. Amyloid-related imaging abnormalities-edema/effusion (ARIA-E) continued to be observed in <5% of participants (blinded data; N=4/149 across 1.8 and 3.6 mg/kg dose cohorts). All cases were radiographically mild, one was associated with mild and transient symptoms. Diagnostics Roche will present data on a new study comparing the pTau217/Ab42 plasma ratio to the high-throughput, fully automated Elecsys pTau217 assay. The presentation will report on the accuracy of these tools in detecting amyloid pathology. Together with the high throughput and full automation of the assay, these data will assess the potential of Elecsys pTau217 as an accurate standalone rule-in and rule-out test that could be scaled up for broad implementation in routine clinical practice worldwide. Additionally, results from a cohort-based model of healthcare utilization in the U.S. demonstrated that using the Elecsys® pTau181 blood-based rule-out test in primary care scenarios improved diagnostic accuracy and reduced resource use compared with the current standard-of-care clinical, cognitive and imaging tests. If made available in primary care settings, the Roche Elecsys® pTau181 blood test has the potential to reliably avoid the need for further confirmatory testing in nearly all people who receive a negative result. This will avoid the need for these people to undergo unnecessary testing using CSF or PET, which often come with long wait times and high cost, resulting in further delays to diagnosis and cost to healthcare systems. Medicine Abstract title Presentation number (type) Presentation date (session) Time Abstracts will be available on the AAIC website. Pharmaceuticals Next wave of innovation in Alzheimer's disease therapeutics: The value of novel active transport mechanisms Featured Research Session (FRS), Talk 1 Room 718 27 July 2025, 2pm - 3:30pm EDT Cath Mummery, Roberto Villaseñor, Jens Niewoehner, Scarlett Barker, Luka Kulic Latest results from the dose-expansion part (Part 2) of the Brainshuttle™ AD study of trontinemab in people with Alzheimer's disease Featured Research Session (FRS), Talk 2 Room 718 27 July 2025, 2pm - 3:30pm EDT Luka Kulic, Fabien Alcaraz, Gregory Klein, Stephen Salloway, Carsten Hofmann, João A. Abrantes, Stella Yilmaz, Denise Sickert, Maddalena Marchesi, Jakub Wojtowicz, Andres Schneider, Ruth Croney, David Agnew, Silke Ahlers, Paul Delmar, Hanno Svoboda, Iris Wiesel Interim biomarker results for trontinemab, a novel Brainshuttle™ antibody in development for the treatment of Alzheimer's disease Featured Research Session (FRS), Talk 3 Room 718 27 July 2025, 2pm - 3:30pm EDT Gregory Klein, Gil Rabinovici, Henrik Zetterberg, Matteo Tonietto, Tobias Bittner, Daria Rukina, Fabien Alcaraz, Carsten Hofmann, Maddalena Marchesi, Jakub Wojtowicz, Ruth Croney, David Agnew, João A. Abrantes, Franziska Schaedeli Stark, Silke Ahlers, Paul Delmar, Hanno Svoboda, Iris Wiesel, Luka Kulic TRONTIER 1 and TRONTIER 2: Pivotal trials of trontinemab in early symptomatic Alzheimer's disease Featured Research Session (FRS), Talk 4 Room 718 27 July 2025, 2pm - 3:30pm EDT Janice Smith, Catherine Mummery, Jeffrey L. Cummings, Gil Rabinovici, Stephen Salloway, Reisa Sperling, Henrik Zetterberg, Angeliki Thanasopolou, Christopher Lane, Paul Delmar, Gregory Klein, Ruth Croney, Jakub Wojtowicz, Carsten Hofmann, Luka Kulic, Hideki Garren Diagnostics Evaluating the Impact on Diagnostic Performance and Healthcare Resource Utilization of Introducing a plasma rule-out test in the Alzheimer's Disease Diagnostic Pathway Poster #102729 27 July 2025, 7:30am - 4:15pm EDT Sophie Roth, Gustaf Ortsäter, Joana Amorim Freire Location tbc Evaluating the Clinical Performance of the Elecsys pTau217 Plasma Immunoassay to Detect Amyloid Pathology in a Routine Clinical Practice Cohort Poster #96679 28 July 2025, 7:30am – 4:15pm EDT Sayuri Hortsch, Niels Borlinghaus, Alexander Jethwa, David Caley, Annunziata Di Domenico, Craig Ritchie Clinical performance and effect of pre-analytical variation of plasma pTau217 alone versus the plasma pTau217/Aβ42 ratio for the identification of amyloid pathology Oral Developing Topics #108585 3-23-DEV Developing Topics on Tau Biomarkers 29 July 2025, 2:00pm – 3:30pm EDT Christopher M. Rank, Joana Amorim Freire, Alexander Jethwa, Annunziata Di Domenico, Christina Rabe, Marc Suárez-Calvet, Colin L. Masters, Tobias Bittner Accuracy of cerebrospinal fluid biomarker ratios to determine amyloid positron-emission tomography status: a diagnostic test accuracy meta-analysis Poster #100941 28 July 2025, 7:30am – 4:15pm EDT Pablo Martinez-Lage, Eino Solje, Julian G. Martins, Sraboni Sarkar Equity in diagnosis through adequate clinical trial design in diagnostic performance studies Poster #102804 30 July 2025, 7:30am - 4:15pm EDT Imke Kirste, David Caley, Clara Quijano Rubio, Margherita Carboni Investigating Differences in Patients Enrolled in a Clinical Study Based on Referral Type Poster #108110 30 July 2025, 7:30am - 4:15pm EDT Sophie Roth, Laura Schlieker, Sayuri Hortsch, Joana Amorim Freire, David Caley About trontinemab Trontinemab is an investigational Brainshuttle bispecific 2+1 amyloid-beta targeting monoclonal antibody specifically engineered for enhanced access to the brain to enable rapid reduction of amyloid in people with Alzheimer's disease. Trontinemab is designed for the efficient transport across the blood-brain barrier to target aggregated forms of amyloid beta and remove amyloid plaques in the brain. The uniqueness of trontinemab is based on Roche's proprietary Brainshuttle technology combining an amyloid beta-binding antibody with a transferring receptor (TfR1) shuttle module. As a result, high central nervous system (CNS) exposure of trontinemab may be achieved at low doses, leading to a rapid and deep amyloid clearance. Due to its unique properties, trontinemab might unlock the full potential of disease-modifying monoclonal antibodies by effectively penetrating the brain and potentially leading to slowing of disease progression. About Roche in Alzheimer's Disease With more than two decades of scientific research in Alzheimer's disease, Roche is working towards a day when we can detect and treat the disease early, in order to slow down, stop or even prevent its progression to preserve what makes people who they are. Today, the company's Alzheimer's disease portfolio spans investigational medicines for different targets, types and stages of the disease, including trontinemab. On the diagnostics side, it also includes approved and investigational tools, including digital and blood-based tests and CSF assays, aiming to more effectively detect, diagnose and monitor the disease. Yet the global challenges of Alzheimer's disease go well beyond the capabilities of science, and making a meaningful impact requires collaboration both within the Alzheimer's community and outside of healthcare. Roche will continue to work together with numerous partners with the hope to transform millions of lives. About Genentech in Neuroscience Neuroscience is a major focus of research and development at Genentech. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer's disease, Huntington's disease, Parkinson's disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit View source version on Contacts Media Contact: Meghan Hindman (650) 467-6800Advocacy Contact: Jenee Williams (650) 303-2958Investor Contacts: Loren Kalm (650) 225-3217Bruno Eschli +41616875284 Error while retrieving data Sign in to access your portfolio Error while retrieving data Error while retrieving data Error while retrieving data Error while retrieving data

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